好色先生

好色先生

Explore the latest content from across our publications

Log In

Forgot Password?
Create New Account

Loading... please wait

Abstract Details

Time to Onset of Efficacy of Cannabidiol (CBD) During Titration in Patients with Lennox-Gastaut Syndrome and Dravet Syndrome Enrolled in Three Randomized Controlled Trials
Epilepsy/Clinical Neurophysiology (EEG)
S48 - Epilepsy/Clinical Neurophysiology (EEG) III (2:28 PM-2:39 PM)
009

Add-on CBD significantly reduced seizures associated with DS and LGS and was generally well tolerated in three Phase 3 randomized controlled trials.

To determine the time to onset of efficacy of add-on CBD treatment using a post-hoc analysis of efficacy by cumulative day during titration in three Phase 3 randomized controlled trials in patients with Dravet syndrome (DS) (GWPCARE1/NCT02091375) and Lennox-Gastaut syndrome (LGS) (GWPCARE3/NCT02224560; GWPCARE4/NCT02224690).

Patients received a plant-derived pharmaceutical formulation of highly purified CBD in oral solution (Epidiolex®; 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). Adverse events (AEs) were assessed.

Overall, 296 patients were randomized to CBD and 220 to placebo. Mean age was 9 years (DS; GWPCARE1) and 15 years (LGS; GWPCARE3/GWPCARE4). In GWPCARE1, nominal statistical significance vs placebo was achieved at day 10 (p=0.0261), and in GWPCARE3/GWPCARE4 (pooled data), at day 6 for the 20 mg/kg/d arm (p=0.0061) and at day 8 for the 10 mg/kg/d 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 diarrhea.

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.

Authors/Disclosures

PRESENTER
No disclosure on file
Michael D. Privitera, MD, FAAN (Univ of Cincinnati/Dept of Neurology) Dr. Privitera has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for SK life science. Dr. Privitera has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NeuroPace. Dr. Privitera has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for SK life science. Dr. Privitera has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Jazz. The institution of Dr. Privitera has received research support from Neurelis. The institution of Dr. Privitera has received research support from Biohaven. Dr. Privitera has received research support from Neurava.
Eric D. Marsh, MD, PhD (Children's Hospital of Philadlephia) Dr. Marsh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia Pharmacuticals. Dr. Marsh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Stoke Therapeutics. Dr. Marsh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acadia Pharmaceuticals. The institution of Dr. Marsh has received research support from NIH. The institution of Dr. Marsh has received research support from Rett Syndrome Research Trust. The institution of Dr. Marsh has received research support from International Rett Syndrome Foundation. The institution of Dr. Marsh has received research support from Eagles Autism Challenge. The institution of Dr. Marsh has received research support from LouLou Foundation. The institution of Dr. Marsh has received research support from International CDKL5 Resarch Foundation. The institution of Dr. Marsh has received research support from Acadia Pharmaceuticals. The institution of Dr. Marsh has received research support from Marinus. The institution of Dr. Marsh has received research support from Stoke Therapeutics. The institution of Dr. Marsh has received research support from Takeda Pharmaceuticals. Dr. Marsh has received personal compensation in the range of $500-$4,999 for serving as a Grant Review with NIH. Dr. Marsh has received personal compensation in the range of $5,000-$9,999 for serving as a Expert Witness with Department of Human Services. Dr. Marsh has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Medscape.
Vicente Villanueva No disclosure on file
Kevan E. VanLandingham, MD, PhD, FAAN (US Food and Drug Administration) Dr. VanLandingham has received personal compensation for serving as an employee of Greenwich Biosciences. Dr. VanLandingham has received stock or an ownership interest from Greenwich Biosciences.
No disclosure on file
Volker A. Knappertz, MD (Lacum Neurology) No disclosure on file