| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| patients with a diagnosis of moderate to very severe COPD |
|
| 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 | 10006458 |
| E.1.2 | Term | Bronchitis chronic |
|
| 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 primary objectives of this long−term study are to assess the bronchodilator efficacy as determined by FEV1, the effect on dyspnoea as determined by the Mahler BDI and TDI, the effect on the health status as determined by the SGRQ, and the effect on COPD exacerbations. |
|
| E.2.2 | Secondary objectives of the trial |
| The secondary objective is to compare the safety of once−daily FDC Tiotropium/Salmeterol (7.5 microgram/25 microgram) Inhalation Powder versus single−agent therapy of its components and versus combination therapy of FDC Tiotropium/Salmeterol (7.5 microgram/25 microgram) Inhalation Powder (morning) plus salmeterol (evening). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| −All patients must sign an informed consent consistent with ICH−GCP guidelines and local legislations prior to any study−related procedures, which includes medication washout and restrictions. −All patients must have a diagnosis of COPD and must meet the following criteria: relatively stable* airway obstruction with a post−bronchodilator FEV1 < 80% of predicted normal (ECSC criteria) and post−bronchodilator FEV1 < 70% of post−bronchodilator FVC at Visit 1. Following a pre−bronchodilator measurement of FEV1 and FVC, patients will inhale 4 puffs of salbutamol/albuterol 100 µg (MDI) and 45 minutes after inhalation the post−bronchodilator FEV1 and FVC will be measured. * The randomisation of patients with any respiratory infection or COPD exacerbation in the 6 weeks prior to the Screening Visit (Visit 1) or during the baseline period should be postponed. Patients may be randomised 6 weeks following recovery from the infection or exacerbation −Male or female patients 40 years of age or older. −Patients must be current or ex−smokers with a smoking history of e 10 pack−years (patients who have never smoked cigarettes must be excluded). Pack Years = (Number of cigarettes/day)x years of smoking/20 −Patients must be able to perform technically acceptable pulmonary function tests during the study period as required in the protocol (including the PEF and FEV1 recordings with the electronic peak flow meter AM2+). −Patients must be able to inhale medication in a competent manner from the HandiHaler devices. −Patients must be able to perform all necessary recordings in the AM2+. |
|
| E.4 | Principal exclusion criteria |
| −Significant diseases other than COPD. A significant disease is defined as a disease or condition which, in the opinion of the investigator, may either 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. −Patients with clinically significant abnormal baseline haematology, blood chemistry or urinalysis, if the abnormality defines a significant disease as defined in exclusion criterion No. 1. −Patients with a recent history (i.e., six months or less) of myocardial infarction. −Patients with any unstable or life−threatening cardiac arrhythmia requiring intervention or change in drug therapy during the past year. −Hospitalization for cardiac failure during the past year. −Malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years. Patients with treated basal cell carcinoma are allowed. −Patients with a history of asthma or who have a total blood eosinophil count >=600/mm**3. A repeat eosinophil count will not be conducted in these patients. −Patients with a history of life threatening pulmonary obstruction, or a history of cystic fibrosis or clinically evident bronchiectasis. −Known active tuberculosis. −Patients with a history (within the past two years) of and/or active significant alcohol or drug abuse. See exclusion criterion No. 1. −Patients who have undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons should be evaluated as per exclusion criterion No. 1. −Patients who have completed a pulmonary rehabilitation program in the six weeks prior to the Screening Visit (Visit 1) or patients who are currently in a pulmonary rehabilitation program that will not be maintained throughout the duration of the study. −Patients who regularly use daytime oxygen therapy for more than 1 hour per day and in the investigator’s opinion will be unable to abstain from the use of oxygen therapy during the clinic visits. −Patients who have taken an investigational drug within 30 days or six half−lives (whichever is greater) prior to Screening Visit (Visit 1). −Use of antihistamines (H1 receptor antagonists), anti−leukotrienes or leukotriene receptor antagonists for asthma or excluded allergic conditions. See exclusion criterion No 7. −Use of cromolyn sodium or nedocromil sodium. −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 of prednisone per day or 20 mg every other day. −Known hypersensitivity to anticholinergic drugs, ²2−adrenergic drugs, lactose or any other component of the study medication delivery system. −Pregnant or nursing women −Women of childbearing potential not using a highly effective method of birth control. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner. Female patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation, or post−menopausal for at least two years. −Treatment with oral beta−adrenergics within 4 weeks prior to Screening Visit (Visit 1) or during the 2−week run−in period. −Treatment with the long−acting anticholinergic tiotropium (Spiriva) within 4 weeks prior to Screening Visit (Visit 1) or during the 2−week run−in period. −Patients who are currently participating in another study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| There are three co−primary endpoints in this trial: trough FEV1 (forced expiratory volume in one second), FEV1 AUC0−8h, and Mahler TDI (focal score). There are also two additional co−primary endpoints: the St George’s Respiratory Questionnaire (SGRQ) and the time to first moderate to severe COPD exacerbation |
|
| 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 | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | Yes |
| 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 | 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| 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 |
|
| 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
| |
| 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 | 0 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 0 |
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