A Study of RPL554 Drug Administered by Metered Dose Inhaler to Treat Chronic Obstructive Pulmonary Disease
- Conditions
- COPD
- Interventions
- Drug: Placebos
- Registration Number
- NCT04091360
- Lead Sponsor
- Verona Pharma plc
- Brief Summary
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).
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
- 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 ≤0.70.
- 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.
- Patients must be clinically stable without recent COPD exacerbations or hospitalisations.
- They must not have uncontrolled disease or chronic heart failure.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description RPL554 100 mcg Placebos Part A: Patients receive 1 dose of either RPL554 100mcg via metered dose inhaler. Part B: not applicable RPL554 300 mcg Placebos 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. RPL554 1000 mcg Placebos 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. RPL554 3000 mcg Placebos 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. RPL554 6000 mcg Placebos Part A: Patients receive 1 dose of either RPL554 6000mcg via metered dose inhaler. Part B: not applicable RPL554 Placebo Placebos 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.
- Primary Outcome Measures
Name Time Method Part A: Pharmacokinetic Parameter AUC0-12 Day 1 Area under the curve from 0 to 12 hours after single dose drug administration.
Part A: Pharmacokinetic Parameter Cmax Day 1 Pharmacokinetic Parameter Cmax after a Single Dose
Part A: Pharmacokinetic Parameter AUC0-t 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) Day 1 RPL554 Plasma Pharmacokinetics concentration after single dose
Part B: Change From Baseline in Peak FEV1 (Over 4 Hours) on Day 7 Day 7 Change from Baseline FEV1 to Peak FEV1 (over 4 hours) after morning dosing on Day 7
- Secondary Outcome Measures
Name Time Method Part B: Change From Baseline in Average FEV1 (Over 12 Hours) After 1st Dose Day 1 Change from baseline FEV1 in average FEV1 (over 12 hours) on Day 1
Part B: RPL554 Plasma Pharmacokinetic Parameter (Onset of Action) Day 1 Determination of onset of action (\>10% increase in FEV1 from pre- to post-first dose, censored at 120 minutes) on Day 1
Part B: Safety and Tolerability / Hematology Safety Assessments 1 day Number of patients with treatment-emergent hematology abnormal laboratory assessments
Part B: Safety and Tolerability / Blood Chemistry Safety Assessments 1 day Number of patients with treatment-emergent blood chemistry abnormal laboratory assessments
Part B: Safety and Tolerability / Urinalysis Safety Assessments 1 day Number of patients with treatment-emergent urinalysis abnormal laboratory assessments
Part B: Safety and Tolerability / ECG - QTcF Start of treatment to day 70 Number of patients with treatment-emergent abnormal ECG parameters, QTcF in msec
Part B: Safety and Tolerability / ECG - Heart Rate Start of treatment to day 70 Number of patients with treatment-emergent abnormal ECG parameters, heart rate in bpm
Part A: Change From Baseline in Peak FEV1 (Over 4 Hours) After 1 Dose Day 1 Change from Baseline FEV1 to Peak FEV1 (over 4 hours) After Single Dose
Part A: Change From Baseline in Average FEV1 (Over 4 Hours) After 1 Dose Day 1 Change from Baseline FEV1 to Average FEV1 (over 4 hours) After Single Dose
Part A: Change From Baseline in Average FEV1 (Over 12 Hours) After 1 Dose Day 1 Change from Baseline FEV1 to Average FEV1 (over 12 hours) After Single Dose
Part A: Safety and Tolerability / Hematology Safety Assessments 1 day Number of patients with treatment-emergent hematology abnormal laboratory assessments
Part A: Safety and Tolerability / Blood Chemistry Safety Assessments: Number of Patients With Treatment-emergent Blood Chemistry Abnormal Laboratory Assessments 1 day Number of patients with treatment-emergent blood chemistry abnormal laboratory assessments
Part A: Safety and Tolerability / Urinalysis Safety Assessments: Number of Patients With Treatment-emergent Urinalysis Abnormal Laboratory Assessments 1 day Number of patients with treatment-emergent urinalysis abnormal laboratory assessments
Part A: Safety and Tolerability / Supine Vitals Signs - Pulse Rate Start of treatment to day 1 Number of patients with treatment-emergent abnormal vital signs (pulse rate in bpm)
Part A: Safety and Tolerability / Supine Vitals Signs - Blood Pressure Start of treatment to day 1 Number of patients with treatment-emergent abnormal vital signs (blood pressure in mm Hg)
Part A: Safety and Tolerability / ECG - QTcF Start of treatment to day 1 Number of patients with treatment-emergent abnormal ECG parameters, QTcF in msec
Part A: Safety and Tolerability / ECG - Heart Rate Start of treatment to day 1 Number of patients with treatment-emergent abnormal ECG parameters, heart rate in bpm
Part B: Change From Baseline in Average FEV1 (Over 4 Hrs) After 7 Days Day 7 Change from baseline in average FEV1 (over 4 hours) on Day 7 after morning dose
Part B: Change From Baseline in Average FEV1 (Over 12 Hours) After 7 Days Day 7 Change from baseline FEV1 in average FEV1 (over 12 hours) on Day 7 after morning dose
Part B: Change From Baseline in Trough FEV1 After 7 Days Day 7 Change from Baseline FEV1 to Morning Trough FEV1 on Day 7 after morning dose
Part B: Change From Baseline in Peak FEV1 (Over 4 Hours) After 1st Dose Day 1 Change from baseline FEV1 in peak FEV1 (over 4 hours) after first dose
Part B: Change From Baseline in Average FEV1 (Over 4 Hours) After 1st Dose Day 1 Change from baseline FEV1 in average FEV1 (over 4 hours) on Day 1
Part B: Safety and Tolerability / Supine Vital Signs - Pulse Rate Start of treatment to day 1 Number of patients with treatment-emergent abnormal vital signs (pulse rate in bpm)
Part B: Safety and Tolerability / Supine Vital Signs - Blood Pressure Start of treatment to day 1 Number of patients with treatment-emergent abnormal vital signs (blood pressure in mm Hg)
Trial Locations
- Locations (2)
Medicines Evaluation Unit Limited
🇬🇧Wythenshawe, United Kingdom
Respiratory Clinical Trials Ltd
🇬🇧London, United Kingdom