Tiotropium / Respimat One-Year Study

Sponsor

Boehringer Ingelheim (Industry)

Overall Status

Completed

CT.gov ID

NCT00168844

Collaborator

(none)

983

Enrollment

Locations

Arms

13.5

Patients Per Site

Study Details

Study Description

Brief Summary

To evaluate the long term effects of treatment with two doses of Tiotropium delivered by the Respimat inhaler in patients with COPD.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Disease, Chronic Obstructive	Drug: Tiotropium Inhalation Solution Other: Placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

983 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double

Primary Purpose:

Treatment

Official Title:

A Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Efficacy and Safety Comparison of One-Year Treatment of Two Doses (5mg and 10mg) of Tiotropium Inhalation Solution Delivered by the Respimat Device in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Study Start Date :

Jan 1, 2003

Actual Primary Completion Date :

Jun 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Other: Tiotropium Respimat 5mcg (Tio R5)	Drug: Tiotropium Inhalation Solution
Other: Tiotropium Respimat 10mcg (Tio R10)	Drug: Tiotropium Inhalation Solution
Other: Placebo	Other: Placebo

Arm

Intervention/Treatment

Other: Tiotropium Respimat 5mcg (Tio R5)

Drug: Tiotropium Inhalation Solution

Other: Tiotropium Respimat 10mcg (Tio R10)

Drug: Tiotropium Inhalation Solution

Other: Placebo

Other: Placebo

Outcome Measures

Primary Outcome Measures

Change From Baseline in Trough FEV1 at Week 48, Full Analysis Set - Clinic Spirometry (FAS-PFT) [10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication]
Trough Forced Expiratory Volume in 1 second (FEV1)
Saint George's Respiratory Questionnaire (SGRQ) Total Score, Full Analysis Set - Saint George's Respiratory Questionnaire (FAS-QOL) [Week 48]
Rating scale of 3 domains - symptoms, activities and impact (weighted). Worst score = 100, best score = 0
TDI Focal Score, Full Analysis Set - Transitional Dyspnoea Index (FAS-TDI) (Combined Studies) [Week 48]
Rating scale of 3 components - change in functional impairment, change in magnitude of tasks, change in magnitude of efforts. Worst score = -9, best score = +9 For this endpoint data of twin studies NCT00168844 and NCT00168831 was combined.
COPD Exacerbation Rate, Safety Set (SS) (Combined Studies) [48 weeks]
Number of Chronic Obstructive Pulmonary Disease (COPD) exacerbations per patient year. For this endpoint data of the twin studies NCT00168844 and NCT00168831 was combined.

Secondary Outcome Measures

Change From Baseline in Heart Rate [Baseline to Week 40 pre-dose]
Week 40 pre-dose - baseline
Change From Baseline in PR Interval [Baseline to Week 40 pre-dose]
Change From Baseline in QRS Interval [Baseline to Week 40 pre-dose]
Week 40 pre-dose - baseline
Change From Baseline in QT Interval [Baseline to Week 40 pre-dose]
Week 40 pre-dose - baseline
Change From Baseline in QT Interval (Bazett) [Baseline to Week 40 pre-dose]
Week 40 pre-dose - baseline
Change From Baseline in QT Interval (Fridericia) [Baseline to Week 40 pre-dose]
Week 40 pre-dose - baseline
Change From Baseline in Heart Rate [Baseline to Week 40]
Week 40 - baseline
Change From Baseline in Supraventricular Premature Beat (SVPB) Total [Baseline to Week 40]
Week 40 - baseline
Holter (24-hour Period) - SVPB (Supraventricular Premature Beat) Run Events Change From Baseline in Supraventricular Premature Beat (SVPB) Run Events [Baseline to Week 40]
Week 40 - baseline
Change From Baseline in SVPB Pairs [Baseline to Week 40]
Week 40 - baseline
Change From Baseline in Ventricular Premature Beat (VPB) Total [Baseline to Week 40]
Week 40 - baseline
Change From Baseline in VPB Run Events [Baseline to Week 40]
Week 40 - baseline
Change From Baseline in VPB Pairs [Baseline to Week 40]
Week 40 - baseline
Change From Baseline in Haematocrit, Packed Cell Volume (PCV) [Baseline to Week 48 or at premature discontinuation if before Week 48]
Volume of red cells (erythrocytes) in blood, expressed as a fraction (percentage) of the total volume of blood
Change From Baseline in Haemoglobin [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Red Blood Cell Count [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in White Blood Cell Count [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Platelets [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Neutrophils [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Eosinophils [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Basophils [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Lymphocytes [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Monocytes [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Neutrophils (Absolute) [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Lymphocytes (Absolute) [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Eosinophils (Absolute) [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Basophils (Absolute) [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Monocytes (Absolute) [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Calcium [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Phosphate [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Aspartate Transaminase (AST)/Glutamic-Oxaloacetic Transaminase (GOT), Serum GOT (SGOT) [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Alanine Transaminase (ALT)/Glutamic Pyruvic Transaminase (GPT), Serum GPT (SGPT) [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Alkaline Phosphatase [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Lactic Dehydrogenase (LDH) [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Glucose [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Urea [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Blood Urea Nitrogen [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Creatinine [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Bilirubin, Total [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Uric Acid [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Protein, Total [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Albumin [Baseline to Week 48 or at premature discontinuation if before Week 48]
Week 48 - baseline
Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks [10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication]
Change From Baseline in Trough Forced Expiratory Volume in 1 second (FEV1) after 2, 8, 16, 24, 32 and 40 weeks. The means are adjusted for centre, smoking status at entry and baseline value.
Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks [10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication]
Change From Baseline in Trough Forced vital capacity (FVC) after 2, 8, 16, 24, 32, 40 and 48 weeks. The means are adjusted for centre, smoking status at entry and baseline value.
Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks [10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication]
FEV1 AUC0-3 represents the Area under Curve over the time interval from 0 to 3 hours after 2, 8, 16, 24, 32, 40 and 48 weeks. The means are adjusted for centre, smoking status at entry and baseline value.
Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks [10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication]
FVC AUC0-3 represents the Area under Curve over the time interval from 0 to 3 hours after 2, 8, 16, 24, 32, 40 and 48 weeks. The means are adjusted for centre, smoking status at entry and baseline value.
Weekly Mean Morning Pre-dose PEFRs [Weeks 2, 8, 16, 24, 32, 40, 48]
Weekly mean morning pre-dose peak expiratory flow rates (PEFRs). The means are adjusted for centre, smoking status at entry, and baseline value.
Weekly Mean Evening PEFRs [Weeks 2, 8, 16, 24, 32, 40, 48]
Weekly mean evening peak expiratory flow rates (PEFRs). The means are adjusted for centre, smoking status at entry, and baseline value.
Weekly Mean Number of Puffs of Rescue Medication Per Day [Weeks 2, 8, 16, 24, 32, 40, 48]
Weekly mean number of puffs of rescue medication used per day as required (PRN salbutamol). The means are adjusted for centre, smoking status at entry, and baseline value.
Mahler TDI Scores [Week 48]
Mahler Transitional Dyspnoea Index (TDI) scores measured as change in functional impairment, change in magnitude of tasks and change in magnitude of efforts over the treatment period. The means are adjusted for centre, smoking status at entry and baseline value. Worst score = -3, best score = +3
Saint George's Respiratory Questionnaire (SGRQ) Scores [Week 48]
Saint George's Respiratory Questionnaire (SGRQ) Scores impacts, activities and symptoms. Worst score = 100, best score = 0. The means are adjusted for centre, smoking status at entry and baseline value.
COPD Symptoms Scores [Week 48]
COPD symptoms Scores - wheezing, shortness of breath, coughing and tightness of chest over the treatment period. Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe The means are adjusted for centre, smoking status at entry and baseline value.
PGE Scores [Week 48]
Physician's Global evaluation (PGE) scores over the treatment period. Scale: 1-2 = Poor, 3-4 = Fair, 5-6 = Good, 7-8 = Excellent The means are adjusted for centre, smoking status at entry and baseline value.
PGR Score [Week 48]
Patient's Global rating (PGR) score over the treatment period. Scale: 1=much better to 7=much worse The means are adjusted for centre, smoking status at entry and baseline value.

