AsthmaPhase 2NCT02427165
Comparison of RPL554 With Placebo and Salbutamol in Asthmatic Patients
A Phase 2 study testing RPL554 and Salbutamol in people with Asthma, run by Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA at 2 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Asthma
- What is being tested?
- RPL554 and Salbutamol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 29 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Apr 2015to Nov 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
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
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.
Read the 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.
- Conditions
- Asthma
- Being tested
- RPL554, Salbutamol, Placebo
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RPL554Drug
Also called VMX554, VRP554
A dual PDE3 and PDE4 inhibitor
SalbutamolDrug
a beta-2 receptor agonist
PlaceboDrug
RPL554 placebo containing no active ingredients
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Single dose of nebulised placebo solution Receives: Drug: Placebo |
| RPL554 Dose 1 | Experimental | 0.4 mg single dose nebulised RPL554 Receives: Drug: RPL554 |
| RPL554 Dose 2 | Experimental | 1.5 mg single dose nebulised RPL554 Receives: Drug: RPL554 |
| RPL554 Dose 3 | Experimental | 6 mg single dose nebulised RPL554 Receives: Drug: RPL554 |
| RPL554 Dose 4 | Experimental | 24 mg single dose nebulised RPL554 Receives: Drug: RPL554 |
| Salbutamol Dose 1 | Active comparator | 2.5 mg single dose nebulised salbutamol Receives: Drug: Salbutamol |
| Salbutamol Dose 2 | Active comparator | 7.5 mg single dose nebulised salbutamol Receives: Drug: Salbutamol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Spirometry
FEV1
Measured: 12 hours
Secondary outcomes (12)
Spirometry
FEV1
Measured: 4, 6 and 8 hours
Systemic pharmacodynamic effect on blood pressure
Supine blood pressure in the 4 hours after nebulisation
Measured: 4 hours
Systemic pharmacodynamic effect on pulse rate
Supine Pulse rate in the 4 hours after nebulisation
Measured: 4 hours
Systemic pharmacodynamic effect on ECG heart rate
ECG heart rate in the 4 hours after nebulisation
Measured: 4 hours
Vital signs (Supine pulse rate)
Supine pulse rate
Measured: 12 hours
Vital signs (Supine blood pressure)
Supine systolic and diastolic blood pressure
Measured: 12 hours
ECG
12-lead ECG parameters
Measured: 12 hours
Pharmacokinetics (AUC)
RPL554 AUC
Measured: 12 hours
Pharmacokinetics (Cmax)
RPL554 Cmax
Measured: 12 hours
Pharmacokinetics (tmax)
RPL554 tmax
Measured: 12 hours
Pharmacokinetics (half life)
RPL554 half life
Measured: 12 hours
Pharmacokinetics (MRT)
RPL554 MRT
Measured: 12 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2015 (estimated)
- Study startApr 2015
- Primary completionNov 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lief Bjermer, Principal investigator, Skane University Hospital, SwedenJohnston Stewart, Principal investigator, Celerion, Northern Ireland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02427165
- Sponsor's protocol ID
- RPL554-008-2014
- Status last verified
- Sep 2016
- First submitted
- 14 Apr 2015
- Last updated
- 9 Sep 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 31202957
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02427165
- Acronym / sponsor ID
- RPL554-008-2014
- Conditions
- Asthma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USAIndustry (pharma, biotech, devices)
- Study start
- Apr 2015
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 27 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboSingle dose of nebulised placebo solution |
| RPL554 Dose 1 | Experimental | Drug: RPL5540.4 mg single dose nebulised RPL554 |
| RPL554 Dose 2 | Experimental | Drug: RPL5541.5 mg single dose nebulised RPL554 |
| RPL554 Dose 3 | Experimental | Drug: RPL5546 mg single dose nebulised RPL554 |
| RPL554 Dose 4 | Experimental | Drug: RPL55424 mg single dose nebulised RPL554 |
| Salbutamol Dose 1 | Active comparator | Drug: Salbutamol2.5 mg single dose nebulised salbutamol |
| Salbutamol Dose 2 | Active comparator | Drug: Salbutamol7.5 mg single dose nebulised salbutamol |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RPL554Also: VMX554, VRP554A dual PDE3 and PDE4 inhibitor | Drug | RPL554 Dose 1, RPL554 Dose 2, RPL554 Dose 3, RPL554 Dose 4 |
| Salbutamola beta-2 receptor agonist | Drug | Salbutamol Dose 1, Salbutamol Dose 2 |
| PlaceboRPL554 placebo containing no active ingredients | Drug | Placebo |
Primary outcome
Spirometry
Time frame: 12 hours
FEV1
12 secondary outcomes
Spirometry
Time frame: 4, 6 and 8 hours
Systemic pharmacodynamic effect on blood pressure
Time frame: 4 hours
Systemic pharmacodynamic effect on pulse rate
Time frame: 4 hours
Systemic pharmacodynamic effect on ECG heart rate
Time frame: 4 hours
Vital signs (Supine pulse rate)
Time frame: 12 hours
Vital signs (Supine blood pressure)
Time frame: 12 hours
ECG
Time frame: 12 hours
Pharmacokinetics (AUC)
Time frame: 12 hours
Pharmacokinetics (Cmax)
Time frame: 12 hours
Pharmacokinetics (tmax)
Time frame: 12 hours
Pharmacokinetics (half life)
Time frame: 12 hours
Pharmacokinetics (MRT)
Time frame: 12 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2016.
- Derived from this study: PubMed 31202957Bjermer 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lief Bjermer principal investigator
Skane University Hospital, Sweden
Johnston Stewart principal investigator
Celerion, Northern Ireland
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RPL554 and Salbutamol in people with Asthma, run by Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Sweden, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Spirometry (time frame: 12 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02427165, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2016.