Trial Outcomes & Findings for Tiotropium / Respimat One-Year Study (NCT NCT00168844)

NCT ID: NCT00168844

Last Updated: 2014-05-20

Results Overview

Trough Forced Expiratory Volume in 1 second (FEV1)

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 983 participants
• Primary outcome timeframe: 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication
• Results posted on: 2014-05-20

Participant Flow

Feb 2003 - Jun 2004, hospital and primary care clinics

Participant milestones

Measure	Tiotropium Respimat 5mcg (Tio R5) Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg (Tio R10) Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Overall Study STARTED	332	332	319
Overall Study COMPLETED	277	277	228
Overall Study NOT COMPLETED	55	55	91

Reasons for withdrawal

Measure	Tiotropium Respimat 5mcg (Tio R5) Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg (Tio R10) Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Overall Study Adverse Event	31	32	48
Overall Study Lost to Follow-up	4	5	11
Overall Study Withdrawal by Subject	12	9	19
Overall Study Protocol Violation	2	2	4
Overall Study Other	6	7	9

Baseline Characteristics

Tiotropium / Respimat One-Year Study

Baseline characteristics by cohort

Measure	Tiotropium Respimat 5mcg n=332 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=332 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=319 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)	Total n=983 Participants Total of all reporting groups
Age, Continuous	65 years STANDARD_DEVIATION 8.2 • n=5 Participants	64.6 years STANDARD_DEVIATION 8.4 • n=7 Participants	64.7 years STANDARD_DEVIATION 8.9 • n=5 Participants	64.8 years STANDARD_DEVIATION 8.5 • n=4 Participants
Sex: Female, Male Female	89 Participants n=5 Participants	80 Participants n=7 Participants	67 Participants n=5 Participants	236 Participants n=4 Participants
Sex: Female, Male Male	243 Participants n=5 Participants	252 Participants n=7 Participants	252 Participants n=5 Participants	747 Participants n=4 Participants

PRIMARY outcome

Timeframe: 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication

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

Trough Forced Expiratory Volume in 1 second (FEV1)

Outcome measures

Measure	Tiotropium Respimat 5mcg n=326 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=320 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=296 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Trough FEV1 at Week 48, Full Analysis Set - Clinic Spirometry (FAS-PFT)	0.097 Litres Standard Error 0.013	0.116 Litres Standard Error 0.014	-0.046 Litres Standard Error 0.014

PRIMARY outcome

Timeframe: Week 48

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

Rating scale of 3 domains - symptoms, activities and impact (weighted). Worst score = 100, best score = 0

Outcome measures

Measure	Tiotropium Respimat 5mcg n=318 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=315 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=275 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Saint George's Respiratory Questionnaire (SGRQ) Total Score, Full Analysis Set - Saint George's Respiratory Questionnaire (FAS-QOL)	39.648 Points on a scale Standard Error 0.676	38.675 Points on a scale Standard Error 0.679	42.917 Points on a scale Standard Error 0.728

PRIMARY outcome

Timeframe: Week 48

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

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.

Outcome measures

Measure	Tiotropium Respimat 5mcg n=628 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=618 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=552 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
TDI Focal Score, Full Analysis Set - Transitional Dyspnoea Index (FAS-TDI) (Combined Studies)	1.890 Points on a scale Standard Error 0.112	1.913 Points on a scale Standard Error 0.113	0.837 Points on a scale Standard Error 0.120

PRIMARY outcome

Timeframe: 48 weeks

Population: 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.

Number of Chronic Obstructive Pulmonary Disease (COPD) exacerbations per patient year.

For this endpoint data of the twin studies NCT00168844 and NCT00168831 was combined.

Outcome measures

Measure	Tiotropium Respimat 5mcg n=670 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=667 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=653 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
COPD Exacerbation Rate, Safety Set (SS) (Combined Studies)	0.93 Number of exacerbations per patient year Standard Deviation 2.02	1.02 Number of exacerbations per patient year Standard Deviation 3.05	1.91 Number of exacerbations per patient year Standard Deviation 8.17

SECONDARY outcome

Timeframe: Baseline to Week 40 pre-dose

Population: 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)

Week 40 pre-dose - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=155 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=135 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=109 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Heart Rate	2.1 beats per minute (bpm) Standard Deviation 12.4	3.6 beats per minute (bpm) Standard Deviation 10.5	1.8 beats per minute (bpm) Standard Deviation 9.7

