E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Obstructive Pulmonary Disease (COPD) |
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E.1.1.1 | Medical condition in easily understood language |
'Chronic bronchitis' 'Smoker's lung' 'Emphysema' |
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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 | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009026 |
E.1.2 | Term | Chronic obstructive airways disease |
E.1.2 | System Organ Class | 100000004855 |
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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 evaluate the relative effects on heart and lung (airway) responses at rest and during exercise following beta-blocker treatment with bisoprolol versus celiprolol in COPD patients. |
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E.2.2 | Secondary objectives of the trial |
To evaluate possible safety differences between exposure to bisoprolol and celiprolol including their effects on sensitive measures of pulmonary function.
To examine the effects on biochemical markers of heart function following beta-blocker treatment in COPD.
To assess the beta-2-agonist activity (airway opening) of bisoprolol and celiprolol including their effects on serum potassium and total/HDL cholesterol and creatinine kinase (blood tests).
To assess COPD-specific quality of life differences between treatments.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Stable moderate to severe COPD (GOLD stage 2/3). Post-bronchodilator FEV1 30-80% predicted and FEV1/FVC ratio <70%. Stable defined as no exacerbation in previous 1 month. Smoking history ≥10 pack-years. Oxygen saturations ≥92% on room air at rest. ECG demonstrating sinus rhythm. |
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E.4 | Principal exclusion criteria |
Use of domiciliary oxygen. History of other primary obstructive lung disease including asthma or bronchiectasis. Hospitalisation with exacerbation of COPD within past 3 months. History of unstable angina, uncontrolled hypertension or heart failure NYHA class 3-4. Overt clinical signs of right heart failure. Average resting systolic BP<110mmHg or average resting HR<55bpm. Pregnancy or lactation. Known or suspected sensitivity to/intolerance of IMP. Inability to comply with compulsory aspects of protocol. Any degree (first, second or third) of heart block. Sino-atrial block. Sick sinus syndrome. Severe forms of peripheral arterial occlusive disease or severe forms of Raynaud’s syndrome. Untreated phaeochromocytoma. Severe renal impairment (eGFR<15ml/min). Concomitant prescription of beta-blockers, rate-limiting calcium channel blockers, digoxin, amiodarone. Any clinically significant medical condition that may endanger the health or safety of the participant, or jeopardise the protocol. Participation in another trial within the previous 30 days. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome for this study will be the difference from baseline in the change in Inspiratory Capacity (IC) from rest to isotime peak (i.e. same time point during endurance exercise test) between beta-blocker treatments at 4 weeks. This will evaluate any differences in dynamic hyperinflation during exercise between treatments. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At baseline, at the end of the first treatment period, at the beginning of the second treatment period and at the end of the second treatment period. |
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E.5.2 | Secondary end point(s) |
• Remaining CPET outcomes include: VO2peak, Anaerobic threshold (AT), Heart rate (HR), heart rate reserve (HRR) and heart rate recovery (HRrec), Respiratory rate (RR) and breathing reserve (BR), Ventilatory equivalents at AT (VEVO2, VEVCO2), Pulse oximetry pre- and post exercise, Oxygen Pulse (O2P), Total exercise time. • Non-invasive cardiac output monitor outcomes: stroke volume, cardiac output, cardiac index (all at peak exercise). • Spirometry. • Impulse oscillometry. • Total body plethysmography. • Lying/Standing blood pressure. • Cardiovascular bloods (BNP, Galectin). • Beta-2 agonist activity bloods (Cholesterol/HDL, CK, Serum potassium). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At baseline, at the end of the first treatment period, at the beginning of the second treatment period and at the end of the second treatment period. |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |