To summarize adverse events (AEs) from development programs for ganaxolone in epilepsy and other neuropsychiatric disorders.

Ganaxolone is a new chemical entity under investigation for use as an antiseizure medication in rare pediatric epilepsies and status epilepticus. It has been administered to healthy volunteers and subjects with a range of disorders in 46 company-sponsored, Phase 1-3 trials. In aggregate, the data provide an extensive characterization of the safety profile of ganaxolone.

Over 1900 study subjects have received at least one dose of ganaxolone. 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.

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) and higher in ganaxolone-treated subjects compared to placebo were somnolence (22.4% ganaxolone, 8.1% placebo), dizziness (12.6% ganaxolone, 3.9% placebo), and fatigue (9.3% ganaxolone, 4.8% placebo). CNS-related events appeared to be dose related. There was no discernable 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 clinically significant trends in ECG parameters or vital signs.

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