Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
To evaluate the long term effects of treatment with two doses of Tiotropium delivered by the Respimat inhaler in patients with COPD.
Interventions
OTHERPlacebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Trough FEV1 at Week 48, Full Analysis Set - Clinic Spirometry (FAS-PFT) | 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication | Trough Forced Expiratory Volume in 1 second (FEV1) |
| Saint George's Respiratory Questionnaire (SGRQ) Total Score, Full Analysis Set - Saint George's Respiratory Questionnaire (FAS-QOL) | Week 48 | Rating scale of 3 domains - symptoms, activities and impact (weighted). Worst score = 100, best score = 0 |
| TDI Focal Score, Full Analysis Set - Transitional Dyspnoea Index (FAS-TDI) (Combined Studies) | Week 48 | Rating scale of 3 components - change in functional impairment, change in magnitude of tasks, change in magnitude of efforts. Worst score = -9, best score = +9 For this endpoint data of twin studies NCT00168844 and NCT00168831 was combined. |
| COPD Exacerbation Rate, Safety Set (SS) (Combined Studies) | 48 weeks | Number of Chronic Obstructive Pulmonary Disease (COPD) exacerbations per patient year. For this endpoint data of the twin studies NCT00168844 and NCT00168831 was combined. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in QT Interval (Bazett) | Baseline to Week 40 pre-dose | Week 40 pre-dose - baseline |
| Change From Baseline in QT Interval (Fridericia) | Baseline to Week 40 pre-dose | Week 40 pre-dose - baseline |
| Change From Baseline in Supraventricular Premature Beat (SVPB) Total | Baseline to Week 40 | Week 40 - baseline |
| Holter (24-hour Period) - SVPB (Supraventricular Premature Beat) Run Events Change From Baseline in Supraventricular Premature Beat (SVPB) Run Events | Baseline to Week 40 | Week 40 - baseline |
| Change From Baseline in SVPB Pairs | Baseline to Week 40 | Week 40 - baseline |
| Change From Baseline in Ventricular Premature Beat (VPB) Total | Baseline to Week 40 | Week 40 - baseline |
| Change From Baseline in VPB Run Events | Baseline to Week 40 | Week 40 - baseline |
| Change From Baseline in VPB Pairs | Baseline to Week 40 | Week 40 - baseline |
| Change From Baseline in Haematocrit, Packed Cell Volume (PCV) | Baseline to Week 48 or at premature discontinuation if before Week 48 | Volume of red cells (erythrocytes) in blood, expressed as a fraction (percentage) of the total volume of blood |
| Change From Baseline in Haemoglobin | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Red Blood Cell Count | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in White Blood Cell Count | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Platelets | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Neutrophils | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Eosinophils | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Basophils | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Lymphocytes | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Monocytes | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Neutrophils (Absolute) | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Lymphocytes (Absolute) | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Eosinophils (Absolute) | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Basophils (Absolute) | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Monocytes (Absolute) | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Calcium | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Phosphate | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Aspartate Transaminase (AST)/Glutamic-Oxaloacetic Transaminase (GOT), Serum GOT (SGOT) | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Alanine Transaminase (ALT)/Glutamic Pyruvic Transaminase (GPT), Serum GPT (SGPT) | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Alkaline Phosphatase | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Lactic Dehydrogenase (LDH) | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Glucose | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Urea | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Blood Urea Nitrogen | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Creatinine | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Bilirubin, Total | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Uric Acid | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Protein, Total | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Albumin | Baseline to Week 48 or at premature discontinuation if before Week 48 | Week 48 - baseline |
| Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks | 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication | Change From Baseline in Trough Forced Expiratory Volume in 1 second (FEV1) after 2, 8, 16, 24, 32 and 40 weeks. The means are adjusted for centre, smoking status at entry and baseline value. |
| Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks | 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication | Change From Baseline in Trough Forced vital capacity (FVC) after 2, 8, 16, 24, 32, 40 and 48 weeks. The means are adjusted for centre, smoking status at entry and baseline value. |
| Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication | FEV1 AUC0-3 represents the Area under Curve over the time interval from 0 to 3 hours after 2, 8, 16, 24, 32, 40 and 48 weeks. The means are adjusted for centre, smoking status at entry and baseline value. |
| Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication | FVC AUC0-3 represents the Area under Curve over the time interval from 0 to 3 hours after 2, 8, 16, 24, 32, 40 and 48 weeks. The means are adjusted for centre, smoking status at entry and baseline value. |
| Weekly Mean Morning Pre-dose PEFRs | Weeks 2, 8, 16, 24, 32, 40, 48 | Weekly mean morning pre-dose peak expiratory flow rates (PEFRs). The means are adjusted for centre, smoking status at entry, and baseline value. |
| Weekly Mean Evening PEFRs | Weeks 2, 8, 16, 24, 32, 40, 48 | Weekly mean evening peak expiratory flow rates (PEFRs). The means are adjusted for centre, smoking status at entry, and baseline value. |
| Weekly Mean Number of Puffs of Rescue Medication Per Day | Weeks 2, 8, 16, 24, 32, 40, 48 | Weekly mean number of puffs of rescue medication used per day as required (PRN salbutamol). The means are adjusted for centre, smoking status at entry, and baseline value. |
| Mahler TDI Scores | Week 48 | Mahler Transitional Dyspnoea Index (TDI) scores measured as change in functional impairment, change in magnitude of tasks and change in magnitude of efforts over the treatment period. The means are adjusted for centre, smoking status at entry and baseline value. Worst score = -3, best score = +3 |
| Change From Baseline in Heart Rate | Baseline to Week 40 pre-dose | Week 40 pre-dose - baseline |
| COPD Symptoms Scores | Week 48 | COPD symptoms Scores - wheezing, shortness of breath, coughing and tightness of chest over the treatment period. Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe The means are adjusted for centre, smoking status at entry and baseline value. |
| PGE Scores | Week 48 | Physician's Global evaluation (PGE) scores over the treatment period. Scale: 1-2 = Poor, 3-4 = Fair, 5-6 = Good, 7-8 = Excellent The means are adjusted for centre, smoking status at entry and baseline value. |
| PGR Score | Week 48 | Patient's Global rating (PGR) score over the treatment period. Scale: 1=much better to 7=much worse The means are adjusted for centre, smoking status at entry and baseline value. |
| Saint George's Respiratory Questionnaire (SGRQ) Scores | Week 48 | Saint George's Respiratory Questionnaire (SGRQ) Scores impacts, activities and symptoms. Worst score = 100, best score = 0. The means are adjusted for centre, smoking status at entry and baseline value. |
| Change From Baseline in PR Interval | Baseline to Week 40 pre-dose | — |
| Change From Baseline in QRS Interval | Baseline to Week 40 pre-dose | Week 40 pre-dose - baseline |
| Change From Baseline in QT Interval | Baseline to Week 40 pre-dose | Week 40 pre-dose - baseline |
Countries
Australia, Belgium, Canada, France, Germany, Greece, Netherlands, Norway, Russia, Spain, Sweden, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
Feb 2003 - Jun 2004, hospital and primary care clinics
Participants by arm
| Arm | Count |
|---|---|
| Tiotropium Respimat 5mcg Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (5 mcg) | 332 |
| Tiotropium Respimat 10mcg Tiotropium Bromide inhalation solution delivered from Respimat Inhaler (10 mcg) | 332 |
| Placebo Placebo inhalation solution delivered from Respimat Inhaler (matching placebo) | 319 |
| Total | 983 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 31 | 32 | 48 |
| Overall Study | Lost to Follow-up | 4 | 5 | 11 |
| Overall Study | Other | 6 | 7 | 9 |
| Overall Study | Protocol Violation | 2 | 2 | 4 |
| Overall Study | Withdrawal by Subject | 12 | 9 | 19 |
Baseline characteristics
| Characteristic | Tiotropium Respimat 5mcg | Tiotropium Respimat 10mcg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 65 years STANDARD_DEVIATION 8.2 | 64.6 years STANDARD_DEVIATION 8.4 | 64.7 years STANDARD_DEVIATION 8.9 | 64.8 years STANDARD_DEVIATION 8.5 |
| Sex: Female, Male Female | 89 Participants | 80 Participants | 67 Participants | 236 Participants |
| Sex: Female, Male Male | 243 Participants | 252 Participants | 252 Participants | 747 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 147 / — | 160 / — | 145 / — |
| serious Total, serious adverse events | 45 / — | 53 / — | 54 / — |
Outcome results
Primary
Change From Baseline in Trough FEV1 at Week 48, Full Analysis Set - Clinic Spirometry (FAS-PFT)
Trough Forced Expiratory Volume in 1 second (FEV1)
Time frame: 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication
Population: Full Analysis Set - Clinic Spirometry (FAS-PFT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Trough FEV1 at Week 48, Full Analysis Set - Clinic Spirometry (FAS-PFT) | 0.097 Litres | Standard Error 0.013 |
| Tiotropium Respimat 10mcg | Change From Baseline in Trough FEV1 at Week 48, Full Analysis Set - Clinic Spirometry (FAS-PFT) | 0.116 Litres | Standard Error 0.014 |
| Placebo | Change From Baseline in Trough FEV1 at Week 48, Full Analysis Set - Clinic Spirometry (FAS-PFT) | -0.046 Litres | Standard Error 0.014 |
p-value: <0.0001ANCOVA
p-value: <0.0001ANCOVA
Primary
COPD Exacerbation Rate, Safety Set (SS) (Combined Studies)
Number of Chronic Obstructive Pulmonary Disease (COPD) exacerbations per patient year. For this endpoint data of the twin studies NCT00168844 and NCT00168831 was combined.
Time frame: 48 weeks
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | COPD Exacerbation Rate, Safety Set (SS) (Combined Studies) | 0.93 Number of exacerbations per patient year | Standard Deviation 2.02 |
| Tiotropium Respimat 10mcg | COPD Exacerbation Rate, Safety Set (SS) (Combined Studies) | 1.02 Number of exacerbations per patient year | Standard Deviation 3.05 |
| Placebo | COPD Exacerbation Rate, Safety Set (SS) (Combined Studies) | 1.91 Number of exacerbations per patient year | Standard Deviation 8.17 |
p-value: 0.000295% CI: [0.687, 0.89]Poisson regression
p-value: <0.000195% CI: [0.635, 0.828]Poisson regression
Primary
Saint George's Respiratory Questionnaire (SGRQ) Total Score, 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
Time frame: Week 48
Population: Full Analysis Set - Saint George's Respiratory Questionnaire (FAS-QOL)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | 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 |
| Tiotropium Respimat 10mcg | Saint George's Respiratory Questionnaire (SGRQ) Total Score, Full Analysis Set - Saint George's Respiratory Questionnaire (FAS-QOL) | 38.675 Points on a scale | Standard Error 0.679 |
| Placebo | Saint George's Respiratory Questionnaire (SGRQ) Total Score, Full Analysis Set - Saint George's Respiratory Questionnaire (FAS-QOL) | 42.917 Points on a scale | Standard Error 0.728 |
p-value: 0.0011ANCOVA
p-value: <0.0001ANCOVA
Primary
TDI Focal Score, Full Analysis Set - Transitional Dyspnoea Index (FAS-TDI) (Combined Studies)
Rating scale of 3 components - change in functional impairment, change in magnitude of tasks, change in magnitude of efforts. Worst score = -9, best score = +9 For this endpoint data of twin studies NCT00168844 and NCT00168831 was combined.
Time frame: Week 48
Population: Full Analysis Set - Transitional Dyspnoea Index (FAS-TDI)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | TDI Focal Score, Full Analysis Set - Transitional Dyspnoea Index (FAS-TDI) (Combined Studies) | 1.890 Points on a scale | Standard Error 0.112 |
| Tiotropium Respimat 10mcg | TDI Focal Score, Full Analysis Set - Transitional Dyspnoea Index (FAS-TDI) (Combined Studies) | 1.913 Points on a scale | Standard Error 0.113 |
| Placebo | TDI Focal Score, Full Analysis Set - Transitional Dyspnoea Index (FAS-TDI) (Combined Studies) | 0.837 Points on a scale | Standard Error 0.12 |
p-value: <0.0001ANCOVA
p-value: <0.0001ANCOVA
Secondary
Change From Baseline in Alanine Transaminase (ALT)/Glutamic Pyruvic Transaminase (GPT), Serum GPT (SGPT)
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Alanine Transaminase (ALT)/Glutamic Pyruvic Transaminase (GPT), Serum GPT (SGPT) | -2 U/L | Standard Deviation 13 |
| Tiotropium Respimat 10mcg | Change From Baseline in Alanine Transaminase (ALT)/Glutamic Pyruvic Transaminase (GPT), Serum GPT (SGPT) | -1 U/L | Standard Deviation 15 |
| Placebo | Change From Baseline in Alanine Transaminase (ALT)/Glutamic Pyruvic Transaminase (GPT), Serum GPT (SGPT) | -1 U/L | Standard Deviation 15 |
Secondary
Change From Baseline in Albumin
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Albumin | 1 g/L | Standard Deviation 4 |
| Tiotropium Respimat 10mcg | Change From Baseline in Albumin | 1 g/L | Standard Deviation 4 |
| Placebo | Change From Baseline in Albumin | 1 g/L | Standard Deviation 4 |
Secondary
Change From Baseline in Alkaline Phosphatase
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Alkaline Phosphatase | -3 U/L | Standard Deviation 21 |
