TY - JOUR
T1 - Suppression of the photoparoxysmal response in photosensitive epilepsy with cenobamate (YKP3089)
AU - Kasteleijn-Nolst Trenite, Dorothee G.A.
AU - Diventura, Bree D.
AU - Pollard, John R.
AU - Krauss, Gregory L.
AU - Mizne, Sarah
AU - French, Jacqueline A.
N1 - Funding Information:
The authors thank Janet Peterson, PhD, of MedVal Scientific Information Services, LLC (Princeton, NJ, USA) for her medical writing contributions to the first draft. Medical writing and editing assistance were provided by MedVal Scientific Information Services, LLC (Princeton, NJ), which was funded by SK Life Science, Inc. SK Life Science, Inc performed the statistical analysis. This manuscript was prepared according to the International Society for Medical Publication Professionals’ “Good Publication Practice for Communicating Company-Sponsored Medical Research: GPP3.”
Funding Information:
The Article Processing Charge was funded by SK Life Science.
Publisher Copyright:
© American Academy of Neurology.
PY - 2019/8/6
Y1 - 2019/8/6
N2 - 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.
AB - 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.
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U2 - 10.1212/WNL.0000000000007894
DO - 10.1212/WNL.0000000000007894
M3 - Article
C2 - 31292226
AN - SCOPUS:85071067555
VL - 93
SP - E559-E567
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 6
ER -