A Study to Assess Bioavailability and Pharmacokinetics of CAT- 354

Phase 1

Completed

Conditions: Asthma
Healthy

Interventions: Biological: CAT-354 150 mg (subcutaneous)
Biological: CAT-354 150 mg (intravenous)
Biological: CAT-354 300 mg (subcutaneous)

Registration Number: NCT00638989

Lead Sponsor: MedImmune LLC

Brief Summary: To compare bioavailability and pharmacokinetics of CAT-354 following subcutaneous administration compared with intravenous administration.

Detailed Description: To compare the bioavailability and pharmacokinetics of CAT-354 following subcutaneous administration of 150 milligram (mg) and 300 mg compared with 150 mg given intravenously.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 30

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).

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Absolute Bioavailability of CAT-354 After Subcutaneous Dose	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	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).

Secondary Outcome Measures

Name	Time	Method
Number of Participants Exhibiting Anti-Drug Antibodies for CAT-354 at Any Visit	Day 0 and Day 56
Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC[0 - 56])	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
Dose Normalized Maximum Observed Concentration (Cmax/Dose)	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
Apparent Systemic Clearance (CL/F) After Intravenous Dose	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	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)	Day 0 to 56	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 to Reach Maximum Observed Serum Concentration (Tmax)	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
Volume of Distribution at Steady State (Vss) After Intravenous Infusion	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	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).
Area Under the Concentration-time Curve From Zero to Infinity (AUC [0 - Infinity])	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	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).
Terminal Phase Elimination Half Life (t1/2)	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	Terminal phase elimination half-life is the time measured for the serum concentration to decrease by one half.
Dose Normalized Area Under the Concentration-time Curve From Zero to Infinity ([AUC {0 - Infinity}]/Dose)	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	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.
Maximum Observed Serum Concentration (Cmax)	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
Apparent Systemic Clearance (CL/F) After Subcutaneous Dose	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	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).