Phase 4
Completed N=1,945
Roflumilast in Chronic Obstructive Pulmonary Disease (COPD) Patients Treated With Fixed Combinations of Long-acting β2-agonists (LABA) and Inhaled Glucocorticosteroid (ICS)
Source: ClinicalTrials.gov NCT01329029 ↗Enrolled (actual)
1,945
Serious AEs
27.6%
Results posted
Oct 2015
Primary outcomePrimary: Rate of Moderate or Severe COPD Exacerbations Per Patient Per Year — 0.805; 0.927 exacerbations per patient per year — p=0.0529
Summary
The objective of the REACT trial is to investigate the effect of roflumilast 500 μg tablets once daily versus placebo on exacerbation rate and pulmonary function in COPD patients who are concomitantly treated with a fixed combination of long-acting β2-agonists (LABA) and inhaled glucocorticosteroids (ICS). In addition, data on safety and tolerability of roflumilast will be obtained. An additional objective is to further characterize the population pharmacokinetic profile of roflumilast and roflumilast N oxide and to further characterize their pharmacokinetics/pharmacodynamics (PK/PD) relationship in terms of efficacy and relevant safety aspects.
Patients to be included are required to have severe COPD associated with chronic bronchitis and a history of frequent exacerbations and must be concomitantly treated with a fixed combination of LABA and ICS. Two parallel treatment arms (roflumilast 500 μg once daily and placebo) are included.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Rate of Moderate or Severe COPD Exacerbations Per Patient Per Year |
0.805; 0.927 | 0.0529 |
| SECONDARY Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in the First Second (FEV1) |
0.052; -0.004 | <0.0001 sig |
| SECONDARY Rate of Severe COPD Exacerbations Per Patient Per Year |
0.239; 0.315 | 0.0175 sig |
| SECONDARY Rate of COPD Exacerbations Per Patient Per Year All Categories |
0.574; 0.627; 3.078; 3.879; 0.238; 0.313 | 0.2875 |
| SECONDARY Percentage of Participants Experiencing at Least 1 COPD Exacerbation |
55.2; 60.5 | — |
| SECONDARY Time to First COPD Exacerbation All Categories |
218.0; 180.0 | 0.1461 |
| SECONDARY Time to Second Moderate or Severe COPD Exacerbation |
421.0; NA | 0.0270 sig |
| SECONDARY Time to Third Moderate or Severe COPD Exacerbation |
NA; NA | 0.0731 |
| SECONDARY Number of Patients Needed to Treat to Avoid 1 Moderate or Severe COPD Exacerbation Derived From Exacerbation Per Patient Per Year |
0.805; 0.927 | — |
| SECONDARY Number of Moderate or Severe COPD Exacerbation Days |
26.9; 30.9 | — |
| SECONDARY Duration of Moderate or Severe COPD Exacerbations Per Participant |
15.9; 16.6 | — |
| SECONDARY Change From Baseline in Post-Bronchodilator Forced Vital Capacity (FVC) |
0.036; -0.057 | <0.0001 sig |
| SECONDARY Change From Baseline in Post-Bronchodilator Forced Expiratory Flow at 25% to 75% of Vital Capacity (FEF25-75%) |
0.035; 0.009 | <0.0001 sig |
| SECONDARY Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in the First 6 Seconds (FEV6) |
0.061; -0.033 | <0.0001 sig |
| SECONDARY Change From Baseline in Post-Bronchodilator FEV1/FVC |
1.170; 0.580 | — |
| SECONDARY Change From Baseline in Use of Rescue Medication From Daily Diary |
-0.109; 0.173 | 0.0027 sig |
| SECONDARY Change From Baseline in COPD Symptom Score From Daily Diary |
-0.412; -0.398 | 0.7392 |
| SECONDARY Percentage of Symptom-Free Days |
7.09; 6.88 | — |
| SECONDARY Percentage of Rescue Medication-Free Days |
23.25; 22.77 | — |
| SECONDARY Change From Baseline in COPD Assessment Test (CAT) Total Score |
-1.270; -0.985 | 0.1909 |
| SECONDARY Percentage of Participants With Improvement in CAT |
71.2; 72.5 | — |
| SECONDARY Time to Mortality Due to Any Reason During the Treatment Period Score |
NA; NA | 0.9414 |
| SECONDARY Time to Mortality Due to COPD Exacerbation During the Treatment Period |
NA; NA | 0.8876 |
| SECONDARY Time to Withdrawal During the Treatment Period |
420.0; 444.0 | <0.0001 sig |
| SECONDARY Time to Withdrawal Due to COPD Exacerbation During the Treatment Period |
NA; NA | 0.3477 |
| SECONDARY Percentage of Participants With Major Adverse Cardiovascular Event (MACE) During the Treatment Period |
1.7; 1.7 | — |
| SECONDARY Time to First Major Adverse Cardiovascular Event (MACE) During the Treatment Period |
NA; NA | 0.8208 |
| SECONDARY Percentage of Participant With All-Cause Hospitalisation During the Treatment Period |
24.9; 29.3 | — |
| SECONDARY Time to First Hospitalisation Due to Any Cause During the Treatment Period |
400.0; 408.0 | 0.7943 |
| SECONDARY Time to Trial Withdrawal Due to an Adverse Event |
NA; NA | — |
| SECONDARY Percentage of Participants Who Experienced at Least 1 Treatment Emergent Adverse Event (TEAE) |
66.9; 59.2 | — |
| SECONDARY Change From Baseline in Body Weight |
-2.66; -0.14 | — |
| SECONDARY Change From Baseline in Body Mass Index (BMI) |
-0.94; -0.04 | — |
Eligibility Criteria
Inclusion Criteria
- Giving written informed consent
- History of COPD (according to GOLD 2009) for at least 12 months prior to baseline Visit V0 associated with chronic productive cough for 3 months in each of the 2 years prior to baseline visit (with other causes of productive cough excluded)
- Age ≥ 40 years
- Forced expiratory volume after one second (FEV1)/forced vital capacity (FVC) ratio (post-bronchodilator) < 70%
- FEV1 (post-bronchodilator) ≤ 50% of predicted
- At least two documented moderate or severe COPD exacerbations within one year prior to baseline visit
- Patients must be pre-treated with LABA and ICS for at least 12 months before baseline Visit V0. Up to 3 months before baseline Visit V0 free or fixed combinations of LABA and ICS are allowed, including changes in dose, active substances, and brands. In the last 3 months before baseline Visit V0 patients must be pre-treated with fixed combinations of LABA and ICS at a constant dose (maximum approved dosage strength of the combination).
- Former smoker (defined as smoking cessation at least one year ago) or current smoker both with a smoking history of at least 20 pack years
Main Exclusion Criteria:
- Exacerbations not resolved at first baseline visit
- Diagnosis of asthma and/or other relevant lung disease
- Known alpha-1-antitrypsin deficiency
- Other protocol-defined exclusion criteria may apply
Data sourced from ClinicalTrials.gov (NCT01329029). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.