Clinical trial NCT04091360: A Study of RPL554 Drug Administered by Metered Dose Inhaler to Treat Chronic Obstructive Pulmonary Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COPD
Keywords: COPD
Adults
Phase II
RPL554
Ensifentrine
Lead sponsor: Verona Pharma plc
Sponsor class: INDUSTRY
Collaborators: name: Iqvia Pty Ltd
First posted: 2019-09-16
Enrollment: 40
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Part A: Pharmacokinetic Parameter AUC0-12
timeFrame: Day 1
measure: Part A: Pharmacokinetic Parameter Cmax
timeFrame: Day 1
measure: Part A: Pharmacokinetic Parameter AUC0-t
timeFrame: Day 1
measure: Part A: RPL554 Plasma Pharmacokinetic Parameter (Half-life)
timeFrame: Day 1
measure: Part B: Change From Baseline in Peak FEV1 (Over 4 Hours) on Day 7
timeFrame: Day 7
Secondary outcomes:
measure: Part A: Change From Baseline in Peak FEV1 (Over 4 Hours) After 1 Dose
timeFrame: Day 1
measure: Part A: Change From Baseline in Average FEV1 (Over 4 Hours) After 1 Dose
timeFrame: Day 1
measure: Part A: Change From Baseline in Average FEV1 (Over 12 Hours) After 1 Dose
timeFrame: Day 1
measure: Part A: Safety and Tolerability / Hematology Safety Assessments
timeFrame: 1 day
measure: Part A: Safety and Tolerability / Blood Chemistry Safety Assessments: Number of Patients With Treatment-emergent Blood Chemistry Abnormal Laboratory Assessments
timeFrame: 1 day
measure: Part A: Safety and Tolerability / Urinalysis Safety Assessments: Number of Patients With Treatment-emergent Urinalysis Abnormal Laboratory Assessments
timeFrame: 1 day
measure: Part A: Safety and Tolerability / Supine Vitals Signs - Pulse Rate
timeFrame: Start of treatment to day 1
measure: Part A: Safety and Tolerability / Supine Vitals Signs - Blood Pressure
timeFrame: Start of treatment to day 1
measure: Part A: Safety and Tolerability / ECG - QTcF
timeFrame: Start of treatment to day 1
measure: Part A: Safety and Tolerability / ECG - Heart Rate
timeFrame: Start of treatment to day 1
measure: Part B: Change From Baseline in Average FEV1 (Over 4 Hrs) After 7 Days
timeFrame: Day 7
measure: Part B: Change From Baseline in Average FEV1 (Over 12 Hours) After 7 Days
timeFrame: Day 7
measure: Part B: Change From Baseline in Trough FEV1 After 7 Days
timeFrame: Day 7
measure: Part B: Change From Baseline in Peak FEV1 (Over 4 Hours) After 1st Dose
timeFrame: Day 1
measure: Part B: Change From Baseline in Average FEV1 (Over 4 Hours) After 1st Dose
timeFrame: Day 1
measure: Part B: Change From Baseline in Average FEV1 (Over 12 Hours) After 1st Dose
timeFrame: Day 1
measure: Part B: RPL554 Plasma Pharmacokinetic Parameter (Onset of Action)
timeFrame: Day 1
measure: Part B: Safety and Tolerability / Hematology Safety Assessments
timeFrame: 1 day
measure: Part B: Safety and Tolerability / Blood Chemistry Safety Assessments
timeFrame: 1 day
measure: Part B: Safety and Tolerability / Urinalysis Safety Assessments
timeFrame: 1 day
measure: Part B: Safety and Tolerability / Supine Vital Signs - Pulse Rate
timeFrame: Start of treatment to day 1
measure: Part B: Safety and Tolerability / Supine Vital Signs - Blood Pressure
timeFrame: Start of treatment to day 1
measure: Part B: Safety and Tolerability / ECG - QTcF
timeFrame: Start of treatment to day 70
measure: Part B: Safety and Tolerability / ECG - Heart Rate
timeFrame: Start of treatment to day 70
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Respiratory Clinical Trials Ltd
city: Wythenshawe
country: United Kingdom
facility: Medicines Evaluation Unit Limited
Study officials:
References: