['chronic obstructive pulmonary disease']
['salbutamol', 'ipratropium', 'rpl554', 'salbutamol matched placebo', 'ipratropium matched placebo', 'rpl554 matched placebo']

        Inclusion Criteria:

          -  Provide informed consent

          -  Males not donating sperm and using adequate contraception or females who are
             surgically sterile or postmenopausal

          -  12-lead ECG showing:Heart rate 45 to 90 bpm, QTcF≤450 msec, QRS ≤120 msec, PR interval
             ≤220 msec, no clinically significant abnormality

          -  Capable of complying with all study restrictions and procedures including ability to
             use the study nebuliser correctly.

          -  BMI 18 to 33 kg/m2 with a minimum weight of 45 kg.

          -  COPD diagnosis for at least 1 year and clinically stable COPD in previous 4 weeks

          -  Demonstrates reversibility to bronchodilator (two puffs of salbutamol followed by two
             puffs of ipratropium) via spirometry:

               -  Post-bronchodilator FEV1/forced vital capacity (FVC) ratio of ≤0.70

               -  Post-bronchodilator FEV1 ≥40 % and ≤80% of predicted normal

               -  ≥150 mL increase from pre-bronchodilator FEV1

          -  Chest X-ray showing no abnormalities

          -  Meet the concomitant medication restrictions and be expected to do so for the rest of
             the study.

          -  Smoking history of ≥10 pack years.

          -  Capable of withdrawing from long acting bronchodilators throughout the study and short
             acting bronchodilators for 8 hours prior to study treatment.

        Exclusion Criteria:

          -  History of life-threatening COPD including Intensive Care Unit admission and/or
             requiring intubation.

          -  COPD exacerbation requiring oral steroids in the previous 3 months

          -  History of one or more hospitalisations for COPD in the previous 12 months

          -  Respiratory tract infection (both upper and lower) treated with antibiotics in
             previous 12 weeks

          -  Evidence of cor pulmonale or clinically significant pulmonary hypertension.

          -  Other respiratory disorders

          -  Previous lung resection or lung reduction surgery.

          -  Oral therapies for COPD in the previous 3 months and throughout the study.

          -  Drug or alcohol abuse in the past 3 years

          -  Received an experimental drug within 3 months or five half lives, whichever is longer.

          -  Prior exposure to RPL554

          -  Patients with a history of chronic uncontrolled disease that the Investigator believes
             are clinically significant.

          -  Documented cardiovascular disease in last 3 months

          -  Major surgery, (requiring general anaesthesia) in the previous 6 weeks, or will not
             have fully recovered from surgery, or planned surgery through the end of the study.

          -  History of malignancy of any organ system within 5 years with the exception of
             localised skin cancers (basal or squamous cell)

          -  Clinically significant abnormal values for safety laboratory tests

          -  A disclosed history, or one known to the Investigator, of significant non compliance
             in previous investigational studies or with prescribed medications.

          -  Requires oxygen therapy, even on an occasional basis.

          -  Inability to adequately perform whole body plethysmography.

          -  Any other reason that the Investigator considers makes the subject unsuitable to
             participate.

          -  Patients with known hypersensitivity to atropine or its derivatives, or to ipratropium
             bromide, salbutamol or RPL554 or their excipients/components.
      