Journal
ACTA NEUROLOGICA SCANDINAVICA
Volume 142, Issue 6, Pages 531-540Publisher
WILEY
DOI: 10.1111/ane.13305
Keywords
Cannabidiol; Clobazam; Dravet syndrome; Drug-drug interaction; Epilepsy; Lennox-Gastaut syndrome; Seizures
Categories
Funding
- GW Research Ltd
Ask authors/readers for more resources
Objective The efficacy of cannabidiol (CBD) with and without concomitant clobazam (CLB) was evaluated in stratified analyses of four large randomized controlled trials, two in Lennox-Gastaut syndrome, and two in Dravet syndrome. Methods Each trial of CBD (Epidiolex(R)in the US; Epidyolex(R)in the EU; 10 and 20 mg/kg/day) was evaluated by CLB use. The treatment ratio was analyzed using negative binomial regression for changes in seizure frequency and logistic regression for the 50% responder rate, where the principle analysis combined both indications and CBD doses in a stratified meta-analysis. Pharmacokinetic data were examined for an exposure/response relationship based on CLB presence/absence. Safety data were analyzed using descriptive statistics. Results The meta-analysis favored CBD vs. placebo regardless of CLB use. The treatment ratio (95% CI) of CBD over placebo for the average reduction in seizure frequency was 0.59 (0.52, 0.68;P < .0001) with CLB and 0.85 (0.73, 0.98;P = .0226) without CLB, and the 50% responder rate odds ratio (95% CI) was 2.51 (1.69, 3.71;P < .0001) with CLB and 2.40 (1.38, 4.16;P = .0020) without CLB. Adverse events (AEs) related to somnolence, rash, pneumonia, or aggression were more common in patients with concomitant CLB. There was a significant exposure/response relationship for CBD and its active metabolite. Conclusions These results indicate CBD is efficacious with and without CLB, but do not exclude the possibility of a synergistic effect associated with the combination of agents. The safety and tolerability profile of CBD without CLB show a lower rate of certain AEs than with CLB.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available