Clinical trial NCT00549679 (phase 2, status: completed)
Conditions: pulmonary disease, chronic obstructive
ICD codes: J44.9, J44.1, J44.0
Drugs: gsk256066, placebo
SMILES: COC1=CC=CC(=C1)N=C1C(=CNC2=C1C=C(C=C2C)S(=O)(=O)C1=CC=CC(=C1)C(=O)N(C)C)C(O)=N, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        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.