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
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 23
- 试验地点
- 2
- 主要终点
- Observed Serum Drug Concentration for CAT-354 28 Days (C28) After First Dose
研究概览
简要总结
The study includes participants with moderate asthma who were randomly assigned to receive the study medication (CAT-354) or placebo.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Body weight between 50-120 kg
- •Subjects aged between 18-40 years inclusive must have body mass index (BMI) 18-32 kilogram per square meter (kg/m^2) inclusive. Subjects aged between 41-60 years must have BMI between 18-30 kg/m^2 inclusive.
排除标准
- •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
- •Lower respiratory tract infection within 4 weeks of Day-14
- •Any acute illness in the two weeks before Day 0
- •Current smokers, those who have smoked in previous year, and those with smoking history of greater than or equal to 10 pack years
- •Considered by the investigator to be at risk of transmitting, through blood, the agents responsible for infectious diseases
- •Blood donation (550 ml) in the previous 2 months
- •Excessive intake of alcohol (more than 21 units a week for females or 28 units a week for males)
- •The subject's general practitioner has suggested a reason the subject should not participate in the study
- •The Investigator considers the subject should not take part for any reason.
结局指标
主要结局
Observed Serum Drug Concentration for CAT-354 28 Days (C28) After First Dose
时间窗: Pre-dose on Day 28
Observed Serum Drug Concentration for CAT-354 28 Days (C28) After Second Dose
时间窗: Pre-dose on Day 56
Maximum Observed Serum Concentration (Cmax) for CAT-354 After First Dose
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: Day 84
Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC[0 - Infinity]) for CAT-354 After First Dose
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)(Day 0 to Day 147)