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 journalArticle

Abstract

OBJECTIVE: To 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. METHODS: In 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. RESULTS: Of 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- and 400-mg doses. Area under the plasma concentration-time curve (before dose to last measurable concentration) values between 201 and 400 μg/h/mL resulted in partial suppression in 4 of 6 (66%) patients. Most common adverse events were dizziness and somnolence. CONCLUSIONS: This proof-of-principle study demonstrated that cenobamate is a potentially effective product for epilepsy. CLINICALTRIALSGOV IDENTIFIER: NCT00616148. CLASSIFICATION OF EVIDENCE: This 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
Externally publishedYes

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Reflex Epilepsy
Photic Stimulation
Electroencephalography
Epilepsy
Placebos
Single-Blind Method
Dizziness
Anticonvulsants
Pharmacokinetics
Safety
Drug Therapy

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Kasteleijn-Nolst Trenite, D. G. A., DiVentura, B. D., Pollard, J. R., Krauss, G. L., Mizne, S., & French, J. A. (2019). Suppression of the photoparoxysmal response in photosensitive epilepsy with cenobamate (YKP3089). Neurology, 93(6), e559-e567. https://doi.org/10.1212/WNL.0000000000007894

Suppression of the photoparoxysmal response in photosensitive epilepsy with cenobamate (YKP3089). / Kasteleijn-Nolst Trenite, Dorothee G.A.; DiVentura, Bree D.; Pollard, John R.; Krauss, Gregory L.; Mizne, Sarah; French, Jacqueline A.

In: Neurology, Vol. 93, No. 6, 06.08.2019, p. e559-e567.

Research output: Contribution to journalArticle

Kasteleijn-Nolst Trenite, DGA, DiVentura, BD, Pollard, JR, Krauss, GL, Mizne, S & French, JA 2019, 'Suppression of the photoparoxysmal response in photosensitive epilepsy with cenobamate (YKP3089)', Neurology, vol. 93, no. 6, pp. e559-e567. https://doi.org/10.1212/WNL.0000000000007894
Kasteleijn-Nolst Trenite DGA, DiVentura BD, Pollard JR, Krauss GL, Mizne S, French JA. Suppression of the photoparoxysmal response in photosensitive epilepsy with cenobamate (YKP3089). Neurology. 2019 Aug 6;93(6):e559-e567. https://doi.org/10.1212/WNL.0000000000007894
Kasteleijn-Nolst Trenite, Dorothee G.A. ; DiVentura, Bree D. ; Pollard, John R. ; Krauss, Gregory L. ; Mizne, Sarah ; French, Jacqueline A. / Suppression of the photoparoxysmal response in photosensitive epilepsy with cenobamate (YKP3089). In: Neurology. 2019 ; Vol. 93, No. 6. pp. e559-e567.
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abstract = "OBJECTIVE: To 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. METHODS: In 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. RESULTS: Of 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- and 400-mg doses. Area under the plasma concentration-time curve (before dose to last measurable concentration) values between 201 and 400 μg/h/mL resulted in partial suppression in 4 of 6 (66{\%}) patients. Most common adverse events were dizziness and somnolence. CONCLUSIONS: This proof-of-principle study demonstrated that cenobamate is a potentially effective product for epilepsy. CLINICALTRIALSGOV IDENTIFIER: NCT00616148. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that, for patients with photosensitive epilepsy, cenobamate suppresses IPS-induced PPR.",
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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.

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N2 - OBJECTIVE: To 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. METHODS: In 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. RESULTS: Of 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- and 400-mg doses. Area under the plasma concentration-time curve (before dose to last measurable concentration) values between 201 and 400 μg/h/mL resulted in partial suppression in 4 of 6 (66%) patients. Most common adverse events were dizziness and somnolence. CONCLUSIONS: This proof-of-principle study demonstrated that cenobamate is a potentially effective product for epilepsy. CLINICALTRIALSGOV IDENTIFIER: NCT00616148. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that, for patients with photosensitive epilepsy, cenobamate suppresses IPS-induced PPR.

AB - OBJECTIVE: To 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. METHODS: In 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. RESULTS: Of 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- and 400-mg doses. Area under the plasma concentration-time curve (before dose to last measurable concentration) values between 201 and 400 μg/h/mL resulted in partial suppression in 4 of 6 (66%) patients. Most common adverse events were dizziness and somnolence. CONCLUSIONS: This proof-of-principle study demonstrated that cenobamate is a potentially effective product for epilepsy. CLINICALTRIALSGOV IDENTIFIER: NCT00616148. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that, for patients with photosensitive epilepsy, cenobamate suppresses IPS-induced PPR.

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