Comparison of RPL554 With Placebo and Salbutamol in Asthmatic Patients
- Registration Number
- NCT02427165
- Lead Sponsor
- Verona Pharma plc
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 29
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description RPL554 Dose 4 RPL554 24 mg single dose nebulised RPL554 Placebo Placebo Single dose of nebulised placebo solution RPL554 Dose 1 RPL554 0.4 mg single dose nebulised RPL554 RPL554 Dose 3 RPL554 6 mg single dose nebulised RPL554 RPL554 Dose 2 RPL554 1.5 mg single dose nebulised RPL554 Salbutamol Dose 2 Salbutamol 7.5 mg single dose nebulised salbutamol Salbutamol Dose 1 Salbutamol 2.5 mg single dose nebulised salbutamol
- Primary Outcome Measures
Name Time Method Spirometry 12 hours FEV1
- Secondary Outcome Measures
Name Time Method Systemic pharmacodynamic effect on blood pressure 4 hours Supine blood pressure in the 4 hours after nebulisation
Vital signs (Supine pulse rate) 12 hours Supine pulse rate
Spirometry 4, 6 and 8 hours FEV1
Vital signs (Supine blood pressure) 12 hours Supine systolic and diastolic blood pressure
ECG 12 hours 12-lead ECG parameters
Pharmacokinetics (AUC) 12 hours RPL554 AUC
Pharmacokinetics (Cmax) 12 hours RPL554 Cmax
Pharmacokinetics (tmax) 12 hours RPL554 tmax
Systemic pharmacodynamic effect on pulse rate 4 hours Supine Pulse rate in the 4 hours after nebulisation
Systemic pharmacodynamic effect on ECG heart rate 4 hours ECG heart rate in the 4 hours after nebulisation
Pharmacokinetics (half life) 12 hours RPL554 half life
Pharmacokinetics (MRT) 12 hours RPL554 MRT
Trial Locations
- Locations (2)
Skane University Hospital
🇸🇪Lund, Sweden
Celerion
🇬🇧Belfast, United Kingdom