RV6153 is a new medicine being developed for possible treatment of asthma and smoking related lung disease (also known as chronic obstructive pulmonary disease - COPD). The main purpose of this study is to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and repeat doses of RV6153
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
55
Safety and tolerability of single doses
Safety and tolerability of single doses
Safety and tolerability of repeat doses
Unnamed facility
Manchester, United Kingdom
Unnamed facility
Nottingham, United Kingdom
Safety and tolerability of single and repeat doses assessed by incidence of treatment emergent adverse events
Assessment of the number of adverse events reported by subjects following dosing
Time frame: Up to 29 days post final dose
Safety and tolerability of single and repeat doses assessed by ECG (12-lead ECG)
12-lead ECGs will be obtained using an ECG machine that automatically calculates heart rate and measures PR, QRS, QT, and QTcB/QTcF intervals. ECGs will be measured after resting for 5 minutes
Time frame: Up to 29 days post final dose
Safety and tolerability of single and repeat doses assessed by vital sign measurement (blood pressure & heart rate)
Blood pressure heart rate will be assessed together using an automated device after resting for 5 minutes. Blood pressure will include systolic and diastolic measurements.
Time frame: Up to 29 days post final dose
Safety and tolerability of single and repeat doses assessed by respiration rate
Respiration rate will be measured after resting for 5 minutes
Time frame: Up to 29 days post final dose
Safety and tolerability of single and repeat doses assessed by temperature
Temperature will be measured orally
Time frame: Up to 29 days post final dose
Safety and tolerability of single and repeat doses assessed by spirometry
Pulmonary function test measured from forced expiratory volume in 1 second (FEV1). Pulmonary function test will be repeated until three technically acceptable measurements have been made.
Time frame: Up to 29 days post final dose
Safety and tolerability of single and repeat doses by assessment of clinical laboratory tests
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Safety and tolerability of repeat doses
Safety and tolerability of repeat doses
Safety and tolerability of repeat doses
Clinical laboratory tests include haematology, clinical chemistry, urinalysis and additional parameters
Time frame: Up to 29 days post final dose
Pharmacodynamic (PD) effect of repeat doses of RV6153 assessed by sputum cell biomarkers
Sputum samples will be collected to evaluate PD effects of repeat doses of RV6153 by assessment of phosphatidylinositol biphosphate (PIP2) and phosphatidylinositol triphosphate (PIP3).
Time frame: Cohort 13 (subjects who smoke) only - assessments at screening and Days 1, 7 & 14
Plasma RV6153 levels
Time frame: Cohorts 1-9: Day 1, 10 samples, Days 2,8,15&29, 1 sample per day; Cohorts 10, 12 & 13: Days 1,7&14, 10 samples per day, Days 2,8-13,1,21,28&42, 1 sample per day; Cohort 11: Days 1,14&28, 10 samples per day, Days 7,21,26,27,29,35,42&56, 1 sample per day