A Safety Study of AZD4041 in Healthy Participants

Study identifier:D7460C00002

ClinicalTrials.gov identifier:NCT05233085

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of AZD4041 in Healthy Adult Subjects

Medical condition

Opioid Use Disorder (OUD)

Phase

Phase 1

Healthy volunteers

Yes

Study drug

AZD4041

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 55 Years

Date

Study Start Date: 17 Dec 2021

Primary Completion Date: 07 Jun 2022

Study Completion Date: 07 Jun 2022

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Nov 2023 by AstraZeneca

Collaborators

Altasciences Company Inc.

Inclusion and exclusion criteria

Inclusion Criteria

• Provision of signed and dated written informed consent form prior to any study specific procedures
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Healthy adult male or female participants. Female participants must be of non-childbearing potential (postmenopausal and/or surgically sterile)
• If female, meets one of the following criteria:
(1) Physiological postmenopausal status, defined as the following:
a) absence of menses for at least 12 months following cessation of all exogenous hormonal treatments (without an alternative medical condition) at Screening and prior to the first study drug administration; and
b) follicle stimulating hormone (FSH) levels ≥ 40 mIU/mL at Screening; and
c) must have a negative pregnancy test result at screening and check-in.
and/or
(2) Surgical sterile, defined as those who have had:
hysterectomy, bilateral oophorectomy and/or bilateral salpingectomy, or bilateral tubal ligation. Women who are surgically sterile must provide documentation of the procedure by an operative report, ultrasound, or other verifiable documentation; and must have a negative pregnancy test result at screening and check-in.
If postmenopausal and has an FSH of < 40 mIU/mL, but meets all other criteria in (1) or (2) above as well as all the other inclusion criteria, screening oestradiol serum level must be equal to or below 150 pmol/L.
• Men who are biologically capable of fathering children must agree and commit to use an adequate form of contraception for the duration of the treatment period and for no less than 120 days (4 months) after the last administration of study intervention. A male participant is considered capable of fathering children even if his sexual partner is sterile or using contraceptives.
• Men who are biologically capable of fathering children must also agree to refrain from sperm donation for the duration of the treatment period and for at least 90 days after the last administration of study intervention.
• Aged at least 18 years but not older than 55 years on the day of randomization
• Body mass index (BMI) within 18.0 kg/m^2 to 30.0 kg/m^2, inclusive
• Body weight of within 50 kg to 100 kg, inclusive
• Non- or ex-smoker (An ex-smoker is defined as someone who completely stopped using nicotine products for at least 180 days prior to the first study drug administration)
• Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on the physical or neurological examination (including vital signs) and/or ECG and/or safety laboratory tests, as determined by an Investigator
• Suitable veins for cannulation or repeated venepuncture

Exclusion Criteria

• Female who is lactating
• Female who is pregnant according to the pregnancy test at Screening or prior to the first study drug administration
• Male participants with a history of oligospermia or azoospermia or any other disorder of the reproductive system
• Male participants who are undergoing treatment or evaluation for infertility.
• History of significant allergy/ hypersensitivity to AZD4041 or products related to AZD4041 as well as severe allergy/hypersensitivity reactions (like angioedema) to any drugs
• Presence or history of significant gastrointestinal, liver or kidney disease, or any other condition that is known to interfere with drug absorption, distribution, metabolism, or excretion, or known to potentiate or predispose to undesired effects
• History of any significant disease, including [but not necessarily limited to] significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic, or dermatologic disease
• Maintenance therapy with any drug or significant history of drug dependency or alcohol abuse (> 21 units/week or > 3 units/day for men; > 14 units/week or > 2 units/day for women; intake of excessive alcohol, acute or chronic)
• History of any significant psychiatric disorder according to the criteria of the Diagnostic and Statistical manual of Mental Disorders, 5th Edition (DSM-5, American Psychiatric Association 2013) which, in the opinion of the Investigator, could be detrimental to participant safety or could compromise study data interpretation.
• History of substance use disorder, other than nicotine or caffeine (as per DSM-5 criteria)
• Use of any prescription drugs, including hormone replacement therapy in the 28 days prior to the first study drug administration, that in the opinion of an Investigator would put into question the status of the participant as healthy
• Use of St. John’s wort in the 28 days prior to the first study drug administration
• Positive test result for alcohol and/or drugs of abuse at Screening or prior to the first study drug administration
• Any clinically significant illness, medical/surgical procedure or trauma within the 28 days prior to the first study drug administration
• Any abnormal or clinically significant findings in laboratory test results at Screening that would, in the opinion of an Investigator, increase the participant's risk of participation, jeopardize complete participation in the study, or compromise interpretation of study data
• Positive screening results to human immunodeficiency virus (HIV) antigen/antibody (Ag/Ab) combo, hepatitis B surface antigen, or hepatitis C virus tests
• Showing suicidal tendency as per the C-SSRS questionnaire administered at Screening
• Any abnormal vital signs, after 10 minutes supine rest, as defined in the list below, at the Screening Visit/or Day -2 Out of range tests may be repeated once for each visit at the discretion of an Investigator.
a. Systolic blood pressure (BP) < 90 mmHg or >140 mmHg
b. Diastolic BP < 50 mmHg or > 90 mmHg
c. Heart Rate < 45 or > 85 beats per minute (bpm)
• Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG and any clinically important abnormalities in the 12-lead ECG which, in an Investigator’s opinion, may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology, particularly in the protocol-defined primary lead or left ventricular hypertrophy at Screening or prior to the first study drug administration
• Prolonged QT interval corrected for HR using Fridericia’s formula (QTcF) > 440 ms at Screening or prior to the first study drug administration
• Shortened QTcF < 340 ms at Screening or prior to first study drug administration
• Known family history of long QT syndrome
• ECG interval measured from the onset of the P wave to the onset of the complex between Q and S waves (QRS complex) (PR [PQ]) interval shortening < 120 ms (PR > 110 ms but < 120 ms is acceptable if there is no evidence of ventricular preexcitation) at Screening or prior to the first study drug administration
• PR (PQ) interval prolongation (> 220 ms), persistent or intermittent second (Wenckebach block while asleep is not exclusive), or third degree atrioventricular (AV) block, or AV dissociation at Screening or prior to the first study drug administration
• Persistent or intermittent complete bundle branch block, incomplete bundle branch block, or intraventricular conduction delay (IVCD) with ECG interval measured from the onset of the QRS complex to the J point (QRS) > 110 ms. Participants with QRS > 110 ms but < 115 ms are acceptable if there is no evidence of ventricular hypertrophy or preexcitation at Screening or prior to the first study drug administration
• In the pre-dose 24 hour telemetry, presence of ≥ 10 ventricular premature contractions (VPCs) during 1 hour, or ≥ 100 VPCs during 24–hours of telemetry, or any occurrence of paired VPC (ventricular couplets) or other repetitive ventricular rhythms, including non-sustained or sustained (> 30 second duration), slow (< 100 bpm), or fast (≥ 100 bpm) ventricular tachycardias.
• Vaccination with the Coronavirus disease 2019 (COVID-19) vaccine less than 14 days prior to first study dose administration
• Scheduled immunization with a COVID-19 vaccine (first or second dose) during the study that, in the opinion of an Investigator, could potentially interfere with participant participation, participant safety, study results, or any other reason
• Use of any prescribed or nonprescribed oral and topical inhibitors/inducers of CYP3A4 (including shampoo).
• Excessive intake of caffeine-containing drinks or food (eg, coffee, tea, chocolate) as judged by an Investigator
• Participants who have previously received AZD4041
• Any history of tuberculosis
• Involvement of any AstraZeneca or study site employee or their close relatives
• Judgment by an Investigator that the participant should not participate in the study if they have any ongoing or recent (ie, during the Screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions, and requirements
• Presence of any tongue piercings or history of any tongue piercings in the last 90 days prior to the first study drug administration
• Participants who have medical dietary restrictions
• Participants who cannot communicate reliably with the Investigator
• Inclusion in a previous group for this clinical study
• Intake of an investigational product (IP) within at least 28 days or 5 half-lives; whichever is longer, prior to the first study drug administration
• Donation of 50 mL or more of blood in the 28 days prior to the first study drug administration
• Donation of 500 mL or more of blood in the 56 days prior to the first study drug administration

Location

Research Site

Laval, QC, Canada, h7v 4bc

Arms	Assigned Interventions
Experimental: Cohort 1: AZD4041 Dose Level 1 Participants will receive oral solution of AZD4041 dose level 1 once daily (QD) directly into the mouth using a syringe from Days 1 to 14.	Drug: AZD4041 Participants will receive oral solution of AZD4041 as stated in arm description.
Experimental: Cohort 2: AZD4041 Dose Level 2 Participants will receive oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.	Drug: AZD4041 Participants will receive oral solution of AZD4041 as stated in arm description.
Experimental: Cohort 3: AZD4041 Dose Level 3 Participants will receive oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.	Drug: AZD4041 Participants will receive oral solution of AZD4041 as stated in arm description.
Placebo Comparator: Cohorts 1-3: Pooled Placebo Participants will receive oral solution of placebo equivalent to AZD4041 volume QD directly into the mouth using a syringe from Days 1 to 14.	Other: Placebo Participants will receive oral solution of placebo as stated in arm description.

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 once daily (QD) directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.
Cohorts 1-3: Pooled Placebo	Participants received oral solution of placebo equivalent to AZD4041 volume QD directly into the mouth using a syringe from Days 1 to 14.

Participant Flow: Overall Study

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3	Cohorts 1-3: Pooled Placebo
STARTED	9	9	9	9
COMPLETED	8	9	9	9
NOT COMPLETED	1	0	0	0
Adverse Event	1	0	0	0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Safety population included all participants who received at least 1 dose of AZD4041 or placebo.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.
Cohorts 1-3: Pooled Placebo	Participants received oral solution of placebo equivalent to AZD4041 volume QD directly into the mouth using a syringe from Days 1 to 14.

Baseline Measures

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3	Cohorts 1-3: Pooled Placebo	Total
Number of Participants [units: Participants]	9	9	9	9	36
Age Continuous [units: Years] Mean ± Standard Deviation	41.9 ± 11.7	37.1 ± 8.9	40.2 ± 10.8	41.6 ± 11.6	40.2 ± 10.5
Sex: Female, Male [units: Participants]
Female	0	0	0	1	1
Male	9	9	9	8	35
Race (NIH/OMB) [units: Participants]
American Indian or Alaska Native	0	0	0	0	0
Asian	1	0	1	0	2
Native Hawaiian or Other Pacific Islander	0	0	0	0	0
Black or African American	0	1	0	1	2
White	8	8	8	8	32
More than one race	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0
Ethnicity (NIH/OMB) [units: Participants]
Hispanic or Latino	4	3	5	0	12
Not Hispanic or Latino	5	6	4	9	24
Unknown or Not Reported	0	0	0	0	0

Outcome Measures

1. Primary Outcome Measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) [ Time Frame: From Day 1 to Day 31 ]

Measure Type	Primary
Measure Name	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Measure Description	An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Time Frame	From Day 1 to Day 31
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety population included all participants who received at least 1 dose of AZD4041 or placebo.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.
Cohorts 1-3: Pooled Placebo	Participants received oral solution of placebo equivalent to AZD4041 volume QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3	Cohorts 1-3: Pooled Placebo
Number of Participants Analyzed [units:participants]	9	9	9	9
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) [units: Participants]
Any TEAEs	8	6	6	9
Any TESAEs	0	0	0	0

No statistical analysis provided for Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

2. Primary Outcome Measure: Number of Participants With Abnormal Vital Signs Reported as TEAEs [ Time Frame: From Day 1 to Day 31 ]

Measure Type	Primary
Measure Name	Number of Participants With Abnormal Vital Signs Reported as TEAEs
Measure Description	Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (blood pressure, pulse rate, and body temperature).
Time Frame	From Day 1 to Day 31
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety population included all participants who received at least 1 dose of AZD4041 or placebo.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.
Cohorts 1-3: Pooled Placebo	Participants received oral solution of placebo equivalent to AZD4041 volume QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3	Cohorts 1-3: Pooled Placebo
Number of Participants Analyzed [units:participants]	9	9	9	9
Number of Participants With Abnormal Vital Signs Reported as TEAEs [units: Participants]	1	0	0	0

No statistical analysis provided for Number of Participants With Abnormal Vital Signs Reported as TEAEs

3. Primary Outcome Measure: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs [ Time Frame: From Day 1 to Day 31 ]

Measure Type	Primary
Measure Name	Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Measure Description	Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of general biochemistry, hematology, and urinalysis.
Time Frame	From Day 1 to Day 31
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety population included all participants who received at least 1 dose of AZD4041 or placebo.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.
Cohorts 1-3: Pooled Placebo	Participants received oral solution of placebo equivalent to AZD4041 volume QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3	Cohorts 1-3: Pooled Placebo
Number of Participants Analyzed [units:participants]	9	9	9	9
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs [units: Participants]	0	0	0	0

No statistical analysis provided for Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs

4. Primary Outcome Measure: Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs [ Time Frame: From Day 1 to Day 31 ]

Measure Type	Primary
Measure Name	Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs
Measure Description	Number of participants with abnormal ECGs reported as TEAEs are reported.
Time Frame	From Day 1 to Day 31
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety population included all participants who received at least 1 dose of AZD4041 or placebo.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.
Cohorts 1-3: Pooled Placebo	Participants received oral solution of placebo equivalent to AZD4041 volume QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3	Cohorts 1-3: Pooled Placebo
Number of Participants Analyzed [units:participants]	9	9	9	9
Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs [units: Participants]
Ventricular tachycardia	1	0	1	1
Sinus tachycardia	1	0	0	0

No statistical analysis provided for Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs

5. Primary Outcome Measure: Number of Participants with Suicidal Ideation or Behavior Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline (Days -28 to -1) through Day 17 ]

