Dose Ranging Study of RPL554 in Chronic Obstructive Pulmonary Disease (COPD) Patients

Inclusion Criteria

• Provide informed consent
• Male or female aged 40 to 75 years
• Meeting specified contraception requirements
• 12-lead electrocardiogram with heart rate 50-90 beats per minute, QT interval corrected using Fridericia's formula (QTcF) ≤450 msec (males) or ≤470 msec (females), QRS interval ≤120 msec, PR interval ≤200 msec and no clinically significant abnormalities
• Capable of complying with all study restrictions and procedures, including ability to use the study nebulizer correctly.
• Body mass index (BMI) 18 to 35 kg/m2 and minimum weight 45 kg.
• COPD diagnosis with symptoms compatible with COPD for at least 1 year
• Clinically stable COPD in the previous 4 weeks
• Ability to perform acceptable and reproducible spirometry.
• Post-bronchodilator spirometry at screening must demonstrate FEV1/forced vital capacity (FVC) ratio of ≤0.70 and FEV1 must be ≥40 % to ≤80% of predicted normal
• Chest X-ray (posterior-anterior) at screening, or chest X-ray, magnetic resonance imaging (MRI) or computed tomography (CT) scan in the last 12 months, 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 a smoking history of ≥10 pack years.
• Capable of withdrawing long acting bronchodilators until the end of the treatment period, and short acting bronchodilators for 8 hours prior to administration of study medication.

Exclusion Criteria

• A history of life-threatening COPD including Intensive Care Unit admission and requiring intubation.
• COPD exacerbation requiring oral steroids in the previous 3 months
• A history of one or more hospitalizations for COPD in the previous 6 months
• Lower respiratory tract infection treated with antibiotics in the previous 3 months
• Evidence of cor pulmonale or clinically significant pulmonary hypertension.
• Patients with a current diagnosis of asthma, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, interstitial lung diseases, sleep apnea, known alpha-1 antitrypsin deficiency or other active pulmonary diseases.
• Previous lung resection or lung reduction surgery.
• Oral therapies for COPD (e.g. oral steroids, theophylline, and roflumilast) in the previous 3 months and throughout the study.
• Pulmonary rehabilitation, unless such treatment has been stable from 4 weeks prior to Visit 1) and remains stable during the trial.
• A history of, or reason to believe a subject has, drug or alcohol abuse in the previous 3 years.
• Received an experimental drug within 30 days or five half-lives of the first dose
• Prior exposure to RPL554.
• Women who are pregnant or breast-feeding.
• Patients with a history of current uncontrolled disease that the Investigator believes are clinically significant.
• myocardial infarction in the previous 6 month; congestive heart failure, a history of unstable or uncontrolled hypertension, or has been diagnosed with hypertension in last 3 months.
• Use of oral beta blockers.
• Major surgery (requiring general anesthesia) in the previous 6 weeks, lack of full recovery from surgery at screening, or planned surgery through the end of the study.
• 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
• Significant non-compliance in previous investigational studies or with prescribed medications.
• Requirement for oxygen therapy, even on an occasional basis.
• Known hypersensitivity to RPL554 or its excipients/components.
• Abnormal clinically significant 12 lead Holter findings,
• Any other reason that the Investigator considers makes the subject unsuitable to participate.