A Study to Assess Bioavailability and Pharmacokinetics of CAT- 354

Study identifier:CAT-354-0703

ClinicalTrials.gov identifier:NCT00638989

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

An Open-Label, Parallel-Group, Bioavailability Study to Assess the Pharmacokinetics of CAT-354 Following Subcutaneous and Intravenous Administration

Medical condition

asthma, Healthy

Phase

Phase 1

Healthy volunteers

Yes

Study drug

Sex

Male

Actual Enrollment

Study type

Interventional

Age

19 Years - 55 Years

Date

Study Start Date: 11 Apr 2008

Primary Completion Date: 07 Jun 2008

Study Completion Date: 07 Jun 2008

Study design

Allocation: Randomized
Endpoint Classification: Pharmacokinetics/dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Mar 2017 by MedImmune, LLC

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

- Signed and dated written informed consent is obtained prior to any study related procedure taking place
- Males, aged 19-55 years
- No significant abnormality on clinical examination or medical history (excluding atopic skin signs, symptoms and history)
- A normal 12-lead electrocardiogram (ECG) (no clinically significant abnormalities)
- Clinical chemistry, hematology and urinalysis results within the laboratory reference ranges or deemed not clinically significant by the Investigator
- A negative screen for drugs of abuse and alcohol
- Body mass index (BMI) between 18-30 kilogram per square meter (kg/m^2), inclusive
- No other clinically significant abnormality on history and clinical examination
- Able to comply with the requirements of the protocol.

Exclusion Criteria

- Any active concomitant disease including psychological disorders
- History of medication that might carry over effects into study
- Previously received monoclonal antibody, or a similar related protein, that might sensitize subjects to CAT-354
- Participation in another investigational medicinal product study within 3 months of the start of this study or 5 half-lives of the previously administered investigational medicinal product (IMP), whichever is the longer except methodological studies in which no IMP was given
- Any acute illness in the 2 weeks before Day 0 (Visit 2)
- Any blood donation or significant loss of blood within 56 days of study initiation or plasma donation within 7 days of study initiation
- Subject is a participating Investigator, sub-Investigator, study coordinator, or employee of a participating Investigator, or is a first degree relative of the aforementioned
- Any factor which, in the opinion of the Investigator, would jeopardize the evaluation or safety or be associated with poor adherence to the protocol
- The subject's primary care physician recommends the subject should not take part in the study
- Subjects with immunodeficiency disorders
- Subjects who have a positive test for, or have been treated for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).

Location

MDS Pharma Services (US) Inc.

Lincoln, NE, United States, 68502

Arms	Assigned Interventions
Experimental: CAT-354 150 mg (intravenous) A single dose of CAT-354 150 milligram (mg) intravenous infusion over 30 minutes on Day 0.	Biological/Vaccine: CAT-354 150 mg (intravenous) A single dose of CAT-354 150 milligram (mg) intravenous infusion over 30 minutes on Day 0. Other Name: Tralokinumab
Experimental: CAT-354 150 mg (subcutaneous) A single dose of CAT-354 150 mg injection subcutaneously on Day 0.	Biological/Vaccine: CAT-354 150 mg (subcutaneous) A single dose of CAT-354 150 mg injection subcutaneously on Day 0. Other Name: Tralokinumab
Experimental: CAT-354 300 mg (subcutaneous) A single dose of CAT-354 300 mg injection subcutaneously on Day 0.	Biological/Vaccine: CAT-354 300 mg (subcutaneous) A single dose of CAT-354 300 mg injection subcutaneously on Day 0. Other Name: Tralokinumab

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
CAT-354 150 mg (intravenous)	A single dose of CAT-354 150 milligram (mg) intravenous infusion over 30 minutes on Day 0.
CAT-354 150 mg (subcutaneous)	A single dose of CAT-354 150 mg injection, subcutaneously on Day 0.
CAT-354 300 mg (subcutaneous)	A single dose of CAT-354 300 mg injection subcutaneously on Day 0.