Measure Type	Primary
Measure Name	Number of Participants with Suicidal Ideation or Behavior Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS)
Measure Description	The C-SSRS is described as a scale developed at Columbia University that has 2-6 questions each in categories of Suicidal Ideation, Intensity of Ideation, Suicidal Behavior, and Actual Attempts. Four constructs were measured. Severity of Suicidal ideation is rated on a 5-point ordinal scale. Intensity of ideation is comprised of 5 items (frequency, duration, controllability, deterrents, and reason for ideation), each rated on a 5-point ordinal scale. Suicidal behavior is rated on a nominal scale that includes actual, aborted, and interrupted attempts; preparatory behavior; and non-suicidal self-injurious behavior. Lethality, assesses actual attempts; actual lethality is rated on a 6-point ordinal scale, and if actual lethality is 0, potential lethality of attempts is rated on a 3-point ordinal scale.The higher the C-SSRS score, the higher the suicide risk (ie. worse outcome).
Time Frame	Baseline (Days -28 to -1) through Day 17
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety population included all participants who received at least 1 dose of AZD4041 or placebo.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.
Cohorts 1-3: Pooled Placebo	Participants received oral solution of placebo equivalent to AZD4041 volume QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3	Cohorts 1-3: Pooled Placebo
Number of Participants Analyzed [units:participants]	9	9	9	9
Number of Participants with Suicidal Ideation or Behavior Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) [units: Participants]
Suicidal ideation	0	0	0	0
Suicidal behavior	0	0	0	0

No statistical analysis provided for Number of Participants with Suicidal Ideation or Behavior Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS)

6. Primary Outcome Measure: Number of Participants With Clinically Significant Findings in Physical and Neurological Examinations [ Time Frame: Baseline (Days -28 to -1) through Day 31 ]

Measure Type	Primary
Measure Name	Number of Participants With Clinically Significant Findings in Physical and Neurological Examinations
Measure Description	Number of participants with clinically significant findings in physical and neurological examinations are reported.
Time Frame	Baseline (Days -28 to -1) through Day 31
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety population included all participants who received at least 1 dose of AZD4041 or placebo.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.
Cohorts 1-3: Pooled Placebo	Participants received oral solution of placebo equivalent to AZD4041 volume QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3	Cohorts 1-3: Pooled Placebo
Number of Participants Analyzed [units:participants]	9	9	9	9
Number of Participants With Clinically Significant Findings in Physical and Neurological Examinations [units: Participants]	0	0	0	0

No statistical analysis provided for Number of Participants With Clinically Significant Findings in Physical and Neurological Examinations

7. Primary Outcome Measure: Number of Participants With Abnormal Male Hormone Levels as Assessed by the Investigator [ Time Frame: Day -1, pre-dose and 1.5 hours post-dose on Days 1 and 14 ]

Measure Type	Primary
Measure Name	Number of Participants With Abnormal Male Hormone Levels as Assessed by the Investigator
Measure Description	Male hormone levels investigated included testosterone, luteinizing hormone, follicle stimulating hormone, and inhibin B. Number of Participants with abnormal male hormone levels as assessed by the investigator are reported.
Time Frame	Day -1, pre-dose and 1.5 hours post-dose on Days 1 and 14
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety population included all participants who received at least 1 dose of AZD4041 or placebo.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.
Cohorts 1-3: Pooled Placebo	Participants received oral solution of placebo equivalent to AZD4041 volume QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3	Cohorts 1-3: Pooled Placebo
Number of Participants Analyzed [units:participants]	9	9	9	9
Number of Participants With Abnormal Male Hormone Levels as Assessed by the Investigator [units: Participants]	0	0	0	0

No statistical analysis provided for Number of Participants With Abnormal Male Hormone Levels as Assessed by the Investigator

8. Secondary Outcome Measure: Maximum Observed Plasma Concentration (Cmax) of AZD4041 After Day 1 Dose [ Time Frame: Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose ]

Measure Type	Secondary
Measure Name	Maximum Observed Plasma Concentration (Cmax) of AZD4041 After Day 1 Dose
Measure Description	The Cmax of AZD4041 after Day 1 dose is reported.
Time Frame	Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic (PK) population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	9	9	9
Maximum Observed Plasma Concentration (Cmax) of AZD4041 After Day 1 Dose [units: ng/mL] Geometric Mean (Geometric Coefficient of Variation)	165.93 (24.3%)	377.85 (25.7%)	590.78 (12.6%)

No statistical analysis provided for Maximum Observed Plasma Concentration (Cmax) of AZD4041 After Day 1 Dose

9. Secondary Outcome Measure: Maximum Observed Plasma Concentration (Cmax) of AZD4041 After Day 14 Dose [ Time Frame: Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose ]

Measure Type	Secondary
Measure Name	Maximum Observed Plasma Concentration (Cmax) of AZD4041 After Day 14 Dose
Measure Description	The Cmax of AZD4041 after Day 14 dose is reported.
Time Frame	Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic (PK) population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing. Here, number of participants analyzed (N) indicates those participants who had adequate PK samples and excludes participants with inadequate PK samples due to missed blood draw, an AE, meal deviation, or concomitant medication intake.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	8	9	9
Maximum Observed Plasma Concentration (Cmax) of AZD4041 After Day 14 Dose [units: ng/mL] Geometric Mean (Geometric Coefficient of Variation)	232.44 (20.7%)	478.10 (21.7%)	940.99 (25.7%)

No statistical analysis provided for Maximum Observed Plasma Concentration (Cmax) of AZD4041 After Day 14 Dose

10. Secondary Outcome Measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of AZD4041 After Day 1 Dose [ Time Frame: Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose ]

Measure Type	Secondary
Measure Name	Time to Reach Maximum Observed Plasma Concentration (Tmax) of AZD4041 After Day 1 Dose
Measure Description	The Tmax of AZD4041 after Day 1 dose is reported.
Time Frame	Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	9	9	9
Time to Reach Maximum Observed Plasma Concentration (Tmax) of AZD4041 After Day 1 Dose [units: Hour] Median (Full Range)	1.05 (0.50 to 1.53)	1.00 (0.25 to 1.50)	1.02 (0.55 to 1.50)

No statistical analysis provided for Time to Reach Maximum Observed Plasma Concentration (Tmax) of AZD4041 After Day 1 Dose

11. Secondary Outcome Measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of AZD4041 After Day 14 Dose [ Time Frame: Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose ]

Measure Type	Secondary
Measure Name	Time to Reach Maximum Observed Plasma Concentration (Tmax) of AZD4041 After Day 14 Dose
Measure Description	The Tmax of AZD4041 after Day 14 dose is reported.
Time Frame	Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing. Here, number of participants analyzed (N) indicates those participants who had adequate PK samples and excludes participants with inadequate PK samples due to missed blood draw, an AE, meal deviation, or concomitant medication intake.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	8	9	9
Time to Reach Maximum Observed Plasma Concentration (Tmax) of AZD4041 After Day 14 Dose [units: Hour] Median (Full Range)	1.02 (0.50 to 2.00)	1.02 (0.50 to 1.52)	1.00 (0.50 to 3.02)

No statistical analysis provided for Time to Reach Maximum Observed Plasma Concentration (Tmax) of AZD4041 After Day 14 Dose

12. Secondary Outcome Measure: Area Under the Concentration-time Curve From Time Zero to 24 hours (AUC0-24) of AZD4041 After Day 1 Dose [ Time Frame: Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose ]

Measure Type	Secondary
Measure Name	Area Under the Concentration-time Curve From Time Zero to 24 hours (AUC0-24) of AZD4041 After Day 1 Dose
Measure Description	The AUC0-24 of AZD4041 after Day 1 dose is reported.
Time Frame	Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	9	9	9
Area Under the Concentration-time Curve From Time Zero to 24 hours (AUC0-24) of AZD4041 After Day 1 Dose [units: h*ng/mL] Geometric Mean (Geometric Coefficient of Variation)	1802.21 (21.4%)	3682.61 (25.2%)	6951.39 (20.1%)

No statistical analysis provided for Area Under the Concentration-time Curve From Time Zero to 24 hours (AUC0-24) of AZD4041 After Day 1 Dose

13. Secondary Outcome Measure: Area under the Concentration-time Curve From Time 0 (Dose Administration) to the Time of Last Quantifiable Concentration (AUC0-t) of AZD4041 After Day 1 Dose [ Time Frame: Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose ]

Measure Type	Secondary
Measure Name	Area under the Concentration-time Curve From Time 0 (Dose Administration) to the Time of Last Quantifiable Concentration (AUC0-t) of AZD4041 After Day 1 Dose
Measure Description	The AUC0-t of AZD4041 after Day 1 dose is reported.
Time Frame	Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	9	9	9
Area under the Concentration-time Curve From Time 0 (Dose Administration) to the Time of Last Quantifiable Concentration (AUC0-t) of AZD4041 After Day 1 Dose [units: h*ng/mL] Geometric Mean (Geometric Coefficient of Variation)	1802.90 (21.4%)	3683.15 (25.2%)	6953.42 (20.1%)

No statistical analysis provided for Area under the Concentration-time Curve From Time 0 (Dose Administration) to the Time of Last Quantifiable Concentration (AUC0-t) of AZD4041 After Day 1 Dose

14. Secondary Outcome Measure: Area under the Concentration-time Curve From Time 0 (Dose Administration) to the Time of Last Quantifiable Concentration (AUC0-t) of AZD4041 After Day 14 Dose [ Time Frame: Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose ]

Measure Type	Secondary
Measure Name	Area under the Concentration-time Curve From Time 0 (Dose Administration) to the Time of Last Quantifiable Concentration (AUC0-t) of AZD4041 After Day 14 Dose
Measure Description	The AUC0-t of AZD4041 after Day 14 dose is reported.
Time Frame	Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing. Here, number of participants analyzed (N) indicates those participants who had adequate PK samples and excludes participants with inadequate PK samples due to missed blood draw, an AE, meal deviation, or concomitant medication intake.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	8	9	9
Area under the Concentration-time Curve From Time 0 (Dose Administration) to the Time of Last Quantifiable Concentration (AUC0-t) of AZD4041 After Day 14 Dose [units: h*ng/mL] Geometric Mean (Geometric Coefficient of Variation)	4808.19 (60.1%)	9573.98 (47.0%)	20969.29 (49.6%)

No statistical analysis provided for Area under the Concentration-time Curve From Time 0 (Dose Administration) to the Time of Last Quantifiable Concentration (AUC0-t) of AZD4041 After Day 14 Dose

15. Secondary Outcome Measure: Area Under the Concentration-time Curve Extrapolated to Infinity (AUC0-inf) of AZD4041 After Day 1 Dose [ Time Frame: Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose ]

Measure Type	Secondary
Measure Name	Area Under the Concentration-time Curve Extrapolated to Infinity (AUC0-inf) of AZD4041 After Day 1 Dose
Measure Description	The AUC0-inf of AZD4041 after Day 1 dose is reported. This PK parameter (AUC0-inf) requiring apparent elimination rate constant (λz) estimation was not evaluable for Cohorts 1 and 3 due to meeting either the exclusion criteria R^2 < 0.8 or the extrapolated area > 20%.
Time Frame	Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing. Here, number of participants analyzed (N) indicates those participants who had adequate PK samples and excludes participants with inadequate PK samples due to missed blood draw, an AE, meal deviation, or concomitant medication intake.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	0	1	0
Area Under the Concentration-time Curve Extrapolated to Infinity (AUC0-inf) of AZD4041 After Day 1 Dose [units: h*ng/mL] Median (Full Range)		3000.93 (3000.93 to 3000.93)

No statistical analysis provided for Area Under the Concentration-time Curve Extrapolated to Infinity (AUC0-inf) of AZD4041 After Day 1 Dose

16. Secondary Outcome Measure: Area Under the Concentration-time curve Over the Dosing Interval at Steady State (AUCτ) of AZD4041 After Day 14 Dose [ Time Frame: Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose ]

Measure Type	Secondary
Measure Name	Area Under the Concentration-time curve Over the Dosing Interval at Steady State (AUCτ) of AZD4041 After Day 14 Dose
Measure Description	The AUCτ of AZD4041 calculated after Day 14 dose is reported.
Time Frame	Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing. Here, number of participants analyzed (N) indicates those participants who had adequate PK samples and excludes participants with inadequate PK samples due to missed blood draw, an AE, meal deviation, or concomitant medication intake.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	8	9	9
Area Under the Concentration-time curve Over the Dosing Interval at Steady State (AUCτ) of AZD4041 After Day 14 Dose [units: h*ng/mL] Geometric Mean (Geometric Coefficient of Variation)	3022.57 (41.3%)	6306.52 (34.4%)	12622.32 (36.0%)

No statistical analysis provided for Area Under the Concentration-time curve Over the Dosing Interval at Steady State (AUCτ) of AZD4041 After Day 14 Dose

17. Secondary Outcome Measure: Observed Concentration at the end of the Dosing Interval (Ctrough) of AZD4041 [ Time Frame: Predose on Days 2 (Day 1, 24-hours), 3, 4, 5, 6, 7, 8, 9, 10, 14 ]

Measure Type	Secondary
Measure Name	Observed Concentration at the end of the Dosing Interval (Ctrough) of AZD4041
Measure Description	The Ctrough of AZD4041 is reported.
Time Frame	Predose on Days 2 (Day 1, 24-hours), 3, 4, 5, 6, 7, 8, 9, 10, 14
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing. Here, number analyzed (n) denotes those participants who were analyzed for the specified time points.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	9	9	9
Observed Concentration at the end of the Dosing Interval (Ctrough) of AZD4041 [units: ng/mL] Geometric Mean (Geometric Coefficient of Variation)
Day 2	45.5 (39.2%)	86.2 (45.2%)	193 (35.2%)
Day 3	62.5 (46.9%)	113 (48.9%)	285 (39.4%)
Day 4	64.9 (52.4%)	124 (56.2%)	314 (43.9%)
Day 5	65.4 (54.6%)	134 (48.4%)	317 (46.2%)
Day 6	69.3 (63.6%)	139 (56.5%)	336 (46.5%)
Day 7	68.4 (64.8%)	141 (55.2%)	331 (45.8%)
Day 8	73.2 (55.6%)	158 (53.6%)	359 (44.4%)
Day 9	73.3 (59.1%)	152 (61.6%)	349 (49.9%)
Day 10	75.0 (62.8%)	158 (62.9%)	341 (46.9%)
Day 14	82.0 (64.6%)	164 (70.8%)	371 (51.9%)

