Suppression of the photoparoxysmal response in photosensitive epilepsy with cenobamate (YKP3089)

Dorothee G.A. Kasteleijn-Nolst Trenite, Bree D. Diventura, John R. Pollard, Gregory L. Krauss, Sarah Mizne, Jacqueline A. French

Research output: Contribution to journalArticlepeer-review

Abstract

ObjectiveTo evaluate the effect of cenobamate in patients with photoparoxysmal-EEG response (PPR) to intermittent photic stimulation (IPS) as proof of principle of efficacy in patients with epilepsy.MethodsIn this multicenter, single-blind study, adults with photosensitive epilepsy, with/without concomitant antiepileptic drug therapy, underwent IPS under 3 eye conditions after a single dose of placebo (day-1, day 2) or cenobamate (day 1; 100, 250, or 400 mg). Complete suppression was a standardized photosensitivity range reduction to 0 over ≥1 time points for all eye conditions. Partial suppression was a ≥3-point reduction over ≥3 testing times vs the same time points on day-1 in ≥1 eye condition. Pharmacokinetics and safety were assessed.ResultsOf 6 evaluable patients, 5 reentered to receive higher doses. Cenobamate 100 mg produced partial suppression in 1 of 3 patients; 250 mg produced complete suppression in 1 of 4 and partial suppression in 4 of 4 patients; and 400 mg produced complete suppression in 1 of 4 and partial suppression in 2 of 4 patients. PPR was consistently reduced on days 1 and 2 (>24 hours after cenobamate) vs day-1 (placebo) with the 250- A nd 400-mg doses. Area under the plasma concentration-time curve (before dose to last measurable concentration) values between 201 and 400 g/h/mL resulted in partial suppression in 4 of 6 (66%) patients. Most common adverse events were dizziness and somnolence.ConclusionsThis proof-of-principle study demonstrated that cenobamate is a potentially effective product for epilepsy.ClinicalTrials.gov identifierNCT00616148.Classification of evidenceThis study provides Class III evidence that, for patients with photosensitive epilepsy, cenobamate suppresses IPS-induced PPR.

Original languageEnglish (US)
Pages (from-to)E559-E567
JournalNeurology
Volume93
Issue number6
DOIs
StatePublished - Aug 6 2019

ASJC Scopus subject areas

  • Clinical Neurology

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