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 | 10009033 |
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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 compare the efficacy and safety of 2.5 microgram and 5 microgram Tiotropium Inhalation Solution delivered by the Respimat Inhaler with Tiotropium inhalation capsules 18 microgram delivered by the HandiHaler |
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E.2.2 | Secondary objectives of the trial |
-Number of COPD exacerbations -Time to first hospitalisation due to COPD exacerbation -Number of hospitalisations due to COPD exacerbations -Time to first major adverse cardiovascular event |
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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 International Conference on Harmonization Good Clinical Practice (ICH-GCP) guidelines prior to participation in the trial, which includes medication washout and restrictions. 2. Male or female patients 40 years of age or older. 3. Patients must be current or ex-smokers with a smoking history of ≥10 pack-years. (Patients who have never smoked cigarettes must be excluded) 4. All patients must have a diagnosis of COPD, and must meet the following criteria: Relatively stable airway obstruction with a post-bronchodilator FEV1 <=70% of predicted normal and post-bronchodilator FEV1/FVC <=70%. Pulmonary function tests to be conducted after the inhalation of 400 micrograms salbutamol / albuterol (preferred). Testing with either 200 micrograms salbutamol/albuterol or a combination of salbutamol/albuterol with ipratropium bromide (2 to 4 actuations) is acceptable. Furthermore historical data from measurements within the past 6 months either at the site or at a referral site may be used. If the measurements are not performed at the trial site a referral letter and signed copies of the measurement printouts must be provided to the trial site for source data verification. In case several qualifying spirometry measurements are available, the most recent one should be referred to as long as it was not performed during an exacerbation. Patients may not be randomised to the study without the availability of spirometry data at the actual study site. 5. Patients must be able to inhale from the HandiHaler and the Respimat devices. |
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E.4 | Principal exclusion criteria |
1. Significant diseases other than COPD. 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 the patients ability to participate in the study. 2. Patients with a recent history (i.e., six months or less) of myocardial infarction. 3. Patients with any unstable or life-threatening cardiac arrhythmia requiring intervention or change in drug therapy during the last year. 4. Hospitalisation for cardiac failure (New York Heart Association (NYHA) Class III or IV) during the past year. 5. Known active tuberculosis. 6. Patients with a history of asthma, cystic fibrosis, bronchiectasis, interstitial lung disease, or pulmonary thromboembolic disease. 7. A history of thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons should be evaluated as per Exclusion 1. 8. Patients planning to undergo lung transplant or lung volume reduction surgery (LVRS). 9. Malignancy for which the patient has undergone resection, radiation, chemotherapy or biological treatments within the last five years. Patients with treated basal cell carcinoma are allowed. 10. A respiratory infection or exacerbation of COPD in the four weeks prior to screening. 11. Known hypersensitivity to anticholinergic drugs, lactose, benzalkonium chloride (BAC), ethylenediaminetetraacetic acid (EDTA) or any other components of the HandiHaler or Respimat inhalation solution delivery system. 12. Patients with known moderate to severe renal impairment (as judged by the investigator). 13. Patients with known narrow angle glaucoma. 14. Patients with significant symptomatic prostatic hyperplasia or bladder-neck obstruction. Patients whose symptoms are controlled on treatment may be included. 15. Use of systemic corticosteroid medication at unstable doses (i.e., less than six weeks on stable dose) or at doses in excess of the equivalent of 10 milligrams (mg) prednisolone per day 16. 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 three months prior to and for the duration of the trial. 17. Significant alcohol or drug abuse within the past 12 months. 18. Patients requiring the use of supplemental oxygen therapy for >12 hours per day 19. Patients who have completed a pulmonary rehabilitation program in the six weeks prior to the screening visit or patients who are currently in a pulmonary rehabilitation program that will not be maintained throughout the duration of the study. 20. Patients who have taken an investigational drug within 30 days prior to Screening Visit. 21.Previous participation (receipt of randomised treatment) in this study. 22.Patients who are currently participating in an interventional study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoints: - Time to death (all-cause mortality) - Time to first COPD exacerbation |
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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 | 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) | 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 | 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 | 30 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 634 |
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 | 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 | 3 |
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 | 3 |
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 |