Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effect of Roflumilast in COPD Patients Treated With Salmeterol. A 24-week, Double-blind Study With 500 μg Roflumilast Once Daily Versus Placebo. The EOS Study
Brief Summary: The aim of the study is to compare the efficacy of roflumilast on pulmonary function and symptomatic parameters in patients with chronic obstructive pulmonary disease (COPD) during concomitant administration of salmeterol. The study duration will last up to 28 weeks. The study will provide further data on safety and tolerability of roflumilast.


Options:
A: 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
B: 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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C: Inclusion Criteria:

* 1. Male or female patients at least 40 years of age
* 2. History of COPD (according to Global Initiative for Chronic Obstructive Lung Disease \[GOLD\] 2010) for at least 12 months prior to Screening (Visit 1) associated with chronic productive cough for 3 months in each of 2 consecutive years (with other causes of productive cough excluded). Only patients with chronic bronchitis will be included (concomitant emphysema is permitted)
* 3. Forced expiratory volume after 1 second (FEV1)/forced vital capacity (FVC) ratio (postbronchodilator) \< 70% at Screening (Visit 1)
* 4. FEV1 (postbronchodilator) ≤ 50% of predicted at Screening (Visit 1)
* 5. At least two documented moderate or severe COPD exacerbations within 12 months prior to Screening (Visit 1)
* 6. Patients must be on FDC LABA/ICS treatment ≥ 3 months prior to Screening (Visit 1)
* 7. Former smokers (defined as smoking cessation at least 1 year ago) or current smokers (including patients who ceased smoking within the past year) both with a smoking history of at least 20 pack-years

Exclusion Criteria:

* 1. Moderate or severe COPD exacerbation and/or COPD exacerbations treated with antibiotics or systemic glucocorticosteroids within 4 weeks of Screening (Visit 1) (ie, patients must be clinically stable)
* 2. Known alpha-1-antitrypsin deficiency
* 3. Current diagnosis of asthma (either controlled or uncontrolled) (Note: History of childhood asthma is not exclusionary.)
* 4. Body mass index (BMI) ≥ 45 kg/m2
* 5. Patients with a history (within 5 years) or current diagnosis of cancer other than basal or squamous cell skin cancer
D: 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

Answer: D