Relative Bioavailability of Cenobamate 200 mg Administered as a Crushed Tablet, Either Orally or via Nasogastric Tube, vs. an Intact 200 mg Cenobamate Tablet
Janice Laramy1, Louis Ferrari1, Marc Kamin1, Vijaykumar Vashi1
1SK Life Science, Inc.
Objective:
This study examined the pharmacokinetics (PK) and safety of crushed cenobamate tablets in suspension delivered orally and via nasogastric tube.
Background:
Cenobamate is an antiseizure medication (ASM) approved in the US and Europe for the treatment of focal seizures in adult patients. Crushing tablets offers flexibility for administration, including dosing by nasogastric tube.
Design/Methods:
This phase 1, randomized, open-label, single-dose, three-way crossover (6-sequence, 3-period, 3-treatment) study enrolled 31 healthy subjects aged 18-50 years. Subjects received one dose each of cenobamate 200 mg as an intact tablet administered with 240 mL of water (treatment A, reference), a crushed tablet suspended in water and taken orally (treatment B, test 1), and a crushed tablet suspended in water and administered via nasogastric tube (treatment C, test 2). All doses were administered in a fasting state (13-day washout between treatments). Blood samples for PK assessments were collected out to 264 hours following each treatment on Days 1, 14, and 27. Natural log-transformed cenobamate PK parameters (Cmax, AUClast, and AUCinf) were used to estimate relative bioavailability and construct 90% CIs using a mixed-effects model approach, with treatment, sequence, and period as fixed effects and subject within sequence as random effect. Absence of effect was concluded if the 90% CIs fell within the 80%-125% predefined boundaries.
Results:
Test-to-reference ratios for treatment B vs reference (90% CIs) were: Cmax, 95.6% (89.6%-102%); AUClast, 90.9% (87.2%-94.7%); AUCinf, 92.8% (89.7%-96.0%). Test-to-reference ratios for treatment C vs reference (90% CIs) were: Cmax, 101.7% (95.4%-108.4%); AUClast, 93.3% (89.6%-97.2%); AUCinf, 94.1% (91.0%-97.3%). Treatment-emergent adverse events were mild and resolved.
Conclusions:
All 90% CIs of test-to-reference ratios for Cmax, AUClast, and AUCinf were within 80%-125% boundaries, demonstrating bioequivalence between all 3 cenobamate administration routes. These results support the administration of cenobamate as a crushed tablet in suspension either orally or via nasogastric tube, providing additional dosing flexibility.