Abstract Details

Title Long-term Safety and Efficacy of Add-on Cannabidiol (CBD) Treatment in Patients with Lennox Gastaut Syndrome in an Open-label Extension Trial (GWPCARE5)

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P5 - Poster Session 5 (5:30 PM-6:30 PM)

Poster/Presentation
Number 6-001

Objective

To assess long-term safety and efficacy of add-on CBD treatment in patients with Lennox-Gastaut syndrome (LGS) in a second interim analysis of the open label extension (OLE) of two phase 3, randomized controlled trials (RCTs) GWPCARE3 (NCT02224560) and GWPCARE4 (NCT02224690).

Background

LGS is a rare epileptic encephalopathy that is often treatment-resistant. The efficacy of CBD was demonstrated, with an acceptable safety profile, in the two RCTs.

Design/Methods

Patients who completed a 14-week, double-blind, randomised controlled trial (GWPCARE3/NCT02224560; GWPCARE4/NCT02224690) could enter this OLE trial (GWPCARE5/NCT02224573). Patients received a plant-derived pharmaceutical formulation of highly purified CBD in oral solution (Epidiolex^®; 100 mg/mL) for ≤3 years. Primary endpoint: safety. Secondary endpoints: drop and total seizure frequency; Subject/Caregiver Global Impression of Change (S/CGIC).

Results

Overall, 99% (366/368) of eligible patients with LGS entered the OLE trial. Median follow-up was 61 weeks (3 days to 87 weeks); 88 patients (24%) withdrew. Mean age: 16 years; 33% ≥18 years; 54% male. Baseline median seizure frequency/28 days: 80 drop seizures; 168 total seizures. During the extended follow-up, adverse event (AE) incidence: 94%; serious AE incidence: 33%; 11% discontinued owing to AEs. Most common AEs (≥20%): diarrhoea, convulsion, somnolence, pyrexia, vomiting and decreased appetite. Forty-seven patients (13%) had elevations in liver transaminases >3× upper limit of normal; 35 (74%) were taking concomitant valproate. There were 5 deaths; none deemed treatment-related by the investigator(s). Median percentage reductions in seizure frequency (12-week windows over 72 weeks): 48–70% for drop seizures; 48–63% for total seizures. Approximately 88% of patients/caregivers reported an improvement in overall condition on the S/CGIC at Weeks 24 and 48.

Conclusions

Long-term add-on CBD treatment had a similar AE profile to that observed previously. Reductions in drop and total seizure frequency and improvements in overall condition were maintained through 72 weeks.

Authors/Disclosures
Anup D. Patel, MD, FAAN (Nationwide Children's Hospital and the Ohio State University College of Medicine) PRESENTER	Dr. Patel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB Pharma. Dr. Patel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. The institution of Dr. Patel has received research support from PCORI. Dr. Patel has received personal compensation in the range of $10,000-$49,999 for serving as a Webinar Development with Medscape. Dr. Patel has received personal compensation in the range of $500-$4,999 for serving as a Other capacity with Guidepoint. Dr. Patel has a non-compensated relationship as a Chair Quality Committee with AAN that is relevant to AAN interests or activities. Dr. Patel has a non-compensated relationship as a Committee Member with Child Neurology Society that is relevant to AAN interests or activities. Dr. Patel has a non-compensated relationship as a Board of Directors - member with AAN Institute that is relevant to AAN interests or activities.
Antonio Gil-Nagel, MD (Hospital Ruber Internacional)	Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biocodex. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EISAI . Dr. Gil-Nagel has received personal compensation in the range of $0-$499 for serving as a Consultant for GW Pharma. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Angelini Pharma. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EISAI. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GW Pharma. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PTC Therapeutics . Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Stoke . Dr. Gil-Nagel has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Zogenix . Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Angelini Pharma. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BIAL . Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for EISAI . Dr. Gil-Nagel has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for GW Pharma. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Jazz Pharma. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for PTC Therapeutics . Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB Pharma. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Zogenix . The institution of Dr. Gil-Nagel has received research support from Jazz Pharmaceuticals. The institution of Dr. Gil-Nagel has received research support from PTC Therapeutics. The institution of Dr. Gil-Nagel has received research support from Zogenix. The institution of Dr. Gil-Nagel has received research support from Agencia Estatal Innovacion.
	No disclosure on file
Wendy G. Mitchell, MD (Children'S Hospital Los Angeles)	Dr. Mitchell has nothing to disclose.
M. S. Perry, MD (Cook Childrens Medical Center)	Dr. Perry has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for stoke therapeutics. Dr. Perry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurelis. Dr. Perry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Marinus. Dr. Perry has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for jazz pharmaceuticals. Dr. Perry has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for UCB. Dr. Perry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for pyros. Dr. Perry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for azurity. Dr. Perry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biocodex. Dr. Perry has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Stoke Therapeutics. Dr. Perry has stock in Praxis Precision Medicine. Dr. Perry has stock in Biohaven. Dr. Perry has stock in Rapport. Dr. Perry has stock in Alto Neurosciences. Dr. Perry has a non-compensated relationship as a president with child neurology foundation that is relevant to AAN interests or activities. Dr. Perry has a non-compensated relationship as a President with Pediatric Epilepsy Research Consortium that is relevant to AAN interests or activities.
Leon A. Weinstock, MD (University Neurology, INC)	Dr. Weinstock has nothing to disclose.
Claire Roberts	No disclosure on file
	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.

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