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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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009033 |
E.1.2 | Term | Chronic obstructive pulmonary disease |
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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 |
The primary objective of this study is to compare the effects of BI 1744 CL versus placebo on constant work rate exercise tolerance after 6 weeks of treatment in patients with COPD. Exercise tolerance will be assessed by measurement of symptom-limited endurance time during constant work rate cycle ergometry. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives of this study are: - to compare the effects of BI 1744 CL versus placebo on lung hyperinflation during constant work rate exercise in patients with COPD. Lung hyperinflation will be assessed by measurement of inspiratory capacity (IC). - to compare the effects of BI 1744 CL versus placebo on the intensity of breathing discomfort experienced during constant work rate exercise in patients with COPD. The intensity of breathing discomfort will be rated by the patients using the Borg Category-Ratio Scale.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. All patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial, which includes medication washout and restrictions 2. All patients must have a diagnosis of chronic obstructive pulmonary disease (P06-12085) and must meet the following spirometric criteria: Patients must have relatively stable airway obstruction with a post-bronchodilator FEV1 <80% of predicted normal (ECSC, Quanjer et al, Eur Respir J, 1993) and a post-bronchodilator FEV1/FVC <70% at Visit 1 (ECSC predicted normal equations) 3. Male or female patients, between 40 and 75 years of age 4. Patients must be current or ex-smokers with a smoking history of more than 10 pack years: Pack Years = Number of cigarettes/day 20 cigarettes/pack x years of smoking Patients who have never smoked cigarettes must be excluded 5. Patients must be able to perform technically acceptable pulmonary function tests (body plethysmography, spirometry), must be able to complete multiple symptom-limited cycle ergometry tests, and must be able to maintain records (Patient Daily Diary) during the study period as required in the protocol 6. Patients must be able to inhale medication in a competent manner from the Respimat® inhaler and from a metered dose inhaler (MDI)
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E.4 | Principal exclusion criteria |
1. Patients with a significant disease other than COPD; a significant disease is defined as a disease which, in the opinion of the investigator, may (i) put the patient at risk because of participation in the study, (ii) influence the results of the study, or (iii) cause concern regarding the patient’s ability to participate in the study 2. Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis; all patients with an SGOT >x2 ULN, SGPT >x2 ULN, bilirubin >x2 ULN or creatinine >x2 ULN will be excluded regardless of clinical condition (a repeat laboratory evaluation will not be conducted in these patients) 3. Patients with a history of asthma. For patients with allergic rhinitis or atopy, source documentation is required to verify that the patient does not have asthma. If a patient has a total blood eosinophil count 600/mm3, source documentation is required to verify that the increased eosinophil count is related to a non-asthmatic condition. 4. Patients with any of the following conditions: - a diagnosis of thyrotoxicosis (due to the known class side effect profile of ß2-agonists) - a diagnosis of paroxysmal tachycardia (>100 beats per minute) (due to the known class side effect profile of ß2-agonists) 5. Patients with any of the following conditions: -a history of myocardial infarction within 1 year of screening visit (Visit 1) -unstable or life-threatening cardiac arrhythmia. -hospitalized for heart failure within the past year. -known active tuberculosis -a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years (patients with treated basal cell carcinoma are allowed) -a history of life-threatening pulmonary obstruction -a history of cystic fibrosis -clinically evident bronchiectasis -a history of significant alcohol or drug abuse -any contraindications for exercise testing as outlined below 6. Patients who have undergone thoracotomy with pulmonary resection (patients with a history of thoracotomy for other reasons should be evaluated as per exclusion criterion No. 1) 7. Patients being treated with any of the following concomitant medications: -oral β-adrenergics -oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day 8. Patients who regularly use daytime oxygen therapy for more than one hour per day and in the investigator’s opinion will be unable to abstain from the use of oxygen therapy during clinic visits 9. Patients who have completed a pulmonary rehabilitation program in the six weeks prior to the screening visit (Visit 1) or patients who are currently in a pulmonary rehabilitation program 10. Patients who have a limitation of exercise performance as a result of factors other than fatigue or exertional dyspnea, such as arthritis in the leg, angina pectoris or claudication or morbid obesity. 11. Patients with known hypersensitivity to β-adrenergics drugs, BAC, EDTA or any other component of the Respimat® inhalation solution delivery system 12. Pregnant or nursing women 13. Women of childbearing potential not using two effective methods of birth control (one barrier and one non-barrier). Female patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation, or post-menopausal for at least two years
Note: 1. Extreme caution should be used when including patients: -with cardiovascular disorders, especially coronary insufficiency and hypertension* -being treated with monoamine oxidase inhibitors or tricyclic antidepressants* 2. Caution should be used when including patients on treatment with non potassium-sparing diuretics* 3. Beta-blockers not only block the pulmonary effect of beta-agonists, but may also produce severe bronchospasm in patients with COPD. Therefore, patients should not normally be treated with beta-blockers. However, under certain circumstances, e.g., as prophylaxis after myocardial infarction, there may be no acceptable alternatives to the use of beta-adrenergic blocking agents in patients with COPD. In this setting, cardioselective beta-blockers could be considered, although they should be administered with caution.* 4. The randomization of patients with any respiratory infection or COPD exacerbation in the 6 weeks prior to the Screening Visit (Visit 1) or during the baseline period should be postponed. Patients may be randomized 6 weeks following recovery from the infection or exacerbation. *cf. prescribing information for registered LABAs (salmeterol / formoterol)
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E.5 End points |
E.5.1 | Primary end point(s) |
Endurance time during constant work rate cycle ergometry to symptom limitation at 75%Wcap* after 6 weeks of treatment (Day 43). * Wcap (maximal work capacity) is the maximum work rate achieved for at least 30 seconds during the incremental cycle ergometry performed at Visit 1.
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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 | Yes |
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) | Yes |
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 | 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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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 | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |