Neuropediatrics 2019; 50(S 02): S1-S55
DOI: 10.1055/s-0039-1698214
Poster Presentations
Poster Area GNP Epilepsy 1
Georg Thieme Verlag KG Stuttgart · New York

Time to Onset of Efficacy of Cannabidiol (CBD) During Titration in Patients with Lennox-Gastaut Syndrome or Dravet Syndrome Enrolled in Three Randomised Controlled Trials

Maria Mazurkiewicz-Beldzinska
1   Medical University of Gdańsk, Department of Developmental Neurology, Gdańsk, Poland
,
Michael Privitera
2   University of Cincinnati Medical Center, Neurology & Rehabilitation Medicine, Cincinnati, Ohio, United States
,
Eric Marsh
3   The Children’s Hospital of Philadelphia, Division of Neurology, Philadelphia, Pennsylvania, United States
,
Vicente Villanueva
4   University and Polytechnic Hospital La Fe, Neurology Service, Valencia, Spain
,
Kevan VanLandingham
5   Greenwich Biosciences, Inc., Neurology, Carlsbad, California, United States
,
Daniel Checketts
6   GW Research Ltd, Neurology, Cambridge, United Kingdom
,
Volker Knappertz
5   Greenwich Biosciences, Inc., Neurology, Carlsbad, California, United States
› Author Affiliations
Further Information

Publication History

Publication Date:
11 September 2019 (online)

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    Research Question: Add-on CBD significantly reduced seizures with an acceptable safety profile in 3 Phase 3 randomised controlled trials in patients with Dravet syndrome (DS; GWPCARE1/NCT02091375) and Lennox-Gastaut syndrome (LGS; GWPCARE3/NCT02224560; GWPCARE4/NCT02224690). A post-hoc analysis of these studies was conducted to determine the time to onset of efficacy by cumulative day during titration.

    Materials and Methods: Patients received GW Pharmaceuticals’ formulation of plant-derived highly purified CBD in oral solution (100 mg/mL) at 10 mg/kg/day (GWPCARE3) or 20 mg/kg/day (all trials), or placebo. CBD treatment started at 2.5 mg/kg/day and reached 10 mg/kg/day on Days 7/8 and 20 mg/kg/day by Day 11 in higher dose groups. Cumulative frequencies of convulsive (DS) and drop seizures (LGS) were calculated as 28-day averages for each titration day (including previous treatment days). Treatment-emergent adverse events (AEs) were assessed.

    Results: Overall, 296 patients were randomised to CBD and 220 to placebo. Mean age was 10 years (DS; GWPCARE1) and 15 years (LGS; GWPCARE3/GWPCARE4). In GWPCARE1, nominal statistical significance versus placebo was achieved at Day 10 (p = 0.0261) and, in GWPCARE3/GWPCARE4 (pooled data), at Day 6 for the 20 mg/kg/day arm (p = 0.0061) and at Day 8 for the 10 mg/kg/day arm (p = 0.0368). Of patients with AEs, 60% had their first during titration. Differences for CBD versus placebo in overall AEs and some common AEs were evident during titration but generally to a lesser degree than during the treatment period. Most common (≥10%) AEs: somnolence, decreased appetite, fatigue, and diarrhoea.

    Discussion and Conclusion: Findings suggest that the titration schedule used in the GWPCARE trials led to a significant treatment effect for CBD within 6–10 days during up titration.

    Funding: GW Research Ltd, Cambridge, UK.


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    No conflict of interest has been declared by the author(s).