Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effect of Roflumilast on Exacerbation Rate in Patients With COPD Treated With Fixed Combinations of LABA and ICS. A 52-week, Randomised Double-blind Trial With Roflumilast 500 µg Versus Placebo. The REACT Trial
Brief 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.


Options:
A: 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
B: Main Inclusion Criteria:

* FEV1/FVC ratio (post-bronchodilator) ≤70%
* FEV1 (post-bronchodilator) ≤50% of predicted
* Current smoker or ex-smoker
* Clinically stable COPD indicated by no exacerbation and no change in COPD treatment of within 4 weeks prior to baseline
* Availability of chest x-ray dated a maximum of 6 months prior to study baseline or a willingness to have a chest x-ray performed at baseline

Main Exclusion Criteria:

* COPD exacerbation indicated by a treatment with systemic glucocorticoids not stopped 4 weeks prior to baseline
* Lower respiratory tract infection not resolved 4 weeks prior to baseline
* Diagnosis of asthma and/or other relevant lung disease
* Known alpha-1-antitrypsin deficiency
* Need for long-term oxygen therapy defined as ≥16 hours/day
C: Main Inclusion Criteria:

* History of COPD for at least 12 months prior to baseline visit
* FEV1/FVC ratio (post-bronchodilator) ≤ 70%
* FEV1 (post-bronchodilator) between ≥ 40% and ≤ 70% of predicted

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
D: Inclusion Criteria:

1. Male and female subjects, \> 40 years of age
2. Clinical diagnosis of moderate to severe COPD as defined by the GOLD criteria:

   Post-bronchodilator FEV1/FVC \< 70% Post-bronchodilator FEV1 \< 70% predicted
3. Cigarette consumption of 10 pack-years or more. Patients may be active smokers.
4. The presence of chronic cough and sputum production
5. Willingness to make return visits and telephone availability for the study duration

Exclusion Criteria:

1. A diagnosis of asthma as established by the study investigator on the basis of the recent American Thoracic Society/European Respiratory Society guidelines
2. Clinically significant bronchiectasis
3. Oxygen use \>12 hours/day
4. Known sensitivity to roflumilast
5. Use of other methylxanthines within 1 month (theophylline)
6. Changes to current maintenance COPD therapy within one month
7. Pregnancy
8. An acute illness requiring antibiotics and/or corticosteroids within the month prior to enrolment.
9. Immunosuppression

   1. HIV
   2. Solid organ transplant
   3. Active malignancy
   4. Systemic corticosteroid use ≥ prednisone 20mg / day
   5. Other immunosuppressants
10. Terminal illness defined as anticipated survival \<12 months
11. Severe comorbidities including uncontrolled angina, congestive heart failure, end-stage renal disease, liver failure, or other conditions that would preclude the patient from safely completing the required tests or the study.

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Answer: A