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

COPD Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04091360
• Other study ID #: RPL554-MD-201
• Status: Completed
• Phase: Phase 2
• Start date: April 29, 2019
• Est. completion date: January 21, 2021

Study information

• Verified date: August 2022
• Source: Verona Pharma plc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: January 21, 2021
• Est. primary completion date: December 10, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• COPD

Intervention

Drug:
• Part A: RPL554
Single dose RPL554 via metered dose inhaler.
• 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.
• Part B: RPL554
Part B: Repeat doses via metered dose inhaler in crossover fashion. One dose administered twice daily over 7 days.

Locations

Country	Name	City	State
United Kingdom	Respiratory Clinical Trials Ltd	London
United Kingdom	Medicines Evaluation Unit Limited	Wythenshawe

Sponsors (2)

Lead Sponsor	Collaborator
Verona Pharma plc	Iqvia Pty Ltd

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Pharmacokinetic Parameter AUC0-12	Area under the curve from 0 to 12 hours after single dose drug administration.	Day 1
Primary	Part A: Pharmacokinetic Parameter Cmax	Pharmacokinetic Parameter Cmax after a Single Dose	Day 1
Primary	Part A: Pharmacokinetic Parameter AUC0-t	Area under the curve at maximum concentration 0-24 hrs after single dose drug administration	Day 1
Primary	Part A: RPL554 Plasma Pharmacokinetic Parameter (Half-life)	RPL554 Plasma Pharmacokinetics concentration after single dose	Day 1
Primary	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	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
Secondary	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
Secondary	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
Secondary	Part A: Safety and Tolerability / Hematology Safety Assessments	Number of patients with treatment-emergent hematology abnormal laboratory assessments	1 day
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Part B: Safety and Tolerability / Hematology Safety Assessments	Number of patients with treatment-emergent hematology abnormal laboratory assessments	1 day
Secondary	Part B: Safety and Tolerability / Blood Chemistry Safety Assessments	Number of patients with treatment-emergent blood chemistry abnormal laboratory assessments	1 day
Secondary	Part B: Safety and Tolerability / Urinalysis Safety Assessments	Number of patients with treatment-emergent urinalysis abnormal laboratory assessments	1 day
Secondary	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
Secondary	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
Secondary	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
Secondary	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