Abstracts

Rationale: The efficacy and safety of CBD in the treatment of seizures associated with LGS were analyzed in 2 trials of similar design over a 14-week (wk) period, GWPCARE 3 (NCT02224560) and GWPCARE 4 (NCT02224690). Analyses of pooled results provide additional insights across the larger population. Methods: Outcomes were pooled from 2 randomized, multicenter, double-blind, placebo (PBO)-controlled trials investigating the efficacy and safety of CBD as add-on to existing antiepileptic drugs (AEDs) in patients (pts) aged 2-55 years (y) with treatment-resistant LGS. Eligibility criteria included clinical diagnosis of LGS, ≥2 drop seizures/wk during a 4-wk baseline, and documented failure on ≥1 AED. Pts were randomized to PBO or to a plant-derived pharmaceutical formulation of CBD (100 mg/mL) in oral solution, dosed at 10 mg/kg/day (CBD10) or 20 mg/kg/day (CBD20) in 2 equally divided doses for 14 wks (2-wk titration period followed by a 12-wk maintenance period). The primary efficacy endpoint of both studies was median percentage change from baseline in drop seizure frequency for CBD vs PBO during the treatment period. Results: A total of 396 pts were randomized (73 CBD10; 162 CBD20; 161 PBO). Demographic characteristics were comparable at baseline; mean age was 15 y (32% ≥18 y). Median monthly baseline drop seizure frequency for CBD10, CBD20, and PBO was 87, 78, and 79, respectively. Pts had previously tried a median of 6 and were taking a median of 3 concomitant AEDs. During the treatment period, CBD10 and CBD20 significantly reduced monthly drop seizure frequency vs PBO (37% and 43% vs 20%) with greater reductions during maintenance (40% and 48% vs 20%). Drop seizure responder rates were significantly higher with CBD10 and CBD20 vs PBO (Table 1). During the entire maintenance period, 3 CBD10, 8 CBD20, and 1 PBO pt were drop seizure free. Significantly greater reductions in total seizures for both CBD doses vs PBO were also observed during the treatment period (36% and 39% vs 17%) and maintenance period (40% and 44% vs 17%). CBD pts/caregivers were significantly more likely to report an improvement in overall condition compared with PBO as measured by Subject/Caregiver Global Impression of Change (64% and 52% vs 38%). Overall, 84% of CBD10, 90% of CBD20, and 71% of PBO pts had adverse events (AEs); most common were somnolence, decreased appetite, and diarrhea. Serious AEs were reported in 13 CBD10, 33 CBD20, and 12 PBO pts; considered treatment-related in 2 CBD10, 14 CBD20, and 1 PBO pt. There was 1 death in the CBD20 group considered unrelated to treatment. Elevated transaminases (>3x ULN) were reported in 3 CBD10, 31 CBD20, and 1 PBO pt, most of whom were on concomitant valproic acid. Some withdrew from treatment; all elevations resolved either spontaneously or with CBD/AED dose adjustment. Conclusions: These results support that add-on CBD is efficacious in the treatment of seizures associated with LGS with more AEs than PBO but generally well-tolerated. Funding: GW Research Ltd