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Contacts and Locations

Locations

	Site	City	State	Country
1	Boehringer Ingelheim Investigational Site	Los Angeles	California	United States
2	Boehringer Ingelheim Investigational Site	Pismo Beach	California	United States
3	Boehringer Ingelheim Investigational Site	San Diego	California	United States
4	Boehringer Ingelheim Investigational Site	Fort Collins	Colorado	United States
5	Boehringer Ingelheim Investigational Site	Minneapolis	Minnesota	United States
6	Boehringer Ingelheim Investigational Site	Larchmont	New York	United States
7	Boehringer Ingelheim Investigational Site	Raleigh	North Carolina	United States
8	Boehringer Ingelheim Investigational Site	Chattanooga	Tennessee	United States
9	Boehringer Ingelheim Investigational Site	Harker Heights	Texas	United States
10	Boehringer Ingelheim Investigational Site	Houston	Texas	United States
11	Boehringer Ingelheim Investigational Site	Fredericksburg	Virginia	United States
12	Boehringer Ingelheim Investigational Site	Harrisonburg	Virginia	United States
13	Boehringer Ingelheim Investigational Site	Toorak Gardens	South Australia	Australia
14	Boehringer Ingelheim Investigational Site	Woodville	South Australia	Australia
15	Boehringer Ingelheim Investigational Site	Clayton	Victoria	Australia
16	Boehringer Ingelheim Investigational Site	Frankston	Victoria	Australia
17	Boehringer Ingelheim Investigational Site	Perth	Western Australia	Australia
18	Boehringer Ingelheim Investigational Site	Antwerpen		Belgium
19	Boehringer Ingelheim Investigational Site	Brussel		Belgium
20	Boehringer Ingelheim Investigational Site	Bruxelles		Belgium
21	Boehringer Ingelheim Investigational Site	Genk		Belgium
22	Boehringer Ingelheim Investigational Site	Gent		Belgium
23	Boehringer Ingelheim Investigational Site	Liège		Belgium
24	Boehringer Ingelheim Investigational Site	Wavre		Belgium
25	Boehringer Ingelheim Investigational Site	Edmonton	Alberta	Canada
26	Boehringer Ingelheim Investigational Site	Halifax	Nova Scotia	Canada
27	Boehringer Ingelheim Investigational Site	Courtice	Ontario	Canada
28	Boehringer Ingelheim Investigational Site	Mississauga	Ontario	Canada
29	Boehringer Ingelheim Investigational Site	Ottawa	Ontario	Canada
30	Boehringer Ingelheim Investigational Site	Toronto	Ontario	Canada
31	Boehringer Ingelheim Investigational Site	Sainte-Foy	Quebec	Canada
32	Boehringer Ingelheim Investigational Site	Angers		France
33	Boehringer Ingelheim Investigational Site	Beuvry		France
34	Boehringer Ingelheim Investigational Site	Cambrai		France
35	Boehringer Ingelheim Investigational Site	Lille		France
36	Boehringer Ingelheim Investigational Site	Metz cedex 01		France
37	Boehringer Ingelheim Investigational Site	Berlin		Germany
38	Boehringer Ingelheim Investigational Site	Darmstadt		Germany
39	Boehringer Ingelheim Investigational Site	Gelnhausen		Germany
40	Boehringer Ingelheim Investigational Site	Kassel		Germany
41	Boehringer Ingelheim Investigational Site	Rüdersdorf		Germany
42	Boehringer Ingelheim Investigational Site	Athens		Greece
43	Boehringer Ingelheim Investigational Site	Heraklion		Greece
44	Boehringer Ingelheim Investigational Site	Larissa		Greece
45	Boehringer Ingelheim Investigational Site	Maroussi, Athens		Greece
46	Boehringer Ingelheim Investigational Site	Melissia-Athens		Greece
47	Boehringer Ingelheim Investigational Site	Breda		Netherlands
48	Boehringer Ingelheim Investigational Site	Dordrecht		Netherlands
49	Boehringer Ingelheim Investigational Site	Groningen		Netherlands
50	Boehringer Ingelheim Investigational Site	Harderwijk		Netherlands
51	Boehringer Ingelheim Investigational Site	Heerlen		Netherlands
52	Boehringer Ingelheim Investigational Site	Zutphen		Netherlands
53	Boehringer Ingelheim Investigational Site	Oslo		Norway
54	Boehringer Ingelheim Investigational Site	Trondheim		Norway
55	Boehringer Ingelheim Investigational Site	Ålesund		Norway
56	Boehringer Ingelheim Investigational Site	Moscow		Russian Federation
57	Boehringer Ingelheim Investigational Site	Alicante		Spain
58	Boehringer Ingelheim Investigational Site	Las Palmas de Gran Canaria		Spain
59	Boehringer Ingelheim Investigational Site	Madrid		Spain
60	Boehringer Ingelheim Investigational Site	Vic (Barcelona)		Spain
61	Boehringer Ingelheim Investigational Site	Motala		Sweden
62	Boehringer Ingelheim Investigational Site	Skövde		Sweden
63	Boehringer Ingelheim Investigational Site	Uppsala		Sweden
64	Boehringer Ingelheim Investigational Site	Varberg		Sweden
65	Boehringer Ingelheim Investigational Site	Ankara		Turkey
66	Boehringer Ingelheim Investigational Site	Bursa		Turkey
67	Boehringer Ingelheim Investigational Site	Istanbul		Turkey
68	Boehringer Ingelheim Investigational Site	Birmingham		United Kingdom
69	Boehringer Ingelheim Investigational Site	Bristol		United Kingdom
70	Boehringer Ingelheim Investigational Site	Nottingham		United Kingdom
71	Boehringer Ingelheim Investigational Site	Sheffield		United Kingdom
72	Boehringer Ingelheim Investigational Site	Swansea		United Kingdom
73	Boehringer Ingelheim Investigational Site	Torquay		United Kingdom

Sponsors and Collaborators

Boehringer Ingelheim

Investigators

Study Chair: Boehringer Ingelheim Study Coordinator, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.