Participant Flow: Overall Study

	CAT-354 150 mg (intravenous)	CAT-354 150 mg (subcutaneous)	CAT-354 300 mg (subcutaneous)
STARTED	10	10	10
COMPLETED	10	10	9
NOT COMPLETED	0	0	1
Lost to Follow-up	0	0	1

Baseline Characteristics

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

Analysis population included all enrolled participants.

Reporting Groups

	Description
CAT-354 150 mg (intravenous)	A single dose of CAT-354 150 milligram (mg) intravenous infusion over 30 minutes on Day 0.
CAT-354 150 mg (subcutaneous)	A single dose of CAT-354 150 mg injection, subcutaneously on Day 0.
CAT-354 300 mg (subcutaneous)	A single dose of CAT-354 300 mg injection subcutaneously on Day 0.

Baseline Measures

	CAT-354 150 mg (intravenous)	CAT-354 150 mg (subcutaneous)	CAT-354 300 mg (subcutaneous)	Total
Number of Participants [units: Participants]	10	10	10	30
Age Continuous [units: years] Mean ± Standard Deviation	30.4 ± 8.3	39.3 ± 8.6	27.8 ± 10.4	32.5 ± 10.1
Gender, Male/Female [units: participants]
Female	0	0	0	0
Male	10	10	10	30

Outcome Measures

1. Primary Outcome Measure: Absolute Bioavailability of CAT-354 After Subcutaneous Dose [ Time Frame: Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56 ]

Measure Type	Primary
Measure Name	Absolute Bioavailability of CAT-354 After Subcutaneous Dose
Measure Description	Bioavailability (F) is a measurement of the rate and extent to which a drug reaches the systemic circulation. Absolute bioavailability of the subcutaneous doses was assessed by the geometric least-square means ratios of subcutaneous to intravenous dose-normalized area under the serum concentration-time curve from time zero to infinity (AUC [0 - infinity]/Dose). AUC (0 - infinity) = Area under the serum concentration versus time curve (AUC) from time zero (predose) to extrapolated infinite time (0 - infinity). It is obtained from AUC (0 - t) plus AUC (t - infinity).
Time Frame	Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56
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.
Pharmacokinetic (PK) population included all evaluable participants who received at least 1 dose of study medication and had sufficient post-dose blood samples to estimate maximum observed serum concentration (Cmax).

Reporting Groups

	Description
CAT-354 150 mg (subcutaneous)	A single dose of CAT-354 150 mg injection, subcutaneously on Day 0.
CAT-354 300 mg (subcutaneous)	A single dose of CAT-354 300 mg injection subcutaneously on Day 0.

Measured Values

	CAT-354 150 mg (subcutaneous)	CAT-354 300 mg (subcutaneous)
Number of Participants Analyzed [units:participants]	10	10
Absolute Bioavailability of CAT-354 After Subcutaneous Dose [units: percent bioavailability] Geometric Mean (90% Confidence Interval)	62.1 (48.5 to 79.6)	60.1 (46.9 to 77.1)

No statistical analysis provided for Absolute Bioavailability of CAT-354 After Subcutaneous Dose

2. Secondary Outcome Measure: Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [ Time Frame: Day 0 to 56 ]

Measure Type	Secondary
Measure Name	Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Measure Description	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was 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. Treatment-emergent are events between administration of study drug and up to Day 56 that were absent before treatment or that worsened relative to pre-treatment state.
Time Frame	Day 0 to 56
Safety Issue?	Yes

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 randomized to treatment, and received at least 1 dose of study medication.

Reporting Groups

	Description
CAT-354 150 mg (intravenous)	A single dose of CAT-354 150 milligram (mg) intravenous infusion over 30 minutes on Day 0.
CAT-354 150 mg (subcutaneous)	A single dose of CAT-354 150 mg injection, subcutaneously on Day 0.
CAT-354 300 mg (subcutaneous)	A single dose of CAT-354 300 mg injection subcutaneously on Day 0.

Measured Values

	CAT-354 150 mg (intravenous)	CAT-354 150 mg (subcutaneous)	CAT-354 300 mg (subcutaneous)
Number of Participants Analyzed [units:participants]	10	10	10
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [units: participants]
TEAEs	5	5	4
TESAEs	0	0	0

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

3. Secondary Outcome Measure: Number of Participants Exhibiting Anti-Drug Antibodies for CAT-354 at any Visit [ Time Frame: Day 0 and Day 56 ]

Measure Type	Secondary
Measure Name	Number of Participants Exhibiting Anti-Drug Antibodies for CAT-354 at any Visit
Measure Description
Time Frame	Day 0 and Day 56
Safety Issue?	Yes

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 randomized to treatment, and received at least 1 dose of study medication.

Reporting Groups

	Description
CAT-354 150 mg (intravenous)	A single dose of CAT-354 150 milligram (mg) intravenous infusion over 30 minutes on Day 0.
CAT-354 150 mg (subcutaneous)	A single dose of CAT-354 150 mg injection, subcutaneously on Day 0.
CAT-354 300 mg (subcutaneous)	A single dose of CAT-354 300 mg injection subcutaneously on Day 0.

Measured Values

	CAT-354 150 mg (intravenous)	CAT-354 150 mg (subcutaneous)	CAT-354 300 mg (subcutaneous)
Number of Participants Analyzed [units:participants]	10	10	10
Number of Participants Exhibiting Anti-Drug Antibodies for CAT-354 at any Visit [units: participants]	0	0	0

No statistical analysis provided for Number of Participants Exhibiting Anti-Drug Antibodies for CAT-354 at any Visit

4. Secondary Outcome Measure: Area Under the Concentration-time Curve From Zero to Infinity (AUC [0 - infinity]) [ Time Frame: Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56 ]

Measure Type	Secondary
Measure Name	Area Under the Concentration-time Curve From Zero to Infinity (AUC [0 - infinity])
Measure Description	AUC (0 - infinity) = Area under the serum concentration versus time curve (AUC) from time zero (predose) to extrapolated infinite time (0 - infinity). It is obtained from AUC (0 - t) plus AUC (t - infinity).
Time Frame	Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56
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.
PK population included all evaluable participants who received at least 1 dose of study medication and had sufficient post-dose blood samples to estimate Cmax.

Reporting Groups

	Description
CAT-354 150 mg (intravenous)	A single dose of CAT-354 150 milligram (mg) intravenous infusion over 30 minutes on Day 0.
CAT-354 150 mg (subcutaneous)	A single dose of CAT-354 150 mg injection, subcutaneously on Day 0.
CAT-354 300 mg (subcutaneous)	A single dose of CAT-354 300 mg injection subcutaneously on Day 0.

Measured Values

	CAT-354 150 mg (intravenous)	CAT-354 150 mg (subcutaneous)	CAT-354 300 mg (subcutaneous)
Number of Participants Analyzed [units:participants]	10	10	10
Area Under the Concentration-time Curve From Zero to Infinity (AUC [0 - infinity]) [units: (microgramday)/milliliter (mcgday/mL)] Mean (Standard Deviation)	903 (291)	548 (143 )	1080 (315)

No statistical analysis provided for Area Under the Concentration-time Curve From Zero to Infinity (AUC [0 - infinity])

5. Secondary Outcome Measure: Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC[0 - 56]) [ Time Frame: Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56 ]

Measure Type	Secondary
Measure Name	Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC[0 - 56])
Measure Description
Time Frame	Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56
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.
PK population included all evaluable participants who received at least 1 dose of study medication and had sufficient post-dose blood samples to estimate Cmax.

Reporting Groups

	Description
CAT-354 150 mg (intravenous)	A single dose of CAT-354 150 milligram (mg) intravenous infusion over 30 minutes on Day 0.
CAT-354 150 mg (subcutaneous)	A single dose of CAT-354 150 mg injection, subcutaneously on Day 0.
CAT-354 300 mg (subcutaneous)	A single dose of CAT-354 300 mg injection subcutaneously on Day 0.

