Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effect of Roflumilast on Exacerbation Rate in Patients With COPD. The HERMES Study
Brief Summary: The aim of the study is to compare the effect of roflumilast on exacerbation rate and pulmonary function in patients with chronic obstructive pulmonary disease (COPD). Roflumilast will be administered orally once daily in the morning at one dose level. The study duration will be up to 56 weeks. The study will provide further data on safety and tolerability of roflumilast.

For additional information (for US patients only) see www.COPDSTUDY.net or dial 866-788-2673 (toll free).


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:

* 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
C: 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.
D: Inclusion Criteria:

* Moderate-severe COPD (Global inititiative for chronic Obstructive Lung Disease, GOLD, 2003 definition)
* Smoking history of at least 10 pack-years

Exclusion Criteria:

* Any significant co-morbid disease
* Use of any maintenance therapy except short acting bronchodilators

Answer: A