A phase 1 study to assess the pharmacokinetics of AZD9977 administered alone and in combination with itraconazole in healthy volunteers

Study identifier:D6401C00003

ClinicalTrials.gov identifier:NCT03843060

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A phase 1 single center open-label, non-randomized, fixed sequence study in healthy volunteers to assess the pharmacokinetics (PK) of AZD9977 when administered alone and with itraconazole

Medical condition

Heart Failure with Preserved Ejection Fraction (HFpEF)

Phase

Phase 1

Healthy volunteers

Yes

Study drug

AZD9977, Itraconazole

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 55 Years

Date

Study Start Date: 22 Feb 2019

Primary Completion Date: 01 Apr 2019

Study Completion Date: 01 Apr 2019

Study design

Allocation: Non-randomized
Endpoint Classification: -
Intervention Model: Sequential Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Apr 2021 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

1. Provision of signed and dated, written informed consent prior to any study specific procedures.
2. Healthy male and female participants of non-childbearing potential aged 18 – 55 years with suitable veins for cannulation or repeated venipuncture.
3. Females must have a negative pregnancy test at screening and on admission to the unit, must not be lactating and must be of non-childbearing potential, confirmed at screening by fulfilling one of the following criteria:
a. Postmenopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle stimulating hormone (FSH) levels ≥40 mlU/ml.
b. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
4. Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.

Exclusion Criteria

1. History of any clinically significant disease or disorder which, in the opinion of the PI, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer’s ability to participate in the study..
2. History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
3. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, as judged by the PI including serum potassium > 5.0 mmol/L, serum hsTnI > 25.6 pg/mL, and NT-pro-BNP > 124 pg/mL.
5. Any clinically significant abnormal findings in vital signs as specified below and as judged by the PI at screening and on admission including:
a. Systolic blood pressure (SBP) < 90 mmHg or > 140 mmHg.
b. Diastolic blood pressure (DBP) < 50 mmHg or > 90 mmHg.
c. HR < 45 or > 90 beats per minute (bpm).
6. Any clinically significant abnormalities on 12-lead ECG, as judged by the PI.
7. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
8. Known or suspected history of drug abuse in the last 12 months as judged by the Investigator.
9. Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration of IMP in this study. The period of exclusion begins 3 months after the final dose or 1 month after the last visit whichever is the longest.
10. Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening.
11. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the PI or history of hypersensitivity to drugs with a similar chemical structure or class to AZD9977.
12. Current smokers or those who have smoked or used nicotine products (including e cigarettes) within the 3 months prior to screening.
13. Positive screen for drugs of abuse, cotinine or alcohol at screening or on each admission to the study center.
14. Use of drugs with enzyme-inducing properties such as St John’s Wort within 3 weeks prior to the first administration of IMP.
15. Use of any prescribed or non prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of IMP or longer if the medication has a long half life.
16. Known or suspected history of alcohol or drug abuse or excessive intake of alcohol in the last 12 months as judged by the PI.
17. Involvement of any AstraZeneca, PAREXEL or study site employee or their close relatives.
18. Participants who have previously received AZD9977.
19. Judgment by the PI that the participant should not participate in the study if they have any ongoing or recent (i.e., 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.
20. Vulnerable participants , e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
21. Participants with any special dietary restrictions such as participants that are lactose intolerant or are vegetarians/vegans.
22. Drugs affecting CYP3A4 (itraconazole) should be refrained from use for 3 weeks prior to study commencement and thereafter until study completion.
23. The following exclusion criterion is driven by contraindications from the proposed concomitant CYP3A4 (itraconazole) inhibitor medications: Itraconazole (Sporanox) capsules are contra-indicated in patients with known hypersensitivity to itraconazole or to any of the excipients.

Location

Research Site

Baltimore, MD, United States, 21225

Arms	Assigned Interventions
Experimental: Single AZD9977 During this treatment period, healthy participants will be administered with a single AZD9977 (Dose 1) dose, in the fed state, on Day 1 followed by at least 3 days washout period.	Drug: AZD9977 Participants will receive single AZD9977 (Dose 1) capsule orally once daily in fed state, on Day 1 followed by at least 3 days washout period. Other Name: NA
Experimental: Itraconazole + AZD9977 During this treatment period, healthy participants will be administered with Itraconazole (Dose 2) from Day 4 to Day 8 plus will be administrated with AZD9977 (Dose 1, fed state) as a single dose on Day 7. Dose of itraconazole will be taken at -1 hour (1 hour prior to AZD9977 dosing) when co-administered with AZD9977.	Drug: Itraconazole Participants will receive Itraconazole daily (Dose 2) capsule orally once daily from Day 4 to Day 8 plus will be administered AZD9977 (Dose 1, fed state) as a single dose on Day 7. Dose of itraconazole has to be taken at -1 hour (1 hour prior to AZD9977 dosing) when co-administered with AZD9977. Other Name: Sporanox

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants who met all the inclusion and none of the exclusion criteria were enrolled at Parexel Early Phase Clinical Unit Baltimore

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
All participants underwent inclusion and exclusion criteria assessment and all eligible subjects signed the informed consent before undergoing any study related procedures. All the study assessments were performed as per the schedule of assessment.

Reporting Groups

	Description
Overall Study	All participants were administered AZD9977 orally, alone and in combination with multiple doses of itraconazole

Participant Flow: Overall Study

	Overall Study
STARTED	14
COMPLETED	14
NOT COMPLETED	0

Baseline Characteristics

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

Reporting Groups

	Description
Overall Study	All participants were administered AZD9977 orally, alone and in combination with multiple doses of itraconazole

Baseline Measures

	Overall Study
Number of Participants [units: Participants]	14
Age Continuous [units: years] Mean ± Standard Deviation	43.4 ± 8.05
Sex: Female, Male [units: ]
Female	1
Male	13
Race (NIH/OMB) [units: ]
American Indian or Alaska Native	0
Asian	0
Native Hawaiian or Other Pacific Islander	0
Black or African American	13
White	0
More than one race	0
Unknown or Not Reported	1

Outcome Measures

1. Primary Outcome Measure: Area under plasma concentration-time curve from time zero to infinity (AUC) [ Time Frame: Day 1 to 3: Pre-dose on Day 1, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose ]

Measure Type	Primary
Measure Name	Area under plasma concentration-time curve from time zero to infinity (AUC)
Measure Description	To assess pharmacokinetics (PK) of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole
Time Frame	Day 1 to 3: Pre-dose on Day 1, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
Safety Issue?	No

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.

Reporting Groups

	Description
AZD9977	Healthy participants were administered with a single AZD9977 (Dose 1) dose, in the fed state, on Day 1 followed by at least 3 days washout period.
Itraconazole + AZD9977	Healthy participants were administered with Itraconazole (Dose 2) from Day 4 to Day 8 plus AZD9977 (Dose 1, fed state) as a single dose on Day 7. Dose of itraconazole was taken at -1 hour (1 hour prior to AZD9977 dosing) when co-administered with AZD9977.

Measured Values

	AZD9977	Itraconazole + AZD9977
Number of Participants Analyzed [units:participants]	14	14
Area under plasma concentration-time curve from time zero to infinity (AUC) [units: h*nmol/L] Geometric Mean (Geometric Coefficient of Variation)	9341 (36.52%)	28960 (17.63%)

Statistical Analysis 1 for Area under plasma concentration-time curve from time zero to infinity (AUC)

Groups^[1]	All groups
Other^[5]	310.07
90% Confidence Interval	( 273.75 to 351.20 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

2. Primary Outcome Measure: Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUClast) [ Time Frame: Day 1 to 3: Pre-dose on Day 1, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose ]

Measure Type	Primary
Measure Name	Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUClast)
Measure Description	To assess PK of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole
Time Frame	Day 1 to 3: Pre-dose on Day 1, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
Safety Issue?	No

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.

