Effect of Roflumilast in Chronic Obstructive Pulmonary Disease (COPD) Patients Treated With Tiotropium: The HELIOS Study (BY217/M2-128)

Study Overview
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Brief Summary
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The aim of the study is to compare the efficacy of roflumilast to placebo on pulmonary function and symptomatic parameters in patients with chronic obstructive pulmonary disease (COPD) during concomitant administration of tiotropium. The study duration will last up to 28 weeks. The study will provide further data on safety and tolerability of roflumilast.

Official Title
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Effect of Roflumilast in COPD Patients Treated With Tiotropium. A 24-week, Double-blind Study With 500 µg Roflumilast Once Daily Versus Placebo. The HELIOS Study

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Roflumilast
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: History of COPD for at least 12 months prior to baseline visit and chronic productive cough for 3 months in each of the 2 years prior to baseline visit FEV1/FVC ratio (post-bronchodilator) ≤ 70% FEV1 (post-bronchodilator) between ≥ 40% and ≤ 70% of predicted Treated with tiotropium for at least 3 months before enrollment At least 28 puffs of rescue medication during last week prior to randomization Main Exclusion Criteria: COPD exacerbation indicated by a treatment with systemic glucocorticosteroids and/or antibiotics not stopped at least 4 weeks prior to baseline visit

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 |
| --- | --- |
| Active Comparator: Roflumilast<br>Roflumilast 500 µg underlying medication: tiotropium 18 µg, once daily, inhaled | Drug: Roflumilast<br>* 500 µg, once daily, oral administration in the morning<br>|
| Placebo Comparator: Placebo<br>Placebo underlying medication: tiotropium 18 µg, once daily, inhaled | Drug: Placebo<br>* once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pre-bronchodilator Forced Expiratory Volume in First Second (FEV1) | Mean change from baseline during the treatment period in pre-bronchodilator FEV1 [L] | Change from baseline over 24 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-bronchodilator FEV1 | Mean change from baseline during the treatment period in post-bronchodilator FEV1 [L] | Change from baseline over 24 weeks of treatment | 
| COPD Exacerbation Rate (Moderate or Severe) | Mean rate of COPD exacerbations requiring oral or parenteral glucocorticosteroids (=moderate COPD exacerbations), or requiring hospitalization, or leading to death (=severe COPD exacerbations), per patient per year. A COPD exacerbation is an event in the natural course of the disease characterized by a change in the patient's baseline dyspnea, cough and/or sputum beyond day-to-day variability sufficient to warrant a change in management [American Thoracic Society (ATS) / European Respiratory Society (ERS) 2005]. | 24 weeks treatment period | 
| Transition Dyspnea Index (TDI) Focal Score | The TDI is a recognized questionnaire to measure dyspnea in an out patient COPD population. At baseline, 3 components of dyspnea, each graded with 4 questions, were asked: - Functional Impairment - Magnitude of Task - Magnitude of Effort At each of the post-randomization visits questions from the TDI were asked related to 3 components: Change in - Functional Impairment - Magnitude of Task - Magnitude of Effort Each question in the TDI is graded from -3 (major deterioration) to +3 (major improvement). This results in a TDI Focal Score ranging from -9 to +9. | Change from baseline over 24 weeks of treatment | 
| Shortness of Breath Questionnaire (SOBQ) Total Score | Mean change from baseline during the treatment period in SOBQ. This is a 24-item measure that assesses self-reported shortness of breath while performing a variety of activities of daily living. The questions were administered at visits V0, V2, V3, V4, V5, V6 and Vend to assess the perceived shortness of breath of the patient. For each activity listed in the questionnaire the patient should rate his/her breathlessness on a scale between zero and five, where zero is not at all breathless and five is maximally breathless or too breathless to do the activity. | Change from baseline over 24 weeks of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Roflumilast