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

• ClinicalTrials.gov Identifier: NCT01572948
• Recruitment Status: Completed
• First Posted: April 6, 2012
• Results First Posted: July 31, 2015
• Last Update Posted: October 19, 2015
• Sponsor: University of Alabama at Birmingham
• Information provided by (Responsible Party): J Edwin Blalock, University of Alabama at Birmingham

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
COPD	Drug: roflumilast; Drug: placebo	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 27 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Placebo-controlled Trial of Roflumilast (Daliresp) on Markers of Inflammation in Chronic Obstructive Pulmonary Disease (COPD)
• Study Start Date: June 2012
• Actual Primary Completion Date: June 2014
• Actual Study Completion Date: June 2014

Arms and Interventions

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 Name: Daliresp

Outcome Measures

Primary Outcome Measures :

1. Induced Sputum Proline-glycine-proline (PGP) Levels at Baseline [ Time Frame: baseline ]
2. Mean Induced Sputum Proline-glycine-proline (PGP) Levels at 1 Month After Randomization. [ Time Frame: 1 month after baseline ]
3. Mean Induced Sputum Proline-glycine-proline (PGP) Levels at 3 Months After Randomization [ Time Frame: 3 months after baseline ]

Secondary Outcome Measures :

1. Induced Sputum Neutrophil Count [ Time Frame: 1 month ]
2. Induced Sputum Neutrophil Count [ Time Frame: baseline ]
3. Induced Sputum Neutrophil Count [ Time Frame: 3 months after baseline ]

Eligibility Criteria

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

Criteria

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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Contacts and Locations

Locations

United States, Alabama

UAB Lung Health Center

Birmingham, Alabama, United States, 35294

Sponsors and Collaborators

University of Alabama at Birmingham

Investigators

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: J Edwin Blalock, Professor, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT01572948
• Other Study ID Numbers: DAL-MD-01
• First Posted: April 6, 2012
• Results First Posted: July 31, 2015
• Last Update Posted: October 19, 2015
• Last Verified: September 2015

Additional relevant MeSH terms:

Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Lung Diseases; Respiratory Tract Diseases