Neuropediatrics 2019; 50(S 02): S1-S55
DOI: 10.1055/s-0039-1698181
Oral Presentations
Varia
Georg Thieme Verlag KG Stuttgart · New York

(CBD) Significantly Reduces Convulsive Seizure Frequency in Dravet Syndrome: Results of a Dose-Ranging, Multicentre, Randomised, Double-Blind, Placebo-Controlled Trial

Ian Miller
1   Nicklaus Children’s Hospital, Neurology Department, Miami, FL, United States
,
Ingrid Scheffer
2   University of Melbourne, Austin Health and The Royal Children's Hospital, Departments of Medicine & Paediatrics, Melbourne, Australia
,
Boudewijn Gunning
3   Stichting Epilepsie Instellingen Nederland, Neurology, Zwolle, Netherlands
,
Rocío Sánchez-Carpintero
4   Clínica Universidad de Navarra, Pediatric Neurology Unit, Pamplona, Spain
,
Antonio Gil-Nagel
5   Hospital Ruber Internacional, Department of Neurology, Madrid, Spain
,
M. Scott Perry
6   Cook Children’s Medical Center, Department of Neurosciences, Fort Worth, TX, United States
,
Russell Saneto
7   Seattle Children’s Hospital, Neurology, Seattle, WA, United States
,
Daniel Checketts
8   GW Research Ltd, Neurology, Cambridge, United Kingdom
,
Eduardo Dunayevich
9   Greenwich Biosciences Inc., Neurology, Carlsbad, CA, United States
,
Volker Knappertz
9   Greenwich Biosciences Inc., Neurology, Carlsbad, CA, United States
› Author Affiliations
Further Information

Publication History

Publication Date:
11 September 2019 (online)

 

Research Question: To assess the efficacy and safety of 2 doses of cannabidiol (CBD) as an add-on treatment for drug-resistant seizures in patients with Dravet syndrome (DS) (GWPCARE2/NCT02224703).

Materials and Methods: 199 patients were randomized to receive GW Pharmaceuticals’ formulation of plant-derived highly purified CBD in oral solution (100 mg/mL) at 20 mg/kg/day (CBD20; n = 67), 10 mg/kg/day (CBD10; n = 67), or placebo (n = 65). The primary endpoint was change in convulsive seizure frequency over the 14-week treatment period compared to a 4-week baseline.

Results: Mean age was 9 years. Patients were taking a median of 3 antiepileptic drugs (AEDs), having discontinued a median of 4 AEDs. Percentage reduction in convulsive seizures was higher for CBD20 (46%) and CBD10 (49%) vs. placebo (27%; p = 0.0299 and p = 0.0095), as were ≥50% responder rates (49% and 44% vs. 26%; p = 0.0069 and p = 0.0332) and ≥75% responder rates (18% and 30% vs. 6%; p = 0.0468 and p = 0.0004 [nominal p-values]). Caregiver-reported improvement in overall condition was higher for CBD20 (61%) and CBD10 (68%) vs. placebo (42%; p = 0.0279 and p = 0.0009). The incidence of treatment-emergent adverse events (AEs) was similar across all groups (90% CBD20, 88% CBD10, 89% placebo). The 5 most common AEs were decreased appetite, diarrhoea, somnolence, pyrexia, and fatigue. Serious AEs were reported in 25% CBD20, 20% CBD10, and 15% of placebo patients. Discontinuations due to AEs only occurred for CBD20 patients (7%). Elevated transaminases exceeding 3× upper limit of normal (ULN) occurred in 19% CBD20 and 5% of CBD10 patients; none had elevations in bilirubin; all were taking concomitant valproate; all elevations resolved. There were no deaths.

Discussion and Conclusion: CBD20 and CBD10 significantly reduced seizure frequency vs. placebo. Elevated transaminases and certain AEs and discontinuations due to AEs occurred more frequently for CBD20 than CBD10 or placebo. Dose increases above 10 mg/kg/day should be tailored to individual efficacy and safety.

Funding: GW Research Ltd, Cambridge, UK.