SECONDARY outcome

Timeframe: Baseline to Week 40 pre-dose

Population: 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)

Outcome measures

Measure	Tiotropium Respimat 5mcg n=150 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=131 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=105 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in PR Interval	-0.8 milliseconds (msec) Standard Deviation 20.2	-2.5 milliseconds (msec) Standard Deviation 15.1	-0.5 milliseconds (msec) Standard Deviation 15.3

SECONDARY outcome

Timeframe: Baseline to Week 40 pre-dose

Population: 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)

Week 40 pre-dose - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=155 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=135 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=109 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in QRS Interval	0.9 msec Standard Deviation 9.4	1.7 msec Standard Deviation 12.1	-1.1 msec Standard Deviation 10.3

SECONDARY outcome

Timeframe: Baseline to Week 40 pre-dose

Population: 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)

Week 40 pre-dose - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=155 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=135 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=109 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in QT Interval	-4.6 msec Standard Deviation 26.5	-3.5 msec Standard Deviation 25.2	-3.2 msec Standard Deviation 22.3

SECONDARY outcome

Timeframe: Baseline to Week 40 pre-dose

Population: 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)

Week 40 pre-dose - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=155 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=135 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=109 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in QT Interval (Bazett)	-0.5 msec Standard Deviation 29.9	5.4 msec Standard Deviation 24.0	2.5 msec Standard Deviation 23.4

SECONDARY outcome

Timeframe: Baseline to Week 40 pre-dose

Population: 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)

Week 40 pre-dose - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=155 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=135 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=109 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in QT Interval (Fridericia)	-2.0 msec Standard Deviation 24.3	2.2 msec Standard Deviation 21.3	0.5 msec Standard Deviation 19.5

SECONDARY outcome

Timeframe: Baseline to Week 40

Population: 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)

Week 40 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=77 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=66 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=56 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Heart Rate	0.3 bpm Standard Deviation 5.4	1.2 bpm Standard Deviation 6.4	0.3 bpm Standard Deviation 6.6

SECONDARY outcome

Timeframe: Baseline to Week 40

Population: 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)

Week 40 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=77 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=66 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=56 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Supraventricular Premature Beat (SVPB) Total	-3.4 premature beats per 24 hours Standard Deviation 94.2	6.8 premature beats per 24 hours Standard Deviation 87.4	20.9 premature beats per 24 hours Standard Deviation 125.8

SECONDARY outcome

Timeframe: Baseline to Week 40

Population: 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)

Week 40 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=77 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=66 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=56 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Holter (24-hour Period) - SVPB (Supraventricular Premature Beat) Run Events Change From Baseline in Supraventricular Premature Beat (SVPB) Run Events	0.0 events per 24 hours Standard Deviation 0.6	-0.1 events per 24 hours Standard Deviation 0.5	-0.1 events per 24 hours Standard Deviation 1.6

SECONDARY outcome

Timeframe: Baseline to Week 40

Population: 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)

Week 40 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=77 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=66 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=56 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in SVPB Pairs	-0.4 pairs per 24 hours Standard Deviation 4.0	-0.2 pairs per 24 hours Standard Deviation 2.3	2.0 pairs per 24 hours Standard Deviation 16.4

SECONDARY outcome

Timeframe: Baseline to Week 40

Population: 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)

Week 40 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=77 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=66 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=56 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Ventricular Premature Beat (VPB) Total	-14.3 premature beats per 24 hours Standard Deviation 105.9	4.6 premature beats per 24 hours Standard Deviation 68.8	-24.1 premature beats per 24 hours Standard Deviation 182.3

SECONDARY outcome

Timeframe: Baseline to Week 40

Population: 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)

Week 40 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=77 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=66 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=56 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in VPB Run Events	0.0 events per 24 hours Standard Deviation 0.1	0.0 events per 24 hours Standard Deviation 0.1	0.0 events per 24 hours Standard Deviation 0.0

SECONDARY outcome

Timeframe: Baseline to Week 40

Population: 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)

Week 40 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=77 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=66 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=56 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in VPB Pairs	-0.2 pairs per 24 hours Standard Deviation 1.6	-0.1 pairs per 24 hours Standard Deviation 3.8	-0.9 pairs per 24 hours Standard Deviation 5.7

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Volume of red cells (erythrocytes) in blood, expressed as a fraction (percentage) of the total volume of blood