Measured Values

	CAT-354 150 mg (intravenous)	CAT-354 150 mg (subcutaneous)	CAT-354 300 mg (subcutaneous)
Number of Participants Analyzed [units:participants]	10	10	10
Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC[0 - 56]) [units: mcg*day/mL] Mean (Standard Deviation)	765 (220)	467 (122 )	881 (287)

No statistical analysis provided for Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC[0 - 56])

6. Secondary Outcome Measure: Dose Normalized Area Under the Concentration-time Curve From Zero to Infinity ([AUC {0 - infinity}]/Dose) [ Time Frame: Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56 ]

Measure Type	Secondary
Measure Name	Dose Normalized Area Under the Concentration-time Curve From Zero to Infinity ([AUC {0 - infinity}]/Dose)
Measure Description	AUC (0 - infinity) = Area under the serum concentration versus time curve (AUC) from time zero (predose) to extrapolated infinite time (0 - infinity). It is obtained from AUC (0 - t) plus AUC (t - infinity). (AUC [0 - infinity]) was normalized by CAT-354 dose.
Time Frame	Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56
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.
PK population included all evaluable participants who received at least 1 dose of study medication and had sufficient post-dose blood samples to estimate Cmax.

Reporting Groups

	Description
CAT-354 150 mg (intravenous)	A single dose of CAT-354 150 milligram (mg) intravenous infusion over 30 minutes on Day 0.
CAT-354 150 mg (subcutaneous)	A single dose of CAT-354 150 mg injection, subcutaneously on Day 0.
CAT-354 300 mg (subcutaneous)	A single dose of CAT-354 300 mg injection subcutaneously on Day 0.

Measured Values

	CAT-354 150 mg (intravenous)	CAT-354 150 mg (subcutaneous)	CAT-354 300 mg (subcutaneous)
Number of Participants Analyzed [units:participants]	10	10	10
Dose Normalized Area Under the Concentration-time Curve From Zero to Infinity ([AUC {0 - infinity}]/Dose) [units: ([mcg*day]/mL)/mg] Mean (Standard Deviation)	6.02 (1.94 )	3.66 (0.953)	3.59 (1.05)

No statistical analysis provided for Dose Normalized Area Under the Concentration-time Curve From Zero to Infinity ([AUC {0 - infinity}]/Dose)

7. Secondary Outcome Measure: Maximum Observed Serum Concentration (Cmax) [ Time Frame: Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56 ]

Measure Type	Secondary
Measure Name	Maximum Observed Serum Concentration (Cmax)
Measure Description
Time Frame	Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56
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.
PK population included all evaluable participants who received at least 1 dose of study medication and had sufficient post-dose blood samples to estimate Cmax.

Reporting Groups

	Description
CAT-354 150 mg (intravenous)	A single dose of CAT-354 150 milligram (mg) intravenous infusion over 30 minutes on Day 0.
CAT-354 150 mg (subcutaneous)	A single dose of CAT-354 150 mg injection, subcutaneously on Day 0.
CAT-354 300 mg (subcutaneous)	A single dose of CAT-354 300 mg injection subcutaneously on Day 0.

Measured Values

	CAT-354 150 mg (intravenous)	CAT-354 150 mg (subcutaneous)	CAT-354 300 mg (subcutaneous)
Number of Participants Analyzed [units:participants]	10	10	10
Maximum Observed Serum Concentration (Cmax) [units: microgram/milliliter (mcg/mL)] Mean (Standard Deviation)	58.3 (14.4 )	17.1 (5.91)	36.6 (13.1)

No statistical analysis provided for Maximum Observed Serum Concentration (Cmax)

8. Secondary Outcome Measure: Dose Normalized Maximum Observed Concentration (Cmax/Dose) [ Time Frame: Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56 ]

Measure Type	Secondary
Measure Name	Dose Normalized Maximum Observed Concentration (Cmax/Dose)
Measure Description
Time Frame	Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56
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.
PK population included all evaluable participants who received at least 1 dose of study medication and had sufficient post-dose blood samples to estimate Cmax.

