Bronchodilator Effect of RPL554 Administered in Addition to Tiotropium/Olodaterol in Patients With COPD

Inclusion Criteria: 1. Written informed consent 2. Male or female aged 40 and 80 years 3. For males, not to donate sperm and either be sexually abstinent or use contraception as specified by the protocol. For females, be of non-childbearing potential or use a highly effective form of contraception 4. 12-lead ECG with heart rate between 45 and 90 beats per minute, QTcF ≤450 msec for males, and ≤ 470 msec for females, QRS interval ≤120 msec and no clinically significant abnormality including morphology 5. Screening Holter report with a minimum of 18 hours recording that is able to be evaluated for rhythm analysis showing no abnormality which indicates a significant impairment of patient safety or which may significantly impair interpretation 6. Capable of complying with all study restrictions and procedures including ability to use the study nebulizer and Respimat® correctly. 7. Body mass index (BMI) between 18 and 36 kg/m2 and minimum weight of 45 kg. 8. COPD diagnosis for at least 1 year and clinically stable COPD for 4 week 9. Post-bronchodilator (two puffs of salbutamol/albuterol followed by two puffs of ipratropium) spirometry at Screening: * Post-bronchodilator FEV1/forced vital capacity (FVC) ratio of ≤0.70 * Post-bronchodilator FEV1 ≥30 % and ≤70% of predicted normal * Demonstrates ≥150 mL increase from pre-bronchodilator FEV1 10. A chest X-ray showing no abnormalities, which are both clinically significant and unrelated to COPD. 12\. Meet the concomitant medication restrictions and be expected to do so for the rest of the study. 13\. Current and former smokers with smoking history of ≥10 pack years. 14. Capable of withdrawing from long acting bronchodilators for the duration of the study, and short acting bronchodilators for 8 hours prior to dosing. Exclusion Criteria: 1. A history of life-threatening COPD including Intensive Care Unit admission and/or requiring intubation. 2. COPD exacerbation requiring oral or parenteral steroids, or lower respiratory tract infection requiring antibiotics, in the last 3 months 3. A history of one or more hospitalizations for COPD in the last 12 months 4. Intolerance or hypersensitivity to tiotropium, olodaterol, atropine, ipratropium, or RPL554. 5. Evidence of cor pulmonale or clinically significant pulmonary hypertension. 6. Other respiratory disorders 7. Previous lung resection or lung reduction surgery. 8. Use of oral COPD medications, except mucolytics, in the last 3 months 9. Pulmonary rehabilitation, unless such treatment has been stable in the last 4 weeks 10. History of, or reason to believe a patient has, drug or alcohol abuse within the past 5 years. 11. Inability to perform acceptable spirometry or whole body plethysmography 12. Received an experimental drug within 30 days or five half lives, whichever is longer. 13. Patients with uncontrolled disease that the Investigator believes are clinically significant. This includes any hepatic disease, or an alanine aminotransferase or aspartate aminotransferase\>2 x upper limit of normal (ULN). 14. Documented cardiovascular disease: arrhythmias, angina, recent (\<1 year) or suspected myocardial infarction, congestive heart failure, unstable or uncontrolled hypertension, or diagnosis of hypertension in the last 3 months 15. Use of non-selective oral β-blockers. 16. Major surgery (requiring general anesthesia) in the last 6 weeks or will not have fully recovered from surgery, or planned surgery through the end of the study. 17. A disclosed history or one known to the Investigator, of significant non compliance in previous investigational studies or with prescribed medications. 18. Required use of oxygen therapy, even on an occasional basis. 19. Symptomatic prostatic hyperplasia or bladder-neck obstruction or with narrow-angle glaucoma. 20. History of malignancy of any organ system within 5 years, with the exception of localized skin cancers (basal or squamous cell). 21. Clinically significant abnormal values for safety laboratory tests (hematology, biochemistry, virology or urinalysis) as determined by the Investigator 22. Any other reason that the Investigator considers makes the patient unsuitable to participate.