Efficacy and Safety of GWP42003-P for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults

This study was a 1:1:1 randomized, double-blind, 14-week comparison of 2 dose levels (10 milligram \[mg\] per kilogram \[kg\] per day \[mg/kg/day\] and 20 mg/kg/day) of GWP42003-P versus placebo. Participants who satisfied all inclusion and none of the exclusion criteria began a 28-day baseline observation period. The treatment period consisted of a 2-week titration period followed by a 12-week maintenance period. The 20 mg/kg/day dose was recommended by the Data Safety Monitoring Committee (DSMC) after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206). The 10 mg/kg/day dose was defined as 50% of the 20 mg/kg/day dose. The first participant was not enrolled into this study until the DSMC had reviewed the safety data from Part A of study GWEP1332. Participants who satisfied all eligibility criteria were randomized at Day 1 to receive 10 mg/kg/day GWP42003-P, 20 mg/kg/day GWP42003-P, or placebo at a 1:1:1 ratio. Participants in the placebo group were split into 2 equivalent cohorts; one half received 10 mg/kg/day dosing volumes and one half received 20 mg/kg/day dosing volumes. The 2 placebo cohorts were pooled for the analyses of efficacy. Participants titrated GWP42003-P to the 10 mg/kg/day or 20 mg/kg/day (or equivalent volume of placebo) dose over 7 and 11 days, respectively, and remained at this dose for the 12-week maintenance period. Following the end of treatment (Day 99), participants were invited to continue to receive GWP42003-P in an open-label extension (OLE) study under a separate protocol (GWEP1415; NCT02224573). All participants who did not immediately enter the OLE study tapered investigational medicinal product (IMP) (10% per day over 10 days). However, the taper period could be interrupted if the participant wished to enter the OLE study within a 7-day timeframe. Participants who down-titrated IMP returned for an end of taper period visit (Day 109). Participants who did not enter the OLE study or who withdrew prematurely had a safety follow-up visit 28 days later (Day 137).