Chronic Obstructive Pulmonary Disease ModeratePhase 2NCT03028142

The Effects of RPL554 in Addition to Tiotropium in COPD Patients

A Phase 2 study testing 1.5 mg RPL554 plus tiotropium and 6 mg RPL554 plus tiotropium in people with Chronic Obstructive Pulmonary Disease Moderate, run by Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 40 to 75 years
Conditions the study is for: Chronic Obstructive Pulmonary Disease Moderate
What is being tested?: 1.5 mg RPL554 plus tiotropium and 6 mg RPL554 plus tiotropium
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 30 participants
Where: No sites listed yet
Study dates: Jan 2017to Aug 2017
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Sign an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to participate in the study.
Male or female aged between 40 and 75 years inclusive, at the time of informed consent.
If male: must agree to meet the following from the first dose up to 1 month after the last dose of study treatment:
Not donate sperm
Either: be sexually abstinent in accordance with a patient's usual and preferred lifestyle (but agree to abide by the contraception requirements below should their circumstances change) Or: use a condom with all sexual partners. If the partner is of childbearing potential the condom must be used with spermicide and a second highly effective form of contraception must also be used
If female: either be:

Show all 31Show fewer

Of non-childbearing potential defined as being:
Either: post-menopausal (being spontaneously amenorrhoeic for at least 1 year with an appropriate clinical profile [e.g. age appropriate, history of vasomotor symptoms]
Or: permanently sterilised e.g. tubal occlusion, hysterectomy, bilateral oophorectomy, bilateral salpingectomy
Of childbearing potential and agreeing to use a highly effective method of contraception until completion of the end of study visit.
Have a 12-lead ECG recording at screening and randomisation (pre-dose in Treatment Period 1) showing the following:
Heart rate between 45 and 90 beats per minute (bpm)
QT interval corrected for heart rate using Fridericia's formula (QTcF) ≤450 msec for males and ≤470 ms for females
QRS interval ≤120 msec
No clinically significant abnormalities (as judged by the Investigator) including morphology (e.g. left bundle branch block, atrio-ventricular nodal dysfunction, ST segment abnormalities)
Have a screening Holter report with a minimum of 18 hours recording that is able to be evaluated for rhythm analysis which shows no abnormality which indicates a significant impairment of patient safety or which may significantly impairs interpretation in the opinion of the Investigator including:
Significant arrhythmias including atrial flutter, atrial fibrillation, ventricular tachycardia
Any symptomatic arrhythmia (except isolated extra systoles)
Any sustained second or third degree heart block
Capable of complying with all study restrictions and procedures including ability to use the study nebuliser and HandiHaler® DPI correctly.
Body mass index (BMI) between 18 and 33 kg/m2 (inclusive) with a minimum weight of 45 kg.
COPD diagnosis: Patients with a diagnosis of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines (Celli and MacNee, 2004) with symptoms compatible with COPD for at least 1 year prior to screening.
Post-bronchodilator (four puffs of salbutamol) spirometry at screening:
Post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio of ≤0.70
Post-bronchodilator FEV1 ≥40 % and ≤80% of predicted normal
Demonstrates ≥150 mL increase from pre-bronchodilator FEV1
Clinically stable COPD in the 4 weeks prior to screening and randomisation (pre-dose in Treatment Period 1).
A chest X-ray (post-anterior) at screening, or in the 12 months prior to screening showing no abnormalities, which are both clinically significant and unrelated to COPD.
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 for the duration of the study, and short acting bronchodilators for 8 hours prior to spirometry.

Who cannot join

A history of life-threatening COPD exacerbation including Intensive Care Unit admission and/or requiring intubation.
COPD exacerbation requiring oral steroids, or lower respiratory tract infection requiring antibiotics, in the 3 months prior to screening or randomisation (pre-dose in Treatment Period 1).
A history of one or more hospitalisations for COPD in the 12 months prior to screening or randomisation (pre-dose in Treatment Period 1).
Lactation (female patients only).
Positive urine or serum pregnancy test at screening, or a positive urine pregnancy test prior to randomisation (female patients of childbearing potential only).
Prior exposure to RPL554 or known hypersensitivity to RPL554 or its components.

