Objective:

This phase 1 study (NCT04690751) evaluated the pharmacokinetics (PK), relative bioavailability, and food effect of a new oral cenobamate suspension vs the currently available oral tablet.

Background:

These results informed the appropriate use of the oral suspension formulation in current clinical studies of cenobamate.

Design/Methods:

In this open-label, 3-period, 6-sequence balanced crossover study, healthy volunteers ages 18-50 years were randomized to receive single 200-mg doses of cenobamate (200-mg tablet or 10-mg/mL oral suspension. There was a 21-day washout between doses. Blood samples for PK assessments were collected from predose to 456 hours following each treatment during each period. An absence of effect was concluded if the 90% CIs for the geometric mean ratios (GMRs) for key PK parameters (C_max, AUC_last, and AUC_∞) fell within the 80%-125% predefined boundaries. Safety was also assessed.

Results:

Twenty-eight subjects (82% male, mean age 30.6 years) were included in the study. Following fasting administration of cenobamate 200-mg tablet vs oral suspension, the 90% CIs for the GMRs fell within the 80%-125% predefined boundaries for all three PK parameters. As expected, more rapid absorption occurred with the oral suspension (median T_max 1 hour for suspension vs 3 hours for tablet; P=0.01). Following administration of oral suspension fed vs fasted, the 90% CIs for AUC_∞ and AUC_last GMRs were within the 80%-125% range. Median T_max was significantly increased in the fed state (5 hours) vs the fasted state (0.75 hours), P<0.0001. The C_max GMR was 82% (90% CI, 75%-85%). Although absorption was delayed in the fed state, this impact should not be clinically significant at steady-state dosing. The most common adverse events were dizziness, headache, and oropharyngeal pain.

Conclusions: