COPD
Conditions
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.
Interventions
DRUGroflumilast
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
DRUGplacebo
The placebo (Forest Laboratories, Inc) is manufactured as an odorless and otherwise equivalent tablet to the roflumilast tablet, but contains no active ingredient
Sponsors
University of Alabama at Birmingham
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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. \-
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean Induced Sputum Proline-glycine-proline (PGP) Levels at 3 Months After Randomization | 3 months after baseline |
| 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 |
Secondary
| Measure | Time frame |
|---|---|
| Induced Sputum Neutrophil Count | 1 month |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from a single center.
Participants by arm
| Arm | Count |
|---|---|
| Placebo placebo: The placebo (Forest Laboratories, Inc) is manufactured as an odorless and otherwise equivalent tablet to the roflumilast tablet, but contains no active ingredient | 16 |
| Roflumilast 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 | 11 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | unable to contact | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | Roflumilast |
|---|---|---|---|
| Age, Continuous | 61 years | 61 years | 62 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 8 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 19 Participants | 7 Participants |
| Region of Enrollment United States | 16 participants | 27 participants | 11 participants |
| Sex: Female, Male Female | 6 Participants | 10 Participants | 4 Participants |
| Sex: Female, Male Male | 10 Participants | 17 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 16 | 5 / 11 |
| serious Total, serious adverse events | 0 / 16 | 0 / 11 |
Outcome results
Primary
Induced Sputum Proline-glycine-proline (PGP) Levels at Baseline
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Induced Sputum Proline-glycine-proline (PGP) Levels at Baseline | 0.74 ng/ml | Standard Deviation 0.25 |
| Roflumilast | Induced Sputum Proline-glycine-proline (PGP) Levels at Baseline | 0.64 ng/ml | Standard Deviation 0.21 |
Primary
Mean Induced Sputum Proline-glycine-proline (PGP) Levels at 1 Month After Randomization.
Time frame: 1 month after baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Induced Sputum Proline-glycine-proline (PGP) Levels at 1 Month After Randomization. | .33 ng/ml | Standard Deviation 0.12 |
| Roflumilast | Mean Induced Sputum Proline-glycine-proline (PGP) Levels at 1 Month After Randomization. | .66 ng/ml | Standard Deviation 0.18 |
Primary
Mean Induced Sputum Proline-glycine-proline (PGP) Levels at 3 Months After Randomization
Time frame: 3 months after baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Induced Sputum Proline-glycine-proline (PGP) Levels at 3 Months After Randomization | 0.70 ng/ml | Standard Deviation 0.18 |
| Roflumilast | Mean Induced Sputum Proline-glycine-proline (PGP) Levels at 3 Months After Randomization | 0.30 ng/ml | Standard Deviation 0.11 |
Secondary
Induced Sputum Neutrophil Count
Time frame: 1 month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Induced Sputum Neutrophil Count | 83 percentage of sputum neutrophils | Standard Error 0.24 |
| Roflumilast | Induced Sputum Neutrophil Count | 80 percentage of sputum neutrophils | Standard Error 0.24 |
Secondary
Induced Sputum Neutrophil Count
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Induced Sputum Neutrophil Count | 89 percentage of sputum neutrophils | Standard Error 0.25 |
| Roflumilast | Induced Sputum Neutrophil Count | 83 percentage of sputum neutrophils | Standard Error 0.23 |
Secondary
Induced Sputum Neutrophil Count
Time frame: 3 months after baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Induced Sputum Neutrophil Count | 86 percentage of sputum neutrophils | Standard Error 0.24 |
| Roflumilast | Induced Sputum Neutrophil Count | 58 percentage of sputum neutrophils | Standard Error 0.18 |