Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effect of Roflumilast on Exacerbation Rate in Patients With Chronic Obstructive Pulmonary Disease. A 52-week, Multicenter, Double-blind Study With 500 mcg Roflumilast Once Daily Versus Placebo.
Brief Summary: The purpose of this study is to determine whether roflumilast is effective in the treatment of exacerbations in patients with chronic obstructive pulmonary disease (COPD).


Options:
A: Main Inclusion Criteria:

* COPD patients having at least one exacerbation within last year
* FEV1/FVC ratio (post-bronchodilator) ≤ 70%
* FEV1 (post-bronchodilator) ≤ 50% of predicted

Main Exclusion Criteria:

* COPD exacerbation not resolved at first baseline visit
* Diagnosis of asthma and/or other relevant lung disease
B: Inclusion Criteria:

* Male adults or female adults of non-childbearing potential who are between 40 and 75 years of age (inclusive).
* Subjects with a clinical diagnosis of COPD in accordance with the European Respiratory Society Consensus Statement and subjects categorised with moderate COPD as defined by the GOLD guidelines of 2006 \[GOLD, 2006\]
* Subjects with a cigarette smoking history of ≥ 10 pack years (1 pack year = 20 cigarettes smoked per day for 1 year or the equivalent). Both current and former smokers are eligible to be enrolled. A former smoker is defined as a subject who has not smoked for ≥6 months at Visit 1.
* Subjects with a post-bronchodilator FEV1 to FVC ratio (FEV1/FVC) \< 0.7 at Visit 1. Subjects will be assessed 30 (± 5) minutes after receiving salbutamol 400 μg.
* Subjects with a post-bronchodilator FEV1 ≥ 50% and \< 80% of predicted normal for height, age and sex at Visit 1. Subjects will be assessed 30 (± 5) minutes after receiving salbutamol 400 μg.
* Subjects with a normal echocardiogram at screening, as defined by the absence of clinically significant wall motion, chamber size or valvular abnormalities
* The subject must be capable of giving informed consent and can comply with the study requirements and timetable.

Exclusion Criteria:

* Women who are pre-menopausal and of child-bearing potential.
* Subjects weighing less than 50 kilograms (kg).
* Subjects who are obese defined as having a body mass index (BMI) \> 30.
* Subjects with a current diagnosis of asthma.
* Subjects who have required hospitalisation or treatment with oral corticosteroids and/or antibiotic therapy for acute worsening of COPD or lower respiratory tract infection in the 6 weeks prior to Screening.
* Subjects who have received treatment with oral, intravenous, topical or intra-articular corticosteroids within 6 weeks of Screening or thereafter
* Subjects with active tuberculosis, sarcoidosis or clinically overt bronchiectasis.
* Subjects with a history of any type of malignancy with the exception of successfully treated squamous cell cancer of the skin.
* Subjects with rheumatoid arthritis, connective tissue disorders and other conditions known to be associated with chronic inflammation (e.g. Inflammatory Bowel Disease).
* Subjects with chronic infections (lasting longer than 6 months) such as gingivitis, periodontitis, prostatitis, gastritis, and urinary tract infections.
* Subjects with any acute infection, sinus symptoms, or significant trauma (burns, fractures).
* Subjects with clinically significant renal disease, diabetes mellitus/metabolic syndrome, hypertension or any other clinically significant cardiovascular, neurological, endocrine, or haematological abnormalities that are uncontrolled on permitted therapy.
* Subjects who have participated in any GSK study/studies involving administration of COA.
* The subject has a screening ECG parameters outside of ranges specified in protocol.
* Subjects with hypoxaemia
* Risk factors for human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C infection at Screening (Visit 1).
* Subjects who have undergone surgery including lung volume reduction surgery in the last six months or have conditions that prevent them from performing spirometry.
* Subjects with a history (or suspected history) of alcohol misuse or any other recreational substance abuse.
* Subjects who require treatment with any of the following from the start of the run-in period (Day -14) until the end of the treatment phase:
* Inhaled corticosteroids
* Inhaled cromolyn sodium or nedocromil
* Xanthines (theophylline preparations).
* Leukotriene modifiers
* Tiotropium
* Long-acting inhaled beta2-agonists (salmeterol, formoterol)
* Oral beta2-agonists
* Subjects who are unable to abstain from other courses of medication during the run in phase including non-steroidal anti-inflammatory drugs (NSAIDs), anti-depressant drugs, anti-histamines, anti-rhinitis or hay fever medication, other than short acting inhaled beta-agonists, ipratropium bromide and paracetamol (up to 4 g per day) for the treatment of minor ailments (eg headache) from 48h before the first dose until the follow-up visit. Subjects requiring medication between dosing and follow up may be excluded at the principal investigators discretion.
* Subjects with any known hypersensitivity to salbutamol or ipratropium bromide.
* Subjects who are participating or plan to participate in the active phase of a pulmonary rehabilitation programme during the study.
* Subjects who have received an investigational drug within 30 days or within five drug half-lives of the investigational drug (whichever is longer).
* Subjects with any clinically relevant abnormality detected by the assessments at Screening.
* Subjects who have experienced an exacerbation during the run-in period requiring treatment with oral corticosteroids and/or macrolide antibiotics and/or hospitalisation.
C: 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.

    -
D: 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

Answer: D