A 24 week, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of 18 MCG of Tiotropium inhalation capsules administered by Handihaler® once-daily plus PRN Albuterol (Salbutamol) vs. placebo plus PRN Albuterol (Salbutamol) in Chronic Obstructive Pulmonary Disease subjects naive to maintenance therapy. - N/A

Conditions: Chronic Obstructive Pulmonary Disease
MedDRA version: 8.1Level: LLTClassification code 10009033Term: Chronic obstructive pulmonary disease

Registration Number: EUCTR2006-006276-38-NL

Lead Sponsor: Boehringer-Ingelheim

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 436

Inclusion Criteria

1. All subjects must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial, which includes medication washout and restrictions.
2. All subjects must have a diagnosis of COPD according to GOLD guideline criteria: post-bronchodilator FEV1/FVC ratio < 70% (visit 1).
3. Subjects must be GOLD Stage II and have a post-bronchodilator FEV1 >50% and < 80% of predicted normal (visit 1).
4. Subjects must be male or female, 40-80 years of age.
5. Subjects must be current or ex-smokers with a smoking history of >10 pack years.
6. Subjects must have a Medical Research Council (MRC) dyspnea score > 2.
7. Subjects must be able to demonstrate compliance with the HandiHaler® and an albuterol (salbutamol) MDI during the screening period.
8. Subjects must be able to demonstrate compliance with the activity monitor during the screening period.
9. Subjects must be able to perform acceptable PFTs and follow study procedures.
10. Subjects must be able to perform an Exercise Stress Test.
11. Subjects must be able to demonstrate a stabilized smoking status at least 1 month prior to visit 1.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Subjects who have been treated with maintenance medications for chronic respiratory disease (e.g. long acting ß-agonists, inhaled anticholinergics, inhaled or systemic corticosteroids, theophylline, leukotriene receptor antagonists) within six months prior to screening.
2. Subjects with 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 subject at risk because of participation in the study or may influence either the results of the study or the subject’s ability to participate in the study.
3. Subjects who have ever had a diagnosis of asthma, cystic fibrosis, bronchiectasis, interstitial lung disease, or pulmonary thromboembolic disease documented by a physician.
4. Subjects with a history of pulmonary resection.
5. Subjects with a history of thoracotomy for other reasons should be evaluated as per Exclusion criteria 2.
6. Subjects on chronic systemic corticosteroids.
7. Subjects with any upper and/or lower respiratory tract infection or COPD exacerbation in the 6 weeks prior to the initial visit 1 or during the screening period prior to visit 3.
8. Subjects who exacerbate in the 6 weeks prior to screening can be re-screened after recovery from the exacerbation.
9. Subjects who exacerbate during the screening period can be re-screened 6 weeks following recovery from the exacerbation.
10. Subjects whose activity is significantly limited by non-pulmonary disease (i.e., arthritis). Subjects with a recent (past 6 months) myocardial infarction, any unstable or life-threatening cardiac arrhythmia requiring intervention or change in drug therapy during the last year; or who have been hospitalized for cardiac failure during the past year.
11. Subjects who are known to have clinically significant laboratory and/or electrocardiogram abnormalities in the judgment of the Investigator.
12. Subjects who have any contraindication to exercise or have abnormal exercise stress test results based on criteria established by the ACC/AHA 1997 and/or the ATS/ACCP 2003 and/or thought to be of clinical significance in the judgment of the investigator or his medical designee
13. Subjects with a malignancy and who are currently undergoing radiation therapy or have had chemotherapy within 5 years.
14. Subjects who are pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception for at least three months prior to screening and for the duration of the trial.
15. Subjects who are currently participating or have recently participated in another trial with investigational drug within 30 days or 6 half-lives of the investigational agent (whichever is greater) at the start of the study or who are currently participating in another interventional study.
16. Subjects with a known hypersensitivity to anticholinergic drugs, lactose or any other component of the inhalation capsule or metered dose aerosol delivery systems.
17. Subjects with a known nickel-cutaneous hypersensitivity (component of the activity monitor).
18. Subjects who are currently or have ever been in a pulmonary rehabilitation program.
19. Subjects who are currently or that have been in a cardiac rehabilitation program within 6 months prior to visit 1.
20. Subjects with a history of significant alcohol or drug abuse.
21. Subjects with known active tuberculosis
22. Subjects with known narrow-angle glaucoma.
23. Subjects with moderate

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective will be to evaluate the difference between treatments with tiotropium plus prn albuterol (salbutamol) vs. placebo plus prn albuterol (salbutamol) on AUC(0-3h), FEV1 normalized over three hours. ;Secondary Objective: The effect of tiotropium treatment on other lung function variables and outcomes such as activity, symptoms and productivity will also be assessed as secondary objectives. The activity monitor outputs in this trial will be considered experimental in nature. The correlation between health related Quality of Life and activity will also be examined at baseline as an exploratory objective. ;Primary end point(s): The primary endpoint is the forced expiratory volume in 1 second (FEV1) AUC(0-3h) post-dose response at week 24 (end of study). Baseline is defined as the time point of pre-dose measurement at Week 0. Response is defined as the change from baseline to 3 hours post dose AUC0-3h FEV1 at the final visit (Week 24).

Secondary Outcome Measures