Reporting Groups

	Description
AZD9977	Healthy participants were administered with a single AZD9977 (Dose 1) dose, in the fed state, on Day 1 followed by at least 3 days washout period.
Itraconazole + AZD9977	Healthy participants were administered with Itraconazole (Dose 2) from Day 4 to Day 8 plus AZD9977 (Dose 1, fed state) as a single dose on Day 7. Dose of itraconazole was taken at -1 hour (1 hour prior to AZD9977 dosing) when co-administered with AZD9977.

Measured Values

	AZD9977	Itraconazole + AZD9977
Number of Participants Analyzed [units:participants]	14	14
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUClast) [units: h*nmol/L] Geometric Mean (Geometric Coefficient of Variation)	9135 (37.12%)	28750 (17.73%)

Statistical Analysis 1 for Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUClast)

Groups^[1]	All groups
Other^[5]	314.76
90% Confidence Interval	( 277.91 to 356.49 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

3. Primary Outcome Measure: Maximum observed plasma concentration (Cmax) [ Time Frame: Day 1 to 3: Pre-dose on Day 1, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose ]

Measure Type	Primary
Measure Name	Maximum observed plasma concentration (Cmax)
Measure Description	To assess PK of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole
Time Frame	Day 1 to 3: Pre-dose on Day 1, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
Safety Issue?	No

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.

Reporting Groups

	Description
AZD9977	Healthy participants were administered with a single AZD9977 (Dose 1) dose, in the fed state, on Day 1 followed by at least 3 days washout period.
Itraconazole + AZD9977	Healthy participants were administered with Itraconazole (Dose 2) from Day 4 to Day 8 plus AZD9977 (Dose 1, fed state) as a single dose on Day 7. Dose of itraconazole was taken at -1 hour (1 hour prior to AZD9977 dosing) when co-administered with AZD9977.

Measured Values

	AZD9977	Itraconazole + AZD9977
Number of Participants Analyzed [units:participants]	14	14
Maximum observed plasma concentration (Cmax) [units: nmol/L] Geometric Mean (Geometric Coefficient of Variation)	2244 (30.76%)	4992 (15.86%)

Statistical Analysis 1 for Maximum observed plasma concentration (Cmax)

Groups^[1]	All groups
Other^[5]	222.44
90% Confidence Interval	( 191.72 to 258.09 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

4. Secondary Outcome Measure: Time to reach Maximum Observed Plasma Concentration (tmax) [ Time Frame: Day 1 to 3: Pre-dose on Day 1, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose ]

Measure Type	Secondary
Measure Name	Time to reach Maximum Observed Plasma Concentration (tmax)
Measure Description	To assess PK of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole
Time Frame	Day 1 to 3: Pre-dose on Day 1, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
Safety Issue?	No

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.

Reporting Groups

	Description
AZD9977	Healthy participants were administered with a single AZD9977 (Dose 1) dose, in the fed state, on Day 1 followed by at least 3 days washout period.
Itraconazole + AZD9977	Healthy participants were administered with Itraconazole (Dose 2) from Day 4 to Day 8 plus AZD9977 (Dose 1, fed state) as a single dose on Day 7. Dose of itraconazole was taken at -1 hour (1 hour prior to AZD9977 dosing) when co-administered with AZD9977.

Measured Values

	AZD9977	Itraconazole + AZD9977
Number of Participants Analyzed [units:participants]	14	14
Time to reach Maximum Observed Plasma Concentration (tmax) [units: hour] Median (Full Range)	2.00 (1.00 to 3.00)	2.26 (1.00 to 4.00)

No statistical analysis provided for Time to reach Maximum Observed Plasma Concentration (tmax)

5. Secondary Outcome Measure: Terminal elimination rate constant (λz) [ Time Frame: Day 1 to 3: Pre-dose on Day 1, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose ]

Measure Type	Secondary
Measure Name	Terminal elimination rate constant (λz)
Measure Description	To assess PK of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole
Time Frame	Day 1 to 3: Pre-dose on Day 1, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
Safety Issue?	No

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.

