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 | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010952 |
E.1.2 | Term | COPD |
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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 assess the long-term efficacy and safety of once daily treatment of BI 1744 CL inhalation solution (5 mcg [2 actuations of 2.5 mcg] and 10 mcg [2 actuations of 5 mcg]) delivered via the Respimat inhaler in patients with COPD |
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E.2.2 | Secondary objectives of the trial |
A key secondary efficacy analysis will be the effect of BI 1744 CL on patients’ health-related quality of life as determined by the total score from the Saint George’s Respiratory Questionnaire (SGRQ) after 24 weeks of treatment. The data from this trial and the replicate trial 1222.14 will be combined to examine this endpoint. |
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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 and must meet the following spirometric criteria: -Patients must have relatively stable airway obstruction with a post-bronchodilator FEV1 <80% of predicted normal (ECSC) and a post-bronchodilator FEV1/FVC <70% at Visit 1. 3. Male or female patients, 40 years of age or older. 4. Patients must be current or ex-smokers with a smoking history of more than 10 pack-year: Pack Years = ((Number of cigarettes/day)/20 cigarettes)x years of smoking. 5. Patients must be able to perform technically acceptable pulmonary function tests and PEF measurements, and must be able to maintain records (Patient Daily e-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, a dry powder inhaler (DPI) 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 >=&#61472;600/mm**3, 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 beta2-agonists) - a diagnosis of paroxysmal tachycardia (>100 beats per minute) (due to the known class side effect profile of beta2-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. - have been 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. 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 beta-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 taken an investigational drug within one month or six half lives (whichever is greater) prior to screening visit (Visit 1). 11. Patients with known hypersensitivity to beta-adrenergics drugs, BAC, EDTA, lactose or any other component of the Respimat inhalation solution or Aerolizer DPI 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. 14. Patients who have previously been randomized in this study or are currently participating in another study. 15. Patients who are unable to comply with pulmonary medication restrictions prior to randomization. |
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E.5 End points |
E.5.1 | Primary end point(s) |
There are three co-primary endpoints in this study: FEV1 AUC0-3h response, trough FEV1 response, and the Mahler TDI (focal score). The third co-primary endpoint, Mahler TDI (focal score) will be evaluated after combining the data from this and the replicate study 1222.14. The three endpoints will be evaluated after 24 weeks of treatment. The bronchodilator efficacy of BI 1744 CL will be primarily assessed using forced expiratory volume in one second (FEV1). The co-primary endpoints will be FEV1 AUC0-3h response and trough FEV1 response. The effect of BI 1744 CL on dyspnoea will be primarily assessed using the Mahler TDI focal score. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
doppio cieco, doppio fittizio |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
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 | 10 |
E.8.9.1 | In the Member State concerned days | |
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 | 11 |