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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The overall objective of this study is to evaluate the long-term (one-year) efficacy and safety of tiotropium inhalation solution 5µg (2 puffs of 2.5µg) delivered by the Respimat® inhaler compared to placebo in patients with Chronic Obstructive Pulmonary Disease.
The primary objective will be comparison of bronchodilator efficacy (trough FEV1 response) after one-year of treatment and impact of treatment on time to first COPD exacerbation.
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E.2.2 | Secondary objectives of the trial |
Secondary objectives of the trial include evaluation of bronchodilator efficacy (trough FEV1 and trough FVC) at interim time points and other endpoints related to impact on COPD exacerbations.
Additional secondary objectives of the study relate to assessment of the safety of long-term (one-year) treatment with tiotropium inhalation solution 5µg (2 puffs of 2.5µg) delivered by the Respimat® inhaler compared to placebo. Safety assessments will include monitoring of adverse events, pre- and post-study physical examination and 12-lead ECGs. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male and female patients aged 40 years or more with a diagnosis of relatively stable, moderate to severe COPD and with a smoking history of at least 10 pack years will be eligible for inclusion in the trial. Patients must have a pre-bronchodilator FEV1 ≤ 60% of predicted normal and FEV1 ≤ 70% of FVC both at screening and on entry to the randomised phase of the trial. |
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E.4 | Principal exclusion criteria |
Principal exclusion criteria are summarised as follows:
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 either the results of the study or the patients’ ability to participate in the study. Recent history (i.e six months or less) of myocardial infarction. Unstable or life-threatening cardiac arrhythmia requiring intervention or change in drug therapy during the last year. Hospitalisation for cardiac failure during the past year. Malignancy requiring resection, radiation or chemotherapy within the last five years. Known narrow angle glaucoma. Patients with a history of asthma, allergic rhinitis or who have a blood eosinophil count ≥ 600 / mm3. Patients with a life-threatening pulmonary obstruction, or a history of cystic fibrosis or clinically evident bronchiectasis. Known active tuberculosis. Patients with a history of and /or active significant alcohol or drug abuse. Patients who have undergone thoracotomy with pulmonary resection Patients who regularly use daytime oxygen therapy for more than 1 hour per day. 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 10mg prednisolone per day or 20mg every other day. Known hypersensitivity to anticholinergic drugs, BAC, EDTA or any other components of the Respimat inhalation solution delivery system. Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception.
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E.5 End points |
E.5.1 | Primary end point(s) |
There will be two co-primary endpoints for this study: Trough FEV1 and time to first exacerbation.
Bronchodilator efficacy will be assessed by trough FEV1 response. Trough FEV1 is defined as the FEV1 measured at the -10 minute time point at the end of the dosing interval (24 hours post drug administration). Trough FEV1 response is defined as the change from baseline in trough FEV1. Baseline FEV1 will be the pre-treatment FEV1 measured at Visit 2 in the morning 10 minutes prior to the first dose of study medication.
The effect of tiotropium on COPD exacerbations will be primarily determined by time to first moderate to severe exacerbation (according to the definitions provided in the study protocol)
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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) | 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 | 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) | 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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 140 |
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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The end of the trial will be defined as the timepoint at which all randomised patients have concluded their participation in the trial, all data queries resolved and the trial database locked.
The sponsor reserves the right to discontinue the trial at any time prior to anticipated completion due to failure to meet expected enrolment goals or emergence of any efficacy/safety information that could significantly affect continuation of 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 | 2 |
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 | 2 |
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 |