No statistical analysis provided for Observed Concentration at the end of the Dosing Interval (Ctrough) of AZD4041

18. Secondary Outcome Measure: Concentration at the end of the Dosing Interval (Cτ) of AZD4041 After Day 14 Dose [ Time Frame: Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose ]

Measure Type	Secondary
Measure Name	Concentration at the end of the Dosing Interval (Cτ) of AZD4041 After Day 14 Dose
Measure Description	The Cτ of AZD4041 after Day 14 dose is reported.
Time Frame	Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing. Here, number of participants analyzed (N) indicates those participants who had adequate PK samples and excludes participants with inadequate PK samples due to missed blood draw, an AE, meal deviation, or concomitant medication intake.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	8	9	9
Concentration at the end of the Dosing Interval (Cτ) of AZD4041 After Day 14 Dose [units: ng/mL] Geometric Mean (Geometric Coefficient of Variation)	81.23 (63.2%)	168.42 (62.0%)	358.37 (56.5%)

No statistical analysis provided for Concentration at the end of the Dosing Interval (Cτ) of AZD4041 After Day 14 Dose

19. Secondary Outcome Measure: Terminal Elimination Half-life (t1/2,z) of AZD4041 After Day 1 Dose [ Time Frame: Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose ]

Measure Type	Secondary
Measure Name	Terminal Elimination Half-life (t1/2,z) of AZD4041 After Day 1 Dose
Measure Description	The t1/2,z of AZD4041 after Day 1 dose is reported. This PK parameter (t1/2,z) requiring λz estimation was not evaluable for Cohorts 1 and 3 due to meeting either the exclusion criteria R^2 < 0.8 or the extrapolated area > 20%.
Time Frame	Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing. Here, number of participants analyzed (N) indicates those participants who had adequate PK samples and excludes participants with inadequate PK samples due to missed blood draw, an AE, meal deviation, or concomitant medication intake.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	0	1	0
Terminal Elimination Half-life (t1/2,z) of AZD4041 After Day 1 Dose [units: hour] Median (Full Range)		8.30 (8.30 to 8.30)

No statistical analysis provided for Terminal Elimination Half-life (t1/2,z) of AZD4041 After Day 1 Dose

20. Secondary Outcome Measure: Terminal Elimination Half-life (t1/2,z) of AZD4041 After Day 14 Dose [ Time Frame: Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose ]

Measure Type	Secondary
Measure Name	Terminal Elimination Half-life (t1/2,z) of AZD4041 After Day 14 Dose
Measure Description	The t1/2,z of AZD4041 after Day 14 dose is reported.
Time Frame	Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing. Here, number of participants analyzed (N) indicates those participants who had adequate PK samples and excludes participants with inadequate PK samples due to missed blood draw, an AE, meal deviation, or concomitant medication intake.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	6	9	7
Terminal Elimination Half-life (t1/2,z) of AZD4041 After Day 14 Dose [units: Hour] Geometric Mean (Geometric Coefficient of Variation)	18.87 (27.5%)	20.07 (33.4%)	23.22 (20.3%)

No statistical analysis provided for Terminal Elimination Half-life (t1/2,z) of AZD4041 After Day 14 Dose

21. Secondary Outcome Measure: Effective half-life (t1/2Eff) of AZD4041 After Day 14 Dose [ Time Frame: Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose ]

Measure Type	Secondary
Measure Name	Effective half-life (t1/2Eff) of AZD4041 After Day 14 Dose
Measure Description	The t1/2Eff of AZD4041 after Day 14 dose is reported.
Time Frame	Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing. Here, number of participants analyzed (N) indicates those participants who had adequate PK samples and excludes participants with inadequate PK samples due to missed blood draw, an AE, meal deviation, or concomitant medication intake.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	8	9	9
Effective half-life (t1/2Eff) of AZD4041 After Day 14 Dose [units: Hour] Geometric Mean (Geometric Coefficient of Variation)	17.02 (50.9%)	18.35 (38.7%)	20.33 (34.2%)

No statistical analysis provided for Effective half-life (t1/2Eff) of AZD4041 After Day 14 Dose

22. Secondary Outcome Measure: Accumulation Ratio Evaluated by Comparing Day 14 Cmax to Day 1 Cmax (RAC[Cmax]) of AZD4041 [ Time Frame: Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose; Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose ]

Measure Type	Secondary
Measure Name	Accumulation Ratio Evaluated by Comparing Day 14 Cmax to Day 1 Cmax (RAC[Cmax]) of AZD4041
Measure Description	The RAC(Cmax) of AZD4041 is reported.
Time Frame	Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose; Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing. Here, number of participants analyzed (N) indicates those participants who had adequate PK samples and excludes participants with inadequate PK samples due to missed blood draw, an AE, meal deviation, or concomitant medication intake.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	8	9	9
Accumulation Ratio Evaluated by Comparing Day 14 Cmax to Day 1 Cmax (RAC[Cmax]) of AZD4041 [units: Ratio] Geometric Mean (Geometric Coefficient of Variation)	1.38 (20.9%)	1.27 (22.4%)	1.59 (16.0%)

No statistical analysis provided for Accumulation Ratio Evaluated by Comparing Day 14 Cmax to Day 1 Cmax (RAC[Cmax]) of AZD4041

23. Secondary Outcome Measure: Accumulation Ratio Evaluated by Comparing Day 14 AUCτ to Day 1 AUC0-24 (RAC[AUC]) of AZD4041 [ Time Frame: Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose; Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose ]

Measure Type	Secondary
Measure Name	Accumulation Ratio Evaluated by Comparing Day 14 AUCτ to Day 1 AUC0-24 (RAC[AUC]) of AZD4041
Measure Description	The RAC(AUC) of AZD4041 is reported.
Time Frame	Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose; Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing. Here, number of participants analyzed (N) indicates those participants who had adequate PK samples and excludes participants with inadequate PK samples due to missed blood draw, an AE, meal deviation, or concomitant medication intake.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	8	9	9
Accumulation Ratio Evaluated by Comparing Day 14 AUCτ to Day 1 AUC0-24 (RAC[AUC]) of AZD4041 [units: Ratio] Geometric Mean (Geometric Coefficient of Variation)	1.66 (25.3%)	1.71 (21.7%)	1.82 (22.1%)

No statistical analysis provided for Accumulation Ratio Evaluated by Comparing Day 14 AUCτ to Day 1 AUC0-24 (RAC[AUC]) of AZD4041

24. Secondary Outcome Measure: Apparent Total Clearance (CL/F) of AZD4041 After Day 1 Dose [ Time Frame: Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose ]

Measure Type	Secondary
Measure Name	Apparent Total Clearance (CL/F) of AZD4041 After Day 1 Dose
Measure Description	The CL/F of AZD4041 after Day 1 dose is reported. This PK parameter (CL/F) requiring λz estimation was not evaluable for Cohorts 1 and 3 due to meeting either the exclusion criteria R^2 < 0.8 or the extrapolated area > 20%.
Time Frame	Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing. Here, number of participants analyzed (N) indicates those participants who had adequate PK samples and excludes participants with inadequate PK samples due to missed blood draw, an AE, meal deviation, or concomitant medication intake.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	0	1	0
Apparent Total Clearance (CL/F) of AZD4041 After Day 1 Dose [units: L/hour] Median (Full Range)		5.00 (5.00 to 5.00)

No statistical analysis provided for Apparent Total Clearance (CL/F) of AZD4041 After Day 1 Dose

25. Secondary Outcome Measure: Apparent Total Clearance at Steady State (CL/Fss) of AZD4041 After Day 14 Dose [ Time Frame: Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose ]

Measure Type	Secondary
Measure Name	Apparent Total Clearance at Steady State (CL/Fss) of AZD4041 After Day 14 Dose
Measure Description	The CL/Fss of AZD4041 after Day 14 dose is reported.
Time Frame	Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing. Here, number of participants analyzed (N) indicates those participants who had adequate PK samples and excludes participants with inadequate PK samples due to missed blood draw, an AE, meal deviation, or concomitant medication intake.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	8	9	9
Apparent Total Clearance at Steady State (CL/Fss) of AZD4041 After Day 14 Dose [units: L/hour] Geometric Mean (Geometric Coefficient of Variation)	2.48 (41.3%)	2.38 (34.4%)	1.98 (36.0%)

No statistical analysis provided for Apparent Total Clearance at Steady State (CL/Fss) of AZD4041 After Day 14 Dose

26. Secondary Outcome Measure: Apparent Volume of Distribution (Vz/F) of AZD4041 After Day 1 Dose [ Time Frame: Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose ]

Measure Type	Secondary
Measure Name	Apparent Volume of Distribution (Vz/F) of AZD4041 After Day 1 Dose
Measure Description	The Vz/F of AZD4041 after Day 1 dose is reported. This PK parameter (Vz/F) requiring λz estimation was not evaluable for Cohorts 1 and 3 due to meeting either the exclusion criteria R^2 < 0.8 or the extrapolated area > 20%.
Time Frame	Day 1: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing. Here, number of participants analyzed (N) indicates those participants who had adequate PK samples and excludes participants with inadequate PK samples due to missed blood draw, an AE, meal deviation, or concomitant medication intake.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	0	1	0
Apparent Volume of Distribution (Vz/F) of AZD4041 After Day 1 Dose [units: L] Median (Full Range)		59.90 (59.90 to 59.90)

No statistical analysis provided for Apparent Volume of Distribution (Vz/F) of AZD4041 After Day 1 Dose

27. Secondary Outcome Measure: Apparent Volume of Distribution at Steady State (Vz/Fss) of AZD4041 After Day 14 Dose [ Time Frame: Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose ]

Measure Type	Secondary
Measure Name	Apparent Volume of Distribution at Steady State (Vz/Fss) of AZD4041 After Day 14 Dose
Measure Description	The Vz/Fss of AZD4041 after Day 14 dose is reported.
Time Frame	Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing. Here, number of participants analyzed (N) indicates those participants who had adequate PK samples and excludes participants with inadequate PK samples due to missed blood draw, an AE, meal deviation, or concomitant medication intake.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	8	9	9
Apparent Volume of Distribution at Steady State (Vz/Fss) of AZD4041 After Day 14 Dose [units: L] Geometric Mean (Geometric Coefficient of Variation)	79.50 (21.8%)	68.90 (25.5%)	75.90 (16.0%)

No statistical analysis provided for Apparent Volume of Distribution at Steady State (Vz/Fss) of AZD4041 After Day 14 Dose

28. Secondary Outcome Measure: Apparent Elimination Rate Constant (λZ) of AZD4041 After Day 14 Dose [ Time Frame: Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose ]

Measure Type	Secondary
Measure Name	Apparent Elimination Rate Constant (λZ) of AZD4041 After Day 14 Dose
Measure Description	The λZ of AZD4041 after Day 14 dose is reported.
Time Frame	Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing. Here, number of participants analyzed (N) indicates those participants who had adequate PK samples and excludes participants with inadequate PK samples due to missed blood draw, an AE, meal deviation, or concomitant medication intake.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	6	9	7
Apparent Elimination Rate Constant (λZ) of AZD4041 After Day 14 Dose [units: 1/hour] Geometric Mean (Geometric Coefficient of Variation)	0.0367 (27.5%)	0.0345 (33.4%)	0.0298 (20.3%)

No statistical analysis provided for Apparent Elimination Rate Constant (λZ) of AZD4041 After Day 14 Dose

29. Secondary Outcome Measure: Amount of AZD4041 Excreted Unchanged in Urine Over the 24-hour Dosing Interval (Ae0-24) After Day 1 Dose [ Time Frame: Day 1: Predose spot collection, and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose ]

Measure Type	Secondary
Measure Name	Amount of AZD4041 Excreted Unchanged in Urine Over the 24-hour Dosing Interval (Ae0-24) After Day 1 Dose
Measure Description	The Ae0-24 of AZD4041 after Day 1 dose is reported.
Time Frame	Day 1: Predose spot collection, and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing. Here, number of participants analyzed (N) indicates those participants who had adequate urine PK samples and excludes participants with inadequate urine PK samples due to missed urine collection, an AE, meal deviation, or concomitant medication intake.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	8	9	8
Amount of AZD4041 Excreted Unchanged in Urine Over the 24-hour Dosing Interval (Ae0-24) After Day 1 Dose [units: ng] Geometric Mean (Geometric Coefficient of Variation)	59209.58 (71.1%)	161067.17 (71.1%)	411420.17 (45.7%)

No statistical analysis provided for Amount of AZD4041 Excreted Unchanged in Urine Over the 24-hour Dosing Interval (Ae0-24) After Day 1 Dose

30. Secondary Outcome Measure: Amount of AZD4041 Excreted Unchanged in Urine Over the 24-hour Dosing Interval (Ae0-24) After Day 14 Dose [ Time Frame: Day 14: Predose spot collection, and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose ]

Measure Type	Secondary
Measure Name	Amount of AZD4041 Excreted Unchanged in Urine Over the 24-hour Dosing Interval (Ae0-24) After Day 14 Dose
Measure Description	The Ae0-24 of AZD4041 after Day 14 dose is reported.
Time Frame	Day 14: Predose spot collection, and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing. Here, number of participants analyzed (N) indicates those participants who had adequate urine PK samples and excludes participants with inadequate urine PK samples due to missed urine collection, an AE, meal deviation, or concomitant medication intake.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	6	8	8
Amount of AZD4041 Excreted Unchanged in Urine Over the 24-hour Dosing Interval (Ae0-24) After Day 14 Dose [units: ng] Geometric Mean (Geometric Coefficient of Variation)	177681.47 (55.3%)	334754.86 (99.2%)	1095233.64 (39.7%)

No statistical analysis provided for Amount of AZD4041 Excreted Unchanged in Urine Over the 24-hour Dosing Interval (Ae0-24) After Day 14 Dose

31. Secondary Outcome Measure: Apparent Fraction of AZD4041 Excreted Unchanged in Urine Over the 24-hours Dosing Interval (fe/F0-24) After Day 1 Dose [ Time Frame: Day 1: Predose spot collection, and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose ]

