Stiripentol: Unpublished results from the first phase 2 clinical trial in Lennox–Gastaut syndrome conducted in the early 1990s

OBJECTIVE: This study was undertaken to present the results of an exploratory phase 2 trial of stiripentol in Lennox-Gastaut syndrome (LGS). METHODS: This exploratory single-blind, single-arm, nonrandomized sequential-period phase 2 study was conducted at four centers in France between January 1989 and August 1993. Eligible patients were aged 2-20 years with LGS and experienced at least one seizure per week despite optimized therapy. After a 1-month baseline period under a stable treatment regimen, patients received placebo for 1 month followed by stiripentol for 2 months. RESULTS: Sixteen patients with LGS were enrolled, and efficacy was assessable in 14. The median [Q1-Q3] overall seizure frequency decreased from 31 [16-89] at baseline to 14 [8-21] after the first month of stiripentol (p = .044) and further to 4 [0-18] after the second month (p = .044). The reduction was consistent across seizure types. Eight patients (57%) were responders (≥50% reduction in overall seizure frequency) at the end of stiripentol treatment, including five (36%) who achieved complete seizure freedom and two with a ≥75% reduction in seizure frequency. All patients reported at least one adverse event during stiripentol treatment, most commonly somnolence, decreased appetite, and vomiting. These effects may be related to the high stiripentol doses administered (median = 91 mg/kg/day in the second month). Despite their frequency, no serious adverse events were reported during the stiripentol treatment period, and no clinically meaningful changes in hematological parameters or liver enzyme levels were observed. SIGNIFICANCE: Although this study was conducted before standardized clinical trial designs for LGS were established, a more comprehensive evaluation of stiripentol could have provided further insight into its potential benefits in this severe developmental and epileptic encephalopathy.