A Double-Blind, Placebo Controlled Study to Assess the Pharmacokinetics, Safety and Tolerability of Multiple Intravenous Doses of 3 Dose Levels of CAT-354 in Subjects With Moderate Asthma
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Moderate Asthma
- Sponsor
- MedImmune LLC
- Enrollment
- 23
- Locations
- 1
- Primary Endpoint
- Observed Serum Drug Concentration for CAT-354 28 Days (C28) After First Dose
- Status
- Terminated
- Last Updated
- 9 years ago
Overview
Brief Summary
The study includes participants with moderate asthma who were randomly assigned to receive the study medication (CAT-354) or placebo.
Detailed Description
This study is a randomized, double-blind, placebo controlled study. Following confirmation of eligibility, subjects with moderate asthma will be recruited sequentially to one of three dose groups and randomly assigned within dose group to either CAT-354 or placebo. Doses of the assigned treatment will be administered on three occasions 28 days apart. Follow up for pharmacokinetic blood sampling and safety will continue to Day 147 post-first dose (91 days post-third dose).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Males or infertile females
- •Subjects with asthma, well controlled on inhaled corticosteroid and taken as required (PRN) short acting beta 2 agonist therapy only
- •Unchanged dose of inhaled corticosteroid for 3 months prior to Day 0 and no expected need for change in dose during study
- •Forced expiratory volume in 1 second (FEV1) greater than or equal to 80% predicted at Screening (Baseline)
- •18-60 years
- •General Practitioner diagnosis of asthma of 1 year's minimum duration (with respect to Day 0)
- •No significant abnormality on clinical examination or medical history (excluding atopic skin signs, symptoms and history)
- •12-lead electrocardiogram with no clinical significant abnormality
- •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
Exclusion Criteria
- •Active concomitant disease, with exception of eczema
- •Expected onset of seasonal allergy before the administration of the last dose of study medication
- •History of severe exacerbation within 3 years of Day 0
- •Recorded use of inhaled short acting beta 2 agonist medication for symptoms within 14 days of Day 0 of: More than 6 doses per day on any 1 day or more than 3 doses per day on 6 or more days
- •Any medication other than: inhaled short-acting beta 2 agonist, inhaled corticosteroids, topic eczema treatments (with the exception of fluorinated corticosteroid, dermatological preparations which are not permitted), hormone replacement therapy, vitamin preparation/food supplements, occasional use of proton pump inhibitors, ranitidine, cimetidine, antacids or over-the-counter analgesics
- •Treatment within 6 months of Day 0 with any of the following: methylxanthines, inhaled cromones, leukotriene modifiers, anti- immunoglobulin E (IgE), anticholinergics, ketotifen, oral short acting B2 agonists, long-acting B2 agonists, oral or injected corticosteroids
- •Treatment of atopic symptoms, other than eczema, within 4 weeks of Day 0
- •History of medication that might carry-over effects into the study
- •Previously received monoclonal antibody, or a similar related protein, that might sensitize to CAT-354
- •Participation in another study within three months of the start of the study or 5 half lives of the previously administered investigational medicinal product (IMP), whichever is longer
Outcomes
Primary Outcomes
Observed Serum Drug Concentration for CAT-354 28 Days (C28) After First Dose
Time Frame: Pre-dose on Day 28
Observed Serum Drug Concentration for CAT-354 28 Days (C28) After Second Dose
Time Frame: Pre-dose on Day 56
Maximum Observed Serum Concentration (Cmax) for CAT-354 After First Dose
Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21
Maximum Observed Serum Concentration (Cmax) for CAT-354 After Second Dose
Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 28; Day 35
Maximum Observed Serum Concentration (Cmax) for CAT-354 After Third Dose
Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 56; Day 63, 84, 105 and 147
Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC[0 - t]) for CAT-354 After First Dose
Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21
Observed Serum Concentration for CAT-354 28 Days (C28) After Third Dose
Time Frame: Day 84
Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC[0 - Infinity]) for CAT-354 After First Dose
Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21
AUC (0 - infinity) = Area under the serum concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - infinity). It is obtained from AUC (0 - t) plus AUC (t - infinity).
Apparent Terminal Elimination Phase Half-Life (t[1/2]el) for CAT-354 After First Dose
Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21
Terminal elimination phase half-life is the time measured for the serum concentration to decrease by one half.
Clearance (CL) for CAT-354 After First Dose
Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21
Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. Clearance was normalized by the body weight of the participant.
Volume of Distribution (Vd) for CAT-354 After First Dose
Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21
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 was normalized to the body weight of the participant.
Accumulation Ratio (R0) for CAT-354
Time Frame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0 and 56; Pre-dose on Day 28; Day 4, 7, 14, 21, 63 and 84
Accumulation ratio is calculated as: R0 = AUC(56 - 84)/AUC(0 - 28) where AUC(0 - 28) and AUC(56 - 84) are the area under the serum concentration time curve over a dosage interval determined after the first dose (Day 0 to Day 28) and after the third dose (Day 56 to Day 84), respectively.
Secondary Outcomes
- Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)(Day 0 to Day 147)