SAD/MAD Study of a New Formulation of Nebulised RPL554 in Healthy Subjects and COPD Subjects

Inclusion Criteria: * Informed consent * Males following contraception requirements, and agree not to donate sperm during study * 12-lead ECG within normal range and no clinically significant abnormality * Screening Holter report (minimum 18 hours) recording that is able to be evaluated for rhythm analysis which shows no abnormality which indicates a significant impairment of subject safety or which may significantly impair interpretation * Capable of complying with all study restrictions and procedures including ability to use the study nebuliser correctly. * Body weight ≥50 kg. * Negative for HIV, HBV and HCV * Negative cotinine tests prior to randomisation. Additional Inclusion Criteria - Healthy Subjects (Parts A and B) only: * Males aged 18 and 50 years * Considered to be healthy * Vital sign assessments within ranges: * Systolic blood pressure 90 to 140 mmHg * Diastolic blood pressure 50 to 90 mmHg * Heart rate 45 to 90 bpm * BMI 18 and 33 kg/m2 . * Spirometry readings (FEV1 and FVC) ≥80% of predicted normal. * Never smoked or is ex-smoker for ≥12 months with a smoking history of \<5 pack years Additional Inclusion Criteria - COPD Subjects (Part C) only: * Male and females aged 40 to 75 years * If female must be of non-childbearing potential (postmenopausal or permanently sterilised) * BMI 18 and 33 kg/m2 (inclusive). * COPD diagnosis (defined by ATS/ERS guidelines Celli and MacNee, 2004) with symptoms compatible with COPD for at least 1 year * As defined in GOLD guidelines 2014: Post-bronchodilator spirometry at screening: * Post-salbutamol FEV1/FVC ratio 0.70 * Post-salbutamol FEV1 ≥50 % and ≤80% of predicted normal * No current conditions that may significantly impair subject compliance, safety or influence study results. * Vital sign assessments within ranges: * Systolic blood pressure 100 to 160 mmHg * Diastolic blood pressure 50 to 90 mmHg * Heart rate 45 to 90 bpm * Clinically stable COPD in the last 4 weeks * Chest X-ray (post anterior) at screening, or within 6 months prior to screening showing no abnormalities, which are both clinically significant and unrelated to COPD. * Meet the concomitant medication restrictions * An ex-smoker for ≥6 months with a smoking history of ≥10 pack years * Capable of withdrawing from regular bronchodilators Exclusion Criteria: * Respiratory tract infection (both upper and lower) treated with antibiotics in last 12 weeks * Clinically significant abnormal values for safety laboratory tests or physical examination * History or suspected history of drug or alcohol abuse within the past 5 years. * Known allergy to the study drug or any of the excipients of the formulation. * Donated blood or blood products or had substantial loss of blood (more than 500 mL) in last 4 weeks or intention to donate blood or blood products during the study. * Received an experimental drug or used an experimental medical device within 3 months or within a period less than 5 times the drug's half-life, whichever is longer * Pre-planned surgery or procedures that would interfere with the conduct of the study. * Employee of the Investigator or study site or family members of the employees or the Investigator. * History of regular alcohol consumption within last 6 months * Unable or unwilling to comply fully with the study protocol. * Mentally or legally incapacitated. * Unable or unwilling to undergo multiple venepuncture procedures or having poor access to veins suitable for cannulation. * History of malignancy of any organ system, treated or untreated within the past 5 years, with the exception of localised basal cell carcinoma of the skin. * Any other reason that the Investigator considers makes the subject unsuitable to participate. Additional Exclusion Criteria - Healthy Subjects (Parts A and B) only -Positive test for alcohol or drugs of abuse Additional Exclusion Criteria - COPD Subjects (Part C) only * Positive test for alcohol or drugs of abuse prior to randomisation (unless explained by the subject's medication). * A history of life-threatening COPD including Intensive Care Unit admission and/or requiring intubation. * COPD exacerbation requiring oral steroids within the last 12 months * A history of one or more hospitalization for COPD in last 12 months * Evidence of cor pulmonale or clinically significant pulmonary hypertension. * Other respiratory disorders: Subjects with a current diagnosis of asthma, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, interstitial lung diseases, sleep apnoea, known alpha1-AT deficiency or other active pulmonary diseases. * Previous lung resection or lung reduction surgery. * Active participation in a pulmonary rehabilitation program. * History of chronic uncontrolled disease that the Investigator believes are clinically significant. * Documented severe cardiovascular disease: angina, recent or suspected myocardial infarction, History of unstable, or uncontrolled hypertension, or has been diagnosed with hypertension in last 3 months. * Major surgery, (requiring general anaesthesia) within last 6 weeks before the screening visit, or will not have fully recovered from surgery, or planned surgery through the end of the study. * History of significant non compliance in previous investigational studies or with prescribed medications. * Requires oxygen, even on an occasional basis.