A Study of RPL554 Drug Administered by Metered Dose Inhaler to Treat Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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COPD

Intervention / Treatment
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* Drug: Part A: RPL554
* Drug: Placebos
* Drug: Part B: RPL554


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: Patients must be clinically stable without recent COPD exacerbations or hospitalisations. They must not have uncontrolled disease or chronic heart failure.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RPL554 100 mcg<br>Part A: Patients receive 1 dose of either RPL554 100mcg via metered dose inhaler. Part B: not applicable | Drug: Part A: RPL554<br>* Single dose RPL554 via metered dose inhaler.<br>* Other names: Part A;Drug: Placebos<br>* Part A: Single dose placebo via metered dose inhaler. Part B: Repeat doses of placebo via metered dose inhaler in crossover fashion. One dose administered twice daily over 7 days.<br>|
| Experimental: RPL554 300 mcg<br>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. | Drug: Part A: RPL554<br>* Single dose RPL554 via metered dose inhaler.<br>* Other names: Part A;Drug: Placebos<br>* Part A: Single dose placebo via metered dose inhaler. Part B: Repeat doses of placebo via metered dose inhaler in crossover fashion. One dose administered twice daily over 7 days.<br>Drug: Part B: RPL554<br>* Part B: Repeat doses via metered dose inhaler in crossover fashion. One dose administered twice daily over 7 days.<br>* Other names: Part B;|
| Experimental: RPL554 1000 mcg<br>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. | Drug: Part A: RPL554<br>* Single dose RPL554 via metered dose inhaler.<br>* Other names: Part A;Drug: Placebos<br>* Part A: Single dose placebo via metered dose inhaler. Part B: Repeat doses of placebo via metered dose inhaler in crossover fashion. One dose administered twice daily over 7 days.<br>Drug: Part B: RPL554<br>* Part B: Repeat doses via metered dose inhaler in crossover fashion. One dose administered twice daily over 7 days.<br>* Other names: Part B;|
| Experimental: RPL554 3000 mcg<br>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. | Drug: Part A: RPL554<br>* Single dose RPL554 via metered dose inhaler.<br>* Other names: Part A;Drug: Placebos<br>* Part A: Single dose placebo via metered dose inhaler. Part B: Repeat doses of placebo via metered dose inhaler in crossover fashion. One dose administered twice daily over 7 days.<br>Drug: Part B: RPL554<br>* Part B: Repeat doses via metered dose inhaler in crossover fashion. One dose administered twice daily over 7 days.<br>* Other names: Part B;|
| Experimental: RPL554 6000 mcg<br>Part A: Patients receive 1 dose of either RPL554 6000mcg via metered dose inhaler. Part B: not applicable | Drug: Part A: RPL554<br>* Single dose RPL554 via metered dose inhaler.<br>* Other names: Part A;Drug: Placebos<br>* Part A: Single dose placebo via metered dose inhaler. Part B: Repeat doses of placebo via metered dose inhaler in crossover fashion. One dose administered twice daily over 7 days.<br>|
| Placebo Comparator: RPL554 Placebo<br>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. | Drug: Part A: RPL554<br>* Single dose RPL554 via metered dose inhaler.<br>* Other names: Part A;Drug: Placebos<br>* Part A: Single dose placebo via metered dose inhaler. Part B: Repeat doses of placebo via metered dose inhaler in crossover fashion. One dose administered twice daily over 7 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Pharmacokinetic Parameter AUC0-12 | Area under the curve from 0 to 12 hours after single dose drug administration. | Day 1 | 
| Part A: Pharmacokinetic Parameter Cmax | Pharmacokinetic Parameter Cmax after a Single Dose | Day 1 | 
| Part A: Pharmacokinetic Parameter AUC0-t | Area under the curve at maximum concentration 0-24 hrs after single dose drug administration | Day 1 | 
| Part A: RPL554 Plasma Pharmacokinetic Parameter (Half-life) | RPL554 Plasma Pharmacokinetics concentration after single dose | Day 1 | 
