Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
Roflumilast, COPD, Chronic obstructive pulmonary disease
Brief summary
The aim of the study is to investigate the effect of roflumilast on exacerbation rate and pulmonary function in patients with chronic obstructive pulmonary disease (COPD). Roflumilast will be administered orally once daily in the morning at one dose level. The study duration will last up to 56 weeks. The study will provide further data on safety and tolerability of roflumilast. For additional information (for US patients only) see www.COPDSTUDY.net or dial 866-788-2673 (toll free).
Interventions
DRUGRoflumilast
500 mcg, once daily, oral administration in the morning
DRUGPlacebo
once daily
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * COPD patients having at least one exacerbation within last year * FEV1/FVC ratio (post-bronchodilator) ≤ 70% * FEV1 (post-bronchodilator) ≤ 50% of predicted Main
Exclusion criteria
* COPD exacerbation not resolved at first baseline visit * Diagnosis of asthma and/or other relevant lung disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pre-bronchodilator Forced Expiratory Volume in First Second (FEV1) | Change from baseline over 52 weeks of treatment | Mean change from baseline during the treatment period in pre-bronchodilator FEV1 \[L\] |
| COPD Exacerbation Rate (Moderate or Severe) | 52 weeks treatment period | Mean rate of COPD exacerbations requiring oral or parenteral glucocorticosteroids (=moderate COPD exacerbations), or requiring hospitalization, or leading to death (=severe COPD exacerbations), per patient per year. A COPD exacerbation is an event in the natural course of the disease characterized by a change in the patient's baseline dyspnea, cough and/or sputum beyond day-to-day variability sufficient to warrant a change in management \[American Thoracic Society (ATS) / European Respiratory Society (ERS) 2005\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post-bronchodilator FEV1 [L] | Change from baseline over 52 weeks of treatment | Mean change from baseline during the treatment period in post-bronchodilator FEV1 \[L\] |
| Time to Mortality Due to Any Reason | 52 weeks treatment period | — |
| Natural Log-transformed C-reactive Protein (CRP) | Change from baseline to last post randomization measurement (52 weeks) | Mean change from baseline to the last post randomization measurement in natural log-transformed CRP |
| Mean Transition Dyspnea Index (TDI) Focal Score During the Treatment Period | Change from baseline over 52 weeks of treatment | The TDI is a recognized questionnaire to measure dyspnea in an out patient COPD population. At baseline, 3 components of dyspnea, each graded with 4 questions, were asked: - Functional Impairment - Magnitude of Task - Magnitude of Effort At each of the post-randomization visits questions from the TDI were asked related to 3 components: Change in - Functional Impairment - Magnitude of Task - Magnitude of Effort Each question in the TDI is graded from -3 (major deterioration) to +3 (major improvement). This results in a TDI Focal Score ranging from -9 to +9. |
Countries
Australia, Austria, Brazil, France, Germany, Hungary, New Zealand, Romania, Russia, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Roflumilast 500 mcg, once daily, oral administration in the morning | 765 |
| Placebo once daily | 758 |
| Total | 1,523 |
Baseline characteristics
| Characteristic | Roflumilast | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 63.53 years STANDARD_DEVIATION 9.5 | 63.36 years STANDARD_DEVIATION 9.2 | 63.45 years STANDARD_DEVIATION 9.4 |
| Gender Female | 225 Participants | 220 Participants | 445 Participants |
| Gender Male | 540 Participants | 538 Participants | 1078 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 232 / 769 | 136 / 755 |
| serious Total, serious adverse events | 144 / 769 | 153 / 755 |
Outcome results
Primary
COPD Exacerbation Rate (Moderate or Severe)
Mean rate of COPD exacerbations requiring oral or parenteral glucocorticosteroids (=moderate COPD exacerbations), or requiring hospitalization, or leading to death (=severe COPD exacerbations), per patient per year. A COPD exacerbation is an event in the natural course of the disease characterized by a change in the patient's baseline dyspnea, cough and/or sputum beyond day-to-day variability sufficient to warrant a change in management \[American Thoracic Society (ATS) / European Respiratory Society (ERS) 2005\].
Time frame: 52 weeks treatment period
Population: ITT analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Roflumilast | COPD Exacerbation Rate (Moderate or Severe) | 1.077 exacerbations per patient per year |
| Placebo | COPD Exacerbation Rate (Moderate or Severe) | 1.266 exacerbations per patient per year |
p-value: 0.027895% CI: [0.737, 0.982]Poisson regression
Primary
Pre-bronchodilator Forced Expiratory Volume in First Second (FEV1)
Mean change from baseline during the treatment period in pre-bronchodilator FEV1 \[L\]
Time frame: Change from baseline over 52 weeks of treatment
Population: ITT (Intention to Treat) analysis. Number of participants analyzed = number of participants with data available.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Roflumilast | Pre-bronchodilator Forced Expiratory Volume in First Second (FEV1) | 46 mL | Standard Error 8 |
| Placebo | Pre-bronchodilator Forced Expiratory Volume in First Second (FEV1) | 8 mL | Standard Error 8 |
p-value: 0.000395% CI: [18, 60]ANCOVA
Secondary
Mean Transition Dyspnea Index (TDI) Focal Score During the Treatment Period
The TDI is a recognized questionnaire to measure dyspnea in an out patient COPD population. At baseline, 3 components of dyspnea, each graded with 4 questions, were asked: - Functional Impairment - Magnitude of Task - Magnitude of Effort At each of the post-randomization visits questions from the TDI were asked related to 3 components: Change in - Functional Impairment - Magnitude of Task - Magnitude of Effort Each question in the TDI is graded from -3 (major deterioration) to +3 (major improvement). This results in a TDI Focal Score ranging from -9 to +9.
Time frame: Change from baseline over 52 weeks of treatment
Population: ITT analysis. Number of participants analyzed = number of participants with data available.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Roflumilast | Mean Transition Dyspnea Index (TDI) Focal Score During the Treatment Period | 0.658 scores on a scale | Standard Error 0.084 |
| Placebo | Mean Transition Dyspnea Index (TDI) Focal Score During the Treatment Period | 0.426 scores on a scale | Standard Error 0.082 |
p-value: 0.035695% CI: [0.016, 0.449]ANCOVA
Secondary
Natural Log-transformed C-reactive Protein (CRP)
Mean change from baseline to the last post randomization measurement in natural log-transformed CRP
Time frame: Change from baseline to last post randomization measurement (52 weeks)
Population: ITT analysis. Number of participants analyzed = number of participants with data available.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roflumilast | Natural Log-transformed C-reactive Protein (CRP) | 1.0475 mg/L |
| Placebo | Natural Log-transformed C-reactive Protein (CRP) | 1.1003 mg/L |
p-value: 0.408995% CI: [0.8472, 1.0699]ANCOVA
Secondary
Post-bronchodilator FEV1 [L]
Mean change from baseline during the treatment period in post-bronchodilator FEV1 \[L\]
Time frame: Change from baseline over 52 weeks of treatment
Population: ITT analysis. Number of participants analyzed = number of participants with data available.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Roflumilast | Post-bronchodilator FEV1 [L] | 57 mL | Standard Error 9 |
| Placebo | Post-bronchodilator FEV1 [L] | 8 mL | Standard Error 8 |
p-value: <0.000195% CI: [26, 71]ANCOVA
Secondary
Time to Mortality Due to Any Reason
Time frame: 52 weeks treatment period
Population: ITT analysis. Number of participants analyzed = number of participants who died.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roflumilast | Time to Mortality Due to Any Reason | 213.8 days | Standard Deviation 118.9 |
| Placebo | Time to Mortality Due to Any Reason | 207.5 days | Standard Deviation 108.5 |
p-value: 0.921295% CI: [0.526, 2.034]Cox proportional hazards regression