A Randomized, Double Blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Treatment With Single and Repeat Doses of Inhaled RV6153 in Healthy Subjects and Subjects With Stable Asthma.
Overview
- Phase
- Phase 1
- Intervention
- RV6153 matching placebo 14 day repeat dose
- Conditions
- Asthma
- Sponsor
- Respivert Ltd
- Enrollment
- 55
- Primary Endpoint
- Safety and tolerability of single and repeat doses assessed by incidence of treatment emergent adverse events
- Status
- Terminated
- Last Updated
- 10 years ago
Overview
Brief Summary
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
Investigators
Eligibility Criteria
Inclusion Criteria
- •Cohorts 1 to 13 (all subjects)
- •Subject must be a man or woman aged between 18 to 65 years of age, inclusive: Women of non-childbearing potential only - defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile or permanently sterilised. Men who are willing and able to use suitable contraception methods listed in Section 4.5.1, from the time of the first dose of study medication until 90 days after discharge from the study.
- •A woman must have a negative serum β human chorionic gonadotropin (β-hCG) test at screening and a negative urine pregnancy test at Day -
- •Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol
- •Each subject must sign an informed consent form (ICF)
- •Body weight ≥50 kg and BMI within the range 19-29 kg/m2 (inclusive).
- •Average QTcF \<450 msec at screening and Day -1 visits
- •Vital sign assessments within normal ranges.
- •Cohorts 1 to 11 and 13 (healthy volunteers and smokers only)
- •Healthy as determined by a physician, based on a full medical evaluation including medical history, physical examination, laboratory tests.
Exclusion Criteria
- •Cohorts 1 to 13 (all subjects)
- •Upper or lower respiratory tract infection within 4 weeks of the screening visit and prior to randomisation.
- •A positive pre-study hepatitis B surface antigen or positive hepatitis C antibody result at screening.
- •Current or chronic history of liver disease, or known hepatic or biliary abnormalities.
- •Positive test for alcohol or drugs of abuse.
- •Use of prescription medications within 14 days prior to the screening visit and agree not to use prescription medications throughout the duration of the study.
- •Are taking over the counter (OTC) medications for 14 days prior to Screening visit and agree to refrain from taking such medications throughout the study.
- •History of regular alcohol consumption within 6 months of the study
- •Definite or suspected history of drug or alcohol abuse within the previous 5 years.
- •A positive test for HIV antibody.
Arms & Interventions
14 day repeat dose, asthma patients
Intervention: RV6153 matching placebo 14 day repeat dose
14 day repeat dose, smokers
Intervention: RV6153 14 day repeat dose
14 day repeat dose, smokers
Intervention: RV6153 matching placebo 14 day repeat dose
Single dose, healthy volunteers
Intervention: RV6153 single dose
Single dose, healthy volunteers
Intervention: RV6153 matching placebo single dose
14 day repeat dose, healthy volunteers
Intervention: RV6153 14 day repeat dose
14 day repeat dose, healthy volunteers
Intervention: RV6153 matching placebo 14 day repeat dose
28 day repeat dose, healthy volunteers
Intervention: RV6153 28 day repeat dose
28 day repeat dose, healthy volunteers
Intervention: RV6153 matching placebo 28 day repeat dose
14 day repeat dose, asthma patients
Intervention: RV6153 14 day repeat dose
Outcomes
Primary Outcomes
Safety and tolerability of single and repeat doses assessed by incidence of treatment emergent adverse events
Time Frame: Up to 29 days post final dose
Assessment of the number of adverse events reported by subjects following dosing
Safety and tolerability of single and repeat doses assessed by ECG (12-lead ECG)
Time Frame: Up to 29 days post final dose
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
Safety and tolerability of single and repeat doses assessed by vital sign measurement (blood pressure & heart rate)
Time Frame: Up to 29 days post final dose
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.
Safety and tolerability of single and repeat doses assessed by respiration rate
Time Frame: Up to 29 days post final dose
Respiration rate will be measured after resting for 5 minutes
Safety and tolerability of single and repeat doses assessed by temperature
Time Frame: Up to 29 days post final dose
Temperature will be measured orally
Safety and tolerability of single and repeat doses assessed by spirometry
Time Frame: Up to 29 days post final dose
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.
Safety and tolerability of single and repeat doses by assessment of clinical laboratory tests
Time Frame: Up to 29 days post final dose
Clinical laboratory tests include haematology, clinical chemistry, urinalysis and additional parameters
Pharmacodynamic (PD) effect of repeat doses of RV6153 assessed by sputum cell biomarkers
Time Frame: Cohort 13 (subjects who smoke) only - assessments at screening and Days 1, 7 & 14
Sputum samples will be collected to evaluate PD effects of repeat doses of RV6153 by assessment of phosphatidylinositol biphosphate (PIP2) and phosphatidylinositol triphosphate (PIP3).
Secondary Outcomes
- Plasma RV6153 levels(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)