A Placebo-controlled Trial of Daliresp on Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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The purpose of the study is to propose that roflumilast is associated with meaningful reductions in biomarkers of pulmonary inflammation and sputum neutrophilia, including confirmation of previously described results, and correlate these findings with improvement in pulmonary function, sputum scores, and quality of life in stable moderate to severe COPD. The investigators aim to demonstrate this regardless of concomitant medication use, including inhaled corticosteroids. Additionally, the investigators hope to provide a mechanistic pathway by which these effects occur.

Official Title
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A Placebo-controlled Trial of Roflumilast (Daliresp) on Markers of Inflammation in Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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COPD

Intervention / Treatment
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* Drug: roflumilast
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects, > 40 years of age Clinical diagnosis of moderate to severe COPD as defined by the GOLD criteria: Post-bronchodilator FEV1/FVC < 70% Post-bronchodilator FEV1 < 70% predicted Cigarette consumption of 10 pack-years or more. Patients may be active smokers. The presence of chronic cough and sputum production Willingness to make return visits and telephone availability for the study duration Exclusion Criteria: A diagnosis of asthma as established by the study investigator on the basis of the recent American Thoracic Society/European Respiratory Society guidelines Clinically significant bronchiectasis Oxygen use >12 hours/day Known sensitivity to roflumilast Use of other methylxanthines within 1 month (theophylline) Changes to current maintenance COPD therapy within one month Pregnancy An acute illness requiring antibiotics and/or corticosteroids within the month prior to enrolment. Immunosuppression HIV Solid organ transplant Active malignancy Systemic corticosteroid use ≥ prednisone 20mg / day Other immunosuppressants Terminal illness defined as anticipated survival <12 months Severe comorbidities including uncontrolled angina, congestive heart failure, end-stage renal disease, liver failure, or other conditions that would preclude the patient from safely completing the required tests or the study. -

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 |
| --- | --- |
| Placebo Comparator: Placebo<br>The placebo (Forest Laboratories, Inc) is manufactured as an odorless and otherwise equivalent tablet to the roflumilast tablet, but contains no active ingredient. | Drug: placebo<br>* The placebo (Forest Laboratories, Inc) is manufactured as an odorless and otherwise equivalent tablet to the roflumilast tablet, but contains no active ingredient<br>|
| Active Comparator: Daliresp<br>The study drug (roflumilast, Daliresp™, Forest Laboratories, Inc.) is a targeted inhibitor of phosphodiesterase 4 and is given once daily via oral route. There is proven anti-inflammatory and anti-oxidant potential in both animal and human models | Drug: roflumilast<br>* The study drug (roflumilast, Daliresp™, Forest Laboratories, Inc.) is a targeted inhibitor of phosphodiesterase 4 and is given once daily via oral route. There is proven anti-inflammatory and anti-oxidant potential in both animal and human models<br>* Other names: Daliresp;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Induced Sputum Proline-glycine-proline (PGP) Levels at Baseline |  | baseline | 
| Mean Induced Sputum Proline-glycine-proline (PGP) Levels at 1 Month After Randomization. |  | 1 month after baseline | 
| Mean Induced Sputum Proline-glycine-proline (PGP) Levels at 3 Months After Randomization |  | 3 months after baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Induced Sputum Neutrophil Count |  | 1 month | 
| Induced Sputum Neutrophil Count |  | baseline | 
| Induced Sputum Neutrophil Count |  | 3 months after baseline |