Abstracts

Rationale: Ganaxolone is a new chemical entity under investigation for use as an antiseizure medication in rare pediatric seizure disorders and status epilepticus. Ganaxolone has been dosed in 46 company-sponsored trials including to healthy volunteers in phase 1 studies and subjects with a range of disorders in phase 1-3 studies. In aggregate, the data has provided an extensive characterization of the safety profile of ganaxolone. This analysis summarizes adverse events (AEs) from development programs for ganaxolone in epilepsy and other neuropsychiatric disorders.

Methods: Ganaxolone has been dosed in 46 completed company-sponsored studies with over 1900 subjects receiving at least 1 dose of ganaxolone. Of these, 24 were phase 1 and 22 were phase 2/3. Here we report on the safety and tolerability of ganaxolone in placebo-controlled studies as assessed by the incidence of treatment-emergent adverse events (TEAEs), monitoring of vital signs, physical examinations, electrocardiograms (ECGs), and laboratory tests. Adverse events were coded according to the Medical Dictionary for Regulatory Activities (MedDRA).

Results: In placebo-controlled studies, there were 1844 subjects who received either placebo (743) or ganaxolone (1101). The frequency of TEAEs was 62.9% (693/1101 subjects) for ganaxolone and 53.8% (400/743 subjects) for placebo. The serious adverse event (SAE) rate was similar between ganaxolone- and placebo-treated subjects: 2.8% (31/1101) and 3.8% (28/743), respectively. The only SAE reported in more than 2 subjects in the ganaxolone group was seizure (0.5% ganaxolone and 0.7% placebo). The most frequently reported TEAEs ( >5% of subjects) in ganaxolone-treated subjects were somnolence, dizziness, fatigue, and headache. All but headache occurred more frequently in ganaxolone-treated subjects. CNS-related events appeared to be dose related, with the majority of these events occurring at doses ≥500 mg. There was no discernible safety signal related to bone marrow suppression, bone mineralization, nephrolithiasis, cardiac valvulopathy, or liver function. There have been no significant changes noted in body weight and no trends in clinically significant changes in ECG parameters or vital signs in subjects who received ganaxolone.

Conclusions: The experience with the investigational use of ganaxolone in studies conducted to date suggests an acceptable tolerability and safety profile.

Funding: Please list any funding that was received in support of this abstract.: This study was supported by Marinus Pharmaceuticals.