Outcome measures

Measure	Tiotropium Respimat 5mcg n=280 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=282 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=244 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Haematocrit, Packed Cell Volume (PCV)	0 Percentage of erythrocytes Standard Deviation 4	-1 Percentage of erythrocytes Standard Deviation 4	0 Percentage of erythrocytes Standard Deviation 4

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=291 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=289 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=255 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Haemoglobin	-1 grams per litre (g/L) Standard Deviation 10	-2 grams per litre (g/L) Standard Deviation 11	1 grams per litre (g/L) Standard Deviation 12

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=291 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=289 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=254 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Red Blood Cell Count	0.0 10^12/Litre (L) Standard Deviation 0.3	-0.1 10^12/Litre (L) Standard Deviation 0.3	0.0 10^12/Litre (L) Standard Deviation 0.3

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=291 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=289 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=255 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in White Blood Cell Count	0.1 10^9/Litre (L) Standard Deviation 1.4	0.0 10^9/Litre (L) Standard Deviation 1.5	0.2 10^9/Litre (L) Standard Deviation 1.5

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=288 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=280 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=250 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Platelets	4 10^9/L Standard Deviation 30	1 10^9/L Standard Deviation 31	7 10^9/L Standard Deviation 30

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=288 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=289 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=254 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Neutrophils	1 percentage of white blood cell count Standard Deviation 8	1 percentage of white blood cell count Standard Deviation 8	1 percentage of white blood cell count Standard Deviation 8

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=288 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=289 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=254 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Eosinophils	0 percentage of white blood cell count Standard Deviation 2	0 percentage of white blood cell count Standard Deviation 2	0 percentage of white blood cell count Standard Deviation 2

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=288 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=289 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=254 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Basophils	0 percentage of white blood cell count Standard Deviation 0	0 percentage of white blood cell count Standard Deviation 0	0 percentage of white blood cell count Standard Deviation 0

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=288 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=289 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=254 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Lymphocytes	-1 percentage of white blood cell count Standard Deviation 4	-1 percentage of white blood cell count Standard Deviation 4	0 percentage of white blood cell count Standard Deviation 4

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=288 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=289 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=254 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Monocytes	0 percentage of white blood cell count Standard Deviation 4	0 percentage of white blood cell count Standard Deviation 3	0 percentage of white blood cell count Standard Deviation 4

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=288 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=289 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=254 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Neutrophils (Absolute)	0.2 10^9/L Standard Deviation 1.5	0.1 10^9/L Standard Deviation 1.6	0.2 10^9/L Standard Deviation 1.6

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=288 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=289 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=254 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Lymphocytes (Absolute)	0.0 10^9/L Standard Deviation 0.6	-0.1 10^9/L Standard Deviation 0.7	0.1 10^9/L Standard Deviation 0.6

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=288 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=289 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=254 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Eosinophils (Absolute)	0.0 10^9/L Standard Deviation 0.1	0.0 10^9/L Standard Deviation 0.1	0.0 10^9/L Standard Deviation 0.1

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=288 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=289 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=254 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Basophils (Absolute)	0.0 10^9/L Standard Deviation 0.1	0.0 10^9/L Standard Deviation 0.1	0.0 10^9/L Standard Deviation 0.0

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=288 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=289 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=254 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Monocytes (Absolute)	0.0 10^9/L Standard Deviation 0.2	0.0 10^9/L Standard Deviation 0.2	0.0 10^9/L Standard Deviation 0.2

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=289 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=295 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=259 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Calcium	0.0 millimoles per litre (mmol/L) Standard Deviation 0.1	0.0 millimoles per litre (mmol/L) Standard Deviation 0.1	0.0 millimoles per litre (mmol/L) Standard Deviation 0.2

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=291 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=296 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=261 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Phosphate	0.02 mmol/L Standard Deviation 0.25	0.00 mmol/L Standard Deviation 0.23	0.01 mmol/L Standard Deviation 0.23

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=292 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=296 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=261 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Aspartate Transaminase (AST)/Glutamic-Oxaloacetic Transaminase (GOT), Serum GOT (SGOT)	-3 Units per litre (U/L) Standard Deviation 17	-1 Units per litre (U/L) Standard Deviation 13	0 Units per litre (U/L) Standard Deviation 17

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=292 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=296 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=261 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Alanine Transaminase (ALT)/Glutamic Pyruvic Transaminase (GPT), Serum GPT (SGPT)	-2 U/L Standard Deviation 13	-1 U/L Standard Deviation 15	-1 U/L Standard Deviation 15

