Chronic Obstructive Pulmonary DiseasePhase 2NCT02542254
The Effects of RPL554 on Top of Standard COPD Reliever Medications
A Phase 2 study testing Salbutamol, Ipratropium and RPL554 in people with Chronic Obstructive Pulmonary Disease, run by Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA at 1 site in United Kingdom.
Trial summary
This study evaluates the addition of RPL554 to standard reliever medications for chronic obstructive pulmonary disorder (COPD). All patients will receive the same six treatments in a randomised sequence: 1. salbutamol, 2. ipratropium, 3. salbutamol + RPL554, 4. ipratropium + RPL554, 5. RPL554 6. Placebo Read more about this study
- Who is it for?
- Ages 40 to 70 years
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease
- What is being tested?
- Salbutamol, Ipratropium and RPL554
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2015to Dec 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 40 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provide informed consent
- Males not donating sperm and using adequate contraception or females who are surgically sterile or postmenopausal
- 12-lead ECG showing:Heart rate 45 to 90 bpm, QTcF≤450 msec, QRS ≤120 msec, PR interval ≤220 msec, no clinically significant abnormality
- Capable of complying with all study restrictions and procedures including ability to use the study nebuliser correctly.
- BMI 18 to 33 kg/m2 with a minimum weight of 45 kg.
- COPD diagnosis for at least 1 year and clinically stable COPD in previous 4 weeks
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- Demonstrates reversibility to bronchodilator (two puffs of salbutamol followed by two puffs of ipratropium) via spirometry:
- Post-bronchodilator FEV1/forced vital capacity (FVC) ratio of ≤0.70
- Post-bronchodilator FEV1 ≥40 % and ≤80% of predicted normal
- ≥150 mL increase from pre-bronchodilator FEV1
- Chest X-ray showing no abnormalities
- Meet the concomitant medication restrictions and be expected to do so for the rest of the study.
- Smoking history of ≥10 pack years.
- Capable of withdrawing from long acting bronchodilators throughout the study and short acting bronchodilators for 8 hours prior to study treatment.
Who cannot join
- History of life-threatening COPD including Intensive Care Unit admission and/or requiring intubation.
- COPD exacerbation requiring oral steroids in the previous 3 months
- History of one or more hospitalisations for COPD in the previous 12 months
- Respiratory tract infection (both upper and lower) treated with antibiotics in previous 12 weeks
- Evidence of cor pulmonale or clinically significant pulmonary hypertension.
- Other respiratory disorders
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- Previous lung resection or lung reduction surgery.
- Oral therapies for COPD in the previous 3 months and throughout the study.
- Drug or alcohol abuse in the past 3 years
- Received an experimental drug within 3 months or five half lives, whichever is longer.
- Prior exposure to RPL554
- Patients with a history of chronic uncontrolled disease that the Investigator believes are clinically significant.
- Documented cardiovascular disease in last 3 months
- Major surgery, (requiring general anaesthesia) in the previous 6 weeks, or will not have fully recovered from surgery, or planned surgery through the end of the study.
- History of malignancy of any organ system within 5 years with the exception of localised skin cancers (basal or squamous cell)
- Clinically significant abnormal values for safety laboratory tests
- A disclosed history, or one known to the Investigator, of significant non compliance in previous investigational studies or with prescribed medications.
- Requires oxygen therapy, even on an occasional basis.
- Inability to adequately perform whole body plethysmography.
- Any other reason that the Investigator considers makes the subject unsuitable to participate.
- Patients with known hypersensitivity to atropine or its derivatives, or to ipratropium bromide, salbutamol or RPL554 or their excipients/components.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II, Randomised, Double Blind, Placebo Controlled, Six Way Crossover Study to Assess the Bronchodilator Effect of RPL554 Administered on Top of Salbutamol and Ipratropium in Patients With COPD.
This study evaluates the addition of RPL554 to standard reliever medications for chronic obstructive pulmonary disorder (COPD). All patients will receive the same six treatments in a randomised sequence:
- salbutamol,
- ipratropium,
- salbutamol + RPL554,
- ipratropium + RPL554,
- RPL554
- Placebo
Read the detailed description
The purpose of this study is to investigate if RPL554 has an additive bronchodilator effect when administered in combination with standard of care bronchodilators in patients with COPD.This study investigates the pharmacodynamic effect of RPL554 using spirometry and whole body plethysmography compared to placebo, when administered in addition to a beta2 agonist (salbutamol), a muscarinic antagonist (ipratropium) or placebo.