Responsible Party:

, ,

ClinicalTrials.gov Identifier:

NCT00168844

Other Study ID Numbers:

205.254

First Posted:

Sep 15, 2005

Last Update Posted:

May 20, 2014

Last Verified:

Sep 1, 2013

Additional relevant MeSH terms:

Lung Diseases

Pulmonary Disease, Chronic Obstructive

Tiotropium Bromide

Study Results

Participant Flow

Recruitment Details	Feb 2003 - Jun 2004, hospital and primary care clinics
Pre-assignment Detail

Arm/Group Title	Tiotropium Respimat 5mcg (Tio R5)	Tiotropium Respimat 10mcg (Tio R10)	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Period Title: Overall Study
STARTED	332	332	319
COMPLETED	277	277	228
NOT COMPLETED	55	55	91

Baseline Characteristics

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo	Total
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)	Total of all reporting groups
Overall Participants	332	332	319	983
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65 (8.2)	64.6 (8.4)	64.7 (8.9)	64.8 (8.5)
Sex: Female, Male (Count of Participants)
Female	89 26.8%	80 24.1%	67 21%	236 24%
Male	243 73.2%	252 75.9%	252 79%	747 76%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Trough FEV1 at Week 48, Full Analysis Set - Clinic Spirometry (FAS-PFT)
Description	Trough Forced Expiratory Volume in 1 second (FEV1)
Time Frame	10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication

Outcome Measure Data

Analysis Population Description
Full Analysis Set - Clinic Spirometry (FAS-PFT)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	326	320	296
Mean (Standard Error) [Litres]	0.097 (0.013)	0.116 (0.014)	-0.046 (0.014)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tiotropium Respimat 5mcg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	ANCOVA analysis with terms for treatment, smoking status at entry,centre and baseline value.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.142
	Confidence Interval	() 95% to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.019
	Estimation Comments	Tiotropium Respimat 5mcg - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tiotropium Respimat 10mcg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	ANCOVA analysis with terms for treatment, smoking status at entry,centre and baseline value.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.161
	Confidence Interval	() 95% to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.020
	Estimation Comments	Tiotropium Respimat 10mcg - Placebo

2. Primary Outcome

Title	Saint George's Respiratory Questionnaire (SGRQ) Total Score, Full Analysis Set - Saint George's Respiratory Questionnaire (FAS-QOL)
Description	Rating scale of 3 domains - symptoms, activities and impact (weighted). Worst score = 100, best score = 0
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
Full Analysis Set - Saint George's Respiratory Questionnaire (FAS-QOL)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	318	315	275
Mean (Standard Error) [Points on a scale]	39.648 (0.676)	38.675 (0.679)	42.917 (0.728)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tiotropium Respimat 5mcg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0011
	Comments
	Method	ANCOVA
	Comments	The means are adjusted for centre, smoking status at entry and baseline value.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.269
	Confidence Interval	() 95% to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.996
	Estimation Comments	Tiotropium Respimat 5mcg - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tiotropium Respimat 10mcg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	The means are adjusted for centre, smoking status at entry and baseline value.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.242
	Confidence Interval	() 95% to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.999
	Estimation Comments	Tiotropium Respimat 10mcg - Placebo

3. Primary Outcome

Title	TDI Focal Score, Full Analysis Set - Transitional Dyspnoea Index (FAS-TDI) (Combined Studies)
Description	Rating scale of 3 components - change in functional impairment, change in magnitude of tasks, change in magnitude of efforts. Worst score = -9, best score = +9 For this endpoint data of twin studies NCT00168844 and NCT00168831 was combined.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
Full Analysis Set - Transitional Dyspnoea Index (FAS-TDI)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	628	618	552
Mean (Standard Error) [Points on a scale]	1.890 (0.112)	1.913 (0.113)	0.837 (0.120)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tiotropium Respimat 5mcg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	The means are adjusted for centre, smoking status at entry and baseline value.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.053
	Confidence Interval	(2-Sided) 95% to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.165
	Estimation Comments	Tiotropium Respimat 5mcg - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tiotropium Respimat 10mcg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	The means are adjusted for centre, smoking status at entry and baseline value.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.075
	Confidence Interval	() 95% to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.166
	Estimation Comments

4. Primary Outcome

Title	COPD Exacerbation Rate, Safety Set (SS) (Combined Studies)
Description	Number of Chronic Obstructive Pulmonary Disease (COPD) exacerbations per patient year. For this endpoint data of the twin studies NCT00168844 and NCT00168831 was combined.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description
Safety Set. Combined analysis of studies NCT00168844 and NCT00168831. 670 patients analysed in total comprises 338 patients from NCT00168831 and 332 patients from study NCT00168844, 667 patients - 335 and 332, 653 patients - 334 and 319 respectively.

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	670	667	653
Mean (Standard Deviation) [Number of exacerbations per patient year]	0.93 (2.02)	1.02 (3.05)	1.91 (8.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tiotropium Respimat 5mcg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Poisson regression
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.782
	Confidence Interval	(2-Sided) 95% 0.687 to 0.890
	Parameter Dispersion	Type: Value:
	Estimation Comments	Tiotropium Respimat 5mcg - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tiotropium Respimat 10mcg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Poisson regression
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.725
	Confidence Interval	(2-Sided) 95% 0.635 to 0.828
	Parameter Dispersion	Type: Value:
	Estimation Comments	Tiotropium Respimat 10mcg - Placebo

5. Secondary Outcome

Title	Change From Baseline in Heart Rate
Description	Week 40 pre-dose - baseline
Time Frame	Baseline to Week 40 pre-dose

Outcome Measure Data

Analysis Population Description
Combined analysis of studies NCT00168844 and NCT00168831 in subset of patients who had additional 12-lead electrocardiogram (ECG) and 24-hour Holter monitoring performed (see protocol and clinical trial report)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	155	135	109
Mean (Standard Deviation) [beats per minute (bpm)]	2.1 (12.4)	3.6 (10.5)	1.8 (9.7)

6. Secondary Outcome

Title	Change From Baseline in PR Interval
Description
Time Frame	Baseline to Week 40 pre-dose

Outcome Measure Data

Analysis Population Description
Combined analysis of studies NCT00168844 and NCT00168831 in subset of patients who had additional 12-lead ECG and 24-hour Holter monitoring performed (see protocol and clinical trial report)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	150	131	105
Mean (Standard Deviation) [milliseconds (msec)]	-0.8 (20.2)	-2.5 (15.1)	-0.5 (15.3)

7. Secondary Outcome

Title	Change From Baseline in QRS Interval
Description	Week 40 pre-dose - baseline
Time Frame	Baseline to Week 40 pre-dose