Reporting Groups

	Description
CAT-354 150 mg (intravenous)	A single dose of CAT-354 150 milligram (mg) intravenous infusion over 30 minutes on Day 0.
CAT-354 150 mg (subcutaneous)	A single dose of CAT-354 150 mg injection, subcutaneously on Day 0.
CAT-354 300 mg (subcutaneous)	A single dose of CAT-354 300 mg injection subcutaneously on Day 0.

Measured Values

	CAT-354 150 mg (intravenous)	CAT-354 150 mg (subcutaneous)	CAT-354 300 mg (subcutaneous)
Number of Participants Analyzed [units:participants]	10	10	10
Dose Normalized Maximum Observed Concentration (Cmax/Dose) [units: (mcg/mL)/mg] Mean (Standard Deviation)	0.389 (0.096)	0.114 (0.039)	0.122 (0.044)

No statistical analysis provided for Dose Normalized Maximum Observed Concentration (Cmax/Dose)

9. Secondary Outcome Measure: Time to Reach Maximum Observed Serum Concentration (Tmax) [ Time Frame: Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56 ]

Measure Type	Secondary
Measure Name	Time to Reach Maximum Observed Serum Concentration (Tmax)
Measure Description
Time Frame	Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56
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.
PK population included all evaluable participants who received at least 1 dose of study medication and had sufficient post-dose blood samples to estimate Cmax.

Reporting Groups

	Description
CAT-354 150 mg (intravenous)	A single dose of CAT-354 150 milligram (mg) intravenous infusion over 30 minutes on Day 0.
CAT-354 150 mg (subcutaneous)	A single dose of CAT-354 150 mg injection, subcutaneously on Day 0.
CAT-354 300 mg (subcutaneous)	A single dose of CAT-354 300 mg injection subcutaneously on Day 0.

Measured Values

	CAT-354 150 mg (intravenous)	CAT-354 150 mg (subcutaneous)	CAT-354 300 mg (subcutaneous)
Number of Participants Analyzed [units:participants]	10	10	10
Time to Reach Maximum Observed Serum Concentration (Tmax) [units: days] Median (Full Range)	0.063 (0.042 to 1.02)	5 (3 to 9)	5 (3 to 9)

No statistical analysis provided for Time to Reach Maximum Observed Serum Concentration (Tmax)

10. Secondary Outcome Measure: Terminal Phase Elimination Half Life (t1/2) [ Time Frame: Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56 ]

Measure Type	Secondary
Measure Name	Terminal Phase Elimination Half Life (t1/2)
Measure Description	Terminal phase elimination half-life is the time measured for the serum concentration to decrease by one half.
Time Frame	Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56
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.
PK population included all evaluable participants who received at least 1 dose of study medication and had sufficient post-dose blood samples to estimate Cmax.

Reporting Groups

	Description
CAT-354 150 mg (intravenous)	A single dose of CAT-354 150 milligram (mg) intravenous infusion over 30 minutes on Day 0.
CAT-354 150 mg (subcutaneous)	A single dose of CAT-354 150 mg injection, subcutaneously on Day 0.
CAT-354 300 mg (subcutaneous)	A single dose of CAT-354 300 mg injection subcutaneously on Day 0.

Measured Values

	CAT-354 150 mg (intravenous)	CAT-354 150 mg (subcutaneous)	CAT-354 300 mg (subcutaneous)
Number of Participants Analyzed [units:participants]	10	10	10
Terminal Phase Elimination Half Life (t1/2) [units: days] Mean (Standard Deviation)	21.4 (2.46)	19.2 (3.1 )	19.4 (3.59)

No statistical analysis provided for Terminal Phase Elimination Half Life (t1/2)

11. Secondary Outcome Measure: Apparent Systemic Clearance (CL/F) After Subcutaneous Dose [ Time Frame: Predose, 30 minutes, at 1, 3, 8 and 24 hours post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56 ]

Measure Type	Secondary
Measure Name	Apparent Systemic Clearance (CL/F) After Subcutaneous Dose
Measure Description	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after subcutaneous dose (apparent systemic clearance) is influenced by the fraction of the dose absorbed (bioavailability).
Time Frame	Predose, 30 minutes, at 1, 3, 8 and 24 hours post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56
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.
PK population included all evaluable participants who received at least 1 dose of study medication and had sufficient post-dose blood samples to estimate Cmax.

