Roflumilast in Chronic Obstructive Pulmonary Disease (COPD) Patients Treated With Fixed Combinations of Long-acting β2-agonists (LABA) and Inhaled Glucocorticosteroid (ICS)
Condition: Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: Roflumilast; Placebo
Intervention description: 500 µg, once daily; once daily
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 1945.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: COPD; Roflumilast; Daxas

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.
    

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