Show all 22Show fewer

Intolerance or hypersensitivity to tiotropium.
Evidence of cor pulmonale.
Other respiratory disorders: Patients with a current diagnosis of asthma, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, interstitial lung diseases, sleep apnoea, known alpha-1 antitrypsin deficiency or other active pulmonary diseases.
Previous lung resection or lung reduction surgery.
Use of oral COPD medications (e.g. oral steroids, theophylline and romifulast) in the 3 months prior to screening or randomisation (pre-dose in Treatment Period 1).
History of, or reason to believe, a patient has drug or alcohol abuse within the past 3 years.
Inability to perform technically acceptable spirometry or whole body plethysmography (at screening or randomisation [pre dose in Treatment Period 1])
Received an experimental drug within 30 days or five half lives, whichever is longer.
Patients with a history of chronic uncontrolled disease including, but not limited to, endocrine, active hyperthyroidism, neurological, hepatic, gastrointestinal, renal, haematological, urological, immunological, or ophthalmic diseases that the Investigator believes are clinically significant.
Documented cardiovascular disease: arrhythmias, angina, recent or suspected myocardial infarction, congestive heart failure, a history of unstable, or uncontrolled hypertension, or has been diagnosed with hypertension in the 3 months prior to screening or randomisation.
Concurrent use of non-cardioselective oral beta-blockers.
Has had major surgery, (requiring general anaesthesia) in the 6 weeks prior to screening or randomisation (pre-dose in Treatment Period 1), or will not have fully recovered from surgery, or planned surgery through the end of the study.
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.
Clinically significant prostatic hyperplasia (judged by the Investigator) or bladder-neck obstruction or with narrow-angle glaucoma.
Any other reason that the Investigator considers makes the patient unsuitable to participate.

About this study

This is a phase II, randomised, double blind, placebo controlled, complete block, three way crossover study to investigate treatment with nebulised RPL554 and tiotropium together in patients with moderate to severe chronic obstructive pulmonary disease (COPD). The purpose of this study is to assess the bronchodilator effect (opening of the airways) of RPL554 when used in combination with a long acting anti-muscarinic receptor antagonist (tiotropium) whilst dosing the RPL554 to steady state blood levels. It is planned to randomise up to 30 patients to have 24 evaluable patients at one study centre. In each treatment period, patients will receive an open label dose of tiotropium from a dry power inhaler (DPI) followed immediately by a double blind dose of either RPL554 6mg, 1.5mg or placebo (depending on treatment sequence) from a nebuliser in the morning on Day 1, Day 2 and Day 3. The dose of RPL554 or placebo will be repeated in the evening on Day 1 and Day 2; there will not be an evening dose on Day 3.

Conditions: Chronic Obstructive Pulmonary Disease Moderate
Being tested: 1.5 mg RPL554 plus tiotropium, 6 mg RPL554 plus tiotropium, Placebo plus tiotropium

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

1.5 mg RPL554 plus tiotropiumDrug
6 mg RPL554 plus tiotropiumDrug
Placebo plus tiotropiumDrug

Study groups in NCT03028142
Study group	Role	What they receive
Lower Dose Nebulised Treatment	Experimental	1.5 mg nebulised RPL554 twice daily plus 10 mcg tiotropium DPI once daily for 3 days Receives: Drug: 1.5 mg RPL554 plus tiotropium
Higher Dose Nebulised Treatment	Experimental	6 mg nebulised RPL554 twice daily plus 10 mcg tiotropium DPI once daily for 3 days Receives: Drug: 6 mg RPL554 plus tiotropium
Placebo	Placebo comparator	Nebulised RPL554 matched placebo twice daily plus 10 mcg tiotropium DPI once daily for 3 days Receives: Drug: Placebo plus tiotropium

What is being measured

The primary outcome is the main question the study is designed to answer.

Peak Forced Expired Volume in 1 Second (FEV1) on the Third Day of Dosing
Peak forced expired volume in 1 second (FEV1) over 4 hours on the third day of dosing
Measured: Day 3
Average FEV1 Over 12 Hours on the Third Day of Dosing
Average FEV1 area under the curve (AUC) over 12 hours on the third day of dosing
Measured: Day 3

Secondary outcomes (2)

Peak FEV1 on Day 1
Peak FEV1 over 4 hours on Day 1
Measured: Day 1
Average FEV1 Over 12 Hours on Day 1
Average FEV1 AUC over 12 hours on Day 1
Measured: Day 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2017Aug 2017

First posted23 Jan 2017 (estimated)
Study startJan 2017
Primary completionAug 2017
Study completionAug 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Chronic Obstructive Pulmonary Disease ModerateStudies 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: 30 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03028142
Sponsor's protocol ID: RPL554-CO-202
Status last verified: Jan 2019
First submitted: 3 Jan 2017
Last updated: 27 Feb 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: 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 27 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Effects of RPL554 in Addition to Tiotropium in COPD Patients
ClinicalTrials.gov ID: NCT03028142
Acronym / sponsor ID: RPL554-CO-202
Conditions: Chronic Obstructive Pulmonary Disease Moderate
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 30 participants (actual)
Lead sponsor: Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USAIndustry (pharma, biotech, devices)
Study start: Jan 2017
Primary completion: Aug 2017 (actual)
Study completion: Aug 2017 (actual)
First posted: 23 Jan 2017 (estimated)
Results: Posted 23 Jan 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Lower Dose Nebulised Treatment	Experimental	Drug: 1.5 mg RPL554 plus tiotropium1.5 mg nebulised RPL554 twice daily plus 10 mcg tiotropium DPI once daily for 3 days
Higher Dose Nebulised Treatment	Experimental	Drug: 6 mg RPL554 plus tiotropium6 mg nebulised RPL554 twice daily plus 10 mcg tiotropium DPI once daily for 3 days
Placebo	Placebo comparator	Drug: Placebo plus tiotropiumNebulised RPL554 matched placebo twice daily plus 10 mcg tiotropium DPI once daily for 3 days

Who may qualify

Ages: 40 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (31 listed)

Sign an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to participate in the study.
Male or female aged between 40 and 75 years inclusive, at the time of informed consent.
If male: must agree to meet the following from the first dose up to 1 month after the last dose of study treatment:
If female: either be:
Have a 12-lead ECG recording at screening and randomisation (pre-dose in Treatment Period 1) showing the following:

Key exclusion criteria (22 listed)

A history of life-threatening COPD exacerbation including Intensive Care Unit admission and/or requiring intubation.
COPD exacerbation requiring oral steroids, or lower respiratory tract infection requiring antibiotics, in the 3 months prior to screening or randomisation (pre-dose in Treatment Period 1).
A history of one or more hospitalisations for COPD in the 12 months prior to screening or randomisation (pre-dose in Treatment Period 1).
Lactation (female patients only).
Positive urine or serum pregnancy test at screening, or a positive urine pregnancy test prior to randomisation (female patients of childbearing potential only).

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
1.5 mg RPL554 plus tiotropium	Drug	Lower Dose Nebulised Treatment
6 mg RPL554 plus tiotropium	Drug	Higher Dose Nebulised Treatment
Placebo plus tiotropium	Drug	Placebo

Primary outcome

Peak Forced Expired Volume in 1 Second (FEV1) on the Third Day of Dosing
Time frame: Day 3
Peak forced expired volume in 1 second (FEV1) over 4 hours on the third day of dosing
Average FEV1 Over 12 Hours on the Third Day of Dosing
Time frame: Day 3
Average FEV1 area under the curve (AUC) over 12 hours on the third day of dosing

2 secondary outcomes

Peak FEV1 on Day 1
Time frame: Day 1
Average FEV1 Over 12 Hours on Day 1
Time frame: Day 1

Results and safety

Results posted to the registry on 23 Jan 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo Then Low Dose RPL554 Then High Dose RPL554	5	4
Low Dose Dose RPL554 Then High Dose RPL554 Then Placebo	5	4
High Dose RPL554 Then Placebo Then Low Dose RPL554	6	6
High Dose RPL554 Then Low Dose RPL554 Then Placebo	4	4
Low Dose RPL554 Then Placebo Then High Dose RPL554	6	5
Placebo Then High Dose RPL554 Then Low Dose RPL554	4	3

