Cannabidiol (CBD) reduces convulsive seizure frequency in Dravet syndrome: results of a multi-center, randomized, controlled trial (GWPCARE1) (CT.001)

Objective: Assess the effect of CBD added on to antiepileptic drug therapy for treatment of drug-resistant seizures in Dravet syndrome.

Background: Dravet syndrome is an infantile onset developmental and epileptic encephalopathy associated with drug-resistant seizures.

Design/Methods: This double-blind, placebo-controlled trial randomized 120 children and adolescents with Dravet syndrome and drug-resistant seizures to receive CBD oral solution up to 20 mg/kg/day (n=61) or placebo (n=59). Primary endpoint was the change in convulsive seizure frequency over the 14-week dose escalation and treatment period, compared with a 4-week baseline period.

Results: The groups were well-balanced at baseline for demographics. Mean age was 10 years, with 29% of patients <6 years. Patients had previously tried a median 4 AEDs, and were currently taking a median 3 AEDs. Convulsive seizure frequency per month decreased from a median of 12.4 to 5.9 (median reduction of 39%) with CBD versus 14.9 to 14.1 (median reduction of 13%) with placebo (difference between groups of 23%, CI: −41.1 to v 5.4, p=0.012). The proportion of patients with ≥50% reduction in convulsive seizure frequency was 42.6% with CBD versus 27.1% with placebo (OR=2.0, CI: 0.93 to 4.3, p=0.078). No difference was seen in non-convulsive seizures (p=0.88). Adverse events (AEs) occurred in 93.4% of CBD and 74.6% of placebo patients; of those on CBD who reported an AE, it was deemed to be mild or moderate in 84%. AEs occurring in ≥10% of CBD-treated patients were somnolence, diarrhea, decreased appetite, fatigue, pyrexia, vomiting, lethargy, upper respiratory tract infection, and convulsion. Serious AEs were reported in 16.4% of CBD and 5.1% of placebo patients; considered treatment-related in 8.2% of CBD patients, all discontinued CBD. There were no deaths.

Conclusions: In this study, CBD resulted in greater reduction in seizure frequency than placebo; adverse events were more frequent with CBD, but it was generally well-tolerated. (NCT02091375)

Study Supported by:

GW Research, Ltd

Disclosure: Dr. Cross has received (royalty or license fee or contractual rights) payments from UCL/Royal Holloway and Vitaflo. Dr. Cross has received research support from Vitaflo. Dr. Devinsky has received personal compensation for activities with MiaMed. Dr. Devinsky has received personal compensation for serving on the board of MiaMed and Pairnomix. Dr. Devinsky has received research support from GW Pharma and Novartis. Dr. Marsh has received personal compensation for activities with GLC Consultants and SBSE. Dr. Marsh has received research support from GW Pharma and Neuren Pharmacuticals. Dr. Miller has received personal compensation for activities with GW Pharmaceuticals, Insys, Ultragenyx, and Visualase. Dr. Miller has received research support from GW Pharmaceuticals, Insys, Ultragenyx, and Visualase. Dr. Nabbout has received personal compensation for activities with Novartis, GW Pharma, Zogenix, Shire, and Eisai. Dr. Scheffer has received personal compensation for activities with GSK and GWPharma. Dr. Thiele has received personal compensation for activities with GW Pharma, Zogenix, Eisai Pharmaceuticals, Dravet, Lennox Gastaut and TSC as a consultant or PI. Dr. Thiele has received research support from GW Pharma and Zogenix. Dr. Laux has nothing to disclose. Dr. Wright has received personal compensation for activities with GW Research Limited. Dr. Wright holds stock and/or stock options in GW Pharmaceuticals, GlaxoSmithKline, and Astra Zeneca.