Measure Type	Secondary
Measure Name	Apparent Fraction of AZD4041 Excreted Unchanged in Urine Over the 24-hours Dosing Interval (fe/F0-24) After Day 1 Dose
Measure Description	The fe/F0-24 of AZD4041 after Day 1 dose is reported.
Time Frame	Day 1: Predose spot collection, and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing. Here, number of participants analyzed (N) indicates those participants who had adequate urine PK samples and excludes participants with inadequate urine PK samples due to missed urine collection, an AE, meal deviation, or concomitant medication intake.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	8	9	8
Apparent Fraction of AZD4041 Excreted Unchanged in Urine Over the 24-hours Dosing Interval (fe/F0-24) After Day 1 Dose [units: Percentage] Geometric Mean (Geometric Coefficient of Variation)	0.79 (71.1%)	1.07 (71.1%)	1.65 (45.7%)

No statistical analysis provided for Apparent Fraction of AZD4041 Excreted Unchanged in Urine Over the 24-hours Dosing Interval (fe/F0-24) After Day 1 Dose

32. Secondary Outcome Measure: Apparent Fraction of AZD4041 Excreted Unchanged in Urine Over the 24-hours Dosing Interval (fe/F0-24) After Day 14 Dose [ Time Frame: Day 14: Predose spot collection, and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose ]

Measure Type	Secondary
Measure Name	Apparent Fraction of AZD4041 Excreted Unchanged in Urine Over the 24-hours Dosing Interval (fe/F0-24) After Day 14 Dose
Measure Description	The fe/F0-24 of AZD4041 after Day 14 dose is reported.
Time Frame	Day 14: Predose spot collection, and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing. Here, number of participants analyzed (N) indicates those participants who had adequate urine PK samples and excludes participants with inadequate urine PK samples due to missed urine collection, an AE, meal deviation, or concomitant medication intake.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	6	8	8
Apparent Fraction of AZD4041 Excreted Unchanged in Urine Over the 24-hours Dosing Interval (fe/F0-24) After Day 14 Dose [units: Percentage] Geometric Mean (Geometric Coefficient of Variation)	2.37 (55.3%)	2.23 (99.2%)	4.38 (39.7%)

No statistical analysis provided for Apparent Fraction of AZD4041 Excreted Unchanged in Urine Over the 24-hours Dosing Interval (fe/F0-24) After Day 14 Dose

33. Secondary Outcome Measure: Apparent Renal Clearance Over the 24-hours Dosing Interval (CLR 0-24) of AZD4041 After Day 1 Dose [ Time Frame: Day 1: Predose spot collection, and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose ]

Measure Type	Secondary
Measure Name	Apparent Renal Clearance Over the 24-hours Dosing Interval (CLR 0-24) of AZD4041 After Day 1 Dose
Measure Description	The CLR 0-24 of AZD4041 after Day 1 dose is reported. Apparent renal clearance was calculated as: Ae (0-24) / AUC0-24 on Day 1.
Time Frame	Day 1: Predose spot collection, and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing. Here, number of participants analyzed (N) indicates those participants who had adequate urine PK samples and excludes participants with inadequate urine PK samples due to missed urine collection, an AE, meal deviation, or concomitant medication intake.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	8	9	8
Apparent Renal Clearance Over the 24-hours Dosing Interval (CLR 0-24) of AZD4041 After Day 1 Dose [units: L/hour] Geometric Mean (Geometric Coefficient of Variation)	0.0328 (65.3%)	0.0437 (72.1%)	0.0582 (56.1%)

No statistical analysis provided for Apparent Renal Clearance Over the 24-hours Dosing Interval (CLR 0-24) of AZD4041 After Day 1 Dose

34. Secondary Outcome Measure: Apparent Renal Clearance Over the 24-hours Dosing Interval (CLR 0-24) of AZD4041 After Day 14 Dose [ Time Frame: Day 14: Predose spot collection, and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose ]

Measure Type	Secondary
Measure Name	Apparent Renal Clearance Over the 24-hours Dosing Interval (CLR 0-24) of AZD4041 After Day 14 Dose
Measure Description	The CLR 0-24 of AZD4041 after Day 14 dose is reported. Apparent renal clearance was calculated as: Ae (0-24) / AUCτ on Day 14.
Time Frame	Day 14: Predose spot collection, and 0 to 6 hours, 6 to 12 hours, and 12 to 24 hours postdose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing. Here, number of participants analyzed (N) indicates those participants who had adequate urine PK samples and excludes participants with inadequate urine PK samples due to missed urine collection, an AE, meal deviation, or concomitant medication intake.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	6	8	8
Apparent Renal Clearance Over the 24-hours Dosing Interval (CLR 0-24) of AZD4041 After Day 14 Dose [units: L/hour] Geometric Mean (Geometric Coefficient of Variation)	0.0536 (21.5%)	0.0521 (106.4%)	0.0916 (71.2%)

No statistical analysis provided for Apparent Renal Clearance Over the 24-hours Dosing Interval (CLR 0-24) of AZD4041 After Day 14 Dose

35. Secondary Outcome Measure: Cerebrospinal fluid (CSF) Concentration as a Percentage of Total Plasma concentration of AZD4041 in Cohorts 2 and 3 [ Time Frame: Day 14 post dose (approximately 3 hours ± 1 hour) ]

Measure Type	Secondary
Measure Name	Cerebrospinal fluid (CSF) Concentration as a Percentage of Total Plasma concentration of AZD4041 in Cohorts 2 and 3
Measure Description	The CSF concentration as a percentage of total plasma concentration of AZD4041 in cohorts 2 and 3 is reported.
Time Frame	Day 14 post dose (approximately 3 hours ± 1 hour)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing. Here, number of participants analyzed (N) indicates those participants who had adequate CSF PK samples and excludes participants with inadequate CSF PK samples due to missed CSF draw, an AE, meal deviation, or concomitant medication intake.

Reporting Groups

	Description
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	6	9
Cerebrospinal fluid (CSF) Concentration as a Percentage of Total Plasma concentration of AZD4041 in Cohorts 2 and 3 [units: Percentage] Geometric Mean (Geometric Coefficient of Variation)	4.91 (13.3%)	5.28 (16.3%)

No statistical analysis provided for Cerebrospinal fluid (CSF) Concentration as a Percentage of Total Plasma concentration of AZD4041 in Cohorts 2 and 3

36. Secondary Outcome Measure: CSF Concentration as a Percentage of Free Plasma concentration of AZD4041 in Cohorts 2 and 3 [ Time Frame: Day 14 post dose (approximately 3 hours ± 1 hour) ]

Measure Type	Secondary
Measure Name	CSF Concentration as a Percentage of Free Plasma concentration of AZD4041 in Cohorts 2 and 3
Measure Description	The CSF concentration as a percentage of free plasma concentration of AZD4041 in cohorts 2 and 3 is reported.
Time Frame	Day 14 post dose (approximately 3 hours ± 1 hour)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK population included all participants who had received at least 1 dose of AZD4041 and had at least 1 PK concentration after dosing. Here, number of participants analyzed (N) indicates those participants who had adequate CSF PK samples and excludes participants with inadequate CSF PK samples due to missed CSF draw, an AE, meal deviation, or concomitant medication intake.

