Comparison of RPL554 With Placebo and Salbutamol in Asthmatic Patients

Verona Pharma

Status and phase: Completed; Phase 2

Conditions: Asthma

Treatments: Drug: Placebo; Drug: RPL554; Drug: Salbutamol

Study type: Interventional

Funder types: Industry

Identifiers

NCT02427165

RPL554-008-2014

Details and patient eligibility

About

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.

Full 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.

Enrollment: 29 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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29 participants in 7 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Single dose of nebulised placebo solution

Treatment:

Drug: Placebo

RPL554 Dose 1

Experimental group

Description:

0.4 mg single dose nebulised RPL554

Treatment:

Drug: RPL554

RPL554 Dose 2

Experimental group

Description:

1.5 mg single dose nebulised RPL554

Treatment:

Drug: RPL554

RPL554 Dose 3

Experimental group

Description:

6 mg single dose nebulised RPL554

Treatment:

Drug: RPL554

RPL554 Dose 4

Experimental group

Description:

24 mg single dose nebulised RPL554

Treatment:

Drug: RPL554

Salbutamol Dose 1

Active Comparator group

Description:

2.5 mg single dose nebulised salbutamol

Treatment:

Drug: Salbutamol

Salbutamol Dose 2

Active Comparator group

Description:

7.5 mg single dose nebulised salbutamol

Treatment:

Drug: Salbutamol