Roflumilast in Chronic Obstructive Pulmonary Disease (COPD) Patients Treated With Fixed Dose Combinations of Long-acting β2-agonist (LABA) and Inhaled Corticosteroid (ICS)

Study Overview
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Brief Summary
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To demonstrate the additional benefit of roflumilast when added on to fixed-dose combination (FDC) LABA/ICS in the reduction of exacerbations in subjects with severe to very severe COPD.

Official Title
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Study to Evaluate the Effect of Roflumilast 500 μg on Exacerbation Rate in Subjects With Chronic Obstructive Pulmonary Disease (COPD) Treated With a Fixed-Dose Combination of Long-Acting Beta Agonist and Inhaled Corticosteroid (LABA/ICS)

Conditions
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COPD, COPD Exacerbation, Lung Diseases, Respiratory Disorders, Pulmonary Disease, Chronic Obstructive Lung Diseases, Chronic Obstructive Airway Disease

Intervention / Treatment
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* Drug: Roflumilast
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Male or female patients at least 40 years of age 2. History of COPD (according to Global Initiative for Chronic Obstructive Lung Disease [GOLD] 2010) for at least 12 months prior to Screening (Visit 1) associated with chronic productive cough for 3 months in each of 2 consecutive years (with other causes of productive cough excluded). Only patients with chronic bronchitis will be included (concomitant emphysema is permitted) 3. Forced expiratory volume after 1 second (FEV1)/forced vital capacity (FVC) ratio (postbronchodilator) < 70% at Screening (Visit 1) 4. FEV1 (postbronchodilator) ≤ 50% of predicted at Screening (Visit 1) 5. At least two documented moderate or severe COPD exacerbations within 12 months prior to Screening (Visit 1) 6. Patients must be on FDC LABA/ICS treatment ≥ 3 months prior to Screening (Visit 1) 7. Former smokers (defined as smoking cessation at least 1 year ago) or current smokers (including patients who ceased smoking within the past year) both with a smoking history of at least 20 pack-years Exclusion Criteria: 1. Moderate or severe COPD exacerbation and/or COPD exacerbations treated with antibiotics or systemic glucocorticosteroids within 4 weeks of Screening (Visit 1) (ie, patients must be clinically stable) 2. Known alpha-1-antitrypsin deficiency 3. Current diagnosis of asthma (either controlled or uncontrolled) (Note: History of childhood asthma is not exclusionary.) 4. Body mass index (BMI) ≥ 45 kg/m2 5. Patients with a history (within 5 years) or current diagnosis of cancer other than basal or squamous cell skin cancer

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Roflumilast | Drug: Roflumilast<br>* Roflumilast 500 µg, oral administration, once per day<br>* Other names: Daliresp;|
| Placebo Comparator: 2<br>Placebo | Drug: Placebo<br>* Dose-matched placebo, oral administration, once per day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Moderate or Severe COPD Exacerbations Per Patient Per Year. | Rate of moderate or severe COPD exacerbations, defined as requiring oral or parenteral glucocorticosteroids (moderate) or requiring hospitalization and/or leading to death (severe), during the double-blind treatment period. | Baseline to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of COPD Exacerbations That Led to Hospitalization or Death (ie, Severe COPD Exacerbations) | Rate of moderate or severe COPD exacerbations, defined as requiring hospitalization and/or leading to death (severe), during the double-blind treatment period. | Week 0 (Visit 2) to Week 52 | 
| Rate of Moderate or Severe COPD Exacerbations or COPD Exacerbations Treated With Antibiotics | Rate of moderate or severe COPD exacerbations treated with antibiotics during the double-blind treatment period. | Week 0 (Visit 2) to Week 52 | 
| Mean Change in Predose Forced Expiratory Volume in 1 Second (FEV1) | Mean change from randomization (Visit 2) over 52 weeks of treatment in predose forced expiratory volume in 1 second (FEV1) | Week 0 (Visit 2) to Week 52 | 

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