Reporting Groups

	Description
CAT-354 150 mg (subcutaneous)	A single dose of CAT-354 150 mg injection, subcutaneously on Day 0.
CAT-354 300 mg (subcutaneous)	A single dose of CAT-354 300 mg injection subcutaneously on Day 0.

Measured Values

	CAT-354 150 mg (subcutaneous)	CAT-354 300 mg (subcutaneous)
Number of Participants Analyzed [units:participants]	10	10
Apparent Systemic Clearance (CL/F) After Subcutaneous Dose [units: mL/day] Mean (Standard Deviation)	292 (82.3)	307 (109)

No statistical analysis provided for Apparent Systemic Clearance (CL/F) After Subcutaneous Dose

12. Secondary Outcome Measure: Apparent Systemic Clearance (CL/F) After Intravenous Dose [ Time Frame: Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56 ]

Measure Type	Secondary
Measure Name	Apparent Systemic Clearance (CL/F) After Intravenous Dose
Measure Description	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Time Frame	Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56
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.
PK population included all evaluable participants who received at least 1 dose of study medication and had sufficient post-dose blood samples to estimate Cmax.

Reporting Groups

	Description
CAT-354 150 mg (intravenous)	A single dose of CAT-354 150 milligram (mg) intravenous infusion over 30 minutes on Day 0.

Measured Values

	CAT-354 150 mg (intravenous)
Number of Participants Analyzed [units:participants]	10
Apparent Systemic Clearance (CL/F) After Intravenous Dose [units: mL/day] Mean (Standard Deviation)	188 (84.0)

No statistical analysis provided for Apparent Systemic Clearance (CL/F) After Intravenous Dose

13. Secondary Outcome Measure: Volume of Distribution at Steady State (Vss) After Intravenous Infusion [ Time Frame: Predose, end of infusion, 30 minutes, at 1, 3, 8 and 24 hours post-end of infusion on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56 ]

Measure Type	Secondary
Measure Name	Volume of Distribution at Steady State (Vss) After Intravenous Infusion
Measure Description	Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Volume of distribution at steady state (Vss) after intravenous dosing was estimated by the formula Vss=MRT(Infinity)*CL, where MRT(Infinity)= AUCM(Infinity)/AUC(0 - infinity) where MRT(Infinity) = mean residence time at infinity, CL= clearance, AUCM[Infinity] = area under the moment curve, and AUC (0 - infinity) = area under the serum concentration versus time curve from time zero (predose) to extrapolated infinite time (0 - infinity).
Time Frame	Predose, end of infusion, 30 minutes, at 1, 3, 8 and 24 hours post-end of infusion on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56
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.
PK population included all evaluable participants who received at least 1 dose of study medication and had sufficient post-dose blood samples to estimate Cmax.

Reporting Groups

	Description
CAT-354 150 mg (intravenous)	A single dose of CAT-354 150 milligram (mg) intravenous infusion over 30 minutes on Day 0.

Measured Values

	CAT-354 150 mg (intravenous)
Number of Participants Analyzed [units:participants]	10
Volume of Distribution at Steady State (Vss) After Intravenous Infusion [units: mL] Mean (Standard Deviation)	4960 (1440)

No statistical analysis provided for Volume of Distribution at Steady State (Vss) After Intravenous Infusion

Serious Adverse Events

Time Frame	Day 0 to 56
Additional Description	No text entered.

Reporting Groups

	Description
CAT-354 150 mg (intravenous)	A single dose of CAT-354 150 milligram (mg) intravenous infusion over 30 minutes on Day 0.
CAT-354 150 mg (subcutaneous)	A single dose of CAT-354 150 mg injection, subcutaneously on Day 0.
CAT-354 300 mg (subcutaneous)	A single dose of CAT-354 300 mg injection subcutaneously on Day 0.

Serious Adverse Events

	CAT-354 150 mg (intravenous)	CAT-354 150 mg (subcutaneous)	CAT-354 300 mg (subcutaneous)
Total, serious adverse events
# participants affected / at risk	0/10 (0.00%)	0/10 (0.00%)	0/10 (0.00%)

Other Adverse Events

Time Frame	Day 0 to 56
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
CAT-354 150 mg (intravenous)	A single dose of CAT-354 150 milligram (mg) intravenous infusion over 30 minutes on Day 0.
CAT-354 150 mg (subcutaneous)	A single dose of CAT-354 150 mg injection, subcutaneously on Day 0.
CAT-354 300 mg (subcutaneous)	A single dose of CAT-354 300 mg injection subcutaneously on Day 0.

Other Adverse Events

CAT-354 150 mg (intravenous)

CAT-354 150 mg (subcutaneous)

CAT-354 300 mg (subcutaneous)

Total, other (not including serious) adverse events

# participants affected / at risk

5/10 (50.00%)

4/10 (40.00%)

Eye disorders

Eye pruritus¹,^†

# participants affected / at risk

1/10 (10.00%)

0/10 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

0/10 (0.00%)

1/10 (10.00%)

0/10 (0.00%)

# events

General disorders and administration site conditions

Feeling cold¹,^†

# participants affected / at risk

0/10 (0.00%)

1/10 (10.00%)

0/10 (0.00%)

# events

General disorders and administration site conditions

Feeling hot¹,^†

# participants affected / at risk

1/10 (10.00%)

0/10 (0.00%)

# events

Injury, poisoning and procedural complications

Post-traumatic pain¹,^†

# participants affected / at risk

1/10 (10.00%)

0/10 (0.00%)

# events

Injury, poisoning and procedural complications

Procedural pain¹,^†

# participants affected / at risk

0/10 (0.00%)

1/10 (10.00%)

# events

Injury, poisoning and procedural complications

Sunburn¹,^†

# participants affected / at risk

0/10 (0.00%)

1/10 (10.00%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

1/10 (10.00%)

0/10 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Joint swelling¹,^†

# participants affected / at risk

1/10 (10.00%)

0/10 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Pain in extremity¹,^†

# participants affected / at risk

1/10 (10.00%)

0/10 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Melanocytic naevus¹,^†

# participants affected / at risk

0/10 (0.00%)

1/10 (10.00%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

1/10 (10.00%)

0/10 (0.00%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

4/10 (40.00%)

1/10 (10.00%)

# events

Nervous system disorders

Sinus headache¹,^†

# participants affected / at risk

0/10 (0.00%)

1/10 (10.00%)

0/10 (0.00%)

# events

Nervous system disorders

Somnolence¹,^†

# participants affected / at risk

1/10 (10.00%)

0/10 (0.00%)

# events

Reproductive system and breast disorders

Breast mass¹,^†

# participants affected / at risk

0/10 (0.00%)

1/10 (10.00%)

# events

Reproductive system and breast disorders

Breast tenderness¹,^†

# participants affected / at risk

0/10 (0.00%)

1/10 (10.00%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

1/10 (10.00%)

0/10 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Epistaxis¹,^†

# participants affected / at risk

0/10 (0.00%)

1/10 (10.00%)

# events

Respiratory, thoracic and mediastinal disorders

Nasal congestion¹,^†

# participants affected / at risk

1/10 (10.00%)

0/10 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Paranasal sinus hype¹,^†

# participants affected / at risk

0/10 (0.00%)

2/10 (20.00%)

0/10 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pharyngolaryngeal pa¹,^†

# participants affected / at risk

1/10 (10.00%)

0/10 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Rhinorrhoea¹,^†

# participants affected / at risk

1/10 (10.00%)

0/10 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Sinus congestion¹,^†

# participants affected / at risk

1/10 (10.00%)

0/10 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Sneezing¹,^†

# participants affected / at risk

1/10 (10.00%)

0/10 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 11.0

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:	Meena Jain, MB BChir/Associate Medical Director
Organization:	MedImmune, LLC
Phone	301-398-0000
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

MedImmune LLC

MedImmune

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

MDS Pharma Services (US) Inc.

Trial Results Summaries