Study Evaluating 5 Doses of RPL554 and Placebo in COPD Patients Via a Dry Powder Inhaler

Inclusion Criteria

• 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.
• 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
• 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
• Capable of complying with all study restrictions and procedures including ability to use the DPI correctly.
• Body mass index (BMI) between 18 and 35 kg/m2 (inclusive) with a minimum weight of 45 kg.
• COPD diagnosis for 1 year [prior to screening
• Ability to perform acceptable and reproducible spirometry.
• Post-bronchodilator (four puffs of albuterol) spirometry at Screening demonstrating the following:
• FEV1/Forced Vital Capacity (FVC) ratio of ≤0.70
• FEV1 ≥40 % and ≤80% of predicted normal
• ≥150 mL increase from pre-bronchodilator FEV1
• Clinically stable COPD in the 4 weeks prior to Screening and during the period between Screening and Part A.
• A chest X-ray showing no abnormalities, which are both clinically significant and unrelated to COPD.
• Meet the concomitant medication restrictions and be expected to do so for the rest of the study.
• 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

• A history of life-threatening COPD including Intensive Care Unit admission and/or requiring intubation.
• COPD exacerbation requiring oral or parenteral steroids, or lower respiratory tract infection requiring antibiotics, within 3 months of Screening or prior to Part A.
• A history of one or more hospitalizations for COPD or pneumonia within 6 months of Screening or prior to Part A.
• Intolerance or hypersensitivity to tiotropium, olodaterol, atropine, ipratropium, or RPL554.
• Evidence of cor pulmonale or clinically significant pulmonary hypertension.
• Other respiratory disorders
• Previous lung resection or lung reduction surgery.
• Use of immunosuppressive therapy, including oral corticosteroids
• Pulmonary rehabilitation, unless such treatment has been stable from 4 weeks prior to Screening and remains stable during the study.
• History of, or reason to believe a patient has, drug or alcohol abuse within the past 5 years.
• Received an experimental drug within 30 days or five half lives, whichever is longer.
• Patients with uncontrolled disease including, but not limited to, endocrine, active hyperthyroidism, neurological, hepatic, gastrointestinal, renal, hematological, urological, immunological, psychiatric, or ophthalmic diseases that the Investigator believes are clinically significant.
• Documented cardiovascular disease, including any history of arrhythmias, angina, recent (<1 year) or suspected myocardial infarction, congestive heart failure, unstable or uncontrolled hypertension, or diagnosis of hypertension within 3 months prior to Screening
• Use of non-selective oral β-blockers.
• Major surgery (requiring general anesthesia) within 6 weeks prior to Screening, lack of full recovery from surgery at Screening, or planned surgery through the end of the study.
• A disclosed history or one known to the Investigator, of significant non compliance in previous investigational studies or with prescribed medications.
• Required use of oxygen therapy, even on an occasional basis.
• History of malignancy of any organ system within 5 years, with the exception of localized skin cancers (basal or squamous cell).
• Clinically significant abnormal values for safety laboratory tests (hematology, biochemistry