Results From Cannabidiol Dose-Ranging Safety Trial for Treating Patients With Dravet Syndrome
Previous randomized controlled trials have suggested that orally administered cannabidiol (CBD) is effective as an add-on to existing antiepileptic drugs (AEDs) for the treatment of convulsive seizures in patients with Dravet syndrome (DS). Open-label trials have supported these findings and also suggest that CBD may be effective for the treatment of other generalized and focal epilepsies, included Lennox-Gastaut syndrome, febrile infection-related epilepsy syndrome, and tuberous sclerosis.
In preparation for a larger randomized trial of cannabidiol for the treatment of DS, a clinical trial, A dose-ranging pharmacokinetics and safety study of GWP42003-P in children with DS (GWPCARE1) was conducted, and results were published today (Neurology. 2018:published online March 14, 2018). Patients aged 1 to 4 years with DS and experiences less than 4 convulsive seizures during a 4-week baseline period were randomly assigned to 1 of 4 dosage groups (5 mg/kg, 10 mg/kg, 20 mg/kg or placebo, given twice daily starting at 2.5 mg/kg per day and increasing by 2.5 mg/kg to 5.0 mg/kg every other day until the full dose was met. Dose reductions were permitted for adverse events.
Blood samples were taken on the first day of dosing and at the end of treatment and safety assessments were made via clinical laboratory test, physical examinations, vital signs, electrocardiograms, adverse event (AE) occurrences, seizure frequency, and suicidality. The level of CBD was dose-dependent and affected the level of clobazam metabolite N-desmethylclobazam (N-CLB), but no other concomitantly taken AED levels in subjects’ blood samples.
Adverse events included behavioral changes, ataxia, vomiting, sedation, decreased appetite, somnolence, rash, and fever. Patients taking CBD and valproate developed elevated transamianases but not drug-induced liver injury, and all recovered. Of the 34 subjects randomized, 5 developed serious AEs (1 in 5 mg/kg group, 2 in 10 mg/kg group, 1 in 20 mg/kg group, and 1 in placebo group). While the rate of AEs was higher in treated subjects vs those given placebo, all doses were relatively well tolerated.