Timothy B Saurer, Elaine C Wirrell, Ashley Schreiber, Robert T Wechsler

Objectives: A Phase 3 randomised controlled trial (RCT; NCT02224560) and open-label extension (OLE; NCT02224573) demonstrated the long-term safety and efficacy of cannabidiol (CBD) in reducing drop seizure frequency in patients with Lennox-Gastaut syndrome (LGS). This post-hoc analysis evaluated the effect of dose adjustments on the efficacy and safety of CBD.

 Methods: Patients received plant-derived highly purified CBD medicine (Epidyolex®; 100 mg/mL oral solution) at 10 mg/kg/day (CBD10), 20 mg/kg/day or matched placebo for 14 weeks (RCT). Patients who completed the RCT could enrol in the OLE, with CBD initially titrated to 20 mg/kg/day and subsequent adjustments based on response and tolerability (maximum 30 mg/kg/day). Analyses included patients receiving CBD10 with doses titrated up in the OLE and maintained at a modal dose of ≥12.5 mg/kg/day. Weekly median percent change from baseline in drop seizure frequency was assessed through 96 weeks. 

 Results: Analyses included 43 OLE patients; median (range) age: 12 (3–38) years. Cumulative weekly median seizure reduction: 47% (end of RCT), reduced by a further 14% (OLE) and maintained throughout the trial. Seizure frequency reduction during the OLE was greater in patients (58%) with <50% reduction during the RCT versus patients (42%) with ≥50% reduction. AE incidence: 84% (RCT); 98% (OLE). Most common AEs: somnolence, decreased appetite and upper respiratory tract infection (19% each; RCT); convulsion (51%), diarrhoea (42%) and pyrexia (37%; OLE).

 Conclusion: This post-hoc analysis emphasises the importance of titrating to each patient’s therapeutic dose, which may improve seizure reduction in some patients with LGS. 

Keywords: Lennox-Gastaut syndrome, Cannabidiol, Post hoc, Dos

 Timothy B Saurer 

Jazz Pharmaceuticals 

United States 

 Elaine C Wirrell

 Divisions of Child and Adolescent Neurology and Epilepsy

 United States 

 Ashley Schreiber 

Jazz Pharmaceuticals 

United Kingdom 

 Robert T Wechsler 

Idaho Comprehensive Epilepsy Center 

United States