Cenobamate (YKP3089) in Photosensitive Patients: Proof of Principle (P5.279)

Objective: To evaluate the antiseizure effect of cenobamate in patients with photosensitive epilepsy. Background: Cenobamate (YKP3089) is an antiepileptic drug (AED) that is under investigation for use in patients with partial-onset seizures. The photoparoxysmal response (PPR), a photic-induced electroencephalographic pattern in photosensitive patients, can be used as a “proof-of-principle” model for potential AEDs and to measure pharmacodynamic effects. Design/Methods: In this single-blind, repeated-single-dose study, photosensitive epilepsy patients received cenobamate (100, 250 or 400 mg) on Day 1, and placebo on Days −1 and 2. Prior exposure to the lower doses was required for the 250 mg and 400 mg doses. Photosensitivity ranges (PR) were determined for three eye conditions. Complete suppression was a PR reduction to 0 over ≥1 time point for all eye conditions. Partial suppression was a ≥3-point reduction over ≥3 testing times compared with the range at the same time points on Day −1. Adverse events (AEs) were recorded. Results: Seven patients with generalized (n=6) or partial-onset (n=1) seizures received ≥1 dose of the study drug or placebo (100 mg, n=3; 250 mg, n=4; 400 mg, n=4). Cenobamate 100 mg produced partial suppression in 1/3 patients. At 250 mg, cenobamate produced complete suppression in 1/4 and partial suppression in 4/4 patients in ≥1 eye condition. The 400 mg dose produced complete suppression in 1/4 patients, and partial suppression in 2/4 patients in ≥1 eye condition. Area under the plasma concentration–time curve (0–24 hours) and maximum drug plasma concentration were dose proportional, with the highest values for 400 mg (geometric mean [coefficient of variation]: 197 [32.9%] μg·h/mL and 9.56 [35.3%] μg/mL) and lowest for 100 mg (45.9 [11.8%] μg·h/mL and 2.45 [15.2%] μg/mL). The most common AEs were postural dizziness (n=3) and somnolence (n=3). Conclusions: Cenobamate suppressed PPR in patients with generalized and partial-onset seizures. Disclosure: Dr. Kasteleijn has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, UCB Inc. Dr. DiVentura has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Epilepsy Study consortium. Dr. Pollard has received compensation for serving on the Board of Directors of Cognizance Biomarkers. Dr. Krauss has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Otsuka Labs, Shire Laboratories. Dr. Krauss has received research support from SK Life Sciences, Upsher Smith. Dr. French has received research support from Acorda, Alexza, Eisai Medical Research, LCGH, Lundbeck, Pfizer, SK Life Sciences, Sunovion, Takeda, and UCB.