Abstract Details

Title Time to Onset of Cannabidiol (CBD) Treatment Effect and Resolution of Adverse Events (AEs) in the Tuberous Sclerosis Complex (TSC) Phase 3 Randomized Controlled Trial (GWPCARE6)

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P11 - Poster Session 11 (8:00 AM-9:00 AM)

Poster/Presentation
Number 12-005

Objective Estimate time to onset of CBD treatment effect and resolution of AEs in a post hoc analysis from the GWPCARE6 (NCT02544763) trial evaluating add-on CBD in patients with drug-resistant epilepsy associated with TSC.

Background Add-on CBD significantly reduced seizures associated with TSC across the 16-week treatment period in GWPCARE6.

Design/Methods Patients received plant-derived highly purified CBD (Epidiolex®; 100 mg/mL oral solution) at 25 mg/kg/d (CBD25) or 50 mg/kg/d (CBD50) or placebo for 16 weeks. Treatment started at 5 mg/kg/d for all groups and reached 25 mg/kg/d on Day 9 in CBD25 and 50 mg/kg/d on Day 29 in CBD50. Percentage change from baseline in primary endpoint TSC-associated seizures (countable focal or generalized) was calculated by cumulative day (ie, including all previous days). Time to onset and resolution of AEs were evaluated.

Results Overall 224 patients were randomized 1:1:1 to CBD25 (n=75), CBD50 (n=73), and placebo (n=76). The median (range) age was 11 (1–57) years. Patients had discontinued a median of 4 AEDs and were currently taking a median of 3 AEDs. Differences in seizure reduction between CBD and placebo emerged on Day 6 (when titration reached 15 mg/kg/d) and became nominally significant (p<0.05) by Day 11 (CBD50) or Day 12 (CBD25). More than 90% of patients had an AE, with onset during the first 2 weeks of the titration period in 63%. AEs resolved within 4 weeks of onset in 42% of placebo and 27% of CBD patients and by end of study in 78% of placebo and 51% of CBD patients; most frequent AEs—diarrhea, somnolence, decreased appetite—resolved in 69–88% of CBD patients.

Conclusions Findings suggest that onset of treatment effect (efficacy and AEs) occurred within the first 2 weeks. AEs lasted longer for CBD vs. placebo but resolved within the 16-week study in most patients.

Authors/Disclosures
Joyce Y. Wu, MD (Lurie Children's Hospital) PRESENTER	Dr. Wu has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biocodex. Dr. Wu has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Marinus. The institution of Dr. Wu has received research support from National Institutes of Health. Dr. Wu has received personal compensation in the range of $500-$4,999 for serving as a Study section member with National Institutes of Health.
Hannah Cock, MD (St Georges, University of London)	No disclosure on file
Orrin Devinsky, MD, F�鶹��ýӳ�� (NYU Epilepsy Center)	Dr. Devinsky has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Devinsky has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for California Cannabis Enterprises. Dr. Devinsky has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Engage. Dr. Devinsky has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Privateer Holdings. Dr. Devinsky has received personal compensation in the range of $1,000,000+ for serving on a Scientific Advisory or Data Safety Monitoring board for Receptor Holdings. Dr. Devinsky has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Rettco. Dr. Devinsky has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Silver Spike. Dr. Devinsky has received personal compensation in the range of $100,000-$499,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tevard. Dr. Devinsky has received personal compensation in the range of $1,000,000+ for serving on a Scientific Advisory or Data Safety Monitoring board for Tilray. Dr. Devinsky has received personal compensation in the range of $100,000-$499,999 for serving as an officer or member of the Board of Directors for Engage. Dr. Devinsky has received personal compensation in the range of $50,000-$99,999 for serving as an officer or member of the Board of Directors for Tevard Biosciences. Dr. Devinsky has stock in Engage. Dr. Devinsky has stock in Empatica. Dr. Devinsky has stock in California Cannabis Enterprises. Dr. Devinsky has stock in Empatica. Dr. Devinsky has stock in Silver Spike. Dr. Devinsky has stock in Docklight Brands. Dr. Devinsky has stock in Egg Rock/Papa Barkley. Dr. Devinsky has stock in Leafly. Dr. Devinsky has stock in Left Coast Ventures. Dr. Devinsky has stock in Privateer Holdings. Dr. Devinsky has stock in Receptor Holdings. Dr. Devinsky has stock in Qstate. The institution of Dr. Devinsky has received research support from GW Pharma. The institution of Dr. Devinsky has received research support from Zogenix. The institution of Dr. Devinsky has received research support from PTC Pharma. The institution of Dr. Devinsky has received research support from NIH. The institution of Dr. Devinsky has received research support from DOD. The institution of Dr. Devinsky has received research support from NIH. The institution of Dr. Devinsky has received research support from Epilepsy Foundation. The institution of Dr. Devinsky has received research support from NIH. The institution of Dr. Devinsky has received research support from NIH. The institution of Dr. Devinsky has received research support from NSF. Dr. Devinsky has received intellectual property interests from a discovery or technology relating to health care. Dr. Devinsky has received intellectual property interests from a discovery or technology relating to health care. Dr. Devinsky has received publishing royalties from a publication relating to health care.
Charuta N. Joshi, MD	No disclosure on file
Ian Miller, MD	Dr. Miller has received personal compensation for serving as an employee of Marinus Pharmaceuticals. Dr. Miller has stock in Marinus Pharmaceuticals.
Colin M. Roberts, MD (Pediatric Neurology CDRC-P)	Dr. Roberts has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurelis. Dr. Roberts has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Stoke. Dr. Roberts has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Encoded.
	No disclosure on file
	No disclosure on file
Farhad Sahebkar-Moghaddam, MD (Amgen)	Dr. Sahebkar-Moghaddam has received personal compensation for serving as an employee of Jazz pharmaceuticals. Dr. Sahebkar-Moghaddam has stock in Jazz pharmaceuticals.

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