Tiotropium/Salmeterol Inhalation Powder (Spiriva Handihaler and Salmeterol Polyethylene (PE) Capsule) in Chronic Obstructive Pulmonary Disease (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 forced expiratory volume in one second (FEV1), the effect on dyspnoea as determined by the Baseline Dyspnoea Index/Transition Dyspnoea Index (BDI/TDI), the effect on health status as determined by the St George Respiratory Questionnaire (SGRQ) and the effect on chronic obstructive pulmonary disease (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 QD
* Drug: Placebo
* Drug: Salmeterol
* Drug: Tiotropium/Salmeterol QD+ Salmeterol
* Drug: Tiotropium (Spiriva®)


Participation Criteria
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Eligibility Criteria
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Main Inclusion criteria: Diagnosis of COPD Post-bronchodilator FEV1<80% predicted and FEV1/FVC<70% predicted Main Exclusion criteria: Significant other diseases then COPD Recent myocardial infarction (MI) Unstable or life-threatening arrythmia requiring intervention or change in drug therapy Hospitalisation for cardiac failure in 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 quaque die (QD, once daily)<br>Tiotropium/Salmeterol Inhalation Powder, Hard Polyethylene Capsule | Drug: Tiotropium/Salmeterol QD<br>* Tiotropium/Salmeterol Inhalation Powder, Hard Polyethylene Capsule<br>|
| Active Comparator: Tiotropium quaque die (QD, once daily)<br>Tiotropium Inhalation Powder, hard gelatine capsule (Spiriva®) | Drug: Tiotropium (Spiriva®)<br>* Tiotropium, Spiriva®<br>|
| Active Comparator: Salmeterol bis in die (BID, twice daily)<br>Salmeterol Inhalation Powder, hard PE capsule | Drug: Salmeterol<br>* Salmeterol Inhalation Powder, hard PE capsule<br>|
| Active Comparator: Tiotropium/Salmeterol quaque die (QD, once daily)+ 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 forced expiratory volume in one second (FEV1) response |  | 12 Weeks, 24 Weeks and 48 Weeks | 
| FEV1 area under the curve (AUC) 0-8h response |  | 12 Weeks, 24 Weeks and 48 Weeks | 
| Mahler Transition Dyspnoea Index (TDI) focal score |  | 12 Weeks, 24 Weeks and 48 Weeks | 
| St George Respiratory Questionnaire (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 |
| --- | --- | --- |
| FEV1 AUC 0-8h response |  | 4, 36 and 48 weeks | 
| Trough FEV1 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 | 
| Forced vital capacity (FVC) AUC0-8h and trough FVC response |  | 48 weeks | 
| Individual FEV1, FVC and peak expiratory flow (PEF) measurements |  | 48 weeks | 
| Weekly mean morning pre-dose and evening pre-dose PEFs and FEV1 (recorded by Asthma Monitor® 2 (AM2+)); PEFs determined by spirometry ] |  | 48 weeks | 
| Weekly mean number of COPD related night time awakenings |  | 1 week | 
| 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 |