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A Study to Assess Bioavailability and Pharmacokinetics of CAT- 354

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00638989
First Posted: March 19, 2008
Last Update Posted: May 4, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
MedImmune LLC
  Purpose
To compare bioavailability and pharmacokinetics of CAT-354 following subcutaneous administration compared with intravenous administration.

Condition Intervention Phase
Asthma Healthy Biological: CAT-354 150 mg (intravenous) Biological: CAT-354 150 mg (subcutaneous) Biological: CAT-354 300 mg (subcutaneous) Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Parallel-Group, Bioavailability Study to Assess the Pharmacokinetics of CAT-354 Following Subcutaneous and Intravenous Administration

Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • 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 ]
    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:
  • Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [ Time Frame: 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.

  • Number of Participants Exhibiting Anti-Drug Antibodies for CAT-354 at Any Visit [ Time Frame: Day 0 and Day 56 ]
  • 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 ]
    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).

  • 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 ]
  • 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 ]
    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) [ 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
    Terminal phase elimination half-life is the time measured for the serum concentration to decrease by one half.

  • 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 ]
    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).

  • 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 ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

  • 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 ]
    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).


Enrollment: 30
Actual Study Start Date: April 11, 2008
Study Completion Date: June 7, 2008
Primary Completion Date: June 7, 2008 (Final data collection date for primary outcome measure)
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: 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: 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: CAT-354 300 mg (subcutaneous)
A single dose of CAT-354 300 mg injection subcutaneously on Day 0.
Other Name: Tralokinumab

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   19 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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).
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00638989


Locations
United States, Nebraska
MDS Pharma Services (US) Inc.
Lincoln, Nebraska, United States, 68502
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: MedImmune LLC MedImmune LLC
  More Information

Publications:
Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT00638989     History of Changes
Other Study ID Numbers: CAT-354-0703
First Submitted: March 12, 2008
First Posted: March 19, 2008
Results First Submitted: March 22, 2017
Results First Posted: May 4, 2017
Last Update Posted: May 4, 2017
Last Verified: March 2017

Keywords provided by MedImmune LLC:
Asthma
CAT-354
Tralokinumab
Healthy