| Tiotropium Respimat 10mcg | Change From Baseline in Alkaline Phosphatase | -6 U/L | Standard Deviation 20 |
| Placebo | Change From Baseline in Alkaline Phosphatase | -5 U/L | Standard Deviation 27 |
Secondary
Change From Baseline in Aspartate Transaminase (AST)/Glutamic-Oxaloacetic Transaminase (GOT), Serum GOT (SGOT)
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Aspartate Transaminase (AST)/Glutamic-Oxaloacetic Transaminase (GOT), Serum GOT (SGOT) | -3 Units per litre (U/L) | Standard Deviation 17 |
| Tiotropium Respimat 10mcg | Change From Baseline in Aspartate Transaminase (AST)/Glutamic-Oxaloacetic Transaminase (GOT), Serum GOT (SGOT) | -1 Units per litre (U/L) | Standard Deviation 13 |
| Placebo | Change From Baseline in Aspartate Transaminase (AST)/Glutamic-Oxaloacetic Transaminase (GOT), Serum GOT (SGOT) | 0 Units per litre (U/L) | Standard Deviation 17 |
Secondary
Change From Baseline in Basophils
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Basophils | 0 percentage of white blood cell count | Standard Deviation 0 |
| Tiotropium Respimat 10mcg | Change From Baseline in Basophils | 0 percentage of white blood cell count | Standard Deviation 0 |
| Placebo | Change From Baseline in Basophils | 0 percentage of white blood cell count | Standard Deviation 0 |
Secondary
Change From Baseline in Basophils (Absolute)
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Basophils (Absolute) | 0.0 10^9/L | Standard Deviation 0.1 |
| Tiotropium Respimat 10mcg | Change From Baseline in Basophils (Absolute) | 0.0 10^9/L | Standard Deviation 0.1 |
| Placebo | Change From Baseline in Basophils (Absolute) | 0.0 10^9/L | Standard Deviation 0 |
Secondary
Change From Baseline in Bilirubin, Total
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Bilirubin, Total | 0.0 umol/L | Standard Deviation 4.5 |
| Tiotropium Respimat 10mcg | Change From Baseline in Bilirubin, Total | -0.1 umol/L | Standard Deviation 4.4 |
| Placebo | Change From Baseline in Bilirubin, Total | 0.0 umol/L | Standard Deviation 4 |
Secondary
Change From Baseline in Blood Urea Nitrogen
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Blood Urea Nitrogen | 0.1 milligrams per decilitre (mg/dL) | Standard Deviation 3.2 |
| Tiotropium Respimat 10mcg | Change From Baseline in Blood Urea Nitrogen | 0.0 milligrams per decilitre (mg/dL) | Standard Deviation 3.7 |
| Placebo | Change From Baseline in Blood Urea Nitrogen | -0.1 milligrams per decilitre (mg/dL) | Standard Deviation 3.4 |
Secondary
Change From Baseline in Calcium
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Calcium | 0.0 millimoles per litre (mmol/L) | Standard Deviation 0.1 |
| Tiotropium Respimat 10mcg | Change From Baseline in Calcium | 0.0 millimoles per litre (mmol/L) | Standard Deviation 0.1 |
| Placebo | Change From Baseline in Calcium | 0.0 millimoles per litre (mmol/L) | Standard Deviation 0.2 |
Secondary
Change From Baseline in Creatinine
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Creatinine | 2.7 micromoles per litre (umol/L) | Standard Deviation 9.6 |
| Tiotropium Respimat 10mcg | Change From Baseline in Creatinine | 1.0 micromoles per litre (umol/L) | Standard Deviation 11.1 |
| Placebo | Change From Baseline in Creatinine | 1.7 micromoles per litre (umol/L) | Standard Deviation 10.4 |
Secondary
Change From Baseline in Eosinophils
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Eosinophils | 0 percentage of white blood cell count | Standard Deviation 2 |
| Tiotropium Respimat 10mcg | Change From Baseline in Eosinophils | 0 percentage of white blood cell count | Standard Deviation 2 |
| Placebo | Change From Baseline in Eosinophils | 0 percentage of white blood cell count | Standard Deviation 2 |
Secondary
Change From Baseline in Eosinophils (Absolute)
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Eosinophils (Absolute) | 0.0 10^9/L | Standard Deviation 0.1 |
| Tiotropium Respimat 10mcg | Change From Baseline in Eosinophils (Absolute) | 0.0 10^9/L | Standard Deviation 0.1 |
| Placebo | Change From Baseline in Eosinophils (Absolute) | 0.0 10^9/L | Standard Deviation 0.1 |
Secondary
Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks
FEV1 AUC0-3 represents the Area under Curve over the time interval from 0 to 3 hours after 2, 8, 16, 24, 32, 40 and 48 weeks. The means are adjusted for centre, smoking status at entry and baseline value.
Time frame: 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication
Population: Full Analysis Set - Clinic Spirometry (FAS-PFT)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tiotropium Respimat 5mcg | 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 |
| Tiotropium Respimat 5mcg | 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 |
| Tiotropium Respimat 5mcg | 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 |
| Tiotropium Respimat 5mcg | 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 |
| Tiotropium Respimat 5mcg | 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 |
| Tiotropium Respimat 5mcg | 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 |
| Tiotropium Respimat 5mcg | 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 |
| Tiotropium Respimat 10mcg | Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 24 | 0.241 Litres | Standard Error 0.014 |
| Tiotropium Respimat 10mcg | Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 2 | 0.258 Litres | Standard Error 0.012 |
| Tiotropium Respimat 10mcg | Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 8 | 0.274 Litres | Standard Error 0.013 |
| Tiotropium Respimat 10mcg | Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 16 | 0.248 Litres | Standard Error 0.014 |
| Tiotropium Respimat 10mcg | Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 32 | 0.240 Litres | Standard Error 0.014 |
| Tiotropium Respimat 10mcg | Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 40 | 0.233 Litres | Standard Error 0.014 |
| Tiotropium Respimat 10mcg | Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 48 | 0.226 Litres | Standard Error 0.014 |
| Placebo | Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 32 | 0.019 Litres | Standard Error 0.015 |
| Placebo | Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 8 | 0.041 Litres | Standard Error 0.014 |
| Placebo | Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 48 | -0.008 Litres | Standard Error 0.015 |
| Placebo | Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 40 | 0.003 Litres | Standard Error 0.015 |
| Placebo | Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 24 | 0.026 Litres | Standard Error 0.014 |
| Placebo | Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 16 | 0.024 Litres | Standard Error 0.015 |
| Placebo | Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 2 | 0.045 Litres | Standard Error 0.013 |
Comparison: Analysis for week 48p-value: <0.0001ANCOVA
Comparison: Analysis for week 48p-value: <0.0001ANCOVA
Secondary
Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks
FVC AUC0-3 represents the Area under Curve over the time interval from 0 to 3 hours after 2, 8, 16, 24, 32, 40 and 48 weeks. The means are adjusted for centre, smoking status at entry and baseline value.
Time frame: 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication
Population: Full Analysis Set - Clinic Spirometry (FAS-PFT)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tiotropium Respimat 5mcg | 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 |
| Tiotropium Respimat 5mcg | 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 |
| Tiotropium Respimat 5mcg | 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 |
| Tiotropium Respimat 5mcg | 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 |
| Tiotropium Respimat 5mcg | 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 |
| Tiotropium Respimat 5mcg | 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 |
| Tiotropium Respimat 5mcg | 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 |
| Tiotropium Respimat 10mcg | Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 2 | 0.492 Litres | Standard Error 0.024 |
| Tiotropium Respimat 10mcg | Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 8 | 0.538 Litres | Standard Error 0.026 |
| Tiotropium Respimat 10mcg | Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 16 | 0.487 Litres | Standard Error 0.028 |
| Tiotropium Respimat 10mcg | Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 24 | 0.465 Litres | Standard Error 0.027 |
| Tiotropium Respimat 10mcg | Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 32 | 0.465 Litres | Standard Error 0.028 |
| Tiotropium Respimat 10mcg | Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 40 | 0.453 Litres | Standard Error 0.028 |
| Tiotropium Respimat 10mcg | Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 48 | 0.422 Litres | Standard Error 0.028 |
| Placebo | Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 32 | 0.049 Litres | Standard Error 0.029 |
| Placebo | Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 8 | 0.126 Litres | Standard Error 0.027 |
| Placebo | Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 48 | 0.003 Litres | Standard Error 0.029 |
| Placebo | Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 40 | 0.034 Litres | Standard Error 0.029 |
| Placebo | Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 24 | 0.067 Litres | Standard Error 0.029 |
| Placebo | Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 16 | 0.076 Litres | Standard Error 0.029 |
| Placebo | Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 2 | 0.130 Litres | Standard Error 0.025 |
Comparison: Analysis for week 48p-value: <0.0001ANCOVA
Comparison: Analysis for week 48p-value: <0.0001ANCOVA
Secondary
Change From Baseline in Glucose
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Glucose | -0.09 mmol/L | Standard Deviation 1.82 |
| Tiotropium Respimat 10mcg | Change From Baseline in Glucose | 0.07 mmol/L | Standard Deviation 1.95 |
| Placebo | Change From Baseline in Glucose | 0.17 mmol/L | Standard Deviation 2.21 |
Secondary
Change From Baseline in Haematocrit, Packed Cell Volume (PCV)
Volume of red cells (erythrocytes) in blood, expressed as a fraction (percentage) of the total volume of blood
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Haematocrit, Packed Cell Volume (PCV) | 0 Percentage of erythrocytes | Standard Deviation 4 |
| Tiotropium Respimat 10mcg | Change From Baseline in Haematocrit, Packed Cell Volume (PCV) | -1 Percentage of erythrocytes | Standard Deviation 4 |
| Placebo | Change From Baseline in Haematocrit, Packed Cell Volume (PCV) | 0 Percentage of erythrocytes | Standard Deviation 4 |
Secondary
Change From Baseline in Haemoglobin
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Haemoglobin | -1 grams per litre (g/L) | Standard Deviation 10 |
| Tiotropium Respimat 10mcg | Change From Baseline in Haemoglobin | -2 grams per litre (g/L) | Standard Deviation 11 |
| Placebo | Change From Baseline in Haemoglobin | 1 grams per litre (g/L) | Standard Deviation 12 |
Secondary
Change From Baseline in Heart Rate
Week 40 - baseline
Time frame: 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)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Heart Rate | 0.3 bpm | Standard Deviation 5.4 |
| Tiotropium Respimat 10mcg | Change From Baseline in Heart Rate | 1.2 bpm | Standard Deviation 6.4 |
| Placebo | Change From Baseline in Heart Rate | 0.3 bpm | Standard Deviation 6.6 |
Secondary
Change From Baseline in Heart Rate
Week 40 pre-dose - baseline
Time frame: 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)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Heart Rate | 2.1 beats per minute (bpm) | Standard Deviation 12.4 |
| Tiotropium Respimat 10mcg | Change From Baseline in Heart Rate | 3.6 beats per minute (bpm) | Standard Deviation 10.5 |
| Placebo | Change From Baseline in Heart Rate | 1.8 beats per minute (bpm) | Standard Deviation 9.7 |
Secondary
Change From Baseline in Lactic Dehydrogenase (LDH)
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Lactic Dehydrogenase (LDH) | 4 U/L | Standard Deviation 60 |
| Tiotropium Respimat 10mcg | Change From Baseline in Lactic Dehydrogenase (LDH) | 2 U/L | Standard Deviation 87 |
| Placebo | Change From Baseline in Lactic Dehydrogenase (LDH) | 0 U/L | Standard Deviation 63 |
Secondary
Change From Baseline in Lymphocytes
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Lymphocytes | -1 percentage of white blood cell count | Standard Deviation 4 |
| Tiotropium Respimat 10mcg | Change From Baseline in Lymphocytes | -1 percentage of white blood cell count | Standard Deviation 4 |
| Placebo | Change From Baseline in Lymphocytes | 0 percentage of white blood cell count | Standard Deviation 4 |
Secondary
Change From Baseline in Lymphocytes (Absolute)
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Lymphocytes (Absolute) | 0.0 10^9/L | Standard Deviation 0.6 |
| Tiotropium Respimat 10mcg | Change From Baseline in Lymphocytes (Absolute) | -0.1 10^9/L | Standard Deviation 0.7 |
| Placebo | Change From Baseline in Lymphocytes (Absolute) | 0.1 10^9/L | Standard Deviation 0.6 |
Secondary
Change From Baseline in Monocytes
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Monocytes | 0 percentage of white blood cell count | Standard Deviation 4 |
| Tiotropium Respimat 10mcg | Change From Baseline in Monocytes | 0 percentage of white blood cell count | Standard Deviation 3 |
| Placebo | Change From Baseline in Monocytes | 0 percentage of white blood cell count | Standard Deviation 4 |
Secondary
Change From Baseline in Monocytes (Absolute)
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Monocytes (Absolute) | 0.0 10^9/L | Standard Deviation 0.2 |
| Tiotropium Respimat 10mcg | Change From Baseline in Monocytes (Absolute) | 0.0 10^9/L | Standard Deviation 0.2 |
| Placebo | Change From Baseline in Monocytes (Absolute) | 0.0 10^9/L | Standard Deviation 0.2 |
Secondary
Change From Baseline in Neutrophils
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Neutrophils | 1 percentage of white blood cell count | Standard Deviation 8 |
| Tiotropium Respimat 10mcg | Change From Baseline in Neutrophils | 1 percentage of white blood cell count | Standard Deviation 8 |
| Placebo | Change From Baseline in Neutrophils | 1 percentage of white blood cell count | Standard Deviation 8 |
Secondary
Change From Baseline in Neutrophils (Absolute)
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Neutrophils (Absolute) | 0.2 10^9/L | Standard Deviation 1.5 |
| Tiotropium Respimat 10mcg | Change From Baseline in Neutrophils (Absolute) | 0.1 10^9/L | Standard Deviation 1.6 |
| Placebo | Change From Baseline in Neutrophils (Absolute) | 0.2 10^9/L | Standard Deviation 1.6 |
Secondary
Change From Baseline in Phosphate
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Phosphate | 0.02 mmol/L | Standard Deviation 0.25 |
| Tiotropium Respimat 10mcg | Change From Baseline in Phosphate | 0.00 mmol/L | Standard Deviation 0.23 |
| Placebo | Change From Baseline in Phosphate | 0.01 mmol/L | Standard Deviation 0.23 |
Secondary
Change From Baseline in Platelets
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Platelets | 4 10^9/L | Standard Deviation 30 |
| Tiotropium Respimat 10mcg | Change From Baseline in Platelets | 1 10^9/L | Standard Deviation 31 |
| Placebo | Change From Baseline in Platelets | 7 10^9/L | Standard Deviation 30 |
Secondary
Change From Baseline in PR Interval
Time frame: 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)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in PR Interval | -0.8 milliseconds (msec) | Standard Deviation 20.2 |
| Tiotropium Respimat 10mcg | Change From Baseline in PR Interval | -2.5 milliseconds (msec) | Standard Deviation 15.1 |
| Placebo | Change From Baseline in PR Interval | -0.5 milliseconds (msec) | Standard Deviation 15.3 |
Secondary
Change From Baseline in Protein, Total
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Protein, Total | -1 grams per litre (g/L) | Standard Deviation 5 |
| Tiotropium Respimat 10mcg | Change From Baseline in Protein, Total | -1 grams per litre (g/L) | Standard Deviation 5 |
| Placebo | Change From Baseline in Protein, Total | -1 grams per litre (g/L) | Standard Deviation 5 |
Secondary
Change From Baseline in QRS Interval
Week 40 pre-dose - baseline
Time frame: 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)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in QRS Interval | 0.9 msec | Standard Deviation 9.4 |
| Tiotropium Respimat 10mcg | Change From Baseline in QRS Interval | 1.7 msec | Standard Deviation 12.1 |
| Placebo | Change From Baseline in QRS Interval | -1.1 msec | Standard Deviation 10.3 |
Secondary
Change From Baseline in QT Interval
Week 40 pre-dose - baseline
Time frame: 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)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in QT Interval | -4.6 msec | Standard Deviation 26.5 |
| Tiotropium Respimat 10mcg | Change From Baseline in QT Interval | -3.5 msec | Standard Deviation 25.2 |
| Placebo | Change From Baseline in QT Interval | -3.2 msec | Standard Deviation 22.3 |
Secondary
Change From Baseline in QT Interval (Bazett)
Week 40 pre-dose - baseline
Time frame: 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)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in QT Interval (Bazett) | -0.5 msec | Standard Deviation 29.9 |
| Tiotropium Respimat 10mcg | Change From Baseline in QT Interval (Bazett) | 5.4 msec | Standard Deviation 24 |
| Placebo | Change From Baseline in QT Interval (Bazett) | 2.5 msec | Standard Deviation 23.4 |
Secondary
Change From Baseline in QT Interval (Fridericia)
Week 40 pre-dose - baseline
Time frame: 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)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in QT Interval (Fridericia) | -2.0 msec | Standard Deviation 24.3 |
| Tiotropium Respimat 10mcg | Change From Baseline in QT Interval (Fridericia) | 2.2 msec | Standard Deviation 21.3 |
| Placebo | Change From Baseline in QT Interval (Fridericia) | 0.5 msec | Standard Deviation 19.5 |
Secondary
Change From Baseline in Red Blood Cell Count
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Red Blood Cell Count | 0.0 10^12/Litre (L) | Standard Deviation 0.3 |
| Tiotropium Respimat 10mcg | Change From Baseline in Red Blood Cell Count | -0.1 10^12/Litre (L) | Standard Deviation 0.3 |
| Placebo | Change From Baseline in Red Blood Cell Count | 0.0 10^12/Litre (L) | Standard Deviation 0.3 |
Secondary
Change From Baseline in Supraventricular Premature Beat (SVPB) Total
Week 40 - baseline
Time frame: 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)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Supraventricular Premature Beat (SVPB) Total | -3.4 premature beats per 24 hours | Standard Deviation 94.2 |
| Tiotropium Respimat 10mcg | Change From Baseline in Supraventricular Premature Beat (SVPB) Total | 6.8 premature beats per 24 hours | Standard Deviation 87.4 |
| Placebo | Change From Baseline in Supraventricular Premature Beat (SVPB) Total | 20.9 premature beats per 24 hours | Standard Deviation 125.8 |
Secondary
Change From Baseline in SVPB Pairs
Week 40 - baseline
Time frame: 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)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in SVPB Pairs | -0.4 pairs per 24 hours | Standard Deviation 4 |
| Tiotropium Respimat 10mcg | Change From Baseline in SVPB Pairs | -0.2 pairs per 24 hours | Standard Deviation 2.3 |
| Placebo | Change From Baseline in SVPB Pairs | 2.0 pairs per 24 hours | Standard Deviation 16.4 |
Secondary
Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks
Change From Baseline in Trough Forced Expiratory Volume in 1 second (FEV1) after 2, 8, 16, 24, 32 and 40 weeks. The means are adjusted for centre, smoking status at entry and baseline value.
Time frame: 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication
Population: Full Analysis Set - Clinic Spirometry (FAS-PFT)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks | Week 2 | 0.118 Litres | Standard Error 0.011 |
| Tiotropium Respimat 5mcg | Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks | Week 8 | 0.124 Litres | Standard Error 0.012 |
| Tiotropium Respimat 5mcg | Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks | Week 16 | 0.121 Litres | Standard Error 0.013 |
| Tiotropium Respimat 5mcg | Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks | Week 24 | 0.125 Litres | Standard Error 0.013 |
| Tiotropium Respimat 5mcg | Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks | Week 32 | 0.124 Litres | Standard Error 0.013 |
| Tiotropium Respimat 5mcg | Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks | Week 40 | 0.107 Litres | Standard Error 0.013 |
| Tiotropium Respimat 10mcg | Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks | Week 40 | 0.133 Litres | Standard Error 0.013 |
| Tiotropium Respimat 10mcg | Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks | Week 2 | 0.133 Litres | Standard Error 0.011 |
| Tiotropium Respimat 10mcg | Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks | Week 24 | 0.121 Litres | Standard Error 0.013 |
| Tiotropium Respimat 10mcg | Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks | Week 32 | 0.132 Litres | Standard Error 0.013 |
| Tiotropium Respimat 10mcg | Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks | Week 8 | 0.150 Litres | Standard Error 0.012 |
| Tiotropium Respimat 10mcg | Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks | Week 16 | 0.125 Litres | Standard Error 0.014 |
| Placebo | Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks | Week 8 | -0.004 Litres | Standard Error 0.013 |
| Placebo | Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks | Week 16 | -0.022 Litres | Standard Error 0.014 |
| Placebo | Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks | Week 40 | -0.031 Litres | Standard Error 0.014 |
| Placebo | Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks | Week 24 | -0.009 Litres | Standard Error 0.013 |
| Placebo | Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks | Week 2 | 0.013 Litres | Standard Error 0.012 |
| Placebo | Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks | Week 32 | -0.025 Litres | Standard Error 0.014 |
Secondary
Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks
Change From Baseline in Trough Forced vital capacity (FVC) after 2, 8, 16, 24, 32, 40 and 48 weeks. The means are adjusted for centre, smoking status at entry and baseline value.
Time frame: 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication
Population: Full Analysis Set - Clinic Spirometry (FAS-PFT)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tiotropium Respimat 5mcg | 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 |
| Tiotropium Respimat 5mcg | 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 |
| Tiotropium Respimat 5mcg | 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 |
| Tiotropium Respimat 5mcg | 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 |
| Tiotropium Respimat 5mcg | 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 |
| Tiotropium Respimat 5mcg | 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 |
| Tiotropium Respimat 5mcg | 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 |
| Tiotropium Respimat 10mcg | Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 32 | 0.276 Litres | Standard Error 0.026 |
| Tiotropium Respimat 10mcg | Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 40 | 0.294 Litres | Standard Error 0.027 |
| Tiotropium Respimat 10mcg | Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 48 | 0.253 Litres | Standard Error 0.027 |
| Tiotropium Respimat 10mcg | Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 2 | 0.278 Litres | Standard Error 0.024 |
| Tiotropium Respimat 10mcg | Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 8 | 0.300 Litres | Standard Error 0.024 |
| Tiotropium Respimat 10mcg | Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 16 | 0.267 Litres | Standard Error 0.027 |
| Tiotropium Respimat 10mcg | Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 24 | 0.274 Litres | Standard Error 0.026 |
| Placebo | Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 40 | -0.043 Litres | Standard Error 0.028 |
| Placebo | Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 16 | -0.019 Litres | Standard Error 0.028 |
| Placebo | Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 48 | -0.070 Litres | Standard Error 0.028 |
| Placebo | Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 32 | -0.038 Litres | Standard Error 0.028 |
| Placebo | Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 24 | -0.012 Litres | Standard Error 0.027 |
| Placebo | Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 8 | 0.009 Litres | Standard Error 0.025 |
| Placebo | Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks | Week 2 | 0.025 Litres | Standard Error 0.025 |
Comparison: Analysis for week 48p-value: <0.0001ANCOVA
Comparison: Analysis for week 48p-value: <0.0001ANCOVA
Secondary
Change From Baseline in Urea
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Urea | 0.1 mmol/L | Standard Deviation 2 |
| Tiotropium Respimat 10mcg | Change From Baseline in Urea | 0.0 mmol/L | Standard Deviation 2.3 |
| Placebo | Change From Baseline in Urea | 0.0 mmol/L | Standard Deviation 2.1 |
Secondary
Change From Baseline in Uric Acid
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Uric Acid | 13.55 umol/L | Standard Deviation 78.13 |
| Tiotropium Respimat 10mcg | Change From Baseline in Uric Acid | 1.03 umol/L | Standard Deviation 82.35 |
| Placebo | Change From Baseline in Uric Acid | 7.83 umol/L | Standard Deviation 88.05 |
Secondary
Change From Baseline in Ventricular Premature Beat (VPB) Total
Week 40 - baseline
Time frame: 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)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in Ventricular Premature Beat (VPB) Total | -14.3 premature beats per 24 hours | Standard Deviation 105.9 |
| Tiotropium Respimat 10mcg | Change From Baseline in Ventricular Premature Beat (VPB) Total | 4.6 premature beats per 24 hours | Standard Deviation 68.8 |
| Placebo | Change From Baseline in Ventricular Premature Beat (VPB) Total | -24.1 premature beats per 24 hours | Standard Deviation 182.3 |
Secondary
Change From Baseline in VPB Pairs
Week 40 - baseline
Time frame: 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)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in VPB Pairs | -0.2 pairs per 24 hours | Standard Deviation 1.6 |
| Tiotropium Respimat 10mcg | Change From Baseline in VPB Pairs | -0.1 pairs per 24 hours | Standard Deviation 3.8 |
| Placebo | Change From Baseline in VPB Pairs | -0.9 pairs per 24 hours | Standard Deviation 5.7 |
Secondary
Change From Baseline in VPB Run Events
Week 40 - baseline
Time frame: 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)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in VPB Run Events | 0.0 events per 24 hours | Standard Deviation 0.1 |
| Tiotropium Respimat 10mcg | Change From Baseline in VPB Run Events | 0.0 events per 24 hours | Standard Deviation 0.1 |
| Placebo | Change From Baseline in VPB Run Events | 0.0 events per 24 hours | Standard Deviation 0 |
Secondary
Change From Baseline in White Blood Cell Count
Week 48 - baseline
Time frame: Baseline to Week 48 or at premature discontinuation if before Week 48
Population: Safety Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | Change From Baseline in White Blood Cell Count | 0.1 10^9/Litre (L) | Standard Deviation 1.4 |
| Tiotropium Respimat 10mcg | Change From Baseline in White Blood Cell Count | 0.0 10^9/Litre (L) | Standard Deviation 1.5 |
| Placebo | Change From Baseline in White Blood Cell Count | 0.2 10^9/Litre (L) | Standard Deviation 1.5 |
Secondary
COPD Symptoms Scores
COPD symptoms Scores - wheezing, shortness of breath, coughing and tightness of chest over the treatment period. Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe The means are adjusted for centre, smoking status at entry and baseline value.
Time frame: Week 48
Population: Full Analysis Set - COPD symptoms (FAS-SYM)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tiotropium Respimat 5mcg | COPD Symptoms Scores | Wheezing | 0.67 Points on a scale | Standard Error 0.04 |
| Tiotropium Respimat 5mcg | COPD Symptoms Scores | Shortness of Breath | 1.35 Points on a scale | Standard Error 0.04 |
| Tiotropium Respimat 5mcg | COPD Symptoms Scores | Coughing | 1.05 Points on a scale | Standard Error 0.04 |
| Tiotropium Respimat 5mcg | COPD Symptoms Scores | Tightness of Chest | 0.61 Points on a scale | Standard Error 0.04 |
| Tiotropium Respimat 10mcg | COPD Symptoms Scores | Tightness of Chest | 0.50 Points on a scale | Standard Error 0.04 |
| Tiotropium Respimat 10mcg | COPD Symptoms Scores | Wheezing | 0.65 Points on a scale | Standard Error 0.04 |
| Tiotropium Respimat 10mcg | COPD Symptoms Scores | Coughing | 1.04 Points on a scale | Standard Error 0.04 |
| Tiotropium Respimat 10mcg | COPD Symptoms Scores | Shortness of Breath | 1.31 Points on a scale | Standard Error 0.04 |
| Placebo | COPD Symptoms Scores | Tightness of Chest | 0.78 Points on a scale | Standard Error 0.04 |
| Placebo | COPD Symptoms Scores | Shortness of Breath | 1.51 Points on a scale | Standard Error 0.04 |
| Placebo | COPD Symptoms Scores | Coughing | 1.21 Points on a scale | Standard Error 0.04 |
| Placebo | COPD Symptoms Scores | Wheezing | 0.91 Points on a scale | Standard Error 0.04 |
Secondary
Holter (24-hour Period) - SVPB (Supraventricular Premature Beat) Run Events Change From Baseline in Supraventricular Premature Beat (SVPB) Run Events
Week 40 - baseline
Time frame: 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)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | 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 |
| Tiotropium Respimat 10mcg | Holter (24-hour Period) - SVPB (Supraventricular Premature Beat) Run Events Change From Baseline in Supraventricular Premature Beat (SVPB) Run Events | -0.1 events per 24 hours | Standard Deviation 0.5 |
| Placebo | Holter (24-hour Period) - SVPB (Supraventricular Premature Beat) Run Events Change From Baseline in Supraventricular Premature Beat (SVPB) Run Events | -0.1 events per 24 hours | Standard Deviation 1.6 |
Secondary
Mahler TDI Scores
Mahler Transitional Dyspnoea Index (TDI) scores measured as change in functional impairment, change in magnitude of tasks and change in magnitude of efforts over the treatment period. The means are adjusted for centre, smoking status at entry and baseline value. Worst score = -3, best score = +3
Time frame: Week 48
Population: Full Analysis Set - Transitional Dyspnoea Index (FAS-TDI)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tiotropium Respimat 5mcg | Mahler TDI Scores | Magnitude of Task | 0.650 Points on a scale | Standard Error 0.052 |
| Tiotropium Respimat 5mcg | Mahler TDI Scores | Functional Impairment | 0.606 Points on a scale | Standard Error 0.049 |
| Tiotropium Respimat 5mcg | Mahler TDI Scores | Magnitude of Effort | 0.633 Points on a scale | Standard Error 0.056 |
| Tiotropium Respimat 10mcg | Mahler TDI Scores | Magnitude of Task | 0.673 Points on a scale | Standard Error 0.052 |
| Tiotropium Respimat 10mcg | Mahler TDI Scores | Functional Impairment | 0.679 Points on a scale | Standard Error 0.05 |
| Tiotropium Respimat 10mcg | Mahler TDI Scores | Magnitude of Effort | 0.706 Points on a scale | Standard Error 0.056 |
| Placebo | Mahler TDI Scores | Functional Impairment | 0.255 Points on a scale | Standard Error 0.053 |
| Placebo | Mahler TDI Scores | Magnitude of Effort | 0.240 Points on a scale | Standard Error 0.06 |
| Placebo | Mahler TDI Scores | Magnitude of Task | 0.291 Points on a scale | Standard Error 0.056 |
Secondary
PGE Scores
Physician's Global evaluation (PGE) scores over the treatment period. Scale: 1-2 = Poor, 3-4 = Fair, 5-6 = Good, 7-8 = Excellent The means are adjusted for centre, smoking status at entry and baseline value.
Time frame: Week 48
Population: Full Analysis Set - Physician's Global Evaluation (FAS-PGE)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | PGE Scores | 5.18 Points on a scale | Standard Error 0.06 |
| Tiotropium Respimat 10mcg | PGE Scores | 5.18 Points on a scale | Standard Error 0.06 |
| Placebo | PGE Scores | 4.62 Points on a scale | Standard Error 0.06 |
Secondary
PGR Score
Patient's Global rating (PGR) score over the treatment period. Scale: 1=much better to 7=much worse The means are adjusted for centre, smoking status at entry and baseline value.
Time frame: Week 48
Population: Full Analysis Set - Patient's Global Rating (FAS-PGR)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium Respimat 5mcg | PGR Score | 3.05 Points on a scale | Standard Error 0.07 |
| Tiotropium Respimat 10mcg | PGR Score | 2.86 Points on a scale | Standard Error 0.07 |
| Placebo | PGR Score | 3.52 Points on a scale | Standard Error 0.08 |
Secondary
Saint George's Respiratory Questionnaire (SGRQ) Scores
Saint George's Respiratory Questionnaire (SGRQ) Scores impacts, activities and symptoms. Worst score = 100, best score = 0. The means are adjusted for centre, smoking status at entry and baseline value.
Time frame: Week 48
Population: Full Analysis Set - Saint George's Respiratory Questionnaire (FAS-QOL)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tiotropium Respimat 5mcg | Saint George's Respiratory Questionnaire (SGRQ) Scores | Activities | 56.317 Points on a scale | Standard Error 0.823 |
| Tiotropium Respimat 5mcg | Saint George's Respiratory Questionnaire (SGRQ) Scores | Symptoms | 42.323 Points on a scale | Standard Error 1.064 |
| Tiotropium Respimat 5mcg | Saint George's Respiratory Questionnaire (SGRQ) Scores | Impacts | 29.413 Points on a scale | Standard Error 0.743 |
| Tiotropium Respimat 10mcg | Saint George's Respiratory Questionnaire (SGRQ) Scores | Activities | 55.180 Points on a scale | Standard Error 0.828 |
| Tiotropium Respimat 10mcg | Saint George's Respiratory Questionnaire (SGRQ) Scores | Symptoms | 41.798 Points on a scale | Standard Error 1.07 |
| Tiotropium Respimat 10mcg | Saint George's Respiratory Questionnaire (SGRQ) Scores | Impacts | 28.054 Points on a scale | Standard Error 0.747 |
| Placebo | Saint George's Respiratory Questionnaire (SGRQ) Scores | Symptoms | 47.835 Points on a scale | Standard Error 1.146 |
| Placebo | Saint George's Respiratory Questionnaire (SGRQ) Scores | Impacts | 32.466 Points on a scale | Standard Error 0.801 |
| Placebo | Saint George's Respiratory Questionnaire (SGRQ) Scores | Activities | 58.629 Points on a scale | Standard Error 0.887 |
Secondary
Weekly Mean Evening PEFRs
Weekly mean evening peak expiratory flow rates (PEFRs). The means are adjusted for centre, smoking status at entry, and baseline value.
Time frame: Weeks 2, 8, 16, 24, 32, 40, 48
Population: Full Analysis Set - Diary (FAS-DRY)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tiotropium Respimat 5mcg | Weekly Mean Evening PEFRs | Week 8 | 274.5 Litres/minute | Standard Error 2.7 |
| Tiotropium Respimat 5mcg | Weekly Mean Evening PEFRs | Week 32 | 281.8 Litres/minute | Standard Error 3.4 |
| Tiotropium Respimat 5mcg | Weekly Mean Evening PEFRs | Week 24 | 280.0 Litres/minute | Standard Error 3.3 |
| Tiotropium Respimat 5mcg | Weekly Mean Evening PEFRs | Week 2 | 270.6 Litres/minute | Standard Error 2 |
| Tiotropium Respimat 5mcg | Weekly Mean Evening PEFRs | Week 48 | 282.5 Litres/minute | Standard Error 3.9 |
| Tiotropium Respimat 5mcg | Weekly Mean Evening PEFRs | Week 40 | 283.1 Litres/minute | Standard Error 3.6 |
| Tiotropium Respimat 5mcg | Weekly Mean Evening PEFRs | Week 16 | 278.0 Litres/minute | Standard Error 3.1 |
| Tiotropium Respimat 10mcg | Weekly Mean Evening PEFRs | Week 24 | 287.0 Litres/minute | Standard Error 3.3 |
| Tiotropium Respimat 10mcg | Weekly Mean Evening PEFRs | Week 2 | 279.2 Litres/minute | Standard Error 2 |
| Tiotropium Respimat 10mcg | Weekly Mean Evening PEFRs | Week 8 | 282.1 Litres/minute | Standard Error 2.7 |
| Tiotropium Respimat 10mcg | Weekly Mean Evening PEFRs | Week 16 | 284.1 Litres/minute | Standard Error 3.1 |
| Tiotropium Respimat 10mcg | Weekly Mean Evening PEFRs | Week 32 | 290.6 Litres/minute | Standard Error 3.4 |
| Tiotropium Respimat 10mcg | Weekly Mean Evening PEFRs | Week 40 | 292.2 Litres/minute | Standard Error 3.6 |
| Tiotropium Respimat 10mcg | Weekly Mean Evening PEFRs | Week 48 | 292.5 Litres/minute | Standard Error 3.9 |
| Placebo | Weekly Mean Evening PEFRs | Week 32 | 255.0 Litres/minute | Standard Error 3.6 |
| Placebo | Weekly Mean Evening PEFRs | Week 8 | 253.4 Litres/minute | Standard Error 2.9 |
| Placebo | Weekly Mean Evening PEFRs | Week 48 | 257.0 Litres/minute | Standard Error 4.1 |
| Placebo | Weekly Mean Evening PEFRs | Week 40 | 257.1 Litres/minute | Standard Error 3.7 |
| Placebo | Weekly Mean Evening PEFRs | Week 24 | 254.7 Litres/minute | Standard Error 3.4 |
| Placebo | Weekly Mean Evening PEFRs | Week 16 | 252.7 Litres/minute | Standard Error 3.2 |
| Placebo | Weekly Mean Evening PEFRs | Week 2 | 249.3 Litres/minute | Standard Error 2.1 |
Comparison: Analysis for week 48p-value: <0.0001ANCOVA
Comparison: Analysis for week 48p-value: <0.0001ANCOVA
Secondary
Weekly Mean Morning Pre-dose PEFRs
Weekly mean morning pre-dose peak expiratory flow rates (PEFRs). The means are adjusted for centre, smoking status at entry, and baseline value.
