E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Obstructive Pulmonary Disease (COPD) including chronic bronchitis and emphysema |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
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 objective of this study is to compare the efficacy and safety of 12 weeks treatment with tiotropium via HandiHaler® 18 mcg daily or Combivent® MDI 2 actuations q.i.d. in COPD patients currently prescribed Combivent® MDI.
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the trial are to further evaluate the efficacy of the treatment with tiotropium via HandiHaler® 18 mcg daily or Combivent® MDI 2 actuations in reducing use of rescue medication (albuterol) and improving peak expiratory flow rates (measured daily in the morning and evening) during the treatment period. Patient and physician global evaluation ratings will also be evaluated and compared for the two treatment groups.
Other spirometric parameters including: Peak FEV1 at 12 weeks, peak, FEV1 AUC0-6 hours after first dose and 6 weeks, trough FEV1 at six weeks and individual FEV1 measurements at each timepoint and corresponding FVC measurements will also be evaluated as secondary endpoints.
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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. 2. Male or female patients 40 years of age or older. 3. Current or ex-smokers with a smoking history of >/= to 10 pack years. Patients who have never smoked cigarettes must be excluded. 4. Use of Combivent® Inhalation Aerosol MDI for maintenance COPD treatment at least one month prior to screening. 5. All patients must have a diagnosis of chronic obstructive pulmonary disease (re:ATS/ERS statement on COPD), relatively stable airway obstruction, and must meet the following spirometric criteria: • At Visit 1 – post-bronchodilator FEV1 < or =70% of predicted [after administration of albuterol (salbutamol) 200 mcg] • At Visit 2 – pre-bronchodilator FEV1< or =65% of predicted normal and FEV1/FVC ≤70% Predicted normal values will be calculated according to Morris equation. 6. Ability to perform technically acceptable pulmonary function tests and able to maintain records (electronic Patient Daily Record) during the study period as required in the protocol. 7.Ability to inhale medication from the HandiHaler® and the metered dose inhaler. |
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E.4 | Principal exclusion criteria |
1. Significant diseases other than COPD will be excluded. A significant disease is defined as a disease or condition which, in the opinion of the investigator, may put the patient at risk because of participation in the study or may influence either the results of the study or the patient’s ability to participate in the study. 2. Clinical history of asthma. 3. History of thoracotomy with pulmonary resection. 4. Regularly use daytime supplemental oxygen therapy for more than one hour per day and who in the investigator’s opinion, will be unable to abstain from the use of supplemental oxygen therapy during testing. 5. Use of systemic corticosteroids in an unstable daily dose (less than 6 weeks on a stable dose) or a daily dose of >10 mg of prednisone or its equivalent. 6. Respiratory tract infection or COPD exacerbation in the 6 weeks prior to the initial Visit 1. 7. Recent history (i.e., 6 months or less) of myocardial infarction. 8. Any unstable or life-threatening cardiac arrhythmia requiring intervention or change in drug therapy during the last year; or who have been hospitalized for cardiac failure during the past year. 9. Currently undergoing radiation therapy or chemotherapy for a malignancy. 10. Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (i.e., oral contraceptives, intrauterine devices, diaphragm or subdermal implants e.g., Norplant®) for at least 3 months prior to and for the duration of the trial. 11. Participation in another trial with investigational drug within 30 days or 6 half lives (whichever is greater) of the start of the study. 12. Known hypersensitivity to anticholinergic drugs, soya lecithin or related food products such as soybean and peanut, lactose or any other components of the study medications or derivatives. 13. Current or recent (within 4 weeks of Visit 1) participation in a pulmonary rehabilitation program. 14. Significant alcohol or drug abuse in the previous year. 15. Use of commercially available Spiriva in the preceding 3 months. 16. Current treatment with beta-blocker medications. 17. Current treatment with oral beta-adrenergics. 18. Use of cromolyn sodium or nedocromil sodium, antileukotrienes or leukotriene receptor antagonists within 3 months of Visit 1. 19.Current treatment with monoamine oxidase inhibitors or tricyclic antidepressants. 20. Use of regularly scheduled ipratropium (Atrovent® MDI, nebulizer, or nasal solution) or other short-acting anticholinergic (i.e. oxitropium), nebulized combination of ipratropium and albuterol or other combination of anticholinergic and beta agonist in any formulation (ie:Berdual®)in the previous month. 21. Symptomatic prostatic hypertrophy or bladder neck obstruction. Patients with symptomatically controlled prostatic hypertrophy on medications may be included and should continue their medications. 23. Known narrow-angle glaucoma. 24. Current participation in another interventional study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The co-primary efficacy endpoints will be the trough FEV1 and FEV1 AUC0-6 hours after 12 weeks of treatment. |
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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 | 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) | Yes |
E.8.2.2 | Placebo | No |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
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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The trial will end when the trial clinical monitor has determined that at least 400 evaluable patients will complete the study. The trial will be considered clinically completed when the last randomized patient complets the last study visit. |
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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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |