Adjunctive perampanel in partial-onset seizures: Asia-Pacific, randomized phase III study

Nishida, Takuji; Lee, S. K.; Inoue, Yushi; Saeki, Kazunori; Ishikawa, Kouhei; Kaneko, Sunao

doi:10.1111/ane.12883

Cited by 72 publications

(147 citation statements)

References 17 publications

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“…The phase‐3 multicenter, randomized, double‐blind, placebo‐controlled studies 304 (ClinicalTrials.gov identifier NCT00699972), 305 (NCT00699582), 306 (NCT00700310), and 335 (NCT01618695) were undertaken to assess the efficacy and safety of adjunctive once‐daily perampanel in patients with focal seizures with or without FBTC seizures. Briefly, studies 304, 305, and 306 were conducted in more than 40 countries on 6 continents, and study 335 was conducted in Japan, China, South Korea, Australia, Thailand, Malaysia, and Taiwan.…”

Section: Methodsmentioning

confidence: 99%

“…Perampanel is also indicated for monotherapy use for focal seizures in the United States . Phase‐3 studies have shown that adjunctive perampanel significantly improved seizure control in patients with treatment‐resistant focal seizures with or without focal to bilateral tonic‐clonic (FBTC) seizures (previously referred to as secondarily generalized seizures) …”

Section: Introductionmentioning

confidence: 99%

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Efficacy, safety, and tolerability of perampanel in Asian and non‐Asian patients with epilepsy

et al. 2019

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Summary People of different ethnic or racial backgrounds may experience variations in pharmacokinetic and pharmacodynamic responses to drug therapies. Our post hoc analysis evaluated the efficacy, safety, and tolerability of perampanel in Asian and non‐Asian populations with refractory focal seizures with or without focal to bilateral tonic‐clonic (FBTC) seizures. This analysis pooled data from 4 randomized, placebo‐controlled, phase‐3 studies involving patients aged ≥12 years who have focal seizures with or without FBTC seizures. Patients were receiving 2, 4, 8, or 12 mg perampanel (or placebo) by the end of a 6‐week titration period and for a further 13 weeks during the maintenance phase. Efficacy endpoints included median percent change in seizure frequency per 28 days, and 50% and seizure‐freedom responder rates relative to baseline. The median percent change in seizure frequency per 28 days from baseline was significantly greater than placebo for perampanel 8 and 12 mg (−31.1% and −38.1% change, respectively; each P < 0.0001) in the Asian population, and for perampanel 4, 8, and 12 mg (−21.1% [P = 0.0001], −26.3% [P < 0.0001], and −27.7% [P = 0.0001] change, respectively) in the non‐Asian population. The 50% responder rate relative to baseline was significantly greater than placebo for perampanel 8 and 12 mg (40.1% and 43.8%, respectively; each P < 0.0001) in the Asian population, and for perampanel 4, 8, and 12 mg (29.4% [P = 0.0002], 32.8% [P < 0.0001] and 34.5% [P = 0.0001]), respectively, in the non‐Asian population. Seizure‐freedom rate among all patients was 4.9%‐11.7% for perampanel 2, 4, 8, and 12 mg. The most frequently reported treatment‐emergent adverse events (TEAEs) across both populations were dizziness, somnolence, irritability, headache, and fatigue. The most common psychiatric TEAEs were aggression and irritability. Perampanel demonstrated a favorable and similar risk‐benefit profile in both Asian and non‐Asian populations with refractory focal seizures.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Efficacy, safety, and tolerability of perampanel in Asian and non‐Asian patients with epilepsy

et al. 2019

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“…The designs of studies 307 and 335 have been reported previously . Briefly, in study 307, patients recruited from Africa, Asia, Latin America, Europe, North America, and Australia were aged ≥12 years, had focal seizures with or without FBTC seizures despite taking one to 3 concomitant antiepileptic drugs at baseline, and had completed one of the perampanel phase 3 trials (studies 304, 305, or 306) .…”

Section: Methodsmentioning

confidence: 99%

“…Asian patients were among the global population enrolled in the phase 3 clinical trials and extension study . To specifically assess the efficacy and safety of perampanel as adjunctive therapy in patients aged ≥12 years with refractory focal seizures with or without FBTC seizures from Asia, a randomized, double‐blind, placebo‐controlled trial (study 335; NCT01618695) was conducted, which included an extension phase . At the end of the double‐blind phase of study 335, perampanel demonstrated a statistically significant change in seizure frequency per 28 days from baseline at doses of 8 mg (−29.0%; P = 0.0003) and 12 mg (−38.0%; P < 0.0001) compared with placebo .…”