Time frame: Weeks 2, 8, 16, 24, 32, 40, 48
Population: Full Analysis Set - Diary (FAS-DRY)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tiotropium Respimat 5mcg | Weekly Mean Morning Pre-dose PEFRs | Week 8 | 259.0 Litres/minute | Standard Error 2.5 |
| Tiotropium Respimat 5mcg | Weekly Mean Morning Pre-dose PEFRs | Week 32 | 267.2 Litres/minute | Standard Error 3.4 |
| Tiotropium Respimat 5mcg | Weekly Mean Morning Pre-dose PEFRs | Week 24 | 265.7 Litres/minute | Standard Error 3.2 |
| Tiotropium Respimat 5mcg | Weekly Mean Morning Pre-dose PEFRs | Week 2 | 255.4 Litres/minute | Standard Error 1.8 |
| Tiotropium Respimat 5mcg | Weekly Mean Morning Pre-dose PEFRs | Week 48 | 268.5 Litres/minute | Standard Error 3.6 |
| Tiotropium Respimat 5mcg | Weekly Mean Morning Pre-dose PEFRs | Week 40 | 267.0 Litres/minute | Standard Error 3.4 |
| Tiotropium Respimat 5mcg | Weekly Mean Morning Pre-dose PEFRs | Week 16 | 262.7 Litres/minute | Standard Error 3 |
| Tiotropium Respimat 10mcg | Weekly Mean Morning Pre-dose PEFRs | Week 24 | 270.1 Litres/minute | Standard Error 3.2 |
| Tiotropium Respimat 10mcg | Weekly Mean Morning Pre-dose PEFRs | Week 2 | 261.5 Litres/minute | Standard Error 1.8 |
| Tiotropium Respimat 10mcg | Weekly Mean Morning Pre-dose PEFRs | Week 8 | 265.6 Litres/minute | Standard Error 2.5 |
| Tiotropium Respimat 10mcg | Weekly Mean Morning Pre-dose PEFRs | Week 16 | 269.0 Litres/minute | Standard Error 3 |
| Tiotropium Respimat 10mcg | Weekly Mean Morning Pre-dose PEFRs | Week 32 | 275.1 Litres/minute | Standard Error 3.4 |
| Tiotropium Respimat 10mcg | Weekly Mean Morning Pre-dose PEFRs | Week 40 | 276.7 Litres/minute | Standard Error 3.4 |
| Tiotropium Respimat 10mcg | Weekly Mean Morning Pre-dose PEFRs | Week 48 | 279.0 Litres/minute | Standard Error 3.6 |
| Placebo | Weekly Mean Morning Pre-dose PEFRs | Week 32 | 244.7 Litres/minute | Standard Error 3.6 |
| Placebo | Weekly Mean Morning Pre-dose PEFRs | Week 8 | 241.8 Litres/minute | Standard Error 2.7 |
| Placebo | Weekly Mean Morning Pre-dose PEFRs | Week 48 | 245.9 Litres/minute | Standard Error 3.8 |
| Placebo | Weekly Mean Morning Pre-dose PEFRs | Week 40 | 247.4 Litres/minute | Standard Error 3.6 |
| Placebo | Weekly Mean Morning Pre-dose PEFRs | Week 24 | 244.3 Litres/minute | Standard Error 3.3 |
| Placebo | Weekly Mean Morning Pre-dose PEFRs | Week 16 | 241.1 Litres/minute | Standard Error 3.1 |
| Placebo | Weekly Mean Morning Pre-dose PEFRs | Week 2 | 235.4 Litres/minute | Standard Error 1.9 |
Comparison: Analysis for week 48p-value: <0.0001ANCOVA
Comparison: Analysis for week 48p-value: <0.0001ANCOVA
Secondary
Weekly Mean Number of Puffs of Rescue Medication Per Day
Weekly mean number of puffs of rescue medication used per day as required (PRN salbutamol). The means are adjusted for centre, smoking status at entry, and baseline value.
Time frame: Weeks 2, 8, 16, 24, 32, 40, 48
Population: Full Analysis Set - Diary (FAS-DRY)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tiotropium Respimat 5mcg | Weekly Mean Number of Puffs of Rescue Medication Per Day | Week 2 | 1.9 Puffs | Standard Error 0.1 |
| Tiotropium Respimat 5mcg | Weekly Mean Number of Puffs of Rescue Medication Per Day | Week 32 | 2.2 Puffs | Standard Error 0.1 |
| Tiotropium Respimat 5mcg | Weekly Mean Number of Puffs of Rescue Medication Per Day | Week 24 | 2.1 Puffs | Standard Error 0.1 |
| Tiotropium Respimat 5mcg | Weekly Mean Number of Puffs of Rescue Medication Per Day | Week 8 | 2.0 Puffs | Standard Error 0.1 |
| Tiotropium Respimat 5mcg | Weekly Mean Number of Puffs of Rescue Medication Per Day | Week 48 | 2.3 Puffs | Standard Error 0.1 |
| Tiotropium Respimat 5mcg | Weekly Mean Number of Puffs of Rescue Medication Per Day | Week 40 | 2.2 Puffs | Standard Error 0.1 |
| Tiotropium Respimat 5mcg | Weekly Mean Number of Puffs of Rescue Medication Per Day | Week 16 | 2.1 Puffs | Standard Error 0.1 |
| Tiotropium Respimat 10mcg | Weekly Mean Number of Puffs of Rescue Medication Per Day | Week 2 | 1.9 Puffs | Standard Error 0.1 |
| Tiotropium Respimat 10mcg | Weekly Mean Number of Puffs of Rescue Medication Per Day | Week 8 | 2.0 Puffs | Standard Error 0.1 |
| Tiotropium Respimat 10mcg | Weekly Mean Number of Puffs of Rescue Medication Per Day | Week 16 | 2.0 Puffs | Standard Error 0.1 |
| Tiotropium Respimat 10mcg | Weekly Mean Number of Puffs of Rescue Medication Per Day | Week 24 | 2.2 Puffs | Standard Error 0.1 |
| Tiotropium Respimat 10mcg | Weekly Mean Number of Puffs of Rescue Medication Per Day | Week 32 | 2.2 Puffs | Standard Error 0.1 |
| Tiotropium Respimat 10mcg | Weekly Mean Number of Puffs of Rescue Medication Per Day | Week 40 | 2.2 Puffs | Standard Error 0.1 |
| Tiotropium Respimat 10mcg | Weekly Mean Number of Puffs of Rescue Medication Per Day | Week 48 | 2.2 Puffs | Standard Error 0.1 |
| Placebo | Weekly Mean Number of Puffs of Rescue Medication Per Day | Week 32 | 3.0 Puffs | Standard Error 0.1 |
| Placebo | Weekly Mean Number of Puffs of Rescue Medication Per Day | Week 8 | 2.7 Puffs | Standard Error 0.1 |
| Placebo | Weekly Mean Number of Puffs of Rescue Medication Per Day | Week 48 | 3.1 Puffs | Standard Error 0.1 |
| Placebo | Weekly Mean Number of Puffs of Rescue Medication Per Day | Week 40 | 3.0 Puffs | Standard Error 0.1 |
| Placebo | Weekly Mean Number of Puffs of Rescue Medication Per Day | Week 24 | 3.0 Puffs | Standard Error 0.1 |
| Placebo | Weekly Mean Number of Puffs of Rescue Medication Per Day | Week 16 | 2.8 Puffs | Standard Error 0.1 |
| Placebo | Weekly Mean Number of Puffs of Rescue Medication Per Day | Week 2 | 2.7 Puffs | Standard Error 0.1 |
Comparison: Analysis for week 48p-value: <0.0001ANCOVA
Comparison: Analysis for week 48p-value: <0.0001ANCOVA