Efficacy and Safety of Cannabidiol (CBD) Dose Adjustment in Patients With Lennox-Gastaut Syndrome (LGS): Post Hoc Analysis of Phase 3 Randomized Controlled Trial (RCT) GWPCARE3 and Open-Label Extension (OLE) Trial GWPCARE5 (P12-8.007)

Objective: Evaluate effect of dose adjustments on efficacy and safety of CBD in patients from GWPCARE3 (NCT02224560) and GWPCARE5 (NCT02224573).

Background: Add-on CBD significantly reduced drop seizure frequency with an acceptable safety profile in patients with LGS in GWPCARE3 and GWPCARE5, which enrolled patients who completed GWPCARE3.

Design/Methods: Eligible patients (2–55 years) had ≥2 drop seizures per week during baseline. During RCT, patients received 10 (CBD10) or 20 mg/kg/d CBD (Epidiolex^®; 100 mg/mL oral solution) or placebo. During OLE, the dose was titrated to the initial target of 20 mg/kg/day. These post hoc analyses included patients on CBD10 during RCT whose dose was titrated in OLE and who maintained a modal dose ≥12.5 mg/kg/day. Efficacy evaluation included weekly median percent change from baseline in drop seizure frequency through 96 weeks.

Results: Analyses included 43/71 patients on CBD10 who enrolled in OLE (28 patients had modal dose <12.5mg/kg/d). Median (range) age: 12 (3–38) years. Median concomitant ASMs: 3. During baseline, median (range) drop seizure frequency: 83 (14–7494). At RCT end, cumulative weekly median percent reduction from baseline: 47%. During OLE, an additional 14% reduction was observed. Reduction in seizure frequency during OLE was greater in patients (25/43 [58%]) without ≥50% reduction in drop seizures during RCT than in patients (18/43 [42%]) with ≥50% reduction. Additional reduction in seizure frequency was maintained throughout the OLE. AE incidence: 36/43 patients (84%) during RCT and 42/43 (98%) during OLE. For this subgroup, most common AEs: somnolence, decreased appetite, and upper respiratory tract infection (19% each) during RCT and convulsion (51%), diarrhea (42%), and pyrexia (37%) at any point during OLE.

Conclusions: Additional reductions in drop seizure frequency were observed after CBD dose titration during OLE without new safety concerns. CBD titration to each patient’s therapeutic dose may improve seizure reduction in some patients.

Disclosure: Dr. Wirrell has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Wirrell has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biomarin. Dr. Wirrell has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Encoded. Dr. Wirrell has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amicus. Dr. Wirrell has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurocrine. Dr. Wirrell has received publishing royalties from a publication relating to health care. Mr. Schreiber has received personal compensation for serving as an employee of GW Pharmaceuticals. Mr. Schreiber has received stock or an ownership interest from GW Pharmaceuticals. Dr. Saurer has received personal compensation for serving as an employee of Greenwich Biosciences. Dr. Saurer has received stock or an ownership interest from Jazz Pharmaceuticals. The institution of Dr. Wechsler has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Otsuka. The institution of Dr. Wechsler has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for UCB. The institution of Dr. Wechsler has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for SK Life Science. The institution of Dr. Wechsler has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Aquestive. The institution of Dr. Wechsler has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Engage. The institution of Dr. Wechsler has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Greenwich. The institution of Dr. Wechsler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cerevel. The institution of Dr. Wechsler has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Eisai. The institution of Dr. Wechsler has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sunovion. The institution of Dr. Wechsler has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eliem. The institution of Dr. Wechsler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. The institution of Dr. Wechsler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Epalex. The institution of Dr. Wechsler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Engrail. The institution of Dr. Wechsler has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurona. Dr. Wechsler has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Neurelis. Dr. Wechsler has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Sunovion. Dr. Wechsler has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for UCB. Dr. Wechsler has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Greenwich. Dr. Wechsler has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Eisai. Dr. Wechsler has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Aquestive. Dr. Wechsler has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for SK Life Science. Dr. Wechsler has a non-compensated relationship as a Board President with Epilepsy Foundation of Idaho that is relevant to AAN interests or activities.