Cannabidiol Reduces Number of Seizures in Lennox-Gastaut Syndrome, Rare Epilepsy Disorder| NEJM

Publication

  • Study: GWPCARE3
  • Authors: Devinsky, Zuberi et al
  • Journal: New England Journal of Medicine
  • Date: May 17th, 2018

Conclusions

  • Cannabidiol add-on to conventional antiepileptic therapy reduced drop seizure frequency in patients with Lennox–Gastaut syndrome
  • Both 10 mg/kg and 20 mg/kg cannabidiol effective in reducing number of seizures
  • Dose-dependent increase in adverse events relative to placebo

Endpoints

  • Primary: Median % reduction in drop seizure frequency: 41.9% in 20 mg cannabidiol group, 37.2% in 10 mg cannabidiol group, 17.2% in placebo group
  • Secondary: % patients w/ 50% reduction in drop-seizure frequency: 39% in 20 mg cannabidiol group, 36% in 10 mg cannabidiol group, 14% in placebo
  • Secondary: % change in the frequency of all types of seizures: 38.4% in 20 mg cannabidiol group, 36.4% in 10 mg cannabidiol group, 18.5% in the placebo group
  • Secondary:  # Patients wImprovement in Global Impression of Change in overall condition score: 57% in the 20-mg cannabidiol group, 66% in the 10-mg cannabidiol group, 44% in placebo group

Intervention

  • Treatment Arm: 10 mg/kg cannabidiol oral solution split BID, 20 mg/kg cannabidiol oral solution split BID; start 2.5 mg/kg and increase 2.5-5mg/kg Q2D until target dose; added to conventional anti-epileptic pharmacotherapy
  • Control Arm: Placebo oral solution PO split BID; added to conventional anti-epileptic pharmacotherapy

Adverse Events

  • Overall adverse event frequency: 94% in the 20 mg cannabidiol group, 84% in the 10 mg cannabidiol group, 72% in placebo group
  • Common adverse events: somnolence, decreased appetite, diarrhea, URI, pyrexia, vomiting
  • Serious adverse events: 13 in both cannabidiol groups, 7 in placebo group, primarily elevated liver enzymes
  • Discontinuation due to adverse events: 6 in the 20-mg cannabidiol group, 1 in the 10 mg cannabidiol group, 1 in placebo group

Background

  • Disease: Lennox-Gustaut Syndrome, severe developmental epileptic encephalopathy
  • Phenotype: seizures, cognitive impairment, abnormal EEG
  • Epidemiology: 2 per 100,000
  • Drug: cannabidiol, non-psychotropic cannabinoid
  • Previous Evidence: 2018 study GWPCare4 showed 20 mg cannabidiol effective in Lennox-Gastaut, 2017 study showed same dose effective in Dravet syndrome

Methodology

  • Study Design: Randomized Placebo-Controlled Phase III Clinical Trial
  • Study Size: 225 patients across 30 clinical locations, 76 randomized to 20-mg cannabidiol group, 73 to 10-mg cannabidiol group, 76 to the placebo group
  • Timeline: 4-week baseline, a 14-week treatment, 1-10 day taper down, 4-week safety follow-up
  • Demographics: >80% white, ~60% from U.S., 30% >18y
  • Withdrawals: 11 in tx arm, 2 in placebo
  • Funding: GW Pharmaceuticals

 

Source: Effect of Cannabidiol on Drop Seizures in the Lennox–Gastaut Syndrome | NEJM

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