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

• Status: Completed
• Trial end date: 2015-07-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of the study is to assess the safety of single doses and multiple doses of a new formulation of RPL554 in healthy subjects and subjects with chronic obstructive pulmonary disorder.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Verona Pharma plc

Criteria

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.