Adjunctive perampanel for refractory partial-onset seizures

Randomized phase III study 304

Jacqueline A. French, Gregory Krauss, Victor Biton, David Squillacote, Haichen Yang, Antonio Laurenza, Dinesh Kumar, Michael A. Rogawski

Research output: Contribution to journalArticle

Abstract

Objective: To assess efficacy and safety of once-daily 8 or 12 mg perampanel, a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazole- propionic acid (AMPA) receptor antagonist, when added to concomitant antiepileptic drugs (AEDs) in the treatment of drug-resistant partial-onset seizures. Methods: This was a multicenter, double-blind, placebo-controlled trial (ClinicalTrials.gov identifier: NCT00699972). Patients (≥12 years, with ongoing seizures despite 1-3 AEDs) were randomized (1:1:1) to once-daily perampanel 8 mg, 12 mg, or placebo. Following baseline (6 weeks), patients entered a 19-week double-blind phase: 6-week titration (2 mg/week increments to target dose) followed by a 13-week maintenance period. Percent change in seizure frequency was the primary endpoint; 50% responder rate was the primary endpoint for EU registration. Results: Of 388 patients randomized and treated, 387 provided seizure frequency data. Using this intent-to-treat population over the double-blind phase, the median percent change in seizure frequency was -21.0%, -26.3%, and -34.5% for placebo and perampanel 8 and 12 mg, respectively (p = 0.0261 and p = 0.0158 for 8 and 12 mg vs placebo, respectively). Fifty percent responder rates during the maintenance period were 26.4%, 37.6%, and 36.1%, respectively, for placebo, perampanel 8 mg, and perampanel 12 mg; these differences were not statistically significant for 8 mg (p = 0.0760) or 12 mg (p = 0.0914). Sixty-eight (17.5%) patients discontinued, including 40 (10.3%) for adverse events. Most frequent treatment-emergent adverse events were dizziness, somnolence, irritability, headache, fall, and ataxia. Conclusions: This trial demonstrated that once-daily, adjunctive perampanel at doses of 8 or 12 mg improved seizure control in patients with uncontrolled partial-onset seizures. Doses of perampanel 8 and 12 mg were safe, and tolerability was acceptable. Classification of evidence: This study provides Class I evidence that once-daily 8 and 12 mg doses of adjunctive perampanel are effective in patients with uncontrolled partial-onset seizures.

Original languageEnglish (US)
Pages (from-to)589-596
Number of pages8
JournalNeurology
Volume79
Issue number6
DOIs
StatePublished - Aug 7 2012

Fingerprint

Seizures
Placebos
Anticonvulsants
Maintenance
Isoxazoles
AMPA Receptors
perampanel
Onset
Dizziness
Ataxia
Headache
Placebo
Safety
Dose
Therapeutics
Pharmaceutical Preparations
Population
Drugs

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

French, J. A., Krauss, G., Biton, V., Squillacote, D., Yang, H., Laurenza, A., ... Rogawski, M. A. (2012). Adjunctive perampanel for refractory partial-onset seizures: Randomized phase III study 304. Neurology, 79(6), 589-596. https://doi.org/10.1212/WNL.0b013e3182635735

Adjunctive perampanel for refractory partial-onset seizures : Randomized phase III study 304. / French, Jacqueline A.; Krauss, Gregory; Biton, Victor; Squillacote, David; Yang, Haichen; Laurenza, Antonio; Kumar, Dinesh; Rogawski, Michael A.

In: Neurology, Vol. 79, No. 6, 07.08.2012, p. 589-596.

