E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
moderate to severe Chronic Obstructive Pulmonary Disease (COPD) |
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E.1.1.1 | Medical condition in easily understood language |
moderate to severe Chronic Obstructive Pulmonary Disease (COPD) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10009033 |
E.1.2 | Term | Chronic obstructive pulmonary disease |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the effect of RPL554 or placebo on change from baseline in peak forced expiratory volume in 1 second (FEV1) when administered to patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD) |
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E.2.2 | Secondary objectives of the trial |
• To investigate the effect of RPL554 or placebo on change from baseline in morning trough FEV1 when administered to patients with moderate to severe COPD.
• To investigate the bronchodilator effect of RPL554 or placebo on peak and average FEV1 at first dose; over 3 hours at Weeks 1 to 4.
• To investigate the the effects of RPL554 or placebo on COPD symptoms, as measured by daily diary, patient scales and questionnaires
• To investigate the safety of RPL554 when administered for 4 weeks in patients with COPD, as measured by adverse events, electrocardiograms (ECGs), Holter monitoring and vital signs
• To compare the amount of rescue albuterol/salbutamol use required |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female aged between 40 and 75 years inclusive
- Body mass index (BMI) between 18 and 35 kg/m2 (inclusive) with a minimum weight of 45 kg.
- COPD diagnosis: Patients with a clinical 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.
- Ability to perform acceptable and reproducible spirometry. Post-bronchodilator (albuterol/salbutamol four puffs) spirometry at screening must demonstrate a:
• Post-bronchodilator FEV1/forced vital capacity (FVC) ratio of ≤0.70
• Post-bronchodilator FEV1 ≥40 % and ≤80% of predicted normal
- Clinically stable COPD in the 4 weeks prior to screening and randomization
- For patients taking long acting bronchodilators, capable of withdrawing from these medications until the end of the treatment period, and short acting bronchodilators for 8 hours prior to administration of study medication |
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E.4 | Principal exclusion criteria |
- A history of life-threatening COPD including Intensive Care Unit admission and requiring intubation.
- COPD exacerbation requiring oral steroids in the 3 months prior to screening or prior to randomization; hospitalizations for COPD in the 6 months prior to screening.
- Other respiratory disorders: Patients with a current diagnosis of asthma, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, interstitial lung diseases, sleep apnea, known alpha-1 antitrypsin deficiency or other active pulmonary diseases.
- Oral therapies for COPD (e.g. oral steroids, theophylline, and roflumilast) in the 3 months prior to screening and throughout the study, use of oral beta blockers, requirement for oxygen therapy.
- Patients with a history of chronic uncontrolled disease including, but not limited to, endocrine, active hyperthyroidism, neurological, hepatic, gastrointestinal, renal, hematological, urological, immunological, or ophthalmic diseases that the Investigator believes are clinically significant.
- Documented cardiovascular disease: arrhythmias, unstable angina, recent or suspected myocardial infarction within 6 months prior to screening, congestive heart failure, a history of unstable or uncontrolled hypertension, or has been diagnosed with hypertension in last 3 months.
- Abnormal clinically significant 12 lead Holter findings, including but not limited to:
• Premature ventricular contractions (PVCs) >1000 in 24 hour period
• Sustained ventricular tachycardia >6 beats
• Atrial fibrillation with rapid ventricular response (>100 bpm)
• Atrial flutter
• Sinus pause >2 seconds
- Other protocol defined criteria apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in peak FEV1 (maximum value during 3 hours following dose) after 4 weeks of treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Change from baseline in morning trough FEV1 after 4 weeks of treatment
• Change from baseline in average FEV1 over 12 hours at Visits 2 and 6
• Change from baseline in peak and average FEV1 over 3 hours at Visits 2 to 6
• Change from baseline in COPD symptoms, as measured by daily diary
• Change from baseline in the protocol defined breathlessness scales.
• Change from baseline in rescue medication use
• Safety and tolerability parameters as defined in protocol section 9.2.1.2
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
4 weeks on treatment, visits 3 to 6 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 5 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |