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 |
To compare the effect of tiotropium (18 mcg) inhalation capsule via HandiHaler® and salmeterol (50 mcg) via MDI on COPD exacerbations. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. All patients must have a diagnosis of chronic obstructive pulmonary disease (COPD) and must meet the following criteria at Visit 1: Patients must have relatively stable, moderate to very severe airway obstruction with a post-bronchodilator FEV1 ≤ 70% of predicted normal and FEV1 ≤ 70% of FVC postbronchodilator (i.e. 30 minutes after inhalation of 4 puffs of 100 μg salbutamol or equivalent SABA). Predicted normal values will be calculated according to ECSC [R94-1408]. For Height measured in inches Males: FEV1 predicted (L) = 4.30 x (height (inches) / 39.37)-0.029 x age (yrs) – 2.49 Females: FEV1 predicted (L) = 3.95 x (height (inches) / 39.37)-0.025 x age (yrs) – 2.60 For Height measured in metres Males: FEV1 predicted (L) = 4.30 x (height (metres)) – 0.029 x age (years) –2.49 Females: FEV1 predicted (L) = 3.95 x (height (metres))- 0.025 x age (years) – 2.60 2. All patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial. 3. Male or female patients 40 years of age or older. 4. Patients with a history of at least one exacerbation within the past year requiring treatment with either antibiotics and/or systemic steroids and/or hospitalisation. 5. Patients must be current or ex-smokers with a smoking history of ≥ 10 pack-years. (Patients who have never smoked cigarettes must be excluded.) Pack Years = (Number of cigarettes/day)/20 x years of smoking 6. Patients must be able to perform all study-related procedures including technically acceptable pulmonary function tests (PFTs). 7. Patients must be able to inhale medication in a competent manner from the HandiHaler® (Appendix 10.1) and a metered dose inhaler (MDI) (Appendix 10.2). 8. Patients must be able to maintain records (patient daily diary card) during the study period as required in the protocol. |
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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 either the results of the study or the patients’ ability to participate in the study. 2. Patients with a diagnosis of asthma. 3. Patients with a life-threatening pulmonary obstruction, or a history of cystic fibrosis. 4. Patients with known active tuberculosis. 5. Patients with a known symptomatic prostatic hyperplasia or bladder neck obstruction. Patients with symptomatically-controlled prostatic hyperplasia on medication may be included and should continue their medication. 6. Patients with known narrow-angle glaucoma. 7. Patients with a history of myocardial infarction within the year prior to Visit 1. 8. Patients with a history of hospital admission for heart failure within the year prior to Visit 1. 9. Patients with cardiac arrhythmia requiring medical or surgical treatment. 10. Patients with severe cardiovascular disorders. 11. Patients with a known hypersensitivity to anticholinergic drugs, beta-adrenergics, lactose or any other component of the medication delivery system. 12. Patients with known moderate or severe renal insufficiency (known creatinine clearance of ≤ 50 mL/min). 13. Patients with untreated known hypokalaemia. 14. Patients with untreated known thyrotoxicosis. 15. Patients with brittle/unstable diabetes mellitus. 16. Patients with a history of and/or active significant alcohol or drug abuse. See exclusion criterion 1. 17. Patients who have taken an investigational drug within 30 days or six half-lives (whichever is greater) prior to Screening Visit (Visit 1). 18. 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 mg prednisolone per day or 20 mg every other day. 19. 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. 20. Previous participation (receipt of randomised treatment) in this study. 21. Patients who are currently participating in another study. 22. Patients with any respiratory infection or COPD exacerbation in the four weeks prior to the Screening Visit (Visit 1) or during the run-in period should be postponed. In the case of a respiratory infection or COPD exacerbation during the run-in period, the latter may be extended up to four weeks. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the time to first COPD exacerbation.
For the purpose of this study a COPD exacerbation will be defined as:
A complex of respiratory events / symptoms (increase or new onset) of more than one of the following: cough, sputum, wheezing, dyspnoea or chest tightness with at least one symptom lasting at least three days requiring treatment with antibiotics and/or systemic steroids and/or hospital admission. |
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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 | No |
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 | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 | 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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 760 |
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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |