Abstracts

This is a Late Breaking abstract

Rationale: Ganaxolone, a neuroactive steroid and positive allosteric modulator that targets both synaptic and extrasynaptic GABA_A receptors, has recently been FDA-approved for the treatment of seizures associated with CDKL5 deficiency disorder (CDD) in patients 2 years of age and older. Given ganaxolone and cannabidiol may be co-administered in the treatment of CDD-associated seizures, a pharmacokinetic (PK) study evaluating the potential for drug-drug interactions was conducted.

Methods: In this single center, open-label, fixed-sequence, 2 treatment study, healthy adult subjects received 600 mg oral ganaxolone (50 mg/mL) on Day 1, 12.5 mg/kg oral cannabidiol BID (25 mg/kg/day, Epidiolex^®) on Days 4-15, and a single oral dose of 600 mg ganaxolone co-administered with the morning dose of 12.5 mg/kg cannabidiol on Day 13. Ganaxolone and cannabidiol plasma concentrations were determined using validated bioanalytical methods. Routine safety monitoring was conducted throughout.

Results: Of the 21 healthy adults who were enrolled, 20 completed the PK component of the trial. Preliminary analysis of the PK endpoints indicated that ganaxolone C_max and AUC_0-t were approximately 10% and 20% lower, respectively, when co-administered with cannabidiol. No unexpected safety findings were reported.

Conclusions: Ganaxolone PK parameters C_max and AUC_0-twere slightly reduced when co-administered with cannabidiol. These changes are not expected to be clinically significant. No new safety findings were identified.  These data suggest that clinically significant pharmacokinetic interactions with co-administration of ganaxolone and cannabidiol is unlikely.

Funding: This work was funded by Marinus Pharmaceuticals, Inc.