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

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

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).

Study Overview

• Status: Completed
• Conditions: COPD
• Intervention / Treatment: Drug: Part A: RPL554; Drug: Placebos; Drug: Part B: RPL554

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W1G 8HU
    • Respiratory Clinical Trials Ltd
  • Wythenshawe, United Kingdom, M23 9QZ
    • Medicines Evaluation Unit Limited

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RPL554 100 mcg; Part A: Patients receive 1 dose of either RPL554 100mcg via metered dose inhaler. Part B: not applicable	Drug: Part A: RPL554; Single dose RPL554 via metered dose inhaler.; Other Names: Part A; Drug: Placebos; 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.
Experimental: 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.	Drug: Part A: RPL554; Single dose RPL554 via metered dose inhaler.; Other Names: Part A; Drug: Placebos; 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.; Drug: Part B: RPL554; Part B: Repeat doses via metered dose inhaler in crossover fashion. One dose administered twice daily over 7 days.; Other Names: Part B
Experimental: 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.	Drug: Part A: RPL554; Single dose RPL554 via metered dose inhaler.; Other Names: Part A; Drug: Placebos; 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.; Drug: Part B: RPL554; Part B: Repeat doses via metered dose inhaler in crossover fashion. One dose administered twice daily over 7 days.; Other Names: Part B
Experimental: 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.	Drug: Part A: RPL554; Single dose RPL554 via metered dose inhaler.; Other Names: Part A; Drug: Placebos; 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.; Drug: Part B: RPL554; Part B: Repeat doses via metered dose inhaler in crossover fashion. One dose administered twice daily over 7 days.; Other Names: Part B
Experimental: RPL554 6000 mcg; Part A: Patients receive 1 dose of either RPL554 6000mcg via metered dose inhaler. Part B: not applicable	Drug: Part A: RPL554; Single dose RPL554 via metered dose inhaler.; Other Names: Part A; Drug: Placebos; 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.
Placebo Comparator: 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.	Drug: Part A: RPL554; Single dose RPL554 via metered dose inhaler.; Other Names: Part A; Drug: Placebos; 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.

What is the study measuring?

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 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 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: 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

Collaborators and Investigators

• Sponsor: Verona Pharma plc
• Collaborators: IQVIA Pty Ltd

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2019
• Primary Completion (Actual): December 10, 2020
• Study Completion (Actual): January 21, 2021

Study Registration Dates

• First Submitted: June 20, 2019
• First Submitted That Met QC Criteria: September 13, 2019
• First Posted (Actual): September 16, 2019

Study Record Updates

• Last Update Posted (Actual): September 21, 2022
• Last Update Submitted That Met QC Criteria: August 29, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: COPD; Adults; Phase II; RPL554; Ensifentrine
• Other Study ID Numbers: RPL554-MD-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No