Primary outcome: Peak Forced Expired Volume in 1 Second (FEV1) on the Third Day of Dosing

Time frame: Day 3. Mean (Standard Deviation). Unit: Liters

Measure	Lower Dose Nebulised Treatment n = 28	Higher Dose Nebulised Treatment n = 27	Placebo n = 27
Value	0.477 (0.1673)	0.500 (0.2157)	0.373 (0.1970)

Lower Dose Nebulised Treatment vs Placebo: LS Means ratio: 1.05 (95% CI 1.02 to 1.09), p = 0.0022, ANCOVA
Higher Dose Nebulised Treatment vs Placebo: LS Means ratio: 1.09 (95% CI 1.05 to 1.12), p <0.0001, ANCOVA

Population analysed: All randomized patients with sufficient data collected after intake of study treatment to compute the pharmacodynamics parameters on at least two treatment periods.

Primary outcome: Average FEV1 Over 12 Hours on the Third Day of Dosing

Time frame: Day 3. Mean (Standard Deviation). Unit: Liters*hour

Measure	Lower Dose Nebulised Treatment n = 28	Higher Dose Nebulised Treatment n = 27	Placebo n = 27
Value	3.804 (1.8512)	3.967 (2.2134)	3.197 (2.2826)

Lower Dose Nebulised Treatment vs Placebo: LS Means ratio: 1.03 (95% CI 0.99 to 1.06), p = 0.0988, ANCOVA
Higher Dose Nebulised Treatment vs Placebo: LS Means ratio: 1.06 (95% CI 1.02 to 1.09), p = 0.0009, ANCOVA

Population analysed: All randomized patients with sufficient data collected after intake of study treatment to compute the pharmacodynamics parameters on at least two treatment periods.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: From informed consent until the end of the study.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Lower Dose Nebulised Treatment	1 of 29 (3.4%)	12 of 29 (41.4%)	0 of 29
Higher Dose Nebulised Treatment	0 of 27 (0%)	12 of 27 (44.4%)	0 of 27
Placebo	0 of 28 (0%)	12 of 28 (42.9%)	0 of 28

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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.
Individual participant dataSharing planned: No

Related trials for Chronic Obstructive Pulmonary Disease Moderate

RecruitingPhase 2
A Study of 24 to 52 Weeks Treatment to Evaluate The Efficacy And Safety of Galvokimig in Study Participants With Moderate-to-Severe Chronic Obstructive Pulmonary Disease (COPD) With Chronic Bronchitis
Chronic Obstructive Pulmonary Disease With Chronic Bronchitis
RecruitingPhase 3
Ensifentrine (MK-5884) Study for the Prevention of Chronic Obstructive Pulmonary Disease (COPD) Exacerbations in Adults With a History of Moderate or Severe Exacerbations While Receiving Standard of Care (SOC) (MK-5884-031/RPL554/ENHANCE-3)
Pulmonary Disease, Chronic Obstructive
RecruitingPhase 3
A Study to Investigate the Efficacy and Safety of GSK5784283 (Felcorekibart) Compared With Placebo in Participants With Moderate to Very Severe COPD (PERSIST COPD-1)
Pulmonary Disease, Chronic Obstructive
RecruitingPhase 3
A Study to Investigate the Efficacy and Safety of GSK5784283 (Felcorekibart) Compared With Placebo in Participants With Moderate to Very Severe COPD (PERSIST COPD-2)
Pulmonary Disease, Chronic Obstructive
RecruitingPhase 2
A Study of Brenipatide (LY3537031) in Adult Participants With Moderate-to-Severe Chronic Obstructive Pulmonary Disease (COPD)
Pulmonary Disease, Chronic Obstructive

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.

The record lists no contact. Use the official record to reach the sponsor.

Questions about this trial

What is this clinical trial studying?

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 31 inclusion and 22 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 27 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

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?

Yes. Results are posted in the registry (first posted 23 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Peak Forced Expired Volume in 1 Second (FEV1) on the Third Day of Dosing (time frame: Day 3). The study lists 2 primary outcomes in all. 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 NCT03028142, 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 27 Feb 2019.