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=290 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=295 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=259 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Alkaline Phosphatase	-3 U/L Standard Deviation 21	-6 U/L Standard Deviation 20	-5 U/L Standard Deviation 27

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=290 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=296 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=261 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Lactic Dehydrogenase (LDH)	4 U/L Standard Deviation 60	2 U/L Standard Deviation 87	0 U/L Standard Deviation 63

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=285 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=292 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=256 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Glucose	-0.09 mmol/L Standard Deviation 1.82	0.07 mmol/L Standard Deviation 1.95	0.17 mmol/L Standard Deviation 2.21

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=291 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=296 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=261 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Urea	0.1 mmol/L Standard Deviation 2.0	0.0 mmol/L Standard Deviation 2.3	0.0 mmol/L Standard Deviation 2.1

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=291 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=296 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=261 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Blood Urea Nitrogen	0.1 milligrams per decilitre (mg/dL) Standard Deviation 3.2	0.0 milligrams per decilitre (mg/dL) Standard Deviation 3.7	-0.1 milligrams per decilitre (mg/dL) Standard Deviation 3.4

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=292 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=296 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=261 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Creatinine	2.7 micromoles per litre (umol/L) Standard Deviation 9.6	1.0 micromoles per litre (umol/L) Standard Deviation 11.1	1.7 micromoles per litre (umol/L) Standard Deviation 10.4

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=291 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=296 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=261 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Bilirubin, Total	0.0 umol/L Standard Deviation 4.5	-0.1 umol/L Standard Deviation 4.4	0.0 umol/L Standard Deviation 4.0

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=291 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=296 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=261 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Uric Acid	13.55 umol/L Standard Deviation 78.13	1.03 umol/L Standard Deviation 82.35	7.83 umol/L Standard Deviation 88.05

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=291 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=296 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=261 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Protein, Total	-1 grams per litre (g/L) Standard Deviation 5	-1 grams per litre (g/L) Standard Deviation 5	-1 grams per litre (g/L) Standard Deviation 5

SECONDARY outcome

Timeframe: Baseline to Week 48 or at premature discontinuation if before Week 48

Population: Safety Set

Week 48 - baseline

Outcome measures

Measure	Tiotropium Respimat 5mcg n=291 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=296 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=261 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Albumin	1 g/L Standard Deviation 4	1 g/L Standard Deviation 4	1 g/L Standard Deviation 4

SECONDARY outcome

Timeframe: 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication

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

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.

Outcome measures

Measure	Tiotropium Respimat 5mcg n=326 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=320 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=296 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks Week 2	0.118 Litres Standard Error 0.011	0.133 Litres Standard Error 0.011	0.013 Litres Standard Error 0.012
Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks Week 8	0.124 Litres Standard Error 0.012	0.150 Litres Standard Error 0.012	-0.004 Litres Standard Error 0.013
Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks Week 16	0.121 Litres Standard Error 0.013	0.125 Litres Standard Error 0.014	-0.022 Litres Standard Error 0.014
Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks Week 24	0.125 Litres Standard Error 0.013	0.121 Litres Standard Error 0.013	-0.009 Litres Standard Error 0.013
Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks Week 32	0.124 Litres Standard Error 0.013	0.132 Litres Standard Error 0.013	-0.025 Litres Standard Error 0.014
Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks Week 40	0.107 Litres Standard Error 0.013	0.133 Litres Standard Error 0.013	-0.031 Litres Standard Error 0.014

SECONDARY outcome

Timeframe: 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication

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

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.

Outcome measures

Measure	Tiotropium Respimat 5mcg n=326 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=320 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=296 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks Week 2	0.163 Litres Standard Error 0.023	0.278 Litres Standard Error 0.024	0.025 Litres Standard Error 0.025
Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks Week 8	0.168 Litres Standard Error 0.024	0.300 Litres Standard Error 0.024	0.009 Litres Standard Error 0.025
Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks Week 16	0.145 Litres Standard Error 0.026	0.267 Litres Standard Error 0.027	-0.019 Litres Standard Error 0.028
Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks Week 24	0.155 Litres Standard Error 0.026	0.274 Litres Standard Error 0.026	-0.012 Litres Standard Error 0.027
Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks Week 32	0.156 Litres Standard Error 0.026	0.276 Litres Standard Error 0.026	-0.038 Litres Standard Error 0.028
Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks Week 40	0.130 Litres Standard Error 0.026	0.294 Litres Standard Error 0.027	-0.043 Litres Standard Error 0.028
Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks Week 48	0.108 Litres Standard Error 0.027	0.253 Litres Standard Error 0.027	-0.070 Litres Standard Error 0.028

SECONDARY outcome

Timeframe: 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication

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

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.

