Abstracts

Rationale: The efficacy and safety of CBD in the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) has not been previously demonstrated in controlled trials, although data from an open-label, expanded access program in the United States (US) has suggested that CBD may provide meaningful clinical benefit. Methods: This randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of CBD added on to concomitant antiepileptic drug (AED) therapy in children and adults (2–55 years old) with treatment-resistant LGS at centers in the US, Poland, and the Netherlands. Eligible patients had a clinical diagnosis of LGS, including a history of slow (< 3 Hz) spike?'and?'wave pattern on EEG, experienced at least 2 drop seizures each week during baseline, and had documented failures on more than 1 AED. Patients were randomized (1:1) to receive a pharmaceutical formulation of CBD (100 mg/mL) in oral solution at a dose of 20 mg/kg/day or matched placebo. Patients were treated over a 14?'week period, including an initial 2?'week dose escalation. The classification of seizure types was confirmed by a committee of experts from the Epilepsy Study Consortium. The primary efficacy endpoint was percentage change from baseline in drop seizure frequency (tonic, atonic, and tonic-clonic) over the entire treatment period for patients on CBD vs placebo. Results: A total of 171 patients were randomized (86 to CBD; 85 to placebo). All patients who received 1 or more doses of investigational medicinal product were included in the intent to treat and safety analysis sets; 14 CBD and 1 placebo patient withdrew early.  Demographic characteristics were evenly distributed between the treatment groups at baseline; mean age was 15 years (34% of patients were 18 years or older) and median drop seizure frequency per 28 days was 74. Patients had previously been treated with a mean of 6 AEDs, and took a mean of 3 concomitant AEDs throughout the trial. CBD resulted in a significant median percent reduction in monthly drop seizure frequency, compared with placebo, during the 14?'week treatment period (44% vs. 22%; p=0.0135). The difference between CBD and placebo emerged during the first 4 weeks of stable dosing, and was sustained throughout the treatment period. Drop seizure freedom occurred in 3 CBD patients during the maintenance period. Overall 86% of CBD and 69% of placebo patients had adverse events (AEs); in the CBD group 78% were mild or moderate. The most common AEs (occurring in >