Clinical trial NCT02427165: Comparison of RPL554 With Placebo and Salbutamol in Asthmatic Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Lead sponsor: Verona Pharma plc
Sponsor class: INDUSTRY
First posted: 2015-04-27
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Spirometry
timeFrame: 12 hours
Secondary outcomes:
measure: Spirometry
timeFrame: 4, 6 and 8 hours
measure: Systemic pharmacodynamic effect on blood pressure
timeFrame: 4 hours
measure: Systemic pharmacodynamic effect on pulse rate
timeFrame: 4 hours
measure: Systemic pharmacodynamic effect on ECG heart rate
timeFrame: 4 hours
measure: Vital signs (Supine pulse rate)
timeFrame: 12 hours
measure: Vital signs (Supine blood pressure)
timeFrame: 12 hours
measure: ECG
timeFrame: 12 hours
measure: Pharmacokinetics (AUC)
timeFrame: 12 hours
measure: Pharmacokinetics (Cmax)
timeFrame: 12 hours
measure: Pharmacokinetics (tmax)
timeFrame: 12 hours
measure: Pharmacokinetics (half life)
timeFrame: 12 hours
measure: Pharmacokinetics (MRT)
timeFrame: 12 hours
Other outcomes:
Locations:
city: Lund
country: Sweden
facility: Skane University Hospital
city: Belfast
country: United Kingdom
facility: Celerion
Study officials:
affiliation: Skane University Hospital, Sweden
name: Lief Bjermer
role: PRINCIPAL_INVESTIGATOR
affiliation: Celerion, Northern Ireland
name: Johnston Stewart
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bjermer L, Abbott-Banner K, Newman K. Efficacy and safety of a first-in-class inhaled PDE3/4 inhibitor (ensifentrine) vs salbutamol in asthma. Pulm Pharmacol Ther. 2019 Oct;58:101814. doi: 10.1016/j.pupt.2019.101814. Epub 2019 Jun 14.