Outcome measures

Measure	Tiotropium Respimat 5mcg n=326 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=320 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=296 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks Week 2	0.256 Litres Standard Error 0.012	0.258 Litres Standard Error 0.012	0.045 Litres Standard Error 0.013
Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks Week 8	0.246 Litres Standard Error 0.013	0.274 Litres Standard Error 0.013	0.041 Litres Standard Error 0.014
Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks Week 16	0.241 Litres Standard Error 0.014	0.248 Litres Standard Error 0.014	0.024 Litres Standard Error 0.015
Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks Week 24	0.242 Litres Standard Error 0.014	0.241 Litres Standard Error 0.014	0.026 Litres Standard Error 0.014
Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks Week 32	0.239 Litres Standard Error 0.014	0.240 Litres Standard Error 0.014	0.019 Litres Standard Error 0.015
Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks Week 40	0.225 Litres Standard Error 0.014	0.233 Litres Standard Error 0.014	0.003 Litres Standard Error 0.015
Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks Week 48	0.212 Litres Standard Error 0.014	0.226 Litres Standard Error 0.014	-0.008 Litres Standard Error 0.015

SECONDARY outcome

Timeframe: 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication

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

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.

Outcome measures

Measure	Tiotropium Respimat 5mcg n=326 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=320 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=296 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks Week 2	0.421 Litres Standard Error 0.024	0.492 Litres Standard Error 0.024	0.130 Litres Standard Error 0.025
Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks Week 8	0.397 Litres Standard Error 0.026	0.538 Litres Standard Error 0.026	0.126 Litres Standard Error 0.027
Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks Week 16	0.376 Litres Standard Error 0.028	0.487 Litres Standard Error 0.028	0.076 Litres Standard Error 0.029
Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks Week 24	0.364 Litres Standard Error 0.027	0.465 Litres Standard Error 0.027	0.067 Litres Standard Error 0.029
Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks Week 32	0.357 Litres Standard Error 0.028	0.465 Litres Standard Error 0.028	0.049 Litres Standard Error 0.029
Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks Week 40	0.328 Litres Standard Error 0.028	0.453 Litres Standard Error 0.028	0.034 Litres Standard Error 0.029
Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks Week 48	0.312 Litres Standard Error 0.028	0.422 Litres Standard Error 0.028	0.003 Litres Standard Error 0.029

SECONDARY outcome

Timeframe: Weeks 2, 8, 16, 24, 32, 40, 48

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

Weekly mean morning pre-dose peak expiratory flow rates (PEFRs). The means are adjusted for centre, smoking status at entry, and baseline value.

Outcome measures

Measure	Tiotropium Respimat 5mcg n=323 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=323 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=293 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Weekly Mean Morning Pre-dose PEFRs Week 2	255.4 Litres/minute Standard Error 1.8	261.5 Litres/minute Standard Error 1.8	235.4 Litres/minute Standard Error 1.9
Weekly Mean Morning Pre-dose PEFRs Week 8	259.0 Litres/minute Standard Error 2.5	265.6 Litres/minute Standard Error 2.5	241.8 Litres/minute Standard Error 2.7
Weekly Mean Morning Pre-dose PEFRs Week 16	262.7 Litres/minute Standard Error 3.0	269.0 Litres/minute Standard Error 3.0	241.1 Litres/minute Standard Error 3.1
Weekly Mean Morning Pre-dose PEFRs Week 24	265.7 Litres/minute Standard Error 3.2	270.1 Litres/minute Standard Error 3.2	244.3 Litres/minute Standard Error 3.3
Weekly Mean Morning Pre-dose PEFRs Week 32	267.2 Litres/minute Standard Error 3.4	275.1 Litres/minute Standard Error 3.4	244.7 Litres/minute Standard Error 3.6
Weekly Mean Morning Pre-dose PEFRs Week 40	267.0 Litres/minute Standard Error 3.4	276.7 Litres/minute Standard Error 3.4	247.4 Litres/minute Standard Error 3.6
Weekly Mean Morning Pre-dose PEFRs Week 48	268.5 Litres/minute Standard Error 3.6	279.0 Litres/minute Standard Error 3.6	245.9 Litres/minute Standard Error 3.8

SECONDARY outcome

Timeframe: Weeks 2, 8, 16, 24, 32, 40, 48

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

Weekly mean evening peak expiratory flow rates (PEFRs). The means are adjusted for centre, smoking status at entry, and baseline value.

Outcome measures

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

SECONDARY outcome

Timeframe: Weeks 2, 8, 16, 24, 32, 40, 48

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

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.

Outcome measures

Measure	Tiotropium Respimat 5mcg n=324 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=323 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=293 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Weekly Mean Number of Puffs of Rescue Medication Per Day Week 2	1.9 Puffs Standard Error 0.1	1.9 Puffs Standard Error 0.1	2.7 Puffs Standard Error 0.1
Weekly Mean Number of Puffs of Rescue Medication Per Day Week 8	2.0 Puffs Standard Error 0.1	2.0 Puffs Standard Error 0.1	2.7 Puffs Standard Error 0.1
Weekly Mean Number of Puffs of Rescue Medication Per Day Week 16	2.1 Puffs Standard Error 0.1	2.0 Puffs Standard Error 0.1	2.8 Puffs Standard Error 0.1
Weekly Mean Number of Puffs of Rescue Medication Per Day Week 24	2.1 Puffs Standard Error 0.1	2.2 Puffs Standard Error 0.1	3.0 Puffs Standard Error 0.1
Weekly Mean Number of Puffs of Rescue Medication Per Day Week 32	2.2 Puffs Standard Error 0.1	2.2 Puffs Standard Error 0.1	3.0 Puffs Standard Error 0.1
Weekly Mean Number of Puffs of Rescue Medication Per Day Week 40	2.2 Puffs Standard Error 0.1	2.2 Puffs Standard Error 0.1	3.0 Puffs Standard Error 0.1
Weekly Mean Number of Puffs of Rescue Medication Per Day Week 48	2.3 Puffs Standard Error 0.1	2.2 Puffs Standard Error 0.1	3.1 Puffs Standard Error 0.1

SECONDARY outcome

Timeframe: Week 48

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

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

Outcome measures

Measure	Tiotropium Respimat 5mcg n=318 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=313 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=273 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Mahler TDI Scores Functional Impairment	0.606 Points on a scale Standard Error 0.049	0.679 Points on a scale Standard Error 0.050	0.255 Points on a scale Standard Error 0.053
Mahler TDI Scores Magnitude of Task	0.650 Points on a scale Standard Error 0.052	0.673 Points on a scale Standard Error 0.052	0.291 Points on a scale Standard Error 0.056
Mahler TDI Scores Magnitude of Effort	0.633 Points on a scale Standard Error 0.056	0.706 Points on a scale Standard Error 0.056	0.240 Points on a scale Standard Error 0.060

SECONDARY outcome

Timeframe: Week 48

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

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.

Outcome measures

Measure	Tiotropium Respimat 5mcg n=318 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=315 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=275 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Saint George's Respiratory Questionnaire (SGRQ) Scores Symptoms	42.323 Points on a scale Standard Error 1.064	41.798 Points on a scale Standard Error 1.070	47.835 Points on a scale Standard Error 1.146
Saint George's Respiratory Questionnaire (SGRQ) Scores Activities	56.317 Points on a scale Standard Error 0.823	55.180 Points on a scale Standard Error 0.828	58.629 Points on a scale Standard Error 0.887
Saint George's Respiratory Questionnaire (SGRQ) Scores Impacts	29.413 Points on a scale Standard Error 0.743	28.054 Points on a scale Standard Error 0.747	32.466 Points on a scale Standard Error 0.801

SECONDARY outcome

Timeframe: Week 48

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

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.

Outcome measures

Measure	Tiotropium Respimat 5mcg n=326 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=321 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=295 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
COPD Symptoms Scores Wheezing	0.67 Points on a scale Standard Error 0.04	0.65 Points on a scale Standard Error 0.04	0.91 Points on a scale Standard Error 0.04
COPD Symptoms Scores Shortness of Breath	1.35 Points on a scale Standard Error 0.04	1.31 Points on a scale Standard Error 0.04	1.51 Points on a scale Standard Error 0.04
COPD Symptoms Scores Coughing	1.05 Points on a scale Standard Error 0.04	1.04 Points on a scale Standard Error 0.04	1.21 Points on a scale Standard Error 0.04
COPD Symptoms Scores Tightness of Chest	0.61 Points on a scale Standard Error 0.04	0.50 Points on a scale Standard Error 0.04	0.78 Points on a scale Standard Error 0.04

SECONDARY outcome

Timeframe: Week 48

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

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.