Section: Introductionmentioning

confidence: 99%

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A post hoc analysis of the long‐term safety and efficacy of perampanel in Asian patients with epilepsy

et al. 2019

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Summary This post hoc analysis assessed the long‐term safety, tolerability, and efficacy of perampanel in Asian patients with refractory focal seizures; an additional analysis assessed the effect of perampanel on focal impaired awareness seizures (FIAS) with focal to bilateral tonic‐clonic (FBTC) seizures. In this subanalysis, data from Asian patients ≥12 years of age who had focal seizures with FBTC seizures despite taking one to 3 concomitant antiepileptic drugs at baseline, and who had entered either the long‐term extension phase of 3 phase‐3 perampanel trials (study 307) or the 10‐week extension phase of study 335, were analyzed for the effect of perampanel on duration of exposure, safety, and seizure outcomes. Of 874 Asian patients included in the analysis, 205 had previously received placebo during the double‐blind phase‐3 trials and 669 had previously received perampanel 2‐12 mg/day; 313 had FIAS with FBTC seizures at core study baseline. The median duration of exposure to perampanel was 385.0 days, and the retention rate at one year was 62.6%. Overall, during the first 52 weeks of perampanel treatment, 777 patients (88.9%) had treatment‐emergent adverse events (TEAEs), most of which were mild to moderate in severity. The most frequent TEAEs were dizziness (47.1%), somnolence (22.3%), and nasopharyngitis (17.4%). During the first 52 weeks of perampanel treatment, median percent change in seizure frequency per 28 days from pre‐perampanel baseline for all focal seizures was −28.1%, and −51.7% for FIAS with FBTC seizures. The 50% responder rate relative to pre‐perampanel baseline for all focal seizures was 33.8%, and 51.1% for FIAS with FBTC seizures. Long‐term treatment with perampanel in Asian patients had safety, tolerability, and efficacy similar to that of the global population in the phase‐3 trials and extension study 307. The safety profile and response rate suggest benefit for an Asian population of patients with refractory epilepsy.

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New and Emerging Antiepileptic Drugs

Witkin

Golani

Smith

2021

Burger's Medicinal Chemistry and Drug Discovery

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This article provides the biologist, chemist, and clinician with an overview into currently existing epilepsy medicines, an appreciation of those currently in development, and a glimpse at future possibilities. The discovery and development of antiepileptic drugs with improved efficacy and side‐effect dimensions are urgently needed. We discuss various strategies for discovering new antiepileptic drugs. We then provide summary data on the mechanisms of action, efficacy, and tolerability of some of the newer third‐generation antiepileptic drugs – eslicarbazepine, brivaracetam, retigabine, lacosamide, and perampanel. Additional compounds that are currently in development for epilepsy are also reviewed. These include the novel α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor antagonists CERC‐611 and JNJ‐55511118 that are first‐in‐class drugs blocking only those AMPA receptors associated with the auxiliary protein TAPP γ‐8. The GABA A (α2/3)‐selective compounds, KRM‐II‐81, MP‐III‐080, and PF‐06372865 hold additional promise and potential advantage over nonselective GABA A receptor modulators. The developmental status of another positive allosteric modulator of GABA A receptors, the neuroactive steroid ganaxolone, is also summarized. In addition, two mGlu2 receptor modulators, JNJ‐40411813 and LY2812223 are discussed. Finally, initial data on cannabidiol, anakinra, and padsevonil are reviewed. Literature data derived from studies on both human epileptic tissue and rodent seizure modeling were utilized to glean several compelling novel drug targets for consideration in future antiepileptic drug discovery programs. Thus, in the past decade, key advances have been made that are benefiting the epileptic patient community. The current compounds in development and new drug targets give additional promise of improved antiepileptic drugs.

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Adjunctive perampanel in partial-onset seizures: Asia-Pacific, randomized phase III study

Abstract: Adjunctive perampanel (8 and 12 mg/d) significantly improved seizure control in patients with refractory POS. Safety and tolerability were acceptable at daily doses of perampanel 4-12 mg.

Cited by 72 publications

References 17 publications

Efficacy, safety, and tolerability of perampanel in Asian and non‐Asian patients with epilepsy

Efficacy, safety, and tolerability of perampanel in Asian and non‐Asian patients with epilepsy

A post hoc analysis of the long‐term safety and efficacy of perampanel in Asian patients with epilepsy

New and Emerging Antiepileptic Drugs

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