Tiotropium / Respimat One-Year Study

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

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

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Tiotropium Inhalation Solution
* Other: Placebo


Participation Criteria
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Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Tiotropium Respimat 5mcg (Tio R5)<br> | Drug: Tiotropium Inhalation Solution<br> <br> |
| Other: Tiotropium Respimat 10mcg (Tio R10)<br> | Drug: Tiotropium Inhalation Solution<br> <br> |
| Other: Placebo<br> | Other: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Heart Rate | Week 40 pre-dose - baseline | Baseline to Week 40 pre-dose | 
| Change From Baseline in PR Interval |  | Baseline to Week 40 pre-dose | 
| Change From Baseline in QRS Interval | Week 40 pre-dose - baseline | Baseline to Week 40 pre-dose | 
| Change From Baseline in QT Interval | Week 40 pre-dose - baseline | Baseline to Week 40 pre-dose | 
| Change From Baseline in QT Interval (Bazett) | Week 40 pre-dose - baseline | Baseline to Week 40 pre-dose | 
| Change From Baseline in QT Interval (Fridericia) | Week 40 pre-dose - baseline | Baseline to Week 40 pre-dose | 
| Change From Baseline in Heart Rate | Week 40 - baseline | Baseline to Week 40 | 
| Change From Baseline in Supraventricular Premature Beat (SVPB) Total | Week 40 - baseline | Baseline to Week 40 | 
| Holter (24-hour Period) - SVPB (Supraventricular Premature Beat) Run Events Change From Baseline in Supraventricular Premature Beat (SVPB) Run Events | Week 40 - baseline | Baseline to Week 40 | 
| Change From Baseline in SVPB Pairs | Week 40 - baseline | Baseline to Week 40 | 
| Change From Baseline in Ventricular Premature Beat (VPB) Total | Week 40 - baseline | Baseline to Week 40 | 
| Change From Baseline in VPB Run Events | Week 40 - baseline | Baseline to Week 40 | 
| Change From Baseline in VPB Pairs | Week 40 - baseline | Baseline to Week 40 | 
| 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 | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Haemoglobin | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Red Blood Cell Count | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in White Blood Cell Count | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Platelets | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Neutrophils | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Eosinophils | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Basophils | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Lymphocytes | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Monocytes | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Neutrophils (Absolute) | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Lymphocytes (Absolute) | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Eosinophils (Absolute) | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Basophils (Absolute) | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Monocytes (Absolute) | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Calcium | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Phosphate | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Aspartate Transaminase (AST)/Glutamic-Oxaloacetic Transaminase (GOT), Serum GOT (SGOT) | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Alanine Transaminase (ALT)/Glutamic Pyruvic Transaminase (GPT), Serum GPT (SGPT) | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Alkaline Phosphatase | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Lactic Dehydrogenase (LDH) | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Glucose | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Urea | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Blood Urea Nitrogen | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Creatinine | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Bilirubin, Total | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Uric Acid | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Protein, Total | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| Change From Baseline in Albumin | Week 48 - baseline | Baseline to Week 48 or at premature discontinuation if before Week 48 | 
| 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. | 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 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. | 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 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. | 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 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. | 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication | 
| 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. | Weeks 2, 8, 16, 24, 32, 40, 48 | 
| 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. | Weeks 2, 8, 16, 24, 32, 40, 48 | 
| 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. | Weeks 2, 8, 16, 24, 32, 40, 48 | 
| 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 | Week 48 | 
| 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. | Week 48 | 
| 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. | Week 48 | 
| 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. | Week 48 | 
| 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. | Week 48 |