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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E.1.1.1 | Medical condition in easily understood language |
COPD is a progressive respiratory illness characterised by chronic airflow limitation, shortness of breath, cough, wheezing and increased sputum production. Smoking is the predominant cause of COPD. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10009033 |
E.1.2 | Term | Chronic obstructive pulmonary disease |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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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 2.5mcg and 5mcg Tiotropium Inhalation Solution delivered by the Respimat Inhaler with Tiotropium inhalation capsules 18mcg delivered by the HandiHaler. |
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E.2.2 | Secondary objectives of the trial |
No secondary objectives are defined |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
This study includes assessment of lung function in a total population of 1305 patients recruited from sites in selected countries. The assessment of lung function in this sub-population is described in the study protocol (dated February 17 2010). |
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E.3 | Principal inclusion criteria |
1. All patients must sign an informed consent consistent with ICH-GCP guidelines
prior to participation in the trial, includes medication washout and restrictions.
2. Male or female patients aged 40 years of age or over
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%
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.
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, clinically evident bronchiectasis, interstitial lung
disease, or pulmonary thromboembolic disease
7. A history of thoracotomy with pulmonary resection.
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
randomization.
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.
16. Pregnant or nursing women or women of childbearing potential not using a
medically approved means of contraception.
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) |
The first primary endpoint is time to all-cause mortality.
The second primary endpoint is time to first COPD exacerbation.
A COPD exacerbation is defined as a complex of lower respiratory events / symptoms (increase or new onset) related to the underlying COPD, with duration of three days or more, requiring a change in treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Patients will be given reminder cards to record changes in concomitant medications used to treat a COPD exacerbation. These cards will serve as a reminder for the patients, to be reviewed by the investigator at each visit to ensure that all COPD exacerbations have been recorded and that the exacerbations meet the definition listed above. The reminder cards will be collected as part of the permanent patient record.
Exacerbations will be recorded in the eCRF. The same questions and review of patient symptoms regarding exacerbations will be asked during the interim contacts between treatment visits and will be recorded in the eCRF. |
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E.5.2 | Secondary end point(s) |
- 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.5.2.1 | Timepoint(s) of evaluation of this end point |
Number of COPD exacerbations: see E.5.1.1
Time to first hospitalisation due to COPD exacerbation, Number of hospitalisations due to COPD exacerbations, Time to first major adverse cardiovascular event: will be evaluated ongoing by assessing Adverse Events at all visits during treatment period, End-Of Treatment visit and Follow-up contact.
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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 | 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.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 114 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 527 |
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 | No |
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 |
Serbia |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Bulgaria |
Canada |
China |
Colombia |
Croatia |
Denmark |
Finland |
France |
Georgia |
Germany |
Greece |
Guatemala |
Hungary |
India |
Ireland |
Italy |
Korea, Republic of |
Latvia |
Lithuania |
Malaysia |
Netherlands |
New Zealand |
Norway |
Portugal |
Spain |
Sweden |
Thailand |
Israel |
Mexico |
Panama |
Peru |
Philippines |
Poland |
Romania |
Russian Federation |
Slovakia |
South Africa |
Switzerland |
Taiwan |
Tunisia |
Turkey |
Ukraine |
United Kingdom |
United States |
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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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End of Trial is defined as the last visit of the last patient. The Sponsor will announce the end of trial after 1.266 fatal events have taken place (event-driven 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 |