Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial

Summary Background Patients with Lennox-Gastaut syndrome, a rare, severe form of epileptic encephalopathy, are frequently treatment resistant to available medications. No controlled studies have investigated the use of cannabidiolfor patients with seizures associated with Lennox-Gastaut syndrome. We therefore assessed the efficacy and safety of cannabidiolas an add-on anticonvulsant therapy in this population of patients. Methods In this randomised, double-blind, placebo-controlled trial done at 24 clinical sites in the USA, the Netherlands, and Poland, we investigated the efficacy of cannabidiolas add-on therapy for drop seizures in patients with treatment-resistant Lennox-Gastaut syndrome. Eligible patients (aged 2–55 years) had Lennox-Gastaut syndrome, including a history of slow ( Findings Between April 28, 2015, and Oct 15, 2015, we randomly assigned 171 patients to receive cannabidiol(n=86) or placebo (n=85). 14 patients in the cannabidiolgroup and one in the placebo group discontinued study treatment; all randomly assigned patients received at least one dose of study treatment and had post-baseline efficacy data. The median percentage reduction in monthly drop seizure frequency from baseline was 43·9% (IQR −69·6 to −1·9) in the cannibidiol group and 21·8% (IQR −45·7 to 1·7) in the placebo group. The estimated median difference between the treatment groups was −17·21 (95% CI −30·32 to −4·09; p=0·0135) during the 14-week treatment period. Adverse events occurred in 74 (86%) of 86 patients in the cannabidiolgroup and 59 (69%) of 85 patients in the placebo group; most were mild or moderate. The most common adverse events were diarrhoea, somnolence, pyrexia, decreased appetite, and vomiting. 12 (14%) patients in the cannabidiolgroup and one (1%) patient in the placebo group withdrew from the study because of adverse events. One patient (1%) died in the cannabidiolgroup, but this was considered unrelated to treatment. Interpretation Add-on cannabidiolis efficacious for the treatment of patients with drop seizures associated with Lennox-Gastaut syndromeand is generally well tolerated. The long-term efficacy and safety of cannabidiolis currently being assessed in the open-label extension of this trial. Funding GW Pharmaceuticals.