Abstract
Objective
In this post hoc analysis, we aimed to assess seizure-free days as a potential new outcome measure to use in randomized placebo-controlled trials (RCTs) of patients with Lennox-Gastaut syndrome (LGS).
Methods
In two phase 3 RCTs (GWPCARE3, GWPCARE4), eligible patients were randomized to receive plant-derived highly purified cannabidiol (CBD; Epidiolex® in the US; 100 mg/mL oral solution) at 10 mg/kg/day (CBD10; GWPCARE3 only), 20 mg/kg/day (CBD20), or matched placebo. The treatment period comprised a 2-week dose titration and a 12-week maintenance period. This post hoc analysis evaluated the least-squares (LS) mean changes from baseline and difference versus placebo in the number of drop or total seizure-free days per 28 days during the treatment period or maintenance period alone. LS mean changes were estimated using an analysis of covariance model – categorical age and baseline number of drop or total seizure-free days as covariates; treatment group as a fixed factor.
Results
A total of 396 patients were included in this post hoc analysis. During the 14-week treatment period, LS mean (95% confidence interval [CI]) changes from baseline in number of drop seizure-free days per 28 days for patients receiving placebo (n = 161), CBD10 (n = 73), and CBD20 (n = 162) were 2.81 (1.75–3.88), 5.64 (4.08–7.20), and 6.45 (5.39–7.52), respectively. The LS mean (95% CI) differences in number of drop seizure-free days versus placebo were 2.83 (0.98–4.68) for CBD10 and 3.64 (2.18–5.10) for CBD20. For total seizure-free days, LS mean differences (95% CI) versus placebo were 2.63 (0.92–4.34) for CBD10 and 3.50 (2.16–4.85) for CBD20. The improvements from baseline in seizure-free days were similar during the treatment or maintenance period alone.
Significance
Drop and total seizure-free days represent potential new and clinically meaningful endpoints for future RCTs in patients with LGS.
ABR