Outcome measures

Measure	Tiotropium Respimat 5mcg n=327 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=322 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=295 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
PGE Scores	5.18 Points on a scale Standard Error 0.06	5.18 Points on a scale Standard Error 0.06	4.62 Points on a scale Standard Error 0.06

SECONDARY outcome

Timeframe: Week 48

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

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.

Outcome measures

Measure	Tiotropium Respimat 5mcg n=319 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg n=316 Participants Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo n=276 Participants Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
PGR Score	3.05 Points on a scale Standard Error 0.07	2.86 Points on a scale Standard Error 0.07	3.52 Points on a scale Standard Error 0.08

Adverse Events

Tiotropium Respimat 5mcg

Serious events: 45 serious events

Other events: 147 other events

Deaths: 0 deaths

Tiotropium Respimat 10mcg

Serious events: 53 serious events

Other events: 160 other events

Deaths: 0 deaths

Placebo

Serious events: 54 serious events

Other events: 145 other events

Deaths: 0 deaths

Serious adverse events

Measure	Tiotropium Respimat 5mcg Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Blood and lymphatic system disorders Anaemia	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Blood and lymphatic system disorders Coagulopathy	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Cardiac disorders Angina pectoris	0.60% 2/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Cardiac disorders Angina unstable	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Cardiac disorders Atrial fibrillation	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Cardiac disorders Atrial flutter	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Cardiac disorders Cardiac failure	0.90% 3/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Cardiac disorders Cardiac failure congestive	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Cardiac disorders Coronary artery disease	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Cardiac disorders Coronary artery insufficiency	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Cardiac disorders Myocardial infarction	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.94% 3/319 • From first drug administration until 30 days after last drug administration.
Cardiac disorders Pericardial effusion	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Cardiac disorders Ventricular tachycardia	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Eye disorders Cataract	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Eye disorders Retinal tear	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Gastrointestinal disorders Abdominal pain	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Gastrointestinal disorders Colonic polyp	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Gastrointestinal disorders Gastritis	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.63% 2/319 • From first drug administration until 30 days after last drug administration.
Gastrointestinal disorders Haemorrhoids	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Gastrointestinal disorders Ileus	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Gastrointestinal disorders Inguinal hernia	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.90% 3/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Gastrointestinal disorders Oesophageal haemorrhage	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Gastrointestinal disorders Rectocele	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
General disorders Adverse drug reaction	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
General disorders Asthenia	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
General disorders Chest pain	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
General disorders Death	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	1.5% 5/332 • From first drug administration until 30 days after last drug administration.	0.63% 2/319 • From first drug administration until 30 days after last drug administration.
General disorders Non-cardiac chest pain	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
General disorders Pain	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Hepatobiliary disorders Bile duct stone	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Hepatobiliary disorders Cholelithiasis	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.63% 2/319 • From first drug administration until 30 days after last drug administration.
Immune system disorders Drug hypersensitivity	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Infections and infestations Aspergillosis	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Infections and infestations Bronchial infection	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Infections and infestations Bronchitis	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Infections and infestations Bronchitis acute	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Infections and infestations Bronchopneumonia	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Infections and infestations Cellulitis	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.63% 2/319 • From first drug administration until 30 days after last drug administration.
Infections and infestations Diverticulitis	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Infections and infestations Gastroenteritis	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Infections and infestations Lobar pneumonia	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.63% 2/319 • From first drug administration until 30 days after last drug administration.
Infections and infestations Lower respiratory tract infection	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Infections and infestations Pneumonia	1.8% 6/332 • From first drug administration until 30 days after last drug administration.	1.2% 4/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Infections and infestations Respiratory tract infection	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Infections and infestations Sepsis	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Infections and infestations Superinfection lung	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Infections and infestations Urosepsis	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Injury, poisoning and procedural complications Cardiac pacemaker malfunction	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Injury, poisoning and procedural complications Clavicle fracture	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Injury, poisoning and procedural complications Concussion	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Injury, poisoning and procedural complications Femur fracture	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Injury, poisoning and procedural complications Humerus fracture	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Injury, poisoning and procedural complications Ligament injury	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Injury, poisoning and procedural complications Neck injury	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Metabolism and nutrition disorders Dehydration	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.60% 2/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer stage II	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bronchial carcinoma	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bronchioloalveolar carcinoma	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal carcinoma	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Laryngeal cancer	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal cancer metastatic	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.63% 2/319 • From first drug administration until 30 days after last drug administration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal neoplasm	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Salivary gland adenoma	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer stage unspecified	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Nervous system disorders Cerebral infarction	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Nervous system disorders Cerebrovascular accident	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.63% 2/319 • From first drug administration until 30 days after last drug administration.
Nervous system disorders Dysarthria	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Nervous system disorders Facial paresis	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Nervous system disorders Guillain-Barre syndrome	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Nervous system disorders Ischaemic stroke	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Nervous system disorders Normal pressure hydrocephalus	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Nervous system disorders Sciatica	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Nervous system disorders Syncope	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Psychiatric disorders Aggression	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Psychiatric disorders Confusional state	0.60% 2/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Renal and urinary disorders Cystocele	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Renal and urinary disorders Haematuria	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Renal and urinary disorders Renal cyst	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Renal and urinary disorders Renal failure acute	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Renal and urinary disorders Urinary retention	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.60% 2/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Renal and urinary disorders Urinary tract obstruction	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Respiratory, thoracic and mediastinal disorders Chronic obstructive airways disease exacerbated	3.9% 13/332 • From first drug administration until 30 days after last drug administration.	3.3% 11/332 • From first drug administration until 30 days after last drug administration.	5.3% 17/319 • From first drug administration until 30 days after last drug administration.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Respiratory, thoracic and mediastinal disorders Diaphragmatic hernia	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.60% 2/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Respiratory, thoracic and mediastinal disorders Hypercapnia	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Respiratory, thoracic and mediastinal disorders Lung disorder	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Skin and subcutaneous tissue disorders Eczema	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Skin and subcutaneous tissue disorders Hyperkeratosis	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Skin and subcutaneous tissue disorders Psoriasis	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Skin and subcutaneous tissue disorders Skin ulcer	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Vascular disorders Deep vein thrombosis	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Vascular disorders Hypertension	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.
Vascular disorders Hypotension	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.31% 1/319 • From first drug administration until 30 days after last drug administration.
Vascular disorders Peripheral vascular disorder	0.00% 0/332 • From first drug administration until 30 days after last drug administration.	0.30% 1/332 • From first drug administration until 30 days after last drug administration.	0.00% 0/319 • From first drug administration until 30 days after last drug administration.

