Clinical trial NCT00638989: A Study to Assess Bioavailability and Pharmacokinetics of CAT- 354
Official title: An Open-Label, Parallel-Group, Bioavailability Study to Assess the Pharmacokinetics of CAT-354 Following Subcutaneous and Intravenous Administration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Asthma
Healthy
Keywords: Asthma
CAT-354
Tralokinumab
Healthy
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2008-03-19
Enrollment: 30
Sex: MALE
Minimum age (years): 19
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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).

Primary outcomes:
measure: Absolute Bioavailability of CAT-354 After Subcutaneous Dose
timeFrame: 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 outcomes:
measure: Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: Day 0 to 56
measure: Number of Participants Exhibiting Anti-Drug Antibodies for CAT-354 at Any Visit
timeFrame: Day 0 and Day 56
measure: Area Under the Concentration-time Curve From Zero to Infinity (AUC [0 - Infinity])
timeFrame: 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: Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC[0 - 56])
timeFrame: 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: Dose Normalized Area Under the Concentration-time Curve From Zero to Infinity ([AUC {0 - Infinity}]/Dose)
timeFrame: 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: Maximum Observed Serum Concentration (Cmax)
timeFrame: 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: Dose Normalized Maximum Observed Concentration (Cmax/Dose)
timeFrame: 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: Time to Reach Maximum Observed Serum Concentration (Tmax)
timeFrame: 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: Terminal Phase Elimination Half Life (t1/2)
timeFrame: 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: Apparent Systemic Clearance (CL/F) After Subcutaneous Dose
timeFrame: 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: Apparent Systemic Clearance (CL/F) After Intravenous Dose
timeFrame: 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: Volume of Distribution at Steady State (Vss) After Intravenous Infusion
timeFrame: 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
Other outcomes:
Locations:
city: Lincoln
country: United States
facility: MDS Pharma Services (US) Inc.
state: Nebraska
Study officials:
affiliation: MedImmune LLC
name: MedImmune LLC
role: STUDY_DIRECTOR
References:
citation: 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.