Outcome Measure Data

Analysis Population Description
Combined analysis of studies NCT00168844 and NCT00168831 in subset of patients who had additional 12-lead ECG and 24-hour Holter monitoring performed (see protocol and clinical trial report)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	155	135	109
Mean (Standard Deviation) [msec]	0.9 (9.4)	1.7 (12.1)	-1.1 (10.3)

8. Secondary Outcome

Title	Change From Baseline in QT Interval
Description	Week 40 pre-dose - baseline
Time Frame	Baseline to Week 40 pre-dose

Outcome Measure Data

Analysis Population Description
Combined analysis of studies NCT00168844 and NCT00168831 in subset of patients who had additional 12-lead ECG and 24-hour Holter monitoring performed (see protocol and clinical trial report)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	155	135	109
Mean (Standard Deviation) [msec]	-4.6 (26.5)	-3.5 (25.2)	-3.2 (22.3)

9. Secondary Outcome

Title	Change From Baseline in QT Interval (Bazett)
Description	Week 40 pre-dose - baseline
Time Frame	Baseline to Week 40 pre-dose

Outcome Measure Data

Analysis Population Description
Combined analysis of studies NCT00168844 and NCT00168831 in subset of patients who had additional 12-lead ECG and 24-hour Holter monitoring performed (see protocol and clinical trial report)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	155	135	109
Mean (Standard Deviation) [msec]	-0.5 (29.9)	5.4 (24.0)	2.5 (23.4)

10. Secondary Outcome

Title	Change From Baseline in QT Interval (Fridericia)
Description	Week 40 pre-dose - baseline
Time Frame	Baseline to Week 40 pre-dose

Outcome Measure Data

Analysis Population Description
Combined analysis of studies NCT00168844 and NCT00168831 in subset of patients who had additional 12-lead ECG and 24-hour Holter monitoring performed (see protocol and clinical trial report)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	155	135	109
Mean (Standard Deviation) [msec]	-2.0 (24.3)	2.2 (21.3)	0.5 (19.5)

11. Secondary Outcome

Title	Change From Baseline in Heart Rate
Description	Week 40 - baseline
Time Frame	Baseline to Week 40

Outcome Measure Data

Analysis Population Description
Combined analysis of studies NCT00168844 and NCT00168831 in subset of patients who had additional 12-lead ECG and 24-hour Holter monitoring performed (see protocol and clinical trial report)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	77	66	56
Mean (Standard Deviation) [bpm]	0.3 (5.4)	1.2 (6.4)	0.3 (6.6)

12. Secondary Outcome

Title	Change From Baseline in Supraventricular Premature Beat (SVPB) Total
Description	Week 40 - baseline
Time Frame	Baseline to Week 40

Outcome Measure Data

Analysis Population Description
Combined analysis of studies NCT00168844 and NCT00168831 in subset of patients who had additional 12-lead ECG and 24-hour Holter monitoring performed (see protocol and clinical trial report)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	77	66	56
Mean (Standard Deviation) [premature beats per 24 hours]	-3.4 (94.2)	6.8 (87.4)	20.9 (125.8)

13. Secondary Outcome

Title	Holter (24-hour Period) - SVPB (Supraventricular Premature Beat) Run Events Change From Baseline in Supraventricular Premature Beat (SVPB) Run Events
Description	Week 40 - baseline
Time Frame	Baseline to Week 40

Outcome Measure Data

Analysis Population Description
Combined analysis of studies NCT00168844 and NCT00168831 in subset of patients who had additional 12-lead ECG and 24-hour Holter monitoring performed (see protocol and clinical trial report)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	77	66	56
Mean (Standard Deviation) [events per 24 hours]	0.0 (0.6)	-0.1 (0.5)	-0.1 (1.6)

14. Secondary Outcome

Title	Change From Baseline in SVPB Pairs
Description	Week 40 - baseline
Time Frame	Baseline to Week 40

Outcome Measure Data

Analysis Population Description
Combined analysis of studies NCT00168844 and NCT00168831 in subset of patients who had additional 12-lead ECG and 24-hour Holter monitoring performed (see protocol and clinical trial report)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	77	66	56
Mean (Standard Deviation) [pairs per 24 hours]	-0.4 (4.0)	-0.2 (2.3)	2.0 (16.4)

15. Secondary Outcome

Title	Change From Baseline in Ventricular Premature Beat (VPB) Total
Description	Week 40 - baseline
Time Frame	Baseline to Week 40

Outcome Measure Data

Analysis Population Description
Combined analysis of studies NCT00168844 and NCT00168831 in subset of patients who had additional 12-lead ECG and 24-hour Holter monitoring performed (see protocol and clinical trial report)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	77	66	56
Mean (Standard Deviation) [premature beats per 24 hours]	-14.3 (105.9)	4.6 (68.8)	-24.1 (182.3)

16. Secondary Outcome

Title	Change From Baseline in VPB Run Events
Description	Week 40 - baseline
Time Frame	Baseline to Week 40

Outcome Measure Data

Analysis Population Description
Combined analysis of studies NCT00168844 and NCT00168831 in subset of patients who had additional 12-lead ECG and 24-hour Holter monitoring performed (see protocol and clinical trial report)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	77	66	56
Mean (Standard Deviation) [events per 24 hours]	0.0 (0.1)	0.0 (0.1)	0.0 (0.0)

17. Secondary Outcome

Title	Change From Baseline in VPB Pairs
Description	Week 40 - baseline
Time Frame	Baseline to Week 40

Outcome Measure Data

Analysis Population Description
Combined analysis of studies NCT00168844 and NCT00168831 in subset of patients who had additional 12-lead ECG and 24-hour Holter monitoring performed (see protocol and clinical trial report)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	77	66	56
Mean (Standard Deviation) [pairs per 24 hours]	-0.2 (1.6)	-0.1 (3.8)	-0.9 (5.7)

18. Secondary Outcome

Title	Change From Baseline in Haematocrit, Packed Cell Volume (PCV)
Description	Volume of red cells (erythrocytes) in blood, expressed as a fraction (percentage) of the total volume of blood
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	280	282	244
Mean (Standard Deviation) [Percentage of erythrocytes]	0 (4)	-1 (4)	0 (4)

19. Secondary Outcome

Title	Change From Baseline in Haemoglobin
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	291	289	255
Mean (Standard Deviation) [grams per litre (g/L)]	-1 (10)	-2 (11)	1 (12)

20. Secondary Outcome

Title	Change From Baseline in Red Blood Cell Count
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	291	289	254
Mean (Standard Deviation) [10^12/Litre (L)]	0.0 (0.3)	-0.1 (0.3)	0.0 (0.3)

21. Secondary Outcome

Title	Change From Baseline in White Blood Cell Count
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	291	289	255
Mean (Standard Deviation) [10^9/Litre (L)]	0.1 (1.4)	0.0 (1.5)	0.2 (1.5)

22. Secondary Outcome

Title	Change From Baseline in Platelets
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	288	280	250
Mean (Standard Deviation) [10^9/L]	4 (30)	1 (31)	7 (30)

23. Secondary Outcome

Title	Change From Baseline in Neutrophils
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	288	289	254
Mean (Standard Deviation) [percentage of white blood cell count]	1 (8)	1 (8)	1 (8)

24. Secondary Outcome

Title	Change From Baseline in Eosinophils
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	288	289	254
Mean (Standard Deviation) [percentage of white blood cell count]	0 (2)	0 (2)	0 (2)

25. Secondary Outcome

Title	Change From Baseline in Basophils
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	288	289	254
Mean (Standard Deviation) [percentage of white blood cell count]	0 (0)	0 (0)	0 (0)

26. Secondary Outcome

Title	Change From Baseline in Lymphocytes
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	288	289	254
Mean (Standard Deviation) [percentage of white blood cell count]	-1 (4)	-1 (4)	0 (4)

27. Secondary Outcome

Title	Change From Baseline in Monocytes
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	288	289	254
Mean (Standard Deviation) [percentage of white blood cell count]	0 (4)	0 (3)	0 (4)

28. Secondary Outcome

Title	Change From Baseline in Neutrophils (Absolute)
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	288	289	254
Mean (Standard Deviation) [10^9/L]	0.2 (1.5)	0.1 (1.6)	0.2 (1.6)

29. Secondary Outcome

Title	Change From Baseline in Lymphocytes (Absolute)
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	288	289	254
Mean (Standard Deviation) [10^9/L]	0.0 (0.6)	-0.1 (0.7)	0.1 (0.6)

30. Secondary Outcome

Title	Change From Baseline in Eosinophils (Absolute)
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	288	289	254
Mean (Standard Deviation) [10^9/L]	0.0 (0.1)	0.0 (0.1)	0.0 (0.1)

31. Secondary Outcome

Title	Change From Baseline in Basophils (Absolute)
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	288	289	254
Mean (Standard Deviation) [10^9/L]	0.0 (0.1)	0.0 (0.1)	0.0 (0.0)

32. Secondary Outcome

Title	Change From Baseline in Monocytes (Absolute)
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	288	289	254
Mean (Standard Deviation) [10^9/L]	0.0 (0.2)	0.0 (0.2)	0.0 (0.2)

33. Secondary Outcome

Title	Change From Baseline in Calcium
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	289	295	259
Mean (Standard Deviation) [millimoles per litre (mmol/L)]	0.0 (0.1)	0.0 (0.1)	0.0 (0.2)

34. Secondary Outcome

Title	Change From Baseline in Phosphate
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	291	296	261
Mean (Standard Deviation) [mmol/L]	0.02 (0.25)	0.00 (0.23)	0.01 (0.23)

35. Secondary Outcome

Title	Change From Baseline in Aspartate Transaminase (AST)/Glutamic-Oxaloacetic Transaminase (GOT), Serum GOT (SGOT)
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	292	296	261
Mean (Standard Deviation) [Units per litre (U/L)]	-3 (17)	-1 (13)	0 (17)

36. Secondary Outcome

Title	Change From Baseline in Alanine Transaminase (ALT)/Glutamic Pyruvic Transaminase (GPT), Serum GPT (SGPT)
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	292	296	261
Mean (Standard Deviation) [U/L]	-2 (13)	-1 (15)	-1 (15)

37. Secondary Outcome

Title	Change From Baseline in Alkaline Phosphatase
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	290	295	259
Mean (Standard Deviation) [U/L]	-3 (21)	-6 (20)	-5 (27)

38. Secondary Outcome

Title	Change From Baseline in Lactic Dehydrogenase (LDH)
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	290	296	261
Mean (Standard Deviation) [U/L]	4 (60)	2 (87)	0 (63)

39. Secondary Outcome

Title	Change From Baseline in Glucose
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	285	292	256
Mean (Standard Deviation) [mmol/L]	-0.09 (1.82)	0.07 (1.95)	0.17 (2.21)

40. Secondary Outcome

Title	Change From Baseline in Urea
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	291	296	261
Mean (Standard Deviation) [mmol/L]	0.1 (2.0)	0.0 (2.3)	0.0 (2.1)

41. Secondary Outcome

Title	Change From Baseline in Blood Urea Nitrogen
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	291	296	261
Mean (Standard Deviation) [milligrams per decilitre (mg/dL)]	0.1 (3.2)	0.0 (3.7)	-0.1 (3.4)

42. Secondary Outcome

Title	Change From Baseline in Creatinine
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	292	296	261
Mean (Standard Deviation) [micromoles per litre (umol/L)]	2.7 (9.6)	1.0 (11.1)	1.7 (10.4)

43. Secondary Outcome

Title	Change From Baseline in Bilirubin, Total
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	291	296	261
Mean (Standard Deviation) [umol/L]	0.0 (4.5)	-0.1 (4.4)	0.0 (4.0)

44. Secondary Outcome

Title	Change From Baseline in Uric Acid
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	291	296	261
Mean (Standard Deviation) [umol/L]	13.55 (78.13)	1.03 (82.35)	7.83 (88.05)

45. Secondary Outcome

Title	Change From Baseline in Protein, Total
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	291	296	261
Mean (Standard Deviation) [grams per litre (g/L)]	-1 (5)	-1 (5)	-1 (5)

46. Secondary Outcome

Title	Change From Baseline in Albumin
Description	Week 48 - baseline
Time Frame	Baseline to Week 48 or at premature discontinuation if before Week 48

Outcome Measure Data

Analysis Population Description
Safety Set

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	291	296	261
Mean (Standard Deviation) [g/L]	1 (4)	1 (4)	1 (4)

47. Secondary Outcome

Title	Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks
Description	Change From Baseline in Trough Forced Expiratory Volume in 1 second (FEV1) after 2, 8, 16, 24, 32 and 40 weeks. The means are adjusted for centre, smoking status at entry and baseline value.
Time Frame	10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication

Outcome Measure Data

Analysis Population Description
Full Analysis Set - Clinic Spirometry (FAS-PFT)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	326	320	296
Week 2	0.118 (0.011)	0.133 (0.011)	0.013 (0.012)
Week 8	0.124 (0.012)	0.150 (0.012)	-0.004 (0.013)
Week 16	0.121 (0.013)	0.125 (0.014)	-0.022 (0.014)
Week 24	0.125 (0.013)	0.121 (0.013)	-0.009 (0.013)
Week 32	0.124 (0.013)	0.132 (0.013)	-0.025 (0.014)
Week 40	0.107 (0.013)	0.133 (0.013)	-0.031 (0.014)

48. Secondary Outcome

Title	Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks
Description	Change From Baseline in Trough Forced vital capacity (FVC) after 2, 8, 16, 24, 32, 40 and 48 weeks. The means are adjusted for centre, smoking status at entry and baseline value.
Time Frame	10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication

Outcome Measure Data

Analysis Population Description
Full Analysis Set - Clinic Spirometry (FAS-PFT)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	326	320	296
Week 2	0.163 (0.023)	0.278 (0.024)	0.025 (0.025)
Week 8	0.168 (0.024)	0.300 (0.024)	0.009 (0.025)
Week 16	0.145 (0.026)	0.267 (0.027)	-0.019 (0.028)
Week 24	0.155 (0.026)	0.274 (0.026)	-0.012 (0.027)
Week 32	0.156 (0.026)	0.276 (0.026)	-0.038 (0.028)
Week 40	0.130 (0.026)	0.294 (0.027)	-0.043 (0.028)
Week 48	0.108 (0.027)	0.253 (0.027)	-0.070 (0.028)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tiotropium Respimat 5mcg, Placebo
	Comments	Analysis for week 48
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	ANCOVA analysis with terms for treatment, smoking status at entry,centre and baseline value.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.178
	Confidence Interval	() 95% to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.039
	Estimation Comments	Tiotropium Respimat 5mcg - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tiotropium Respimat 10mcg, Placebo
	Comments	Analysis for week 48
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	ANCOVA analysis with terms for treatment, smoking status at entry,centre and baseline value.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.323
	Confidence Interval	() 95% to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.039
	Estimation Comments	Tiotropium Respimat 10mcg - Placebo

49. Secondary Outcome

Title	Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks
Description	FEV1 AUC0-3 represents the Area under Curve over the time interval from 0 to 3 hours after 2, 8, 16, 24, 32, 40 and 48 weeks. The means are adjusted for centre, smoking status at entry and baseline value.
Time Frame	10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication

Outcome Measure Data

Analysis Population Description
Full Analysis Set - Clinic Spirometry (FAS-PFT)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	326	320	296
Week 2	0.256 (0.012)	0.258 (0.012)	0.045 (0.013)
Week 8	0.246 (0.013)	0.274 (0.013)	0.041 (0.014)
Week 16	0.241 (0.014)	0.248 (0.014)	0.024 (0.015)
Week 24	0.242 (0.014)	0.241 (0.014)	0.026 (0.014)
Week 32	0.239 (0.014)	0.240 (0.014)	0.019 (0.015)
Week 40	0.225 (0.014)	0.233 (0.014)	0.003 (0.015)
Week 48	0.212 (0.014)	0.226 (0.014)	-0.008 (0.015)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tiotropium Respimat 5mcg, Placebo
	Comments	Analysis for week 48
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	ANCOVA analysis with terms for treatment, smoking status at entry, centre and baseline value.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.220
	Confidence Interval	() 95% to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.021
	Estimation Comments	Tiotropium Respimat 5mcg - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tiotropium Respimat 10mcg, Placebo
	Comments	Analysis for week 48
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	ANCOVA analysis with terms for treatment, smoking status at entry, centre and baseline value.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.234
	Confidence Interval	() 95% to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.021
	Estimation Comments	Tiotropium Respimat 10mcg - Placebo

50. Secondary Outcome

Title	Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks
Description	FVC AUC0-3 represents the Area under Curve over the time interval from 0 to 3 hours after 2, 8, 16, 24, 32, 40 and 48 weeks. The means are adjusted for centre, smoking status at entry and baseline value.
Time Frame	10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication

Outcome Measure Data

Analysis Population Description
Full Analysis Set - Clinic Spirometry (FAS-PFT)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	326	320	296
Week 2	0.421 (0.024)	0.492 (0.024)	0.130 (0.025)
Week 8	0.397 (0.026)	0.538 (0.026)	0.126 (0.027)
Week 16	0.376 (0.028)	0.487 (0.028)	0.076 (0.029)
Week 24	0.364 (0.027)	0.465 (0.027)	0.067 (0.029)
Week 32	0.357 (0.028)	0.465 (0.028)	0.049 (0.029)
Week 40	0.328 (0.028)	0.453 (0.028)	0.034 (0.029)
Week 48	0.312 (0.028)	0.422 (0.028)	0.003 (0.029)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tiotropium Respimat 5mcg, Placebo
	Comments	Analysis for week 48
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	ANCOVA analysis with terms for treatment, smoking status at entry, centre and baseline value.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.310
	Confidence Interval	() 95% to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.041
	Estimation Comments	Tiotropium Respimat 5mcg - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tiotropium Respimat 10mcg, Placebo
	Comments	Analysis for week 48
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	ANCOVA analysis with terms for treatment, smoking status at entry, centre and baseline value.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.419
	Confidence Interval	() 95% to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.041
	Estimation Comments	Tiotropium Respimat 10mcg - Placebo

51. Secondary Outcome

Title	Weekly Mean Morning Pre-dose PEFRs
Description	Weekly mean morning pre-dose peak expiratory flow rates (PEFRs). The means are adjusted for centre, smoking status at entry, and baseline value.
Time Frame	Weeks 2, 8, 16, 24, 32, 40, 48

Outcome Measure Data

Analysis Population Description
Full Analysis Set - Diary (FAS-DRY)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	323	323	293
Week 2	255.4 (1.8)	261.5 (1.8)	235.4 (1.9)
Week 8	259.0 (2.5)	265.6 (2.5)	241.8 (2.7)
Week 16	262.7 (3.0)	269.0 (3.0)	241.1 (3.1)
Week 24	265.7 (3.2)	270.1 (3.2)	244.3 (3.3)
Week 32	267.2 (3.4)	275.1 (3.4)	244.7 (3.6)
Week 40	267.0 (3.4)	276.7 (3.4)	247.4 (3.6)
Week 48	268.5 (3.6)	279.0 (3.6)	245.9 (3.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tiotropium Respimat 5mcg, Placebo
	Comments	Analysis for week 48
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	ANCOVA analysis with terms for treatment, centre,smoking status at entry and baseline value.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	22.5
	Confidence Interval	() 95% to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 5.3
	Estimation Comments	Tiotropium Respimat 5mcg - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tiotropium Respimat 10mcg, Placebo
	Comments	Analysis for week 48
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	ANCOVA analysis with terms for treatment, centre,smoking status at entry and baseline value.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	33.1
	Confidence Interval	() 95% to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 5.3
	Estimation Comments	Tiotropium Respimat 10mcg - Placebo

52. Secondary Outcome

Title	Weekly Mean Evening PEFRs
Description	Weekly mean evening peak expiratory flow rates (PEFRs). The means are adjusted for centre, smoking status at entry, and baseline value.
Time Frame	Weeks 2, 8, 16, 24, 32, 40, 48

Outcome Measure Data

Analysis Population Description
Full Analysis Set - Diary (FAS-DRY)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	323	322	293
Week 2	270.6 (2.0)	279.2 (2.0)	249.3 (2.1)
Week 8	274.5 (2.7)	282.1 (2.7)	253.4 (2.9)
Week 16	278.0 (3.1)	284.1 (3.1)	252.7 (3.2)
Week 24	280.0 (3.3)	287.0 (3.3)	254.7 (3.4)
Week 32	281.8 (3.4)	290.6 (3.4)	255.0 (3.6)
Week 40	283.1 (3.6)	292.2 (3.6)	257.1 (3.7)
Week 48	282.5 (3.9)	292.5 (3.9)	257.0 (4.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tiotropium Respimat 5mcg, Placebo
	Comments	Analysis for week 48
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	ANCOVA analysis with terms for treatment, centre,smoking status at entry and baseline value.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	25.5
	Confidence Interval	() 95% to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 5.6
	Estimation Comments	Tiotropium Respimat 5mcg - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tiotropium Respimat 10mcg, Placebo
	Comments	Analysis for week 48
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	ANCOVA analysis with terms for treatment, centre,smoking status at entry and baseline value.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	35.5
	Confidence Interval	() 95% to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 5.6
	Estimation Comments	Tiotropium Respimat 10mcg - Placebo

53. Secondary Outcome

Title	Weekly Mean Number of Puffs of Rescue Medication Per Day
Description	Weekly mean number of puffs of rescue medication used per day as required (PRN salbutamol). The means are adjusted for centre, smoking status at entry, and baseline value.
Time Frame	Weeks 2, 8, 16, 24, 32, 40, 48

Outcome Measure Data

Analysis Population Description
Full Analysis Set - Diary (FAS-DRY)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	324	323	293
Week 2	1.9 (0.1)	1.9 (0.1)	2.7 (0.1)
Week 8	2.0 (0.1)	2.0 (0.1)	2.7 (0.1)
Week 16	2.1 (0.1)	2.0 (0.1)	2.8 (0.1)
Week 24	2.1 (0.1)	2.2 (0.1)	3.0 (0.1)
Week 32	2.2 (0.1)	2.2 (0.1)	3.0 (0.1)
Week 40	2.2 (0.1)	2.2 (0.1)	3.0 (0.1)
Week 48	2.3 (0.1)	2.2 (0.1)	3.1 (0.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tiotropium Respimat 5mcg, Placebo
	Comments	Analysis for week 48
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	ANCOVA analysis with terms for treatment, centre,smoking status at entry and baseline value.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.8
	Confidence Interval	() 95% to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.2
	Estimation Comments	Tiotropium Respimat 5mcg - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tiotropium Respimat 10mcg, Placebo
	Comments	Analysis for week 48
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	ANCOVA analysis with terms for treatment, centre,smoking status at entry and baseline value.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.9
	Confidence Interval	() 95% to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.2
	Estimation Comments	Tiotropium Respimat 10mcg - Placebo

54. Secondary Outcome

Title	Mahler TDI Scores
Description	Mahler Transitional Dyspnoea Index (TDI) scores measured as change in functional impairment, change in magnitude of tasks and change in magnitude of efforts over the treatment period. The means are adjusted for centre, smoking status at entry and baseline value. Worst score = -3, best score = +3
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
Full Analysis Set - Transitional Dyspnoea Index (FAS-TDI)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	318	313	273
Functional Impairment	0.606 (0.049)	0.679 (0.050)	0.255 (0.053)
Magnitude of Task	0.650 (0.052)	0.673 (0.052)	0.291 (0.056)
Magnitude of Effort	0.633 (0.056)	0.706 (0.056)	0.240 (0.060)

55. Secondary Outcome

Title	Saint George's Respiratory Questionnaire (SGRQ) Scores
Description	Saint George's Respiratory Questionnaire (SGRQ) Scores impacts, activities and symptoms. Worst score = 100, best score = 0. The means are adjusted for centre, smoking status at entry and baseline value.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
Full Analysis Set - Saint George's Respiratory Questionnaire (FAS-QOL)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	318	315	275
Symptoms	42.323 (1.064)	41.798 (1.070)	47.835 (1.146)
Activities	56.317 (0.823)	55.180 (0.828)	58.629 (0.887)
Impacts	29.413 (0.743)	28.054 (0.747)	32.466 (0.801)

56. Secondary Outcome

Title	COPD Symptoms Scores
Description	COPD symptoms Scores - wheezing, shortness of breath, coughing and tightness of chest over the treatment period. Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe The means are adjusted for centre, smoking status at entry and baseline value.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
Full Analysis Set - COPD symptoms (FAS-SYM)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	326	321	295
Wheezing	0.67 (0.04)	0.65 (0.04)	0.91 (0.04)
Shortness of Breath	1.35 (0.04)	1.31 (0.04)	1.51 (0.04)
Coughing	1.05 (0.04)	1.04 (0.04)	1.21 (0.04)
Tightness of Chest	0.61 (0.04)	0.50 (0.04)	0.78 (0.04)

57. Secondary Outcome

Title	PGE Scores
Description	Physician's Global evaluation (PGE) scores over the treatment period. Scale: 1-2 = Poor, 3-4 = Fair, 5-6 = Good, 7-8 = Excellent The means are adjusted for centre, smoking status at entry and baseline value.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
Full Analysis Set - Physician's Global Evaluation (FAS-PGE)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	327	322	295
Mean (Standard Error) [Points on a scale]	5.18 (0.06)	5.18 (0.06)	4.62 (0.06)

58. Secondary Outcome

Title	PGR Score
Description	Patient's Global rating (PGR) score over the treatment period. Scale: 1=much better to 7=much worse The means are adjusted for centre, smoking status at entry and baseline value.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
Full Analysis Set - Patient's Global Rating (FAS-PGR)

Arm/Group Title	Tiotropium Respimat 5mcg	Tiotropium Respimat 10mcg	Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Measure Participants	319	316	276
Mean (Standard Error) [Points on a scale]	3.05 (0.07)	2.86 (0.07)	3.52 (0.08)

Adverse Events

	Tiotropium Respimat 5mcg		Tiotropium Respimat 10mcg		Placebo
Time Frame	From first drug administration until 30 days after last drug administration.
Adverse Event Reporting Description