Reporting Groups

	Description
AZD9977	Healthy participants were administered with a single AZD9977 (Dose 1) dose, in the fed state, on Day 1 followed by at least 3 days washout period.
Itraconazole + AZD9977	Healthy participants were administered with Itraconazole (Dose 2) from Day 4 to Day 8 plus AZD9977 (Dose 1, fed state) as a single dose on Day 7. Dose of itraconazole was taken at -1 hour (1 hour prior to AZD9977 dosing) when co-administered with AZD9977.

Measured Values

	AZD9977	Itraconazole + AZD9977
Number of Participants Analyzed [units:participants]	14	14
Terminal elimination rate constant (λz) [units: 1/hour] Mean (Standard Deviation)	0.13403 (0.097076)	0.087065 (0.027397)

No statistical analysis provided for Terminal elimination rate constant (λz)

6. Secondary Outcome Measure: Terminal half life (t½λz) [ Time Frame: Day 1 to 3: Pre-dose on Day 1, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose ]

Measure Type	Secondary
Measure Name	Terminal half life (t½λz)
Measure Description	To assess PK of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole
Time Frame	Day 1 to 3: Pre-dose on Day 1, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
Safety Issue?	No

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.

Reporting Groups

	Description
AZD9977	Healthy participants were administered with a single AZD9977 (Dose 1) dose, in the fed state, on Day 1 followed by at least 3 days washout period.
Itraconazole + AZD9977	Healthy participants were administered with Itraconazole (Dose 2) from Day 4 to Day 8 plus AZD9977 (Dose 1, fed state) as a single dose on Day 7. Dose of itraconazole was taken at -1 hour (1 hour prior to AZD9977 dosing) when co-administered with AZD9977.

Measured Values

	AZD9977	Itraconazole + AZD9977
Number of Participants Analyzed [units:participants]	14	14
Terminal half life (t½λz) [units: hour] Mean (Standard Deviation)	7.695 (5.127)	8.616 (2.380)

No statistical analysis provided for Terminal half life (t½λz)

7. Secondary Outcome Measure: Mean residence time (MRT) [ Time Frame: Day 1 to 3: Pre-dose on Day 1, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose ]

Measure Type	Secondary
Measure Name	Mean residence time (MRT)
Measure Description	To assess PK of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole
Time Frame	Day 1 to 3: Pre-dose on Day 1, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
Safety Issue?	No

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.

Reporting Groups

	Description
AZD9977	Healthy participants were administered with a single AZD9977 (Dose 1) dose, in the fed state, on Day 1 followed by at least 3 days washout period.
Itraconazole + AZD9977	Healthy participants were administered with Itraconazole (Dose 2) from Day 4 to Day 8 plus AZD9977 (Dose 1, fed state) as a single dose on Day 7. Dose of itraconazole was taken at -1 hour (1 hour prior to AZD9977 dosing) when co-administered with AZD9977.

Measured Values

	AZD9977	Itraconazole + AZD9977
Number of Participants Analyzed [units:participants]	14	14
Mean residence time (MRT) [units: hour] Mean (Standard Deviation)	6.059 (2.165)	7.269 (0.8643)

No statistical analysis provided for Mean residence time (MRT)

8. Secondary Outcome Measure: Apparent plasma clearance (CL/F) [ Time Frame: Day 1 to 3: Pre-dose on Day 1, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose ]

Measure Type	Secondary
Measure Name	Apparent plasma clearance (CL/F)
Measure Description	To assess PK of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole
Time Frame	Day 1 to 3: Pre-dose on Day 1, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
Safety Issue?	No

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.

Reporting Groups

	Description
AZD9977	Healthy participants were administered with a single AZD9977 (Dose 1) dose, in the fed state, on Day 1 followed by at least 3 days washout period.
Itraconazole + AZD9977	Healthy participants were administered with Itraconazole (Dose 2) from Day 4 to Day 8 plus AZD9977 (Dose 1, fed state) as a single dose on Day 7. Dose of itraconazole was taken at -1 hour (1 hour prior to AZD9977 dosing) when co-administered with AZD9977.

