A Phase II, Randomised Study to Assess the Pharmacokinetics, Safety and Pharmacodynamics of Single and Repeat Doses of RPL554 Administered by Pressurised Metered Dose Inhaler in Patients With COPD
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Part A: Pharmacokinetic Parameter AUC0-12
研究概览
简要总结
The purpose of this study is to investigate 5 doses of RPL554 and placebo, administered by pressurized metered dose inhaler (pMDI), in patients with moderate to severe chronic obstructive pulmonary disease (COPD).
详细描述
The study will consist of two parts. Part A is a parallel group, placebo-controlled single dose study to ascertain the Pharmacokinetics (PK) profile, safety and bronchodilator effect of a single dose of RPL554 administered via pMDI. Five of the 6 treatment arms will be double-blind and one will be single-blind (due to the different number of capsules administered). Part B is a 7-day placebo-controlled, complete block cross-over, repeat dose study to assess the bronchodilator effect of repeat doses of RPL554 delivered via pMDI.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Double blind
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients with moderate to severe COPD, with a post bronchodilator FEV1 of 40 to 80% of predicted and FEV1/FVC ratio of ≤0.
- •They must have a baseline increase in FEV1 of >150 mL following four puffs of salbutamol.
- •They must have at least a 10 pack-year smoking history, and may be either a current or former smoker.
排除标准
- •Patients must be clinically stable without recent COPD exacerbations or hospitalisations.
- •They must not have uncontrolled disease or chronic heart failure.
研究组 & 干预措施
RPL554 100 mcg
Part A: Patients receive 1 dose of either RPL554 100mcg via metered dose inhaler.
Part B: not applicable
干预措施: Placebos (Drug)
RPL554 300 mcg
Part A: Patients receive 1 dose of RPL554 300mcg via metered dose inhaler. Part B: Patients receive repeat doses of RPL554 300mcg via metered dose inhaler in crossover fashion.
干预措施: Placebos (Drug)
RPL554 1000 mcg
Part A: Patients receive 1 dose of RPL554 1000mcg via metered dose inhaler. Part B: Patients receive repeat doses of RPL554 3000mcg via metered dose inhaler in crossover fashion.
干预措施: Placebos (Drug)
RPL554 3000 mcg
Part A: Patients receive 1 dose of either RPL554 3000mcg via metered dose inhaler.
Part B: Patients receive repeat doses of RPL554 3000mcg via metered dose inhaler in crossover fashion.
干预措施: Placebos (Drug)
RPL554 6000 mcg
Part A: Patients receive 1 dose of either RPL554 6000mcg via metered dose inhaler.
Part B: not applicable
干预措施: Placebos (Drug)
RPL554 Placebo
Part A: Patients receive 1 dose of RPL554 placebo via metered dose inhaler. Part B: Patients receive repeat doses of RPL554 placebo via metered dose inhaler in crossover fashion.
干预措施: Placebos (Drug)
结局指标
主要结局
Part A: Pharmacokinetic Parameter AUC0-12
时间窗: Day 1
Area under the curve from 0 to 12 hours after single dose drug administration.
Part A: Pharmacokinetic Parameter Cmax
时间窗: Day 1
Pharmacokinetic Parameter Cmax after a Single Dose
Part A: Pharmacokinetic Parameter AUC0-t
时间窗: Day 1
Area under the curve at maximum concentration 0-24 hrs after single dose drug administration
Part A: RPL554 Plasma Pharmacokinetic Parameter (Half-life)
时间窗: Day 1
RPL554 Plasma Pharmacokinetics concentration after single dose
Part B: Change From Baseline in Peak FEV1 (Over 4 Hours) on Day 7
时间窗: Day 7
Change from Baseline FEV1 to Peak FEV1 (over 4 hours) after morning dosing on Day 7
次要结局
- Part B: Change From Baseline in Average FEV1 (Over 12 Hours) After 1st Dose(Day 1)
- Part B: RPL554 Plasma Pharmacokinetic Parameter (Onset of Action)(Day 1)
- Part B: Safety and Tolerability / Hematology Safety Assessments(1 day)
- Part B: Safety and Tolerability / Blood Chemistry Safety Assessments(1 day)
- Part B: Safety and Tolerability / Urinalysis Safety Assessments(1 day)
- Part B: Safety and Tolerability / ECG - QTcF(Start of treatment to day 70)
- Part B: Safety and Tolerability / ECG - Heart Rate(Start of treatment to day 70)
- Part A: Change From Baseline in Peak FEV1 (Over 4 Hours) After 1 Dose(Day 1)
- Part A: Change From Baseline in Average FEV1 (Over 4 Hours) After 1 Dose(Day 1)
- Part A: Change From Baseline in Average FEV1 (Over 12 Hours) After 1 Dose(Day 1)
- Part A: Safety and Tolerability / Hematology Safety Assessments(1 day)
- Part A: Safety and Tolerability / Blood Chemistry Safety Assessments: Number of Patients With Treatment-emergent Blood Chemistry Abnormal Laboratory Assessments(1 day)
- Part A: Safety and Tolerability / Urinalysis Safety Assessments: Number of Patients With Treatment-emergent Urinalysis Abnormal Laboratory Assessments(1 day)
- Part A: Safety and Tolerability / Supine Vitals Signs - Pulse Rate(Start of treatment to day 1)
- Part A: Safety and Tolerability / Supine Vitals Signs - Blood Pressure(Start of treatment to day 1)
- Part A: Safety and Tolerability / ECG - QTcF(Start of treatment to day 1)
- Part A: Safety and Tolerability / ECG - Heart Rate(Start of treatment to day 1)
- Part B: Change From Baseline in Average FEV1 (Over 4 Hrs) After 7 Days(Day 7)
- Part B: Change From Baseline in Average FEV1 (Over 12 Hours) After 7 Days(Day 7)
- Part B: Change From Baseline in Trough FEV1 After 7 Days(Day 7)
- Part B: Change From Baseline in Peak FEV1 (Over 4 Hours) After 1st Dose(Day 1)
- Part B: Change From Baseline in Average FEV1 (Over 4 Hours) After 1st Dose(Day 1)
- Part B: Safety and Tolerability / Supine Vital Signs - Pulse Rate(Start of treatment to day 1)
- Part B: Safety and Tolerability / Supine Vital Signs - Blood Pressure(Start of treatment to day 1)