Efficacy / safety of oral S44819 after recent ischemic cerebral event
Randomised Efficacy and Safety Trial with Oral S44819 after Recent ischemic cerebral Event. International, multicentre, randomised, double-blind placebo controlled phase II study.
Servier Research and Development Ltd UK
Duration of Study in the UK
2 years, 4 months, 28 days
This study is looking at the effectiveness and safety of 2 doses of S44819 in patients' functional and cognitive recovery after a recent disabling ischemic stroke. A total of 580 patients, male or female, aged between 18 and 80 years old will take part in the study in 13 countries including the UK.
Preclinical/clinical studies show that post ischemic stroke there is an increased activity of GABAergic neurons to defend the brain from nerve damage during this acute phase, due to reduced oxygen and energy supply. Increased GABAergic activity however has a negative effect on neuroplasticity (how the brain adapts its activities, allowing neurons to compensate for injury). Studies have shown that continued GABAergic activity is linked to poorer outcome. It seems GABA-Aα5 receptors in particular have an important function in this activity.
S44819 is a competitive antagonist of the GABA-Aα5 receptor, currently in phase 1 development for functional recovery (movement/cognition) after ischemic stroke. Patients require a Magnetic resonance imaging (MRI) to exclude a lacunar stroke (blood flow to one of the small arterial vessels deep within the brain becomes blocked).
Patients will be given either 150mg or 300mg of S44819 or dummy drug twice daily over the course of 90 days and have a 15 day follow (no drug).
Efficacy will be evaluated using several rating scales – to evaluate disability and dependency in daily activities after stroke, and 2 patient questionnaires to evaluate cognitive impairment.
Safety evaluation is done regarding adverse events, vital signs, blood analysis (blood cell counting, chemistry), heart check up (electrocardiogram), assessment of suicide ideation/behaviour.
Patients will be asked to participate in an optional pharmacogenetic sub-study to do analysis of genetic variations aiming to allow better understanding of the efficacy and safety of the drug.
West Midlands - Coventry & Warwickshire Research Ethics Committee
Date of REC Opinion
27 Sep 2016
Further Information Favourable Opinion