Reporting Groups

	Description
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3
Number of Participants Analyzed [units:participants]	6	9
CSF Concentration as a Percentage of Free Plasma concentration of AZD4041 in Cohorts 2 and 3 [units: Percentage] Geometric Mean (Geometric Coefficient of Variation)	27.44 (13.3%)	29.51 (16.3%)

No statistical analysis provided for CSF Concentration as a Percentage of Free Plasma concentration of AZD4041 in Cohorts 2 and 3

37. Secondary Outcome Measure: Day 14 / Day 1 Ratio of 4-β-hydroxy-cholesterol Concentrations [ Time Frame: Pre-dose Day 1 and 24 hours post Day 14 dose ]

Measure Type	Secondary
Measure Name	Day 14 / Day 1 Ratio of 4-β-hydroxy-cholesterol Concentrations
Measure Description	Day 14 / Day 1 ratio of 4-β-hydroxy-cholesterol concentrations is reported.
Time Frame	Pre-dose Day 1 and 24 hours post Day 14 dose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacodynamic (PD) population included all participants who had received at least 1 dose of AZD4041 or placebo and had at least 1 plasma 4-β-hydroxy-cholesterol concentration after dosing.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.
Cohorts 1-3: Pooled Placebo	Participants received oral solution of placebo equivalent to AZD4041 volume QD directly into the mouth using a syringe from Days 1 to 14.

Measured Values

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3	Cohorts 1-3: Pooled Placebo
Number of Participants Analyzed [units:participants]	8	9	9	9
Day 14 / Day 1 Ratio of 4-β-hydroxy-cholesterol Concentrations [units: Ratio] Geometric Mean (Geometric Coefficient of Variation)	1.00 (28.67%)	1.02 (18.83%)	0.95 (18.74%)	0.79 (26.41%)

No statistical analysis provided for Day 14 / Day 1 Ratio of 4-β-hydroxy-cholesterol Concentrations

Serious Adverse Events

Time Frame	From Day 1 to Day 31
Additional Description	Safety population included all participants who received at least 1 dose of AZD4041 or placebo.

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.
Cohorts 1-3: Pooled Placebo	Participants received oral solution of placebo equivalent to AZD4041 volume QD directly into the mouth using a syringe from Days 1 to 14.

Serious Adverse Events

	Cohort 1: AZD4041 Dose Level 1	Cohort 2: AZD4041 Dose Level 2	Cohort 3: AZD4041 Dose Level 3	Cohorts 1-3: Pooled Placebo
Total, serious adverse events
# participants affected / at risk	0/9 (0.00%)	0/9 (0.00%)	0/9 (0.00%)	0/9 (0.00%)

Other Adverse Events

Time Frame	From Day 1 to Day 31
Additional Description	Safety population included all participants who received at least 1 dose of AZD4041 or placebo.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
Cohort 1: AZD4041 Dose Level 1	Participants received oral solution of AZD4041 dose level 1 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 2: AZD4041 Dose Level 2	Participants received oral solution of AZD4041 dose level 2 QD directly into the mouth using a syringe from Days 1 to 14.
Cohort 3: AZD4041 Dose Level 3	Participants received oral solution of AZD4041 dose level 3 QD directly into the mouth using a syringe from Days 1 to 14.
Cohorts 1-3: Pooled Placebo	Participants received oral solution of placebo equivalent to AZD4041 volume QD directly into the mouth using a syringe from Days 1 to 14.

Other Adverse Events

Cohort 1: AZD4041 Dose Level 1

Cohort 2: AZD4041 Dose Level 2

Cohort 3: AZD4041 Dose Level 3

Cohorts 1-3: Pooled Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

8/9 (88.89%)

6/9 (66.67%)

9/9 (100.00%)

Eye disorders

Lacrimation increased¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

0/9 (0.00%)

# events

Eye disorders

Ocular hyperaemia¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

0/9 (0.00%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

0/9 (0.00%)

# events

Gastrointestinal disorders

Dry mouth¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

# events

Gastrointestinal disorders

Lip dry¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

0/9 (0.00%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

0/9 (0.00%)

# events

General disorders and administration site conditions

Catheter site pain¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

# events

General disorders and administration site conditions

Chest discomfort¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

0/9 (0.00%)

# events

General disorders and administration site conditions

Fatigue¹,^†

# participants affected / at risk

2/9 (22.22%)

0/9 (0.00%)

# events

Cardiac disorders

Palpitations¹,^†

# participants affected / at risk

1/9 (11.11%)

0/9 (0.00%)

# events

General disorders and administration site conditions

Medical device site reaction¹,^†

# participants affected / at risk

6/9 (66.67%)

0/9 (0.00%)

3/9 (33.33%)

6/9 (66.67%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

1/9 (11.11%)

0/9 (0.00%)

# events

Injury, poisoning and procedural complications

Post lumbar puncture syndrome¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

3/9 (33.33%)

# events

Metabolism and nutrition disorders

Decreased appetite¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

0/9 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Muscle spasms¹,^†

# participants affected / at risk

1/9 (11.11%)

0/9 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Tendonitis¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

0/9 (0.00%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

1/9 (11.11%)

0/9 (0.00%)

1/9 (11.11%)

# events

Nervous system disorders

Dyskinesia¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

0/9 (0.00%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

0/9 (0.00%)

2/9 (22.22%)

# events

Cardiac disorders

Sinus tachycardia¹,^†

# participants affected / at risk

1/9 (11.11%)

0/9 (0.00%)

# events

Psychiatric disorders

Abnormal dreams¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

# events

Psychiatric disorders

Insomnia¹,^†

# participants affected / at risk

1/9 (11.11%)

0/9 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Nasal congestion¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

0/9 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Nasal dryness¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

# events

Respiratory, thoracic and mediastinal disorders

Rhinorrhoea¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

# events

Respiratory, thoracic and mediastinal disorders

Throat irritation¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

# events

Skin and subcutaneous tissue disorders

Acne¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

0/9 (0.00%)

# events

Skin and subcutaneous tissue disorders

Blister¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

# events

Skin and subcutaneous tissue disorders

Erythema¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

# events

Skin and subcutaneous tissue disorders

Pruritus¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

0/9 (0.00%)

2/9 (22.22%)

# events

Cardiac disorders

Ventricular tachycardia¹,^†

# participants affected / at risk

1/9 (11.11%)

0/9 (0.00%)

1/9 (11.11%)

# events

Ear and labyrinth disorders

Ear discomfort¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

# events

Ear and labyrinth disorders

Hypoacusis¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

0/9 (0.00%)

# events

Ear and labyrinth disorders

Tinnitus¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

0/9 (0.00%)

# events

Eye disorders

Eye pain¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

0/9 (0.00%)

# events

Eye disorders

Eye pruritus¹,^†

# participants affected / at risk

0/9 (0.00%)

1/9 (11.11%)

0/9 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 24.1

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca Clinical study Information Center
Phone	+1-877-240-9479
E-mail:	[email protected]

Documents available

CSR Synopsis
Download
Statistical Analysis Plan (SAP)
Download
Protocol
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site