Measured Values

	AZD9977	Itraconazole + AZD9977
Number of Participants Analyzed [units:participants]	14	14
Apparent plasma clearance (CL/F) [units: L/h] Mean (Standard Deviation)	28.55 (11.70)	8.772 (1.596)

No statistical analysis provided for Apparent plasma clearance (CL/F)

9. Secondary Outcome Measure: Apparent volume of distribution at terminal phase (Vz/F) [ Time Frame: Day 1 to 3: Pre-dose on Day 1, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose ]

Measure Type	Secondary
Measure Name	Apparent volume of distribution at terminal phase (Vz/F)
Measure Description	To assess PK of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole
Time Frame	Day 1 to 3: Pre-dose on Day 1, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
Safety Issue?	No

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.

Reporting Groups

	Description
AZD9977	Healthy participants were administered with a single AZD9977 (Dose 1) dose, in the fed state, on Day 1 followed by at least 3 days washout period.
Itraconazole + AZD9977	Healthy participants were administered with Itraconazole (Dose 2) from Day 4 to Day 8 plus AZD9977 (Dose 1, fed state) as a single dose on Day 7. Dose of itraconazole was taken at -1 hour (1 hour prior to AZD9977 dosing) when co-administered with AZD9977.

Measured Values

	AZD9977	Itraconazole + AZD9977
Number of Participants Analyzed [units:participants]	14	14
Apparent volume of distribution at terminal phase (Vz/F) [units: L] Mean (Standard Deviation)	308.9 (248.6)	110.3 (40.24)

No statistical analysis provided for Apparent volume of distribution at terminal phase (Vz/F)

Serious Adverse Events

Time Frame	From screening (Day -28) till follow-up visit (5 to 7 days after discharge)
Additional Description	No text entered.

Reporting Groups

	Description
AZD9977	Healthy participants were administered with a single AZD9977 (Dose 1) dose, in the fed state, on Day 1 followed by at least 3 days washout period.
AZD9977+Itraconazole	Healthy participants were administered with Itraconazole (Dose 2) from Day 4 to Day 8 plus AZD9977 (Dose 1, fed state) as a single dose on Day 7. Dose of itraconazole was taken at -1 hour (1 hour prior to AZD9977 dosing) when co-administered with AZD9977.

Serious Adverse Events

	AZD9977	AZD9977+Itraconazole
Total, serious adverse events
# participants affected / at risk	0/14 (0.00%)	0/14 (0.00%)

Other Adverse Events

Time Frame	From screening (Day -28) till follow-up visit (5 to 7 days after discharge)
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
AZD9977	Healthy participants were administered with a single AZD9977 (Dose 1) dose, in the fed state, on Day 1 followed by at least 3 days washout period.
AZD9977+Itraconazole	Healthy participants were administered with Itraconazole (Dose 2) from Day 4 to Day 8 plus AZD9977 (Dose 1, fed state) as a single dose on Day 7. Dose of itraconazole was taken at -1 hour (1 hour prior to AZD9977 dosing) when co-administered with AZD9977.

Other Adverse Events

AZD9977

AZD9977+Itraconazole

Total, other (not including serious) adverse events

# participants affected / at risk

1/14 (7.14%)

Gastrointestinal disorders

Constipation¹

# participants affected / at risk

1/14 (7.14%)

0/14 (0.00%)

# events

General disorders

Influenza like illness¹

# participants affected / at risk

0/14 (0.00%)

1/14 (7.14%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 21.1

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: No unpublished information contained herein may be disclosed without prior written approval from AstraZeneca AB. Access to this document must be restricted to relevant parties.

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:	AstraZeneca Clinical Study Information Center
Organization:	AstraZeneca AB
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Ronald Goldwater

Dr.

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Trial Results Summaries