RT Journal Article
SR Electronic
T1 Effect of Add-on Cannabidiol (CBD) on Seizure Frequency and Seizure-Free Intervals in Patients With Seizures Associated With Tuberous Sclerosis Complex (TSC): Phase 3 Trial GWPCARE6 Post Hoc Analysis (P12-8.005)
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP 890
VO 98
IS 18 Supplement
A1 Elizabeth A. Thiele
A1 E. Martina Bebin
A1 Finbar J. O‘Callaghan
A1 Steven P. Sparagana
A1 Floor E. Jansen
A1 Ashley Schreiber
A1 Farhad Sahebkar
YR 2022
UL http://n.neurology.org/content/98/18_Supplement/890.abstract
AB Objective: Post hoc analysis to determine the proportion of patients with TSC, treated with CBD or placebo, who reached all continuous responder rate thresholds and the longest seizure-free intervals.Background: Add-on CBD demonstrated efficacy against seizures associated with TSC with an acceptable safety profile in phase 3 trial GWPCARE6 (NCT02544763).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, or matched placebo for 16 weeks. Efficacy of CBD25 (n=75) vs placebo (n=76) was evaluated by percent reduction from baseline in TSC-associated seizures and longest seizure-free intervals.Results: Median (range) age: 11 (1–57) years. Median (Q1, Q3) TSC-associated seizure frequency during 4-wk baseline: 56 (21, 101) for CBD25 and 54 (26, 102) for placebo. Mean (standard deviation [SD]) longest seizure-free interval during 4-wk baseline: 3 (3) days for CBD25 and 2 (2) days for placebo. CBD produced significantly greater reduction in TSC-associated seizures than placebo (treatment ratio [95% CI], 0.699 [0.567–0.861]; P=0.0009). Patients with ≥25%, ≥50%, and ≥75% reduction: 68%, 44%, and 19% for CBD25 and 43%, 22%, and 0% for placebo. Mean (SD) longest seizure-free intervals: 11 (17) days for CBD25 and 6 (6) days for placebo; patients with 7-, 14-, 21-, and 28-day seizure-free intervals for CBD25 vs placebo: 45% vs 33%, 24% vs 14%, 12% vs 0%, and 8% vs 0%. AE incidence: 93% of patients taking CBD25 and 95% taking placebo; 11% taking CBD25 and 3% taking placebo discontinued treatment because of an AE. Most common AEs: diarrhea and decreased appetite, occurring more frequently with CBD than placebo. ALT/AST elevations (>3× ULN) occurred in 9 (12%) patients on CBD25 and none on placebo; 78% were on concomitant valproate.Conclusions: CBD was superior to placebo in reducing seizures and producing longer seizure-free intervals in patients with TSC-associated seizures.Disclosure: Dr. Thiele has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for GW Pharma. Dr. Thiele has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for zogenix. Dr. Thiele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aquestive. Dr. Thiele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for West Therapeutics. Dr. Thiele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Thiele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for RegenxBio. Dr. Thiele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for nobelpharma. An immediate family member of Dr. Thiele has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Thor labs. Dr. Thiele has received personal compensation in the range of $0-$499 for serving as a Consultant for Biocodex. The institution of Dr. Thiele has received research support from GW Pharma. The institution of Dr. Thiele has received research support from Zogenix. Dr. Bebin has received personal compensation for serving as an employee of GW Pharma. Dr. Bebin has received personal compensation for serving as an employee of Biocodex. Dr. Bebin has received personal compensation for serving as an employee of Regenxbio. Dr. Bebin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GW Pharma. Dr. Bebin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biocodex. Dr. Bebin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Regenxbio. The institution of Dr. Bebin has received research support from GW Pharma. The institution of Dr. Bebin has received research support from NINDS. Finbar O'Callaghan has nothing to disclose. Dr. Sparagana has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Greenwich Biosciences. Dr. Sparagana has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nobelpharma. The institution of Dr. Sparagana has received research support from Greenwich Biosciences. The institution of Dr. Sparagana has received research support from Tuberous Sclerosis Alliance. The institution of Dr. Sparagana has received research support from Novartis. Dr. Sparagana has a non-compensated relationship as a Professional Advisory Board Member, committee member with Tuberous Sclerosis Alliance that is relevant to AAN interests or activities. Floor Jansen has nothing to disclose. Mr. Schreiber has received personal compensation for serving as an employee of GW Pharmaceuticals. Mr. Schreiber has received stock or an ownership interest from GW Pharmaceuticals. Dr. Sahebkar-Moghaddam has received personal compensation for serving as an employee of gw. Dr. Sahebkar-Moghaddam has received stock or an ownership interest from GW.