Research output: Contribution to journalArticle

French, JA, Krauss, G, Biton, V, Squillacote, D, Yang, H, Laurenza, A, Kumar, D & Rogawski, MA 2012, 'Adjunctive perampanel for refractory partial-onset seizures: Randomized phase III study 304', Neurology, vol. 79, no. 6, pp. 589-596. https://doi.org/10.1212/WNL.0b013e3182635735
French, Jacqueline A. ; Krauss, Gregory ; Biton, Victor ; Squillacote, David ; Yang, Haichen ; Laurenza, Antonio ; Kumar, Dinesh ; Rogawski, Michael A. / Adjunctive perampanel for refractory partial-onset seizures : Randomized phase III study 304. In: Neurology. 2012 ; Vol. 79, No. 6. pp. 589-596.
@article{3ebe44bcb8b24429bce2b02779c4c141,
title = "Adjunctive perampanel for refractory partial-onset seizures: Randomized phase III study 304",
abstract = "Objective: To assess efficacy and safety of once-daily 8 or 12 mg perampanel, a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazole- propionic acid (AMPA) receptor antagonist, when added to concomitant antiepileptic drugs (AEDs) in the treatment of drug-resistant partial-onset seizures. Methods: This was a multicenter, double-blind, placebo-controlled trial (ClinicalTrials.gov identifier: NCT00699972). Patients (≥12 years, with ongoing seizures despite 1-3 AEDs) were randomized (1:1:1) to once-daily perampanel 8 mg, 12 mg, or placebo. Following baseline (6 weeks), patients entered a 19-week double-blind phase: 6-week titration (2 mg/week increments to target dose) followed by a 13-week maintenance period. Percent change in seizure frequency was the primary endpoint; 50{\%} responder rate was the primary endpoint for EU registration. Results: Of 388 patients randomized and treated, 387 provided seizure frequency data. Using this intent-to-treat population over the double-blind phase, the median percent change in seizure frequency was -21.0{\%}, -26.3{\%}, and -34.5{\%} for placebo and perampanel 8 and 12 mg, respectively (p = 0.0261 and p = 0.0158 for 8 and 12 mg vs placebo, respectively). Fifty percent responder rates during the maintenance period were 26.4{\%}, 37.6{\%}, and 36.1{\%}, respectively, for placebo, perampanel 8 mg, and perampanel 12 mg; these differences were not statistically significant for 8 mg (p = 0.0760) or 12 mg (p = 0.0914). Sixty-eight (17.5{\%}) patients discontinued, including 40 (10.3{\%}) for adverse events. Most frequent treatment-emergent adverse events were dizziness, somnolence, irritability, headache, fall, and ataxia. Conclusions: This trial demonstrated that once-daily, adjunctive perampanel at doses of 8 or 12 mg improved seizure control in patients with uncontrolled partial-onset seizures. Doses of perampanel 8 and 12 mg were safe, and tolerability was acceptable. Classification of evidence: This study provides Class I evidence that once-daily 8 and 12 mg doses of adjunctive perampanel are effective in patients with uncontrolled partial-onset seizures.",
author = "French, {Jacqueline A.} and Gregory Krauss and Victor Biton and David Squillacote and Haichen Yang and Antonio Laurenza and Dinesh Kumar and Rogawski, {Michael A.}",
year = "2012",
month = "8",
day = "7",
doi = "10.1212/WNL.0b013e3182635735",
language = "English (US)",
volume = "79",
pages = "589--596",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Adjunctive perampanel for refractory partial-onset seizures

T2 - Randomized phase III study 304

AU - French, Jacqueline A.

AU - Krauss, Gregory

AU - Biton, Victor

AU - Squillacote, David

AU - Yang, Haichen

AU - Laurenza, Antonio

AU - Kumar, Dinesh

AU - Rogawski, Michael A.