Other adverse events

Measure	Tiotropium Respimat 5mcg Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg)	Tiotropium Respimat 10mcg Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg)	Placebo Placebo inhalation solution delivered from Respimat Inhaler (matching placebo)
Gastrointestinal disorders Dry mouth	4.5% 15/332 • From first drug administration until 30 days after last drug administration.	13.3% 44/332 • From first drug administration until 30 days after last drug administration.	1.3% 4/319 • From first drug administration until 30 days after last drug administration.
Infections and infestations Nasopharyngitis	12.3% 41/332 • From first drug administration until 30 days after last drug administration.	9.3% 31/332 • From first drug administration until 30 days after last drug administration.	9.4% 30/319 • From first drug administration until 30 days after last drug administration.
Musculoskeletal and connective tissue disorders Back pain	5.4% 18/332 • From first drug administration until 30 days after last drug administration.	3.9% 13/332 • From first drug administration until 30 days after last drug administration.	4.7% 15/319 • From first drug administration until 30 days after last drug administration.
Respiratory, thoracic and mediastinal disorders Chronic obstructive airways disease exacerbated	28.6% 95/332 • From first drug administration until 30 days after last drug administration.	28.3% 94/332 • From first drug administration until 30 days after last drug administration.	35.7% 114/319 • From first drug administration until 30 days after last drug administration.
Respiratory, thoracic and mediastinal disorders Cough	4.2% 14/332 • From first drug administration until 30 days after last drug administration.	4.8% 16/332 • From first drug administration until 30 days after last drug administration.	5.0% 16/319 • From first drug administration until 30 days after last drug administration.

Additional Information

Boehringer Ingelheim

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER