Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD, Roflumilast
Brief summary
The aim of the study is to compare the efficacy of roflumilast to placebo on pulmonary function and symptomatic parameters in patients with chronic obstructive pulmonary disease (COPD) during concomitant administration of tiotropium. The study duration will last up to 28 weeks. The study will provide further data on safety and tolerability of roflumilast.
Interventions
DRUGRoflumilast
500 µg, 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: * History of COPD for at least 12 months prior to baseline visit and chronic productive cough for 3 months in each of the 2 years prior to baseline visit * FEV1/FVC ratio (post-bronchodilator) ≤ 70% * FEV1 (post-bronchodilator) between ≥ 40% and ≤ 70% of predicted * Treated with tiotropium for at least 3 months before enrollment * At least 28 puffs of rescue medication during last week prior to randomization Main
Exclusion criteria
* COPD exacerbation indicated by a treatment with systemic glucocorticosteroids and/or antibiotics not stopped at least 4 weeks prior to baseline visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pre-bronchodilator Forced Expiratory Volume in First Second (FEV1) | Change from baseline over 24 weeks of treatment | Mean change from baseline during the treatment period in pre-bronchodilator FEV1 \[L\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post-bronchodilator FEV1 | Change from baseline over 24 weeks of treatment | Mean change from baseline during the treatment period in post-bronchodilator FEV1 \[L\] |
| COPD Exacerbation Rate (Moderate or Severe) | 24 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 \[American Thoracic Society (ATS) / European Respiratory Society (ERS) 2005\]. |
| Transition Dyspnea Index (TDI) Focal Score | Change from baseline over 24 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. |
| Shortness of Breath Questionnaire (SOBQ) Total Score | Change from baseline over 24 weeks of treatment | Mean change from baseline during the treatment period in SOBQ. This is a 24-item measure that assesses self-reported shortness of breath while performing a variety of activities of daily living. The questions were administered at visits V0, V2, V3, V4, V5, V6 and Vend to assess the perceived shortness of breath of the patient. For each activity listed in the questionnaire the patient should rate his/her breathlessness on a scale between zero and five, where zero is not at all breathless and five is maximally breathless or too breathless to do the activity. |
Countries
Austria, France, Germany, Hungary, Italy, Spain, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Roflumilast Roflumilast 500 µg, once daily, oral and tiotropium 18 µg, once daily, inhaled | 371 |
| Placebo Placebo, once daily, oral and tiotropium 18 µg, once daily, inhaled | 372 |
| Total | 743 |
Baseline characteristics
| Characteristic | Roflumilast | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 64.2 years STANDARD_DEVIATION 9.1 | 64.0 years STANDARD_DEVIATION 9.3 | 64.1 years STANDARD_DEVIATION 9.2 |
| Gender Female | 109 Participants | 105 Participants | 214 Participants |
| Gender Male | 262 Participants | 267 Participants | 529 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 106 / 374 | 76 / 369 |
| serious Total, serious adverse events | 22 / 374 | 21 / 369 |
Outcome results
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 24 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) | 65 mL | Standard Error 12 |
| Placebo | Pre-bronchodilator Forced Expiratory Volume in First Second (FEV1) | -16 mL | Standard Error 12 |
p-value: <0.000195% CI: [51, 110]ANCOVA
Secondary
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: 24 weeks treatment period
Population: ITT analysis
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Roflumilast | COPD Exacerbation Rate (Moderate or Severe) | 0.262 exacerbations per patient per year |
| Placebo | COPD Exacerbation Rate (Moderate or Severe) | 0.342 exacerbations per patient per year |
p-value: 0.195795% CI: [0.515, 1.146]Poisson regression
Secondary
Post-bronchodilator FEV1
Mean change from baseline during the treatment period in post-bronchodilator FEV1 \[L\]
Time frame: Change from baseline over 24 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 | 74 mL | Standard Error 12 |
| Placebo | Post-bronchodilator FEV1 | -7 mL | Standard Error 11 |
p-value: <0.000195% CI: [51, 110]ANCOVA
Secondary
Shortness of Breath Questionnaire (SOBQ) Total Score
Mean change from baseline during the treatment period in SOBQ. This is a 24-item measure that assesses self-reported shortness of breath while performing a variety of activities of daily living. The questions were administered at visits V0, V2, V3, V4, V5, V6 and Vend to assess the perceived shortness of breath of the patient. For each activity listed in the questionnaire the patient should rate his/her breathlessness on a scale between zero and five, where zero is not at all breathless and five is maximally breathless or too breathless to do the activity.
Time frame: Change from baseline over 24 weeks of treatment
Population: ITT analysis. Number of participants analyzed = number of participants with data available.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Roflumilast | Shortness of Breath Questionnaire (SOBQ) Total Score | -3.4 scores on a scale | Standard Error 0.7 |
| Placebo | Shortness of Breath Questionnaire (SOBQ) Total Score | -0.7 scores on a scale | Standard Error 0.7 |
p-value: 0.005195% CI: [-4.5, -0.8]ANCOVA
Secondary
Transition Dyspnea Index (TDI) Focal Score
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 24 weeks of treatment
Population: ITT analysis. Number of participants analyzed = number of participants with data available.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Roflumilast | Transition Dyspnea Index (TDI) Focal Score | 1.4 scores on a scale | Standard Error 0.1 |
| Placebo | Transition Dyspnea Index (TDI) Focal Score | 0.9 scores on a scale | Standard Error 0.1 |
p-value: 0.003295% CI: [0.1, 0.7]ANCOVA