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

Trenité, Dorothée G.A. Kasteleijn Nolst; DiVentura, Bree; Pollard, John R.; Krauss, Gregory L.; Mizne, Sarah; French, Jacqueline A.

doi:10.1212/wnl.0000000000007894

Cited by 37 publications

(26 citation statements)

References 19 publications

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“…2 Cenobamate suppressed the photoparoxysmal response in photosensitive epilepsy at 250 mg and 400 mg single doses in one small human epilepsy study. 3 Cenobamate (CNB) reduces repetitive neuronal firing by inhibiting voltage-gated sodium currents. 1 Specifically, it enhances the fast and slow inactivation of sodium channels and potently inhibits the noninactivating persistent component of the sodium channel current (I NaP ) by which many ASMs, notably lacosamide, are believed to work.…”

Section: Commentarymentioning

confidence: 99%

“…1 Specifically, it enhances the fast and slow inactivation of sodium channels and potently inhibits the noninactivating persistent component of the sodium channel current (I NaP ) by which many ASMs, notably lacosamide, are believed to work. [2][3][4] Also, CNB is a positive allosteric modulator of the g-aminobutyric acid (GABA A ) ion channel. 1 At least 88% of CNB is absorbed following oral administration, with a T max of 1 to 4 hours, and terminal half-life of 50 to 60 hours.…”

Section: Commentarymentioning

confidence: 99%

“…2 Cenobamate suppressed the photoparoxysmal response in photosensitive epilepsy at 250 mg and 400 mg single doses in one small human epilepsy study. 3…”

Section: Commentarymentioning

confidence: 99%

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Remarkably High Efficacy of Cenobamate in Adults With Focal-Onset Seizures: A Double-Blind, Randomized, Placebo-Controlled Trial

Vossler¹

2020

Epilepsy Curr

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Section: Commentarymentioning

confidence: 99%

Section: Commentarymentioning

confidence: 99%

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Remarkably High Efficacy of Cenobamate in Adults With Focal-Onset Seizures: A Double-Blind, Randomized, Placebo-Controlled Trial

Vossler¹

2020

Epilepsy Curr

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“…7 Cenobamate has demonstrated broad-spectrum anticonvulsant activity in animal epilepsy and seizure models, 5 including pentylenetetrazol kindling and maximal electroshock seizure models; a proof-of-concept study demonstrated suppression of the photoparoxysmal response in patients with photosensitive epilepsy. 8 A randomized, double-blind, placebo-controlled study was conducted to assess the efficacy and safety of adjunctive cenobamate 200 mg/d in adults with uncontrolled focal seizures (YKP3089C013; clinicaltrials.gov NCT01397968).…”

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confidence: 99%

Randomized phase 2 study of adjunctive cenobamate in patients with uncontrolled focal seizures

et al. 2020

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ObjectiveTo evaluate the efficacy and safety of adjunctive cenobamate 200 mg/d in patients with uncontrolled focal (partial-onset) seizures despite treatment with 1 to 3 antiepileptic drugs.MethodsIn this multicenter, double-blind, placebo-controlled study, adults 18 to 65 years of age with focal seizures were randomized 1:1 (cenobamate:placebo) after an 8-week baseline period. The 12-week double-blind treatment period consisted of a 6-week titration phase and a 6-week maintenance phase. The primary outcome was percent change in seizure frequency (from baseline) per 28 days during double-blind treatment.ResultsTwo hundred twenty-two patients were randomized; 113 received cenobamate and 109 received placebo; and 90.3% and 90.8% of patients, respectively, completed double-blind treatment. Median baseline seizure frequency was 6.5 in 28 days (range 0–237). Compared to placebo, cenobamate conferred a greater median percent seizure reduction (55.6% vs 21.5%; p < 0.0001) The responder rate (≥50% reduction in seizure frequency) was 50.4% for cenobamate and 22.2% for placebo (p < 0.0001). Focal seizures with motor component, impaired awareness, and focal to bilateral tonic-clonic seizures were significantly reduced with cenobamate vs placebo. During maintenance, 28.3% of cenobamate-treated and 8.8% of placebo-treated patients were seizure-free. Treatment-emergent adverse events reported in >10% in either group (cenobamate vs placebo) were somnolence (22.1% vs 11.9%), dizziness (22.1% vs 16.5%), headache (12.4% vs 12.8%), nausea (11.5% vs 4.6%), and fatigue (10.6% vs 6.4%).ConclusionAdjunctive treatment with cenobamate 200 mg/d significantly improved seizure control in adults with uncontrolled focal seizures and was well tolerated.ClinicalTrials.gov identifierNCT01397968.Classification of evidenceThis study provides Class I evidence that, for patients with uncontrolled focal seizures, adjunctive cenobamate reduces seizures.

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“…One single-blind study evaluated the efficacy of cenobamate by assessing its effect on photoparoxysmal-EEG responses to intermittent photic stimulation (IPS) in adults with photosensitive epilepsy [ 43 ]. The participants underwent photic stimulation intermittently under three different eye conditions: eye closure, eyes closed, and eyes opened.…”

Section: Cenobamate Studies and Clinical Trialsmentioning

confidence: 99%

Cenobamate, a Sodium Channel Inhibitor and Positive Allosteric Modulator of GABAA Ion Channels, for Partial Onset Seizures in Adults: A Comprehensive Review and Clinical Implications

Latimer

Edinoff

Ruff

et al. 2021

Neurology International

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Medical management of epilepsy seeks to eliminate or to reduce the frequency of seizures, help patients maintain a normal lifestyle, and maintain psychosocial and occupational activities, while avoiding the negative side effects of long-term treatment. Current FDA approved drugs have been shown to have similar efficacy; however, they all share a commonality of having side effects that have the potential to significantly reduce a patient’s quality of life. Cenobamate, a newly-FDA approved drug used to treat partial-onset seizures in adult patients, has demonstrated promise in that it works on two proposed mechanisms that are commonly associated with epilepsy. Cenobamate acts as a positive allosteric modulator of the GABAA ion channels and is effective in reducing repetitive neuronal firing by inhibition of voltage-gated sodium channels, although the complete mechanism of action is currently unknown. The efficacy of Cenobamate with its low toxicity and adverse drug reaction profile emphasizes the need to further evaluate antiepileptic therapies containing sulfamoylphenyl and/or carbamate moieties in their chemical structure. Recent studies have found more patients to be seizure free during the maintenance period when compared to placebo. The most common side effects reported in with Cenobamate are somnolence, dizziness, headache, nausea, and fatigue. There are currently ongoing phase III studies looking to further evaluate the long-term benefits of Cenobamate and investigate adverse events.

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

Cited by 37 publications

References 19 publications

Remarkably High Efficacy of Cenobamate in Adults With Focal-Onset Seizures: A Double-Blind, Randomized, Placebo-Controlled Trial

Remarkably High Efficacy of Cenobamate in Adults With Focal-Onset Seizures: A Double-Blind, Randomized, Placebo-Controlled Trial

Randomized phase 2 study of adjunctive cenobamate in patients with uncontrolled focal seizures

Cenobamate, a Sodium Channel Inhibitor and Positive Allosteric Modulator of GABAA Ion Channels, for Partial Onset Seizures in Adults: A Comprehensive Review and Clinical Implications

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