Roflumilast in Chronic Obstructive Pulmonary Disease (COPD) Patients Treated With Fixed Combinations of Long-acting β2-agonists (LABA) and Inhaled Glucocorticosteroid (ICS) (REACT)

• Post-bronchodilator Forced Expiratory Volume in the First Second (FEV1) [L] [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
• Exacerbation analyses (time to event, proportion of patients experiencing a COPD exacerbation) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
• Forced vital capacity (FVC) [L] [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
• Forced expiratory flow at 25% to 75% of vital capacity (FEF25-75%) [L/s] [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
• Forced expiratory volume in the first 6 seconds (FEV6) [L] [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
• FEV1/FVC [%] [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
• Use of rescue medication from daily diary [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
• COPD symptom score from daily diary [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
• Incidences of Adverse Events [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
• Descriptive summary statistics of clinical laboratory values, ECG, vital signs including blood pressure and heart rate [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
• Changes in body weight [kg] and body mass index [kg/m2] [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]

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.

• Drug: Roflumilast
  500 µg, once daily
• Drug: Placebo
  once daily

• Active Comparator: Roflumilast
  concomitant medication: fixed combination of long-acting β2-agonist and inhaled glucocorticosteroid
  Intervention: Drug: Roflumilast
• Placebo Comparator: Placebo
  concomitant medication: fixed combination of long-acting β2-agonist and inhaled glucocorticosteroid
  Intervention: Drug: Placebo

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 fixed combinations of LABA and ICS at a constant dose (maximum approved dosage strength of the combination) for at least 12 months prior to baseline visit
• 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