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

Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA40 enrolled

Overview

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).

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

COPD

Interventions

Part A: RPL554DRUG

Single dose RPL554 via metered dose inhaler.

PlacebosDRUG

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.

Part B: RPL554DRUG

Part B: Repeat doses via metered dose inhaler in crossover fashion. One dose administered twice daily over 7 days.

Eligibility

Sex: ALLMin age: 40 YearsMax age: 80 Years

Medical Language ↔ Plain English

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.

Locations (2)

Respiratory Clinical Trials Ltd

London, United Kingdom

Medicines Evaluation Unit Limited

Wythenshawe, United Kingdom

Outcomes

Primary Outcomes

Part A: Pharmacokinetic Parameter AUC0-12

Area under the curve from 0 to 12 hours after single dose drug administration.

Time frame: Day 1

Part A: Pharmacokinetic Parameter Cmax

Pharmacokinetic Parameter Cmax after a Single Dose

Time frame: Day 1

Part A: Pharmacokinetic Parameter AUC0-t

Area under the curve at maximum concentration 0-24 hrs after single dose drug administration

Time frame: Day 1

Part A: RPL554 Plasma Pharmacokinetic Parameter (Half-life)

RPL554 Plasma Pharmacokinetics concentration after single dose

Time frame: 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

Time frame: Day 7

Secondary Outcomes

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

Time frame: 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

Time frame: 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

Data from ClinicalTrials.gov

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Part A: Safety and Tolerability / Hematology Safety Assessments

Number of patients with treatment-emergent hematology abnormal laboratory assessments

Time frame: 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

Time frame: 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

Time frame: 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)

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Day 1

Part B: Safety and Tolerability / Hematology Safety Assessments

Number of patients with treatment-emergent hematology abnormal laboratory assessments

Time frame: 1 day

Part B: Safety and Tolerability / Blood Chemistry Safety Assessments

Number of patients with treatment-emergent blood chemistry abnormal laboratory assessments

Time frame: 1 day

Part B: Safety and Tolerability / Urinalysis Safety Assessments

Number of patients with treatment-emergent urinalysis abnormal laboratory assessments

Time frame: 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)

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: Start of treatment to day 70