Arm/Group Title	Tiotropium Respimat 5mcg		Tiotropium Respimat 10mcg		Placebo
Arm/Group Description	Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)		Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)		Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Tiotropium Respimat 5mcg		Tiotropium Respimat 10mcg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	45/ (NaN)		53/ (NaN)		54/ (NaN)
Blood and lymphatic system disorders
Anaemia	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Coagulopathy	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Cardiac disorders
Angina pectoris	2/332 (0.6%)		1/332 (0.3%)		1/319 (0.3%)
Angina unstable	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Atrial fibrillation	1/332 (0.3%)		1/332 (0.3%)		1/319 (0.3%)
Atrial flutter	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Cardiac failure	3/332 (0.9%)		0/332 (0%)		0/319 (0%)
Cardiac failure congestive	1/332 (0.3%)		1/332 (0.3%)		1/319 (0.3%)
Coronary artery disease	1/332 (0.3%)		0/332 (0%)		1/319 (0.3%)
Coronary artery insufficiency	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Myocardial infarction	1/332 (0.3%)		0/332 (0%)		3/319 (0.9%)
Pericardial effusion	1/332 (0.3%)		0/332 (0%)		0/319 (0%)
Ventricular tachycardia	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Eye disorders
Cataract	1/332 (0.3%)		1/332 (0.3%)		0/319 (0%)
Retinal tear	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Gastrointestinal disorders
Abdominal pain	1/332 (0.3%)		0/332 (0%)		0/319 (0%)
Colonic polyp	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Gastritis	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Gastrointestinal haemorrhage	1/332 (0.3%)		0/332 (0%)		2/319 (0.6%)
Haemorrhoids	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Ileus	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Inguinal hernia	0/332 (0%)		3/332 (0.9%)		0/319 (0%)
Intestinal obstruction	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Oesophageal haemorrhage	1/332 (0.3%)		0/332 (0%)		0/319 (0%)
Rectocele	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
General disorders
Adverse drug reaction	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Asthenia	1/332 (0.3%)		1/332 (0.3%)		0/319 (0%)
Chest pain	1/332 (0.3%)		0/332 (0%)		1/319 (0.3%)
Death	0/332 (0%)		5/332 (1.5%)		2/319 (0.6%)
Non-cardiac chest pain	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Pain	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Hepatobiliary disorders
Bile duct stone	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Cholecystitis acute	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Cholelithiasis	0/332 (0%)		1/332 (0.3%)		2/319 (0.6%)
Immune system disorders
Drug hypersensitivity	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Infections and infestations
Aspergillosis	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Bronchial infection	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Bronchitis	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Bronchitis acute	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Bronchopneumonia	1/332 (0.3%)		0/332 (0%)		0/319 (0%)
Cellulitis	0/332 (0%)		1/332 (0.3%)		2/319 (0.6%)
Diverticulitis	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Gastroenteritis	1/332 (0.3%)		0/332 (0%)		1/319 (0.3%)
Lobar pneumonia	0/332 (0%)		0/332 (0%)		2/319 (0.6%)
Lower respiratory tract infection	1/332 (0.3%)		0/332 (0%)		0/319 (0%)
Pneumonia	6/332 (1.8%)		4/332 (1.2%)		0/319 (0%)
Respiratory tract infection	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Sepsis	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Superinfection lung	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Urosepsis	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Injury, poisoning and procedural complications
Cardiac pacemaker malfunction	1/332 (0.3%)		0/332 (0%)		0/319 (0%)
Clavicle fracture	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Concussion	1/332 (0.3%)		0/332 (0%)		0/319 (0%)
Femur fracture	1/332 (0.3%)		0/332 (0%)		1/319 (0.3%)
Hip fracture	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Humerus fracture	1/332 (0.3%)		0/332 (0%)		1/319 (0.3%)
Joint dislocation	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Ligament injury	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Neck injury	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Tendon rupture	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Metabolism and nutrition disorders
Dehydration	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Hypoglycaemia	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Musculoskeletal and connective tissue disorders
Back pain	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Intervertebral disc protrusion	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Osteoarthritis	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	2/332 (0.6%)		0/332 (0%)		0/319 (0%)
Bladder cancer	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Bladder cancer stage II	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Bronchial carcinoma	1/332 (0.3%)		0/332 (0%)		0/319 (0%)
Bronchioloalveolar carcinoma	1/332 (0.3%)		0/332 (0%)		0/319 (0%)
Colon cancer	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Gastrointestinal carcinoma	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Laryngeal cancer	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Lung neoplasm malignant	1/332 (0.3%)		0/332 (0%)		1/319 (0.3%)
Malignant melanoma	1/332 (0.3%)		0/332 (0%)		0/319 (0%)
Neoplasm malignant	1/332 (0.3%)		0/332 (0%)		0/319 (0%)
Oesophageal cancer metastatic	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Prostate cancer	1/332 (0.3%)		1/332 (0.3%)		2/319 (0.6%)
Renal neoplasm	1/332 (0.3%)		0/332 (0%)		0/319 (0%)
Salivary gland adenoma	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Small cell lung cancer stage unspecified	1/332 (0.3%)		0/332 (0%)		0/319 (0%)
Squamous cell carcinoma	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Nervous system disorders
Cerebral infarction	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Cerebrovascular accident	0/332 (0%)		1/332 (0.3%)		2/319 (0.6%)
Dysarthria	1/332 (0.3%)		0/332 (0%)		0/319 (0%)
Facial paresis	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Guillain-Barre syndrome	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Ischaemic stroke	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Normal pressure hydrocephalus	1/332 (0.3%)		0/332 (0%)		0/319 (0%)
Sciatica	1/332 (0.3%)		0/332 (0%)		0/319 (0%)
Syncope	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Psychiatric disorders
Aggression	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Confusional state	2/332 (0.6%)		0/332 (0%)		0/319 (0%)
Renal and urinary disorders
Cystocele	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Haematuria	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Renal cyst	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Renal failure acute	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Urinary retention	0/332 (0%)		2/332 (0.6%)		0/319 (0%)
Urinary tract obstruction	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	1/332 (0.3%)		0/332 (0%)		0/319 (0%)
Acute respiratory failure	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Chronic obstructive airways disease exacerbated	13/332 (3.9%)		11/332 (3.3%)		17/319 (5.3%)
Cough	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Diaphragmatic hernia	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Dyspnoea	2/332 (0.6%)		0/332 (0%)		0/319 (0%)
Haemoptysis	1/332 (0.3%)		1/332 (0.3%)		1/319 (0.3%)
Hypercapnia	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Lung disorder	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Pulmonary hypertension	1/332 (0.3%)		0/332 (0%)		0/319 (0%)
Respiratory failure	1/332 (0.3%)		0/332 (0%)		1/319 (0.3%)
Skin and subcutaneous tissue disorders
Eczema	1/332 (0.3%)		0/332 (0%)		0/319 (0%)
Hyperkeratosis	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Psoriasis	1/332 (0.3%)		0/332 (0%)		0/319 (0%)
Skin ulcer	1/332 (0.3%)		0/332 (0%)		0/319 (0%)
Vascular disorders
Deep vein thrombosis	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Hypertension	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Hypotension	0/332 (0%)		0/332 (0%)		1/319 (0.3%)
Peripheral vascular disorder	0/332 (0%)		1/332 (0.3%)		0/319 (0%)
Other (Not Including Serious) Adverse Events
	Tiotropium Respimat 5mcg		Tiotropium Respimat 10mcg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	147/ (NaN)		160/ (NaN)		145/ (NaN)
Gastrointestinal disorders
Dry mouth	15/332 (4.5%)		44/332 (13.3%)		4/319 (1.3%)
Infections and infestations
Nasopharyngitis	41/332 (12.3%)		31/332 (9.3%)		30/319 (9.4%)
Musculoskeletal and connective tissue disorders
Back pain	18/332 (5.4%)		13/332 (3.9%)		15/319 (4.7%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive airways disease exacerbated	95/332 (28.6%)		94/332 (28.3%)		114/319 (35.7%)
Cough	14/332 (4.2%)		16/332 (4.8%)		16/319 (5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.

Results Point of Contact

Name/Title	Boehringer Ingelheim
Organization	Boehringer Ingelheim
Phone	1-800-243-0127
Email	clintriage.rdg@boehringer-ingelheim.com

Responsible Party:

, ,

ClinicalTrials.gov Identifier:

NCT00168844

Other Study ID Numbers:

205.254

First Posted:

Sep 15, 2005

Last Update Posted:

May 20, 2014

Last Verified:

Sep 1, 2013