A Trial Comparing Treatment With Tiotropium Inhalation Capsules to Combivent Inhalation Aerosol in COPD Patients.

Study Overview
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Brief Summary
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The objective of this study is to evaluate the efficacy and safety of 12 weeks treatment with tiotropium HandiHaler 18 micrograms (mcg) daily compared to Combivent Metered Dose Inhaler (MDI) Chlorofluorocarbon Inhalation Aerosol 2 actuations four times a day in Chronic Obstructive Pulmonary Disease (COPD) patients currently prescribed Combivent® MDI.

Official Title
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A Randomized, Double-blind, Parallel Group Trial Comparing 12 Weeks Treatment With Tiotropium 18 mcg Daily to Combivent MDI 2 Actuations Qid in COPD Patients Previously Prescribed Combivent MDI

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: tiotropium
* Drug: Combivent (Ipratropium/Albuterol)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) Age: greater than or equal to 40 years Current or ex-smoker with a >= 10 pack-year smoking history Use of Combivent® Metered Dose Inhaler (MDI)for >= 1 month prior to Visit 1 Spirometric criteria (determined at study visits): Post-bronchodilator Forced Expiratory Volume in one second (FEV1) <= 70% (Visit 1) Pre-bronchodilator FEV1 <= 65% of predicted and FEV1/Forced Vital Capacity (FVC) <= 70% (Visit 2) Exclusion Criteria: Clinical history of asthma History of thoracotomy with pulmonary resection History of Cystic Fibrosis, alpha 1 antitrypsin deficiency or interstitial lung disease Daytime use of oxygen therapy for > 1 hour per day or if unable to abstain fr om using oxygen during Pulmonary Function Tests Any respiratory tract infection or COPD exacerbation in 6 weeks prior to Visit 1 Recent history 6 months or less of Myocardial Infarction Unstable or life-threatening cardiac arrhythmias Hospitalization for Congestive Heart Failure during past year Malignancy for which patient is receiving chemo or radiation therapy Pregnant or nursing women Known hypersensitivity to ipratropium or carrier substances, including related food products such as soybean, peanuts, or lactose Use of SPIRIVA® 3 months prior to Visit 1 Symptomatic of prostatic hypertrophy or bladder neck obstruction Known narrow- angle glaucoma Participating in a pulmonary rehab program within 4 weeks of Visit 1

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
Intervention Model: Parallel Assignment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: tiotropium|nan|
|Drug: Combivent (Ipratropium/Albuterol)|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Trough FEV1 (Forced Expiratory Volume in 1 Second) at 12 Weeks | Trough FEV1 is measured 10 minutes before drug administration | Baseline and 12 Weeks | 
| Change From Baseline in Average Hourly FEV1 AUC0-6 (Area Under the Curve From Zero to Six Hours) at 12 Weeks | Average hourly FEV1 AUC0-6 minus baseline FEV1 | Baseline and 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Trough FEV1 (Forced Expiratory Volume in 1 Second) at 6 Weeks | Trough FEV1 is measured 10 minutes before drug administration | Baseline and 6 Weeks | 
| Change From Baseline in Average Hourly FEV1 AUC0-6 (Area Under the Curve From Zero to Six Hours) on Day 1 | Average hourly FEV1 AUC0-6 minus baseline FEV1 | Day 1 (after first dose) | 
| Change From Baseline in Average Hourly FEV1 AUC0-6 (Area Under the Curve From Zero to Six Hours) at Week 6 | Average hourly FEV1 AUC0-6 minus baseline FEV1 | Baseline and week 6 | 
| Change From Baseline in Peak FEV1 (Forced Expiratory Volume in 1 Second) on Day 1 | Peak FEV1 is defined as the maximum FEV1 observed in the first three hours after dose of study medication | Day 1 | 
| Change From Baseline in Peak FEV1 (Forced Expiratory Volume in 1 Second) at Week 6 | Peak FEV1 is defined as the maximum FEV1 observed in the first three hours after dose of study medication | Baseline and 6 weeks | 
| Change From Baseline in Peak FEV1 (Forced Expiratory Volume in 1 Second) at Week 12 | Peak FEV1 is defined as the maximum FEV1 observed in the first three hours after dose of study medication | Baseline and 12 weeks | 
| Change From Baseline in Trough FVC (Forced Vital Capacity) at 12 Weeks | Trough FVC is measured 10 minutes before drug administration | Baseline and 12 weeks | 
| Change From Baseline in Average Hourly FVC AUC0-6 (Area Under the Curve From Zero to Six Hours) at 12 Weeks | Average hourly FVC AUC0-6 minus baseline FVC | Baseline and 12 Weeks | 
| Change From Baseline in Trough FVC (Forced Vital Capacity) at 6 Weeks | Trough FVC is measured 10 minutes before drug administration | Baseline and 6 weeks | 
| Change From Baseline in Average Hourly FVC AUC0-6 (Area Under the Curve From Zero to Six Hours) on Day 1 | Average hourly FVC AUC0-6 minus baseline FVC | Day 1 | 
| Change From Baseline in Average Hourly FVC AUC0-6 (Area Under the Curve From Zero to Six Hours) at 6 Weeks | Average hourly FVC AUC0-6 minus baseline FVC | Baseline and 6 Weeks | 
| Change From Baseline in Peak FVC (Forced Vital Capacity) on Day 1 | Peak FVC is defined as the maximum FVC observed in the first three hours after dose of study medication | Day 1 | 
| Change From Baseline in Peak FVC (Forced Vital Capacity) at Week 6 | Peak FVC is defined as the maximum FVC observed in the first three hours after dose of study medication | baseline and 6 Weeks (after first dose) | 
| Change From Baseline in Peak FVC (Forced Vital Capacity) at Week 12 | Peak FVC is defined as the maximum FVC observed in the first three hours after dose of study medication | Baseline and 12 Weeks | 
| FEV1 at 15 Minutes on Day 1 |  | 15 minutes | 
| FEV1 at 30 Minutes on Day 1 |  | 30 minutes | 
| FEV1 at 1 Hour on Day 1 |  | 1 hour | 
| FEV1 at 2 Hours on Day 1 |  | 2 hour | 
| FEV1 at 3 Hours on Day 1 |  | 3 hour | 
| FEV1 at 4 Hours on Day 1 |  | 4 hour | 
| FEV1 at 6 Hours on Day 1 |  | 6 hours | 
| FEV1 at -10 Minutes at Week 6 |  | 10 minutes before dosing | 
| FEV1 at 15 Minutes at Week 6 |  | 15 minutes | 
| FEV1 at 30 Minutes at Week 6 |  | 30 minutes | 
| FEV1 at 1 Hour at Week 6 |  | 1 hour | 
| FEV1 at 2 Hours at Week 6 |  | 2 hour | 
| FEV1 at 3 Hours at Week 6 |  | 3 hour | 
| FEV1 at 4 Hours at Week 6 |  | 4 hour | 
| FEV1 at 6 Hours at Week 6 |  | 6 hour | 
| FEV1 at -10 Minutes at Week 12 |  | 10 minutes before dosing | 
| FEV1 at 15 Minutes at Week 12 |  | 15 minutes | 
| FEV1 at 30 Minutes at Week 12 |  | 30 minutes | 
| FEV1 at 1 Hour at Week 12 |  | 1 hour | 
| FEV1 at 2 Hours at Week 12 |  | 2 hour | 
| FEV1 at 3 Hours at Week 12 |  | 3 hour | 
| FEV1 at 4 Hours at Week 12 |  | 4 hour | 
| FEV1 at 6 Hours at Week 12 |  | 6 hour | 
| FVC at 15 Minutes on Day 1 |  | 15 minutes | 
| FVC at 30 Minutes on Day 1 |  | 30 minutes | 
| FVC at 1 Hour on Day 1 |  | 1 hour | 
| FVC at 2 Hours on Day 1 |  | 2 hour | 
| FVC at 3 Hours on Day 1 |  | 3 hour | 
| FVC at 4 Hours on Day 1 |  | 4 hour | 
| FVC at 6 Hours on Day 1 |  | 6 hour | 
| FVC at -10 Minutes at Week 6 |  | 10 minutes before dosing | 
| FVC at 15 Minutes at Week 6 |  | 15 minutes | 
| FVC at 30 Minutes at Week 6 |  | 30 minutes | 
| FVC at 1 Hour at Week 6 |  | 1 hour | 
| FVC at 2 Hours at Week 6 |  | 2 hour | 
| FVC at 3 Hours at Week 6 |  | 3 hour | 
| FVC at 4 Hours at Week 6 |  | 4 hour | 
| FVC at 6 Hours at Week 6 |  | 6 hour | 
| FVC at -10 Minutes at Week 12 |  | 10 minutes before dosing | 
| FVC at 15 Minutes at Week 12 |  | 15 minutes | 
| FVC at 30 Minutes at Week 12 |  | 30 minutes | 
| FVC at 1 Hour at Week 12 |  | 1 hour | 
| FVC at 2 Hours at Week 12 |  | 2 hour | 
| FVC at 3 Hours at Week 12 |  | 3 hour | 
| FVC at 4 Hours at Week 12 |  | 4 hour | 
| FVC at 6 Hours at Week 12 |  | 6 hour | 
| Day Time Albuterol Use During Week 1 | Puffs of rescue albuterol used during the day in week 1 | Week 1 | 
| Day Time Albuterol Use During Week 2 | Puffs of rescue albuterol used during the day in week 2 | Week 2 | 
| Day Time Albuterol Use During Week 3 | Puffs of rescue albuterol used during the day in week 3 | Week 3 | 
| Day Time Albuterol Use During Week 4 | Puffs of rescue albuterol used during the day in week 4 | Week 4 | 
| Day Time Albuterol Use During Week 5 | Puffs of rescue albuterol used during the day in week 5 | Week 5 | 
| Day Time Albuterol Use During Week 6 | Puffs of rescue albuterol used during the day in week 6 | Week 6 | 
| Day Time Albuterol Use During Week 7 | Puffs of rescue albuterol used during the day in week 7 | Week 7 | 
| Day Time Albuterol Use During Week 8 | Puffs of rescue albuterol used during the day in week 8 | Week 8 | 
| Day Time Albuterol Use During Week 9 | Puffs of rescue albuterol used during the day in week 9 | Week 9 | 
| Day Time Albuterol Use During Week 10 | Puffs of rescue albuterol used during the day in week 10 | Week 10 | 
| Day Time Albuterol Use During Week 11 | Puffs of rescue albuterol used during the day in week 11 | Week 11 | 
| Day Time Albuterol Use During Week 12 | Puffs of rescue albuterol used during the day in week 12 | Week 12 | 
| Night Time Albuterol Use During Week 1 |  | Week 1 | 
| Night Time Albuterol Use During Week 2 | Puffs of rescue albuterol used during the night in week 2 | Week 2 | 
| Night Time Albuterol Use During Week 3 | Puffs of rescue albuterol used during the night in week 3 | Week 3 | 
| Night Time Albuterol Use During Week 4 | Puffs of rescue albuterol used during the night in week 4 | Week 4 | 
| Night Time Albuterol Use During Week 5 | Puffs of rescue albuterol used during the night in week 5 | Week 5 | 
| Night Time Albuterol Use During Week 6 | Puffs of rescue albuterol used during the night in week 6 | Week 6 | 
| Night Time Albuterol Use During Week 7 | Puffs of rescue albuterol used during the night in week 7 | Week 7 | 
| Night Time Albuterol Use During Week 8 | Puffs of rescue albuterol used during the night in week 8 | Week 8 | 
| Night Time Albuterol Use During Week 9 | Puffs of rescue albuterol used during the night in week 9 | Week 9 | 
| Night Time Albuterol Use During Week 10 | Puffs of rescue albuterol used during the night in week 10 | Week 10 | 
| Night Time Albuterol Use During Week 11 | Puffs of rescue albuterol used during the night in week 11 | Week 11 | 
| Night Time Albuterol Use During Week 12 | Puffs of rescue albuterol used during the night in week 12 | Week 12 | 
| Morning Peak Expiratory Flow Rate (PEFR) at Week 1 |  | Week 1 | 
| Morning PEFR at Week 2 | Weekly means for morning PEFR | Week 2 | 
| Morning PEFR at Week 3 | Weekly means for morning PEFR | Week 3 | 
| Morning PEFR at Week 4 | Weekly means for morning PEFR | Week 4 | 
| Morning PEFR at Week 5 | Weekly means for morning PEFR | Week 5 | 
| Morning PEFR at Week 6 | Weekly means for morning PEFR | Week 6 | 
| Morning PEFR at Week 7 | Weekly means for morning PEFR | Week 7 | 
| Morning PEFR at Week 8 | Weekly means for morning PEFR | Week 8 | 
| Morning PEFR at Week 9 | Weekly means for morning PEFR | Week 9 | 
| Morning PEFR at Week 10 | Weekly means for morning PEFR | Week 10 | 
| Morning PEFR at Week 11 | Weekly means for morning PEFR | Week 11 | 
| Morning PEFR at Week 12 | Weekly means for morning PEFR | Week 12 | 
| Evening PEFR at Week 1 | Weekly means for evening PEFR | Week 1 | 
| Evening PEFR at Week 2 | Weekly means for evening PEFR | Week 2 | 
| Evening PEFR at Week 3 | Weekly means for evening PEFR | Week 3 | 
| Evening PEFR at Week 4 | Weekly means for evening PEFR | Week 4 | 
| Evening PEFR at Week 5 | Weekly means for evening PEFR | Week 5 | 
| Evening PEFR at Week 6 | Weekly means for evening PEFR | Week 6 | 
| Evening PEFR at Week 7 | Weekly means for evening PEFR | Week 7 | 
| Evening PEFR at Week 8 | Weekly means for evening PEFR | Week 8 | 
| Evening PEFR at Week 9 | Weekly means for evening PEFR | Week 9 | 
| Evening PEFR at Week 10 | Weekly means for evening PEFR | Week 10 | 
| Evening PEFR at Week 11 | Weekly means for evening PEFR | Week 11 | 
| Evening PEFR at Week 12 | Weekly means for evening PEFR | Week 12 | 
| Patient Global Evaluation | The Patient Global Evaluation reflected the patient's opinion of their overall condition with respect to chronic obstructive pulmonary disease (COPD). The scale responses were: Poor (1,2). Fair (3,4), Good (5,6) and Excellent (7,8) | Week 6 | 
| Patient Global Evaluation | The Patient Global Evaluation reflected the patient's opinion of their overall condition with respect to COPD. The scale responses were: Poor (1,2). Fair (3,4), Good (5,6) and Excellent (7,8). | Week 12 | 
| Physician Global Evaluation | The Physician Global Evaluation reflected the physician's opinion of the patients overall condition with respect to COPD. The scale responses were: Poor (1,2). Fair (3,4), Good (5,6) and Excellent (7,8). | Week 6 | 
| Physician Global Evaluation | The Physician Global Evaluation reflected the physician's opinion of the patients overall condition with respect to COPD. The scale responses were: Poor (1,2). Fair (3,4), Good (5,6) and Excellent (7,8). | Week 12 |