['chronic obstructive pulmonary disease moderate']
['1.5 mg rpl554 plus tiotropium', '6 mg rpl554 plus tiotropium', 'placebo plus tiotropium']

        Inclusion Criteria:

          1. Sign an informed consent document indicating they understand the purpose of and
             procedures required for the study and are willing to participate in the study.

          2. Male or female aged between 40 and 75 years inclusive, at the time of informed
             consent.

          3. If male: must agree to meet the following from the first dose up to 1 month after the
             last dose of study treatment:

               -  Not donate sperm

               -  Either: be sexually abstinent in accordance with a patient's usual and preferred
                  lifestyle (but agree to abide by the contraception requirements below should
                  their circumstances change) Or: use a condom with all sexual partners. If the
                  partner is of childbearing potential the condom must be used with spermicide and
                  a second highly effective form of contraception must also be used

          4. If female: either be:

               1. Of non-childbearing potential defined as being:

                    -  Either: post-menopausal (being spontaneously amenorrhoeic for at least 1
                       year with an appropriate clinical profile [e.g. age appropriate, history of
                       vasomotor symptoms]

                    -  Or: permanently sterilised e.g. tubal occlusion, hysterectomy, bilateral
                       oophorectomy, bilateral salpingectomy

               2. Of childbearing potential and agreeing to use a highly effective method of
                  contraception until completion of the end of study visit.

          5. Have a 12-lead ECG recording at screening and randomisation (pre-dose in Treatment
             Period 1) showing the following:

               -  Heart rate between 45 and 90 beats per minute (bpm)

               -  QT interval corrected for heart rate using Fridericia's formula (QTcF) ≤450 msec
                  for males and ≤470 ms for females

               -  QRS interval ≤120 msec

               -  No clinically significant abnormalities (as judged by the Investigator) including
                  morphology (e.g. left bundle branch block, atrio-ventricular nodal dysfunction,
                  ST segment abnormalities)

          6. Have a screening Holter report with a minimum of 18 hours recording that is able to be
             evaluated for rhythm analysis which shows no abnormality which indicates a significant
             impairment of patient safety or which may significantly impairs interpretation in the
             opinion of the Investigator including:

               -  Significant arrhythmias including atrial flutter, atrial fibrillation,
                  ventricular tachycardia

               -  Any symptomatic arrhythmia (except isolated extra systoles)

               -  Any sustained second or third degree heart block

          7. Capable of complying with all study restrictions and procedures including ability to
             use the study nebuliser and HandiHaler® DPI correctly.

          8. Body mass index (BMI) between 18 and 33 kg/m2 (inclusive) with a minimum weight of 45
             kg.

          9. COPD diagnosis: Patients with a diagnosis of COPD as defined by the American Thoracic
             Society (ATS)/European Respiratory Society (ERS) guidelines (Celli and MacNee, 2004)
             with symptoms compatible with COPD for at least 1 year prior to screening.

         10. Post-bronchodilator (four puffs of salbutamol) spirometry at screening:

               -  Post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital
                  capacity (FVC) ratio of ≤0.70

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

               -  Demonstrates ≥150 mL increase from pre-bronchodilator FEV1

         11. Clinically stable COPD in the 4 weeks prior to screening and randomisation (pre-dose
             in Treatment Period 1).

         12. A chest X-ray (post-anterior) at screening, or in the 12 months prior to screening
             showing no abnormalities, which are both clinically significant and unrelated to COPD.

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

         14. Smoking history of ≥10 pack years.

         15. Capable of withdrawing from long acting bronchodilators for the duration of the study,
             and short acting bronchodilators for 8 hours prior to spirometry.

        Exclusion Criteria:

          1. A history of life-threatening COPD exacerbation including Intensive Care Unit
             admission and/or requiring intubation.

          2. COPD exacerbation requiring oral steroids, or lower respiratory tract infection
             requiring antibiotics, in the 3 months prior to screening or randomisation (pre-dose
             in Treatment Period 1).

          3. A history of one or more hospitalisations for COPD in the 12 months prior to screening
             or randomisation (pre-dose in Treatment Period 1).

          4. Lactation (female patients only).

          5. Positive urine or serum pregnancy test at screening, or a positive urine pregnancy
             test prior to randomisation (female patients of childbearing potential only).

          6. Prior exposure to RPL554 or known hypersensitivity to RPL554 or its components.

          7. Intolerance or hypersensitivity to tiotropium.

          8. Evidence of cor pulmonale.

          9. Other respiratory disorders: Patients with a current diagnosis of asthma, active
             tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, interstitial
             lung diseases, sleep apnoea, known alpha-1 antitrypsin deficiency or other active
             pulmonary diseases.

         10. Previous lung resection or lung reduction surgery.

         11. Use of oral COPD medications (e.g. oral steroids, theophylline and romifulast) in the
             3 months prior to screening or randomisation (pre-dose in Treatment Period 1).

         12. History of, or reason to believe, a patient has drug or alcohol abuse within the past
             3 years.

         13. Inability to perform technically acceptable spirometry or whole body plethysmography
             (at screening or randomisation [pre dose in Treatment Period 1])

         14. Received an experimental drug within 30 days or five half lives, whichever is longer.

         15. Patients with a history of chronic uncontrolled disease including, but not limited to,
             endocrine, active hyperthyroidism, neurological, hepatic, gastrointestinal, renal,
             haematological, urological, immunological, or ophthalmic diseases that the
             Investigator believes are clinically significant.

         16. Documented cardiovascular disease: arrhythmias, angina, recent or suspected myocardial
             infarction, congestive heart failure, a history of unstable, or uncontrolled
             hypertension, or has been diagnosed with hypertension in the 3 months prior to
             screening or randomisation.

         17. Concurrent use of non-cardioselective oral beta-blockers.

         18. Has had major surgery, (requiring general anaesthesia) in the 6 weeks prior to
             screening or randomisation (pre-dose in Treatment Period 1), or will not have fully
             recovered from surgery, or planned surgery through the end of the study.

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

         20. Requires oxygen therapy, even on an occasional basis.

         21. Clinically significant prostatic hyperplasia (judged by the Investigator) or
             bladder-neck obstruction or with narrow-angle glaucoma.

         22. Any other reason that the Investigator considers makes the patient unsuitable to
             participate.
      