PY - 2012/8/7

Y1 - 2012/8/7

N2 - Objective: To assess efficacy and safety of once-daily 8 or 12 mg perampanel, a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazole- propionic acid (AMPA) receptor antagonist, when added to concomitant antiepileptic drugs (AEDs) in the treatment of drug-resistant partial-onset seizures. Methods: This was a multicenter, double-blind, placebo-controlled trial (ClinicalTrials.gov identifier: NCT00699972). Patients (≥12 years, with ongoing seizures despite 1-3 AEDs) were randomized (1:1:1) to once-daily perampanel 8 mg, 12 mg, or placebo. Following baseline (6 weeks), patients entered a 19-week double-blind phase: 6-week titration (2 mg/week increments to target dose) followed by a 13-week maintenance period. Percent change in seizure frequency was the primary endpoint; 50% responder rate was the primary endpoint for EU registration. Results: Of 388 patients randomized and treated, 387 provided seizure frequency data. Using this intent-to-treat population over the double-blind phase, the median percent change in seizure frequency was -21.0%, -26.3%, and -34.5% for placebo and perampanel 8 and 12 mg, respectively (p = 0.0261 and p = 0.0158 for 8 and 12 mg vs placebo, respectively). Fifty percent responder rates during the maintenance period were 26.4%, 37.6%, and 36.1%, respectively, for placebo, perampanel 8 mg, and perampanel 12 mg; these differences were not statistically significant for 8 mg (p = 0.0760) or 12 mg (p = 0.0914). Sixty-eight (17.5%) patients discontinued, including 40 (10.3%) for adverse events. Most frequent treatment-emergent adverse events were dizziness, somnolence, irritability, headache, fall, and ataxia. Conclusions: This trial demonstrated that once-daily, adjunctive perampanel at doses of 8 or 12 mg improved seizure control in patients with uncontrolled partial-onset seizures. Doses of perampanel 8 and 12 mg were safe, and tolerability was acceptable. Classification of evidence: This study provides Class I evidence that once-daily 8 and 12 mg doses of adjunctive perampanel are effective in patients with uncontrolled partial-onset seizures.

AB - Objective: To assess efficacy and safety of once-daily 8 or 12 mg perampanel, a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazole- propionic acid (AMPA) receptor antagonist, when added to concomitant antiepileptic drugs (AEDs) in the treatment of drug-resistant partial-onset seizures. Methods: This was a multicenter, double-blind, placebo-controlled trial (ClinicalTrials.gov identifier: NCT00699972). Patients (≥12 years, with ongoing seizures despite 1-3 AEDs) were randomized (1:1:1) to once-daily perampanel 8 mg, 12 mg, or placebo. Following baseline (6 weeks), patients entered a 19-week double-blind phase: 6-week titration (2 mg/week increments to target dose) followed by a 13-week maintenance period. Percent change in seizure frequency was the primary endpoint; 50% responder rate was the primary endpoint for EU registration. Results: Of 388 patients randomized and treated, 387 provided seizure frequency data. Using this intent-to-treat population over the double-blind phase, the median percent change in seizure frequency was -21.0%, -26.3%, and -34.5% for placebo and perampanel 8 and 12 mg, respectively (p = 0.0261 and p = 0.0158 for 8 and 12 mg vs placebo, respectively). Fifty percent responder rates during the maintenance period were 26.4%, 37.6%, and 36.1%, respectively, for placebo, perampanel 8 mg, and perampanel 12 mg; these differences were not statistically significant for 8 mg (p = 0.0760) or 12 mg (p = 0.0914). Sixty-eight (17.5%) patients discontinued, including 40 (10.3%) for adverse events. Most frequent treatment-emergent adverse events were dizziness, somnolence, irritability, headache, fall, and ataxia. Conclusions: This trial demonstrated that once-daily, adjunctive perampanel at doses of 8 or 12 mg improved seizure control in patients with uncontrolled partial-onset seizures. Doses of perampanel 8 and 12 mg were safe, and tolerability was acceptable. Classification of evidence: This study provides Class I evidence that once-daily 8 and 12 mg doses of adjunctive perampanel are effective in patients with uncontrolled partial-onset seizures.

UR - http://www.scopus.com/inward/record.url?scp=84865719107&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84865719107&partnerID=8YFLogxK

U2 - 10.1212/WNL.0b013e3182635735

DO - 10.1212/WNL.0b013e3182635735

M3 - Article

VL - 79

SP - 589

EP - 596

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 6

ER -