Efficacy and Safety Comparison of Steroid or Placebo in Combination With Salmeterol and Tiotropium in COPD

Study Overview
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Brief Summary
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This efficacy and safety study compares four different combinations of blinded inhaled steroid treatments on top of open-label tiotropium and salmeterol in patients with chronic obstructive pulmonary disease (COPD). The primary objective is the effect on lung function parameters.

Official Title
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A Randomised, Phase II, Double-Blind, Double-Dummy, Four-period Crossover Efficacy and Safety Comparison of 4-Week Treatment Periods of Blinded Fluticasone (500 mcg Bid, MDI), Ciclesonide (400 mcg qd, MDI), Ciclesonide (800 mcg qd, MDI) or Placebo in Free Combination With Open-Label Tiotropium (18 mcg qd, HandiHaler) and Salmeterol (50 mcg Bid, Diskus) in Patients With COPD.

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Tiotropium
* Drug: Salmeterol
* Drug: Fluticasone
* Drug: Ciclesonide low
* Drug: Ciclesonide high
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Relatively stable, moderate to severe COPD Male or female patients 40 years of age or older. Current or ex-smokers with a smoking history of more than 10 pack years Exclusion Criteria: Other significant disease that can influence the study results or be a safety risk for the patient Other medication that can influence the study results Hypersensitivity to the study medication Patients with unstable COPD

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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tiotropium+salmeterol+fluticasone<br> | Drug: Tiotropium<br>* Oral inhalation by HandiHaler® device<br>Drug: Salmeterol<br>* Oral inhalation from Diskus®<br>Drug: Fluticasone<br>* Oral inhalation from metered dose inhaler (MDI)<br>|
| Experimental: Tiotropium+salmeterol+ciclesonide low<br> | Drug: Tiotropium<br>* Oral inhalation by HandiHaler® device<br>Drug: Salmeterol<br>* Oral inhalation from Diskus®<br>Drug: Ciclesonide low<br>* Oral inhalation from MDI<br>|
| Experimental: Tiotropium+salmeterol+ciclesonide high<br> | Drug: Tiotropium<br>* Oral inhalation by HandiHaler® device<br>Drug: Salmeterol<br>* Oral inhalation from Diskus®<br>Drug: Ciclesonide high<br>* Oral inhalation from MDI<br>|
| Placebo Comparator: Placebo<br> | Drug: Tiotropium<br>* Oral inhalation by HandiHaler® device<br>Drug: Salmeterol<br>* Oral inhalation from Diskus®<br>Drug: Placebo<br>* Oral inhalation from MDI<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough FEV1 response at the end of each 4 week period of randomised treatment |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough forced vital capacity (FVC) response after 4 weeks of each blinded treatment |  | after 4 weeks of each blinded treatment | 
| All adverse events |  | 24 weeks | 
| Pulse rate and blood pressure (seated) |  | 24 weeks | 
| FEV1 and FVC morning peak response |  | day 1 and day 28 of each blinded treatment | 
| FEV1 and FVC evening peak response |  | day 1 and day 28 of each blinded treatment | 
| FEV1 AUC (0-3h), after 4 weeks of each blinded treatment |  | after 4 weeks of each blinded treatment | 
| FEV1 AUC (12-15h) after 4 weeks of each blinded treatment |  | after 4 weeks of each blinded treatment | 
| FVC AUC (0-3h) after 4 weeks of each blinded treatment |  | after 4 weeks of each blinded treatment | 
| FVC AUC (12-15h) after 4 weeks of each blinded treatment |  | after 4 weeks of each blinded treatment | 
| Trough and peak inspiratory capacity (IC) and vital capacity (VC) response in the morning of day 1 and at day 28 of each treatment period |  | day 1 and day 28 of each blinded treatment | 
| Weekly mean pre-dose morning and evening peak expiratory flow (PEF) |  | 28 weeks | 
| Weekly mean number of occasions of rescue therapy used per day |  | 28 weeks | 
| Mahler Dyspnea Indices (TDI) collected at the end of each treatment period and each wash-out period |  | 28 weeks | 
| Fractional exhaled nitric oxide after 4 weeks of each blinded treatment |  | after 4 weeks of each blinded treatment |