A Study to Assess Bioavailability and Pharmacokinetics of CAT- 354

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

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

Study Overview

• Status: Completed
• Conditions: Healthy; Asthma
• Intervention / Treatment: Biological: CAT-354 150 mg (intravenous); Biological: CAT-354 150 mg (subcutaneous); Biological: CAT-354 300 mg (subcutaneous)

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Lincoln, Nebraska, United States, 68502
      • Mds Pharma Services (Us) Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CAT-354 150 mg (intravenous); A single dose of CAT-354 150 milligram (mg) intravenous infusion over 30 minutes on Day 0.	Biological: CAT-354 150 mg (intravenous); A single dose of CAT-354 150 milligram (mg) intravenous infusion over 30 minutes on Day 0.; Other Names: Tralokinumab
Experimental: CAT-354 150 mg (subcutaneous); A single dose of CAT-354 150 mg injection subcutaneously on Day 0.	Biological: CAT-354 150 mg (subcutaneous); A single dose of CAT-354 150 mg injection subcutaneously on Day 0.; Other Names: Tralokinumab
Experimental: CAT-354 300 mg (subcutaneous); A single dose of CAT-354 300 mg injection subcutaneously on Day 0.	Biological: CAT-354 300 mg (subcutaneous); A single dose of CAT-354 300 mg injection subcutaneously on Day 0.; Other Names: Tralokinumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Bioavailability of CAT-354 After Subcutaneous Dose	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).	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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: MedImmune LLC

Publications and helpful links

General Publications

• Oh CK, Faggioni R, Jin F, Roskos LK, Wang B, Birrell C, Wilson R, Molfino NA. An open-label, single-dose bioavailability study of the pharmacokinetics of CAT-354 after subcutaneous and intravenous administration in healthy males. Br J Clin Pharmacol. 2010 Jun;69(6):645-55. doi: 10.1111/j.1365-2125.2010.03647.x.

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2008
• Primary Completion (Actual): June 7, 2008
• Study Completion (Actual): June 7, 2008

Study Registration Dates

• First Submitted: March 12, 2008
• First Submitted That Met QC Criteria: March 18, 2008
• First Posted (Estimate): March 19, 2008

Study Record Updates

• Last Update Posted (Actual): May 4, 2017
• Last Update Submitted That Met QC Criteria: March 22, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Asthma; Healthy; Tralokinumab; CAT-354
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: CAT-354-0703