Back to resultsComparison of RPL554 With Placebo and Salbutamol in Asthmatic Patients
Primary Purpose
Asthma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
RPL554
Salbutamol
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Asthma
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
Sites / Locations
- Skane University Hospital
- Celerion
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm Type
Placebo Comparator
Experimental
Experimental
Experimental
Experimental
Active Comparator
Active Comparator
Arm Label
Placebo
RPL554 Dose 1
RPL554 Dose 2
RPL554 Dose 3
RPL554 Dose 4
Salbutamol Dose 1
Salbutamol Dose 2
Arm Description
Single dose of nebulised placebo solution
0.4 mg single dose nebulised RPL554
1.5 mg single dose nebulised RPL554
6 mg single dose nebulised RPL554
24 mg single dose nebulised RPL554
2.5 mg single dose nebulised salbutamol
7.5 mg single dose nebulised salbutamol
Outcomes
Primary Outcome Measures
Spirometry
FEV1
Secondary Outcome Measures
Spirometry
FEV1
Systemic pharmacodynamic effect on blood pressure
Supine blood pressure in the 4 hours after nebulisation
Systemic pharmacodynamic effect on pulse rate
Supine Pulse rate in the 4 hours after nebulisation
Systemic pharmacodynamic effect on ECG heart rate
ECG heart rate in the 4 hours after nebulisation
Vital signs (Supine pulse rate)
Supine pulse rate
Vital signs (Supine blood pressure)
Supine systolic and diastolic blood pressure
ECG
12-lead ECG parameters
Pharmacokinetics (AUC)
RPL554 AUC
Pharmacokinetics (Cmax)
RPL554 Cmax
Pharmacokinetics (tmax)
RPL554 tmax
Pharmacokinetics (half life)
RPL554 half life
Pharmacokinetics (MRT)
RPL554 MRT
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02427165
Brief Title
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
2. Study Status
Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
April 2015 (undefined)
Primary Completion Date
November 2015 (Actual)
Study Completion Date
November 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Verona Pharma plc
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
29 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Single dose of nebulised placebo solution
Arm Title
RPL554 Dose 1
Arm Type
Experimental
Arm Description
0.4 mg single dose nebulised RPL554
Arm Title
RPL554 Dose 2
Arm Type
Experimental
Arm Description
1.5 mg single dose nebulised RPL554
Arm Title
RPL554 Dose 3
Arm Type
Experimental
Arm Description
6 mg single dose nebulised RPL554
Arm Title
RPL554 Dose 4
Arm Type
Experimental
Arm Description
24 mg single dose nebulised RPL554
Arm Title
Salbutamol Dose 1
Arm Type
Active Comparator
Arm Description
2.5 mg single dose nebulised salbutamol
Arm Title
Salbutamol Dose 2
Arm Type
Active Comparator
Arm Description
7.5 mg single dose nebulised salbutamol
Intervention Type
Drug
Intervention Name(s)
RPL554
Other Intervention Name(s)
VMX554, VRP554
Intervention Description
A dual PDE3 and PDE4 inhibitor
Intervention Type
Drug
Intervention Name(s)
Salbutamol
Intervention Description
a beta-2 receptor agonist
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
RPL554 placebo containing no active ingredients
Primary Outcome Measure Information:
Title
Spirometry
Description
FEV1
Time Frame
12 hours
Secondary Outcome Measure Information:
Title
Spirometry
Description
FEV1
Time Frame
4, 6 and 8 hours
Title
Systemic pharmacodynamic effect on blood pressure
Description
Supine blood pressure in the 4 hours after nebulisation
Time Frame
4 hours
Title
Systemic pharmacodynamic effect on pulse rate
Description
Supine Pulse rate in the 4 hours after nebulisation
Time Frame
4 hours
Title
Systemic pharmacodynamic effect on ECG heart rate
Description
ECG heart rate in the 4 hours after nebulisation
Time Frame
4 hours
Title
Vital signs (Supine pulse rate)
Description
Supine pulse rate
Time Frame
12 hours
Title
Vital signs (Supine blood pressure)
Description
Supine systolic and diastolic blood pressure
Time Frame
12 hours
Title
ECG
Description
12-lead ECG parameters
Time Frame
12 hours
Title
Pharmacokinetics (AUC)
Description
RPL554 AUC
Time Frame
12 hours
Title
Pharmacokinetics (Cmax)
Description
RPL554 Cmax
Time Frame
12 hours
Title
Pharmacokinetics (tmax)
Description
RPL554 tmax
Time Frame
12 hours
Title
Pharmacokinetics (half life)
Description
RPL554 half life
Time Frame
12 hours
Title
Pharmacokinetics (MRT)
Description
RPL554 MRT
Time Frame
12 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lief Bjermer
Organizational Affiliation
Skane University Hospital, Sweden
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Johnston Stewart
Organizational Affiliation
Celerion, Northern Ireland
Official's Role
Principal Investigator
Facility Information:
Facility Name
Skane University Hospital
City
Lund
Country
Sweden
Facility Name
Celerion
City
Belfast
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
31202957
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.
Results Reference
derived
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Comparison of RPL554 With Placebo and Salbutamol in Asthmatic Patients
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