Long-Term Trial Assesses Cannabidiol Safety, Efficacy in Patients with LGS

Cannabidiol in oral solution was evaluated for safety, drop-seizure frequency, total-seizure frequency, and S/GIC change in patients with Lennox-Gastaut Syndrome.

Long-term therapy of Lennox-Gastaut Syndrome (LGS) with cannabidiol (CBD) was found to sustain the reduction in total and drop seizure frequency as well as improve a patient’s overall condition, according to results of an interim analysis of an open-label extension of two Phase 3 trials.

Participants in the trial received a plant-derived pharmaceutical formulation of CBD (100mg/mL) in oral solution for up to 2 years. The initial dose of CBD the patients were administered was 20mg/kg daily, which was titrated down or up (max: 30mg/kg/day) by the investigator. The primary outcome of the study was safety; secondary outcomes included drop-seizure frequency, total-seizure frequency, and the Subject/Caregiver Global Impression of Change (S/CGIC).

The 2 trials included a total of 368 LGS patients with 366 (99%) entering into an open-label extension. The average age of patients included in the study was 16 years and 54% of patients were male. The median number of concomitant AEDs patients were taking was 3 (51% clobazam, 37% valproic acid). 

Prior to randomization, a median of 80 drop seizures were experienced by patients in the study and a total of 168 seizures occurred in a 28-day period. The average dose of CBD administered during the treatment phase was 23mg/kg/day (range: 2.5, 30; n=364). The average exposure period for patients included in the study was 36 weeks (range: 3 days, 61 weeks).

A total of 58% of patients experienced what was considered a treatment-related adverse event, with 83% of these reporting that it was mild or moderate in severity.

Diarrhea, drowsiness, convulsion, fever, decreased appetite, vomiting, and upper respiratory tract infection occurred in ≥10% of patients; elevations in transaminases were also observed. Additionally, 26% of patients experienced a serious AE, but only 6% of these were deemed to be treatment-related. Four deaths occurred, however zero were treatment-related.

“When analyzed in 12-week intervals over 60 weeks, median monthly drop seizures decreased by 48%–70%, and total seizures decreased by 48%–62%,” the authors wrote. ”Approximately 88% of patients/caregivers reported an improvement in overall condition on the S/CGIC at Weeks 24 and 48.”

Findings of this interim analysis concluded that add-on CBD in patients with LGS is generally well-tolerated, with an AE profile consistent with previously reported data. Additionally, CBD was found to be efficacious, as a sustained decrease in drop and total seizure frequency was observed and an improved overall condition was reported. 

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Marsh, ED, Mazurkiewicz-Beldzinska M, Halford JJ, Gunning B, Checketts D, Nichol K. Maintained safety and efficacy of cannabidiol (CBD) in a long-term open-label trial inpatients with lennox-gastaut syndrome. Presented at AES annual meeting in Washington, DC. Abstract 2.271.