- Conditions
- Chronic Obstructive Pulmonary Disease
- Being tested
- Salbutamol, Ipratropium, RPL554, Salbutamol matched placebo, Ipratropium matched placebo
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SalbutamolDrug
200 micrograms salbutamol administered using a pressurised metered dose inhaler (pMDI)
IpratropiumDrug
40 micrograms ipratropium administered using a pMDI
RPL554Drug
6 mg RPL554 administered using a nebuliser
Salbutamol matched placeboDrug
Placebo pMDI
Ipratropium matched placeboDrug
Placebo pMDI
RPL554 matched placeboDrug
Nebulised placebo
| Study group | Role | What they receive |
|---|---|---|
| Salbutamol alone | Active comparator | 200 micrograms salbutamol, ipratropium matched placebo and RPL554 matched placebo Receives: Drug: Salbutamol; Drug: Ipratropium matched placebo; Drug: RPL554 matched placebo |
| Salbutamol and RPL554 | Experimental | 200 micrograms salbutamol, ipratropium matched placebo and 6 mg RPL554 Receives: Drug: Salbutamol; Drug: RPL554; Drug: Ipratropium matched placebo |
| Ipratropium | Active comparator | Salbutamol matched placebo, 40 micrograms ipratropium and RPL554 matched placebo Receives: Drug: Ipratropium; Drug: Salbutamol matched placebo; Drug: RPL554 matched placebo |
| Ipratropium and RPL554 | Experimental | Salbutamol matched placebo, 40 micrograms ipratropium and 6 mg RPL554 Receives: Drug: Ipratropium; Drug: RPL554; Drug: Salbutamol matched placebo |
| RPL554 | Experimental | Salbutamol matched placebo, ipratropium matched placebo and 6 mg RPL554 Receives: Drug: RPL554; Drug: Salbutamol matched placebo; Drug: Ipratropium matched placebo |
| Placebo | Placebo comparator | Salbutamol matched placebo, ipratropium matched placebo and RPL554 matched placebo Receives: Drug: Salbutamol matched placebo; Drug: Ipratropium matched placebo; Drug: RPL554 matched placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
8 hour spirometry
Forced expired volume in one second (FEV1) over 8 hours post-dose
Measured: 8 hours
Secondary outcomes (9)
12 hour spirometry
FEV1 over 4, 6 and 12 hours post-dose
Measured: 12 hours
Whole body plethysmography
Functional residual capacity, residual volume, total lung capacity, specific airway conductance, specific airway resistance at 1 and 4 hours post-dose
Measured: 4 hours
Area under the curve (AUC)
AUC for RPL554 plasma concentration
Measured: 12 hours
Maximum plasma concentration (Cmax)
Cmax for RPL554 plasma concentration
Measured: 12 hours
Time to maximum plasma concentration (Tmax)
Tmax for RPL554 plasma concentration
Measured: 12 hours
Adverse events
Continuous measurement of adverse events throughout the study
Measured: Up to 94 days
Safety laboratory tests
Laboratory safety tests at screening, before each treatment and end of study
Measured: Up to 94 days
ECG
12 lead ECG at screening, before and up to 12 hours after each treatment and end of study
Measured: Up to 94 days
Vital signs
Blood pressure and pulse rate at screening, before and up to 12 hours after each treatment and end of study
Measured: Up to 94 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2015 (estimated)
- Study startOct 2015
- Primary completionDec 2015
- Study completionDec 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 Chronic Obstructive Pulmonary DiseaseStudies 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
- 36 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
- Dave Singh, Principal investigator, Medicines Evaluation Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02542254
- Sponsor's protocol ID
- RPL554-009-2015
- Other IDs
- 2015-002536-41, 2015
- Status last verified
- Sep 2016
- First submitted
- 30 Aug 2015
- Last updated
- 9 Sep 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Singh D, Abbott-Banner K, Bengtsson T, Newman K. The short-term bronchodilator effects of the dual phosphodiesterase 3 and 4 inhibitor RPL554 in COPD. Eur Respir J. 2018 Nov 1;52(5):1801074. doi: 10.1183/13993003.01074-2018. Print 2018 Nov.
PubMed 30166326
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, Six Way Crossover Study to Assess the Bronchodilator Effect of RPL554 Administered on Top of Salbutamol and Ipratropium in Patients With COPD.
- ClinicalTrials.gov ID
- NCT02542254
- Acronym / sponsor ID
- RPL554-009-2015
- Conditions
- Chronic Obstructive Pulmonary Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USAIndustry (pharma, biotech, devices)
- Study start
- Oct 2015
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 4 Sep 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.
