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

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

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.

Study Overview

• Status: Completed
• Conditions: COPD
• Intervention / Treatment: Drug: placebo; Drug: roflumilast

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • UAB Lung Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and female subjects, > 40 years of age

2. Clinical diagnosis of moderate to severe COPD as defined by the GOLD criteria:

   Post-bronchodilator FEV1/FVC < 70% Post-bronchodilator FEV1 < 70% predicted

3. Cigarette consumption of 10 pack-years or more. Patients may be active smokers.
4. The presence of chronic cough and sputum production
5. Willingness to make return visits and telephone availability for the study duration

Exclusion Criteria:

1. A diagnosis of asthma as established by the study investigator on the basis of the recent American Thoracic Society/European Respiratory Society guidelines
2. Clinically significant bronchiectasis
3. Oxygen use >12 hours/day
4. Known sensitivity to roflumilast
5. Use of other methylxanthines within 1 month (theophylline)
6. Changes to current maintenance COPD therapy within one month
7. Pregnancy
8. An acute illness requiring antibiotics and/or corticosteroids within the month prior to enrolment.

9. Immunosuppression

   1. HIV
   2. Solid organ transplant
   3. Active malignancy
   4. Systemic corticosteroid use ≥ prednisone 20mg / day
   5. Other immunosuppressants
10. Terminal illness defined as anticipated survival <12 months

11. 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.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 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; The placebo (Forest Laboratories, Inc) is manufactured as an odorless and otherwise equivalent tablet to the roflumilast tablet, but contains no active ingredient
Active Comparator: Daliresp; 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; 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; Other Names: Daliresp

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: James E Blalock, PhD, University of Alabama at Birmingham

Publications and helpful links

General Publications

• Wells JM, Jackson PL, Viera L, Bhatt SP, Gautney J, Handley G, King RW, Xu X, Gaggar A, Bailey WC, Dransfield MT, Blalock JE. A Randomized, Placebo-controlled Trial of Roflumilast. Effect on Proline-Glycine-Proline and Neutrophilic Inflammation in Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2015 Oct 15;192(8):934-42. doi: 10.1164/rccm.201503-0543OC.

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: April 4, 2012
• First Submitted That Met QC Criteria: April 4, 2012
• First Posted (Estimate): April 6, 2012

Study Record Updates

• Last Update Posted (Estimate): October 19, 2015
• Last Update Submitted That Met QC Criteria: September 28, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: DAL-MD-01