A Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of Inhaled QBW276 in Patients With Cystic Fibrosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Cohorts 1 and 2: Pharmacokinetics (Cmax) of QBW276, QBP545, and QBV697 in Plasma
研究概览
简要总结
This is a study of multiple doses of inhaled QBW276 in patients with cystic fibrosis on top of standard of care. The study was divided into 3 Cohorts. Cohorts 1 and 2 are designed to be a randomized, double-blind, placebo-controlled, parallel arm, multiple dose study to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of inhaled QBW276 over 1 week (cohort 1) or 2 weeks (cohort 2) in patients with cystic fibrosis regardless of their genotype.
The study was terminated after Cohort 2 due to the resource issues.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Cohorts 1 and 2 = any genotype on any standard of care treatment
- •Cohort 3 = F508del homozygotes on standard of care at that time
- •FEV₁between 40 and 100%
- •LCI2.5 ≥ 8 if FEV₁is more than 80%
排除标准
- •Adrenal or electrolyte abnormalities
- •Lung transplant
- •Autonomic dysfunction (e.g. recurrent episodes of fainting, palpitations, etc.)
研究组 & 干预措施
CQBW276
Cohorts 1 and 2 will enroll 8 patients each (6:2 QBW276 and placebo, respectively).
Cohort 1: dose is 3 mg bid (6 mg daily) QBW276 or placebo for 7 days. Cohort 2: dose and frequency will be confirmed after cohort 1 is complete. The duration is 14 days.
Cohort 3: dose and frequency will be confirmed after cohort 2 is complete. The duration is approximately 4 months. Patients will be randomized to one of two treatment sequences: QBW276 in Period 1 and Placebo in Period 2 or Placebo in Period 1 and QBW276 in Period 2. Twenty four patients are required to complete cohort 3.
干预措施: QBW276 (Drug)
Placebo
Cohorts 1 and 2 will enroll 8 patients each (6:2 QBW276 and placebo, respectively).
Cohort 1: dose is 3 mg bid (6 mg daily) QBW276 or placebo for 7 days. Cohort 2: dose and frequency will be confirmed after cohort 1 is complete. The duration is 14 days.
Cohort 3: dose and frequency will be confirmed after cohort 2 is complete. The duration is approximately 4 months. Patients will be randomized to one of two treatment sequences: QBW276 in Period 1 and Placebo in Period 2 or Placebo in Period 1 and QBW276 in Period 2. Twenty four patients are required to complete cohort 3.
干预措施: Placebo (Other)
结局指标
主要结局
Cohorts 1 and 2: Pharmacokinetics (Cmax) of QBW276, QBP545, and QBV697 in Plasma
时间窗: Cohort 1: day 1, 7; Cohort 2: day 1, 14
Blood collection will be used to observe the maximum plasma concentration (Cmax) following administration of QBW276. Pharmacokinetic blood samples were collected at the time points. In Cohorts 1 and 2 this consisted of multiple samples through 6 hours after inhalation on Days 1 and 7 in Cohort 1 and Days 1 and 14 in Cohort 2 with predose samples on selected days. The Cmax, was determined using the actual recorded sampling times and noncompartmental methods. Since steady state was likely reached by Day 7, Cmax on Days 7 or 14 correspond to Cmax,ss
Cohorts 1 and 2: Pharmacokinetics Accumulation Ratio (Racc) of QBW276, QBP545, and QBV697 in Plasma
时间窗: Cohort 1: 7 days; Cohort 2: 14 days
The accumulation ratio (Racc) will be reported using blood samples taken on days 1 -7 in cohort 1 and days 1-14 in cohort 2. Accumulation ratio (Racc) for QBW276 and metabolites was not calculated by PK software for patients where BLOQ values were observed for all blood samples in their PK profile.
Cohorts 1 and 2: Pharmacokinetics (Tmax) of QBW276, QBP545, and QBV697 in Plasma
时间窗: Day 1, 7 and 14
Blood collection will be used to observe the maximum plasma concentration (Tmax) following administration of QBW276. Pharmacokinetic blood samples were collected at the time points. In Cohorts 1 and 2 this consisted of multiple samples through 6 hours after inhalation on Days 1 and 7 in Cohort 1 and Days 1 and 14 in Cohort 2 with predose samples on selected days. The Tmax, was determined using the actual recorded sampling times and noncompartmental methods. Since steady state was likely reached by Day 7, Tmax on Days 7 or 14 correspond to Tmax,ss
Cohorts 1 and 2: Pharmacokinetics (AUCtau) of QBW276, QBP545, and QBV697 in Plasma
时间窗: Day 1, 7 and 14
Blood collection will be used to observe the maximum plasma concentration (AUCtau) following administration of QBW276. Pharmacokinetic blood samples were collected at the time points. In Cohorts 1 and 2 this consisted of multiple samples through 6 hours after inhalation on Days 1 and 7 in Cohort 1 and Days 1 and 14 in Cohort 2 with predose samples on selected days. The AUCtau, was determined using the actual recorded sampling times and noncompartmental methods. Since steady state was likely reached by Day 7, AUCtau on Days 7 or 14 correspond to AUClast,ss
Cohorts 1 and 2: Safety Assessments, Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]).
时间窗: Cohort 1: day 1-7; Cohort 2: day 1-14
Adverse events were summarized by the number of patients having any adverse event overall and presented in the safety section. Study was prematurely terminated
次要结局
- Cohorts 1, 2: Change From Baseline in Lung Clearance Index (LCI) From Baseline to Day 7 for Cohort 1, Day 14 for Cohort 2.(Baseline to EOS)
- Cohorts 1 and 2: Change From Baseline in Percent Predicted Forced Expiratory Volume in the First Second by Spirometry (% Predicted FEV1)(Baseline to End of study (EOS))