| Part B: Change From Baseline in Peak FEV1 (Over 4 Hours) on Day 7 | Change from Baseline FEV1 to Peak FEV1 (over 4 hours) after morning dosing on Day 7 | Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Change From Baseline in Peak FEV1 (Over 4 Hours) After 1 Dose | Change from Baseline FEV1 to Peak FEV1 (over 4 hours) After Single Dose | Day 1 | 
| Part A: Change From Baseline in Average FEV1 (Over 4 Hours) After 1 Dose | Change from Baseline FEV1 to Average FEV1 (over 4 hours) After Single Dose | Day 1 | 
| Part A: Change From Baseline in Average FEV1 (Over 12 Hours) After 1 Dose | Change from Baseline FEV1 to Average FEV1 (over 12 hours) After Single Dose | Day 1 | 
| Part A: Safety and Tolerability / Hematology Safety Assessments | Number of patients with treatment-emergent hematology abnormal laboratory assessments | 1 day | 
| Part A: Safety and Tolerability / Blood Chemistry Safety Assessments: Number of Patients With Treatment-emergent Blood Chemistry Abnormal Laboratory 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 | Number of patients with treatment-emergent urinalysis abnormal laboratory assessments | 1 day | 
| Part A: Safety and Tolerability / Supine Vitals Signs - Pulse Rate | Number of patients with treatment-emergent abnormal vital signs (pulse rate in bpm) | Start of treatment to day 1 | 
| Part A: Safety and Tolerability / Supine Vitals Signs - Blood Pressure | Number of patients with treatment-emergent abnormal vital signs (blood pressure in mm Hg) | Start of treatment to day 1 | 
| Part A: Safety and Tolerability / ECG - QTcF | Number of patients with treatment-emergent abnormal ECG parameters, QTcF in msec | Start of treatment to day 1 | 
| Part A: Safety and Tolerability / ECG - Heart Rate | Number of patients with treatment-emergent abnormal ECG parameters, heart rate in bpm | Start of treatment to day 1 | 
| Part B: Change From Baseline in Average FEV1 (Over 4 Hrs) After 7 Days | Change from baseline in average FEV1 (over 4 hours) on Day 7 after morning dose | Day 7 | 
| Part B: Change From Baseline in Average FEV1 (Over 12 Hours) After 7 Days | Change from baseline FEV1 in average FEV1 (over 12 hours) on Day 7 after morning dose | Day 7 | 
| Part B: Change From Baseline in Trough FEV1 After 7 Days | Change from Baseline FEV1 to Morning Trough FEV1 on Day 7 after morning dose | Day 7 | 
| Part B: Change From Baseline in Peak FEV1 (Over 4 Hours) After 1st Dose | Change from baseline FEV1 in peak FEV1 (over 4 hours) after first dose | Day 1 | 
| Part B: Change From Baseline in Average FEV1 (Over 4 Hours) After 1st Dose | Change from baseline FEV1 in average FEV1 (over 4 hours) on Day 1 | Day 1 | 
| Part B: Change From Baseline in Average FEV1 (Over 12 Hours) After 1st Dose | Change from baseline FEV1 in average FEV1 (over 12 hours) on Day 1 | Day 1 | 
| Part B: RPL554 Plasma Pharmacokinetic Parameter (Onset of Action) | Determination of onset of action (>10% increase in FEV1 from pre- to post-first dose, censored at 120 minutes) on Day 1 | Day 1 | 
| Part B: Safety and Tolerability / Hematology Safety Assessments | Number of patients with treatment-emergent hematology abnormal laboratory assessments | 1 day | 
| Part B: Safety and Tolerability / Blood Chemistry Safety Assessments | Number of patients with treatment-emergent blood chemistry abnormal laboratory assessments | 1 day | 
| Part B: Safety and Tolerability / Urinalysis Safety Assessments | Number of patients with treatment-emergent urinalysis abnormal laboratory assessments | 1 day | 
| Part B: Safety and Tolerability / Supine Vital Signs - Pulse Rate | Number of patients with treatment-emergent abnormal vital signs (pulse rate in bpm) | Start of treatment to day 1 | 
| Part B: Safety and Tolerability / Supine Vital Signs - Blood Pressure | Number of patients with treatment-emergent abnormal vital signs (blood pressure in mm Hg) | Start of treatment to day 1 | 
| Part B: Safety and Tolerability / ECG - QTcF | Number of patients with treatment-emergent abnormal ECG parameters, QTcF in msec | Start of treatment to day 70 | 
| Part B: Safety and Tolerability / ECG - Heart Rate | Number of patients with treatment-emergent abnormal ECG parameters, heart rate in bpm | Start of treatment to day 70 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Adults, Phase II, RPL554, Ensifentrine