Tiotropium/Salmeterol Inhalation Powder in COPD

Study Overview
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Brief Summary
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The primary objectives of this study are to assess bronchodilator efficacy as determined by FEV1, the effect on dyspnoea as determined by the BDI/TDI, the effect on health status as determined bt the SGRQ and the effect on COPD exacerbations

Official Title
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1-yr Study Comparing TioSal Combo Regimens Versus Single Agent Therapies (Spiriva HandiHaler and Salmeterol PE Capsule)

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Tiotropium/Salmeterol
* Drug: Tiotropium/Salmeterol QD + Salmeterol
* Drug: Placebo
* Drug: Salmeterol
* Drug: Tiotropium


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Main: Diagnosis of COPD Post-bronchodilator FEV1<80% predicted and FEV1/FVC<70% predicted Exclusion criteria: Main: Significant other diseases then COPD Recent MI Any unstable or life-threatening cardiac arrythmia requiring intervention or change in drug therapy during the past year Hospitalisation for cardiac failure during the past year History of asthma

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 |
| --- | --- |
| Experimental: Tiotropium/Salmeterol QD<br>Tiotropium/Salmeterol Inhalation Powder, Hard Polyethylene Capsule | Drug: Tiotropium/Salmeterol<br>* Tiotropium/Salmeterol Inhalation Powder, Hard Polyethylene Capsule<br>|
| Active Comparator: Tiotropium QD<br>Tiotropium Inhalation Powder, hard gelatine capsule (Spiriva®) | Drug: Tiotropium<br>* Tiotropium Inhalation Powder, hard gelatine capsule (Spiriva®)<br>|
| Active Comparator: Salmeterol BID<br>Salmeterol Inhalation Powder, hard PE capsule | Drug: Salmeterol<br>* Salmeterol Inhalation Powder, hard PE capsule<br>|
| Active Comparator: Tiotropium/Salmeterol QD + Salmeterol<br>Tiotropium/Salmeterol Inhalation Powder, Hard Polyethylene Capsule, plus Salmeterol Inhalation Powder, hard PE capsule | Drug: Tiotropium/Salmeterol QD + Salmeterol<br>* Tiotropium/Salmeterol Inhalation Powder, Hard Polyethylene Capsule, plus Salmeterol Inhalation Powder, hard PE capsule<br>|
| Placebo Comparator: Placebo<br>Placebo Inhalation Powder, hard PE capsule / hard gelatine capsule | Drug: Placebo<br>* Placebo Inhalation Powder, hard PE capsule / hard gelatine capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough FEV1 response |  | 12 Weeks, 24 Weeks and 48 Weeks | 
| FEV1AUC 0 8hr response |  | 12 Weeks, 24 Weeks and 48 Weeks | 
| Mahler TDI focal score |  | 12 Weeks, 24 Weeks and 48 Weeks | 
| SGRQ total score |  | 12 Weeks, 24 Weeks and 48 Weeks | 
| Time to first moderate to severe COPD exacerbation |  | 12 Weeks, 24 Weeks and 48 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough FEV1 response |  | 4, 36 and 48 weeks | 
| FEV1 AUC0-8h response |  | 4, 36 and 48 weeks | 
| Peak FEV1 response |  | 12, 24, 36 and 48 weeks | 
| Use of rescue medication (weekly mean number of puffs of as-needed salbutamol/albuterol per day, daytime and night-time) |  | 24 hours | 
| Weekly mean number of COPD related night time awakenings |  | 1 week | 
| FVC (forced vital capacity) AUC0-8h and trough FVC response |  | 48 weeks | 
| Individual FEV1, FVC and PEF measurements |  | 48 weeks | 
| Weekly mean morning pre-dose and evening pre-dose PEFs (peak expiratory flow) and FEV1 (recorded by AM2+); PEFs determined by spirometry ] |  | 48 weeks | 
| Mahler TDI focal score |  | 4, 36 and 48 weeks | 
| Mahler Dyspnoea Indices (Functional Impairment, Magnitude of Task and Magnitude of Effort) |  | 4, 12, 24, 36 and 48 weeks | 
| SGRQ total score, and the impact, activity and symptoms domain scores from the SGRQ |  | 4, 12, 36 and 48 weeks | 
| All adverse events |  | 48 weeks | 
| Vital signs: pulse rate and blood pressure |  | Baseline and 4 weeks | 
| Routine blood chemistry, haematology and urinalysis |  | Baseline and 48 weeks | 
| Vital status of randomised patients |  | 48 weeks | 
| Number of days in hospital (including ambulance transportation |  | 48 weeks | 
| Number of unscheduled health care provider visits |  | 48 weeks | 
| Number of visits in emergency room (including ambulance transportation) |  | 48 weeks | 
| Number of days in intensive care unit |  | 48 weeks | 
| Concomitant medications (for instance antibiotics and systemic steroids) |  | 48 weeks |