Clinical trial NCT02207452 (phase 1, status: completed)
Conditions: pulmonary disease, chronic obstructive
ICD codes: J44.9, J44.1, J44.0
Drugs: salbutamol, ipratropium
SMILES: CC(C)(C)NCC(O)C1=CC(CO)=C(O)C=C1, [H][C@]12CC[C@]([H])(C[C@@H](C1)OC(=O)C(CO)C1=CC=CC=C1)[N+]2(C)C(C)C
Eligibility criteria:

        Inclusion Criteria:

        - Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) diagnosis: an established
        clinical history of chronic pulmonary disorder in accordance with the following description
        by the American Thoracic Society / European Respiratory Society [ATS / ETS, 2004]

        Chronic obstructive pulmonary disease is a preventable and treatable disease characterised
        by airflow limitation that is not fully reversible. The airflow limitation is usually
        progressive and is associated with an abnormal inflammatory response of the lungs to
        noxious particles or gases, primarily caused by cigarette smoking. Although COPD affects
        the lungs, it also produces significant systemic consequences.

          -  The patient is clinically stable with no change in symptoms or medication, no
             admissions to hospital, and with neither antibiotic therapy nor systemic steroid use
             for at least 6 weeks prior to screening. (Screening may be rescheduled after an
             appropriate period of stability)

          -  Male and female patients aged ≥50 years

          -  A female patient is eligible to participate if she is of non-childbearing potential
             defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or
             postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a
             blood sample with simultaneous follicle stimulating hormone (FSH) ≥40 M1U/mL and
             estradiol ≤ 40 pg/mL (≤140 pmol/L) is confirmatory).

          -  Subjects have refrained from short-acting bronchodilators for 8 hours, long-acting
             β2-agonists (including any long-acting β2 agonist containing inhaler) and
             theophyllines for 24 hours and Tiotropium, phosphodiesterase-4 (PDE4) inhibitors (e.g.
             Roflumilast) and ultra long-acting beta-adrenoceptor agonists (e.g. Indacaterol) for
             48 hours prior to admission to the unit on study days.

          -  Subjects with a post-bronchodilator FEV1 to FVC ratio (FEV1/FVC) < 0.7

          -  Subjects with a post-bronchodilator FEV1 ≥ 30% and ≤ 80% of predicted normal for
             height, age and sex at screening.

          -  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.

          -  Resting SpO2 of >90% on room air

          -  QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block (based
             on a single ECG value).

          -  The patient is able to understand and comply with protocol requirements, instructions
             and protocol-stated restrictions, and to give informed consent.

        Exclusion Criteria:

          -  Unstable cardiac disease or history of clinically significant arrhythmia (including
             established atrial fibrillation).

          -  Patients with a primary diagnosis of α-1 antitrypsin deficiency.

          -  Patients with other significant respiratory disorders.

          -  Patients with any acute infection, exacerbation of COPD or other unstable medical
             condition.

          -  Patients in whom inhaled beta-2 agonists or anticholinergics are contraindicated.

          -  Patients who have undergone thoracic surgery including lung volume reduction surgery
             or have conditions that prevent them from performing spirometry and other
             physiological testing.

          -  Patients who are non Magnetic Resonance Imaging (MRI) compatible (ferro-magnetic
             metallic implants, pacemakers) as per the MRI questionnaire.

          -  Patients with renal complaints relating to potential adverse reactions to Gd-DTPA
             intravascular MRI contrast agent.

          -  Patients who suffer from claustrophobia.

          -  The patient has participated in a clinical trial and has received an investigational
             product within the following time period prior to the first study day in the current
             study: 30 days, 5 half-lives or twice the duration of the biological effect of the
             investigational product (whichever is longer) of that study.

          -  Exposure to more than four new chemical entities within 12 months prior to the first
             dosing day.

          -  History of sensitivity to any of the study medications, or components thereof or a
             history of drug or other allergy that, in the opinion of the investigator or GSK
             Medical Monitor, contraindicates their participation.

          -  Subjects must abstain from taking prescription (not related to their COPD) or
             nonprescription drugs (including vitamins and dietary or herbal supplements), within 7
             days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever
             is longer) prior to the first study day until completion of the follow-up visit,
             unless in the opinion of the Investigator and sponsor the medication will not
             interfere with the study.

          -  Unwillingness or inability to follow the procedures outlined in the protocol.