Comparison of RPL554 With Placebo and Salbutamol in Asthmatic Patients

Asthma Clinical Trial

Official title:

A Phase II, Randomised, Double Blind, Placebo Controlled, Seven Way Crossover Study to Assess the Effect of Single Doses of RPL554 Compared to Salbutamol and Placebo Administered by Nebuliser on Lung Function of Patients With Chronic Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02427165
• Other study ID #: RPL554-008-2014
• Status: Completed
• Phase: Phase 2
• First received: April 14, 2015
• Last updated: September 8, 2016
• Start date: April 2015
• Est. completion date: November 2015

Study information

• Verified date: September 2016
• Source: Verona Pharma plc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencySweden: Institutional Review BoardSweden: Medical Products Agency
• Study type: Interventional

Clinical Trial Summary

The number of people with of asthma and allergy is still increasing and a large number of patients still do not have their asthma well controlled. There is therefore a need for new asthma treatments that work well and have less side effects. The study compares a new experimental drug RPL554 with a marketed asthma drug (salbutamol) and placebo.

Description:

A seven way crossover study to investigate the pharmacodynamics, pharmacokinetics, safety and tolerability of inhaled RPL554 compared to salbutamol and placebo in patients with mild to moderate chronic asthma.

Salbutamol is a marketed beta-2 agonist typically used to treat bronchospasm (due to any cause, allergen asthma or exercise-induced), as well as chronic obstructive pulmonary disease but has associated dose-related systemic side effects.

RPL554 is a dual PDE3 and PDE4 inhibitor that has bronchodilatory and anti-inflammatory actions and also the potential to stimulate increases in mucociliary clearance via its proven ability to activate CFTR. Four different doses of RPL554 will be compared with placebo and a two doses of salbutamol as benchmarks for bronchodilation and systemic side effects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Provided written informed consent

• Males agree not to donate sperm and either be abstinent or use adequate contraception. Females to be post-menopausal or surgically sterile

• Non-smoker or ex-smoker >6 months

• Diagnosed asthma for at least 6 months

• Pre-bronchodilator FEV1 =60% and =90% of predicted normal value and =1.5 L at screening

• Increase in FEV1 of 15% within 30 minutes after a 2.5mg dose of nebulised salbutamol

• Systolic blood pressure 90 to 145 mmHg, diastolic blood pressure 50 to 90 mmHg and heart rate 45 to 80 beats per minute (bpm) after resting for 5 minutes in a supine position (average from two measurements)

• Capable of withdrawing from LABAs, LAMAs and SAMAs before screening and during study and SABAs before screening and for 8 hours before each dose

Exclusion Criteria:

• Asthma exacerbation in the last 3 months

• Any prior life threatening episode of asthma (intensive care admission)

• Any clinically significant disease or disorder or clinically relevant screening result

• QTcF interval >450 ms or QT interval >500 ms or other abnormality in ECG

• History of ischemic heart disease or heart failure. History of recurrent or current clinically significant arrhythmia or ECG abnormality as judged by the investigator

• Treatment with systemic glucocorticosteroids within 30 days before screening

• A suspected/manifested infection according to WHO risk classification 2, 3 or 4

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• RPL554
A dual PDE3 and PDE4 inhibitor
• Salbutamol
a beta-2 receptor agonist
• Placebo
RPL554 placebo containing no active ingredients

Locations

Country	Name	City	State
Sweden	Skane University Hospital	Lund
United Kingdom	Celerion	Belfast

Sponsors (1)

Lead Sponsor	Collaborator
Verona Pharma plc

Countries where clinical trial is conducted

Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Spirometry	FEV1	12 hours	No
Secondary	Spirometry	FEV1	4, 6 and 8 hours	No
Secondary	Systemic pharmacodynamic effect on blood pressure	Supine blood pressure in the 4 hours after nebulisation	4 hours	No
Secondary	Systemic pharmacodynamic effect on pulse rate	Supine Pulse rate in the 4 hours after nebulisation	4 hours	No
Secondary	Systemic pharmacodynamic effect on ECG heart rate	ECG heart rate in the 4 hours after nebulisation	4 hours	No
Secondary	Vital signs (Supine pulse rate)	Supine pulse rate	12 hours	Yes
Secondary	Vital signs (Supine blood pressure)	Supine systolic and diastolic blood pressure	12 hours	Yes
Secondary	ECG	12-lead ECG parameters	12 hours	Yes
Secondary	Pharmacokinetics (AUC)	RPL554 AUC	12 hours	No
Secondary	Pharmacokinetics (Cmax)	RPL554 Cmax	12 hours	No
Secondary	Pharmacokinetics (tmax)	RPL554 tmax	12 hours	No
Secondary	Pharmacokinetics (half life)	RPL554 half life	12 hours	No
Secondary	Pharmacokinetics (MRT)	RPL554 MRT	12 hours	No