Efficacy and Safety Comparison of Tiotropium Inhalation Solution (Respimat Inhaler) and Spiriva HandiHaler in Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
=================
Brief Summary
-----------------
Comparison of lung function response between tiotropium inhalation solution and Spiriva HandiHaler.

Official Title
-----------------
A Randomised, Double-blind, Double-dummy, Placebo-controlled, Crossover Efficacy and Safety Comparison of 4-week Treatment Periods of Two Doses [5 μg (2 Actuations of 2.5 μg) and 10 μg (2 Actuations of 5 μg)] of Tiotropium Inhalation Solution Delivered by the Respimat Inhaler, Tiotropium Inhalation Powder Capsule (18μg) Delivered by the HandiHaler in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Conditions
-----------------
Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
-----------------
* Drug: Tiotropium
* Device: Respimat SMI
* Device: HandiHaler


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of COPD FEV1 < 60% predicted FEV1 < 70% of FVC Smoking history of 10 pack-years Exclusion Criteria: Significant other disease than COPD Recent history of MI (1 year or less) Cardiac arrhythmia requiring drug therapy History of asthma, allergic rhinitis or eosinophil count > 600 mm3 Symptomatic prostatic hypertrophy or bladder neck obstruction Known narrow-angle glaucoma Abnormal baseline hematology, blood chemistry or urinalysis History of cancer within last 5 years Life-threatening pulmonary obstruction Cystic fibrosis or bronchiectasis Tuberculosis Pulmonary resection

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Tiotropium|nan|
|Device: Respimat SMI|nan|
|Device: HandiHaler|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of trough FEV1 values at the end of 4-week treatment with tiotropium inhalation solution (5 mcg, 10 mcg) to that achieved with tiotropium inhalation powder (Spiriva 18 mcg). |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough forced vital capacity (FVC) response after 4 weeks (change from baseline) |  | baseline until week 28 | 
| Peak response (FEV1 and FVC) to first dose |  | within 3 hours to first dose | 
| Peak response (FEV1 and FVC) after 4 weeks |  | within 3 hours after 4 weeks | 
| FEV1 AUC0-12h and FVC AUC0-12h response after 4 weeks |  | after 4 weeks | 
| FEV1 AUC0-3h and FVC AUC0-3h response after the first dose and after 4 weeks |  | after first dose and after 4 weeks | 
| Individual FEV1and FVC measurements at each time point |  | up to 28 weeks | 
| Pre-dose morning and evening peak expiratory flow rate (PEFR) measured by patients |  | up to 28 weeks | 
| Number of occasions of rescue therapy used as required (p.r.n. salbutamol) |  | up to 28 weeks | 
| Median time to onset of therapeutic response after first dose |  | after 4 weeks | 
| Number of patients with 15% response above baseline for each treatment at each timepoint after first dose |  | at week 4, 12, 20 | 
| Number of patients with 15% response above baseline for each treatment at each timepoint after 4 weeks |  | at week 8, 16, 24 |