Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomised, Double-blind, Placebo-controlled Study to Investigate the Safety and Tolerability of Inhaled GSK256066 in Mild to Moderate COPD Patients
Brief Summary: This study will evaluate the safety and tolerability of the cfor the first time in mild to moderate COPD patients.


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:

* 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
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: 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.

Answer: D