This study evaluates the addition of RPL554 to standard reliever medications for chronic obstructive pulmonary disorder (COPD). All patients will receive the same six treatments in a randomised sequence:
- salbutamol,
- ipratropium,
- salbutamol + RPL554,
- ipratropium + RPL554,
- RPL554
- Placebo
Detailed description
The purpose of this study is to investigate if RPL554 has an additive bronchodilator effect when administered in combination with standard of care bronchodilators in patients with COPD.This study investigates the pharmacodynamic effect of RPL554 using spirometry and whole body plethysmography compared to placebo, when administered in addition to a beta2 agonist (salbutamol), a muscarinic antagonist (ipratropium) or placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Salbutamol alone | Active comparator | Drug: Salbutamol, Drug: Ipratropium matched placebo, Drug: RPL554 matched placebo200 micrograms salbutamol, ipratropium matched placebo and RPL554 matched placebo |
| Salbutamol and RPL554 | Experimental | Drug: Salbutamol, Drug: RPL554, Drug: Ipratropium matched placebo200 micrograms salbutamol, ipratropium matched placebo and 6 mg RPL554 |
| Ipratropium | Active comparator | Drug: Ipratropium, Drug: Salbutamol matched placebo, Drug: RPL554 matched placeboSalbutamol matched placebo, 40 micrograms ipratropium and RPL554 matched placebo |
| Ipratropium and RPL554 | Experimental | Drug: Ipratropium, Drug: RPL554, Drug: Salbutamol matched placeboSalbutamol matched placebo, 40 micrograms ipratropium and 6 mg RPL554 |
| RPL554 | Experimental | Drug: RPL554, Drug: Salbutamol matched placebo, Drug: Ipratropium matched placeboSalbutamol matched placebo, ipratropium matched placebo and 6 mg RPL554 |
| Placebo | Placebo comparator | Drug: Salbutamol matched placebo, Drug: Ipratropium matched placebo, Drug: RPL554 matched placeboSalbutamol matched placebo, ipratropium matched placebo and RPL554 matched placebo |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Provide informed consent
- Males not donating sperm and using adequate contraception or females who are surgically sterile or postmenopausal
- 12-lead ECG showing:Heart rate 45 to 90 bpm, QTcF≤450 msec, QRS ≤120 msec, PR interval ≤220 msec, no clinically significant abnormality
- Capable of complying with all study restrictions and procedures including ability to use the study nebuliser correctly.
- BMI 18 to 33 kg/m2 with a minimum weight of 45 kg.
Key exclusion criteria (21 listed)
- History of life-threatening COPD including Intensive Care Unit admission and/or requiring intubation.
- COPD exacerbation requiring oral steroids in the previous 3 months
- History of one or more hospitalisations for COPD in the previous 12 months
- Respiratory tract infection (both upper and lower) treated with antibiotics in previous 12 weeks
- Evidence of cor pulmonale or clinically significant pulmonary hypertension.
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 |
|---|---|---|
| Salbutamol200 micrograms salbutamol administered using a pressurised metered dose inhaler (pMDI) | Drug | Salbutamol alone, Salbutamol and RPL554 |
| Ipratropium40 micrograms ipratropium administered using a pMDI | Drug | Ipratropium, Ipratropium and RPL554 |
| RPL5546 mg RPL554 administered using a nebuliser | Drug | Ipratropium and RPL554, RPL554, Salbutamol and RPL554 |
| Salbutamol matched placeboPlacebo pMDI | Drug | Ipratropium, Ipratropium and RPL554, Placebo, RPL554 |
| Ipratropium matched placeboPlacebo pMDI | Drug | Placebo, RPL554, Salbutamol alone, Salbutamol and RPL554 |
| RPL554 matched placeboNebulised placebo | Drug | Ipratropium, Placebo, Salbutamol alone |
Primary outcome
8 hour spirometry
Time frame: 8 hours
Forced expired volume in one second (FEV1) over 8 hours post-dose
9 secondary outcomes
12 hour spirometry
Time frame: 12 hours
Whole body plethysmography
Time frame: 4 hours
Area under the curve (AUC)
Time frame: 12 hours
Maximum plasma concentration (Cmax)
Time frame: 12 hours
Time to maximum plasma concentration (Tmax)
Time frame: 12 hours
Adverse events
Time frame: Up to 94 days
Safety laboratory tests
Time frame: Up to 94 days
ECG
Time frame: Up to 94 days
Vital signs
Time frame: Up to 94 days
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 30166326Singh D, Abbott-Banner K, Bengtsson T, Newman K. The short-term bronchodilator effects of the dual phosphodiesterase 3 and 4 inhibitor RPL554 in COPD. Eur Respir J. 2018 Nov 1;52(5):1801074. doi: 10.1183/13993003.01074-2018. Print 2018 Nov.
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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.
Dave Singh principal investigator
Medicines Evaluation Unit
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Salbutamol, Ipratropium and RPL554 in people with Chronic Obstructive Pulmonary Disease, run by Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA at 1 site in United Kingdom.
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 14 inclusion and 21 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 1 site in 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?
8 hour spirometry (time frame: 8 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 NCT02542254, 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.