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

Study Overview
=================
Brief Summary
-----------------
Non-inferiority of lung function response to Tiotropium inhalation solution compared to Spiriva HandiHaler

Official Title
-----------------
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: HandiHaler
* Device: Respimat SMI


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: All patients had to sign an informed consent consistent with International Conference of Harmonization-Good Clinical Practice (ICH-GCP) guidelines prior to participation in the trial, which includes medication washout and restrictions. All patients had to have a diagnosis of chronic obstructive pulmonary disease. Patients had to have relatively stable, moderate to severe airway obstruction with an forced expiratory volume in one second (FEV1) ≤ 60% of predicted normal and FEV1 ≤ 70% of forced vital capacity FVC (Visits 1 and 2). Male or female patients 40 years of age or older. Patients had to be current or ex-smokers with a smoking history of more than 10 pack-years. Patients had to be able to perform technically acceptable pulmonary function tests and peak expiratory flow rate (PEFR) measurements, and had to be able to maintain records (Patient Daily Diary Card) during the study period as required in the protocol. Patients had to be able to inhale medication in a competent manner from the Respimat inhaler, the HandiHaler and from a metered dose inhaler (MDI). Exclusion criteria: Patients with significant diseases other than chronic obstructive pulmonary disease (COPD) had to be excluded. A significant disease was defined as a disease which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient's ability to participate in the study. Patients with clinically relevant 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., one year or less) of myocardial infarction. Patients with any cardiac arrhythmia requiring drug therapy or who had been hospitalised for heart failure within the past three years. Patients with a history of cancer within the last five years. Patients with treated basal cell carcinoma were allowed. Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction. Patients with known narrow-angle glaucoma. Patients with a history of asthma, allergic rhinitis or who have a total blood eosinophil count ≥600 mm3. Further exclusion criteria apply

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: HandiHaler|nan|
|Device: Respimat SMI|nan|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough FEV1 response determined at the end of each 4-week period of randomised treatment. |  | at the end of each 4-week period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tiotropium plasma concentration data and urinary excretion data |  | at the end of each 4-week period | 
| Trough forced vital capacity (FVC) response |  | after 4 weeks | 
| Peak response (FEV1 and FVC) |  | within 3 hours after first dose, after 4 weeks | 
| FEV1 AUC 0-12h and FVC AUC 0-12h response |  | after 4 weeks | 
| FEV1 AUC 0-3h and FVC AUC 0-3h response |  | after the first dose, after 4 weeks | 
| Individual FEV1and FVC measurements |  | during study course of 28 weeks | 
| pre-dose morning and evening peak expiratory flow rate (PEFR) |  | during study course of 28 weeks | 
| Number of occasions of rescue therapy used |  | during study course of 28 weeks | 
| Median time to onset of therapeutic response after first dose (FEV1) |  | after first dose and after 4 weeks | 
| Number of patients with 15% response above baseline for each treatment at each time point after first dose and after 4 weeks |  | up to 28 weeks |