Status:
COMPLETED
SAD/MAD Study of a New Formulation of Nebulised RPL554 in Healthy Subjects and COPD Subjects
Lead Sponsor:
Verona Pharma plc
Conditions:
Inflammatory Disorder of the Respiratory Tract
Chronic Obstructive Pulmonary Disorder
Eligibility:
All Genders
18-75 years
Phase:
PHASE1
Brief 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.
Detailed Description
This is a randomised, double blind, placebo controlled study of a new suspension formulation of RPL554 comprising a Single Ascending Dose (SAD) phase (Part A) in healthy subjects, a Multiple Ascending...
Eligibility Criteria
Inclusion
- 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
- 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.
Key Trial Info
Start Date :
December 1 2014
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
July 1 2015
Estimated Enrollment :
112 Patients enrolled
Trial Details
Trial ID
NCT02307162
Start Date
December 1 2014
End Date
July 1 2015
Last Update
October 28 2015
Active Locations (1)
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1
Medicines Evaluation Unit
Manchester, United Kingdom, M23 9QP