Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures

Results of randomized global phase III study 305

Jacqueline A. French, Gregory Krauss, Bernhard J. Steinhoff, David Squillacote, Haichen Yang, Dinesh Kumar, Antonio Laurenza

Research output: Contribution to journalArticle

Abstract

Purpose: To assess the efficacy and safety of once-daily doses of perampanel 8 and 12 mg when added to 1-3 concomitantly administered, approved antiepileptic drugs (AEDs) in patients with uncontrolled partial-onset seizures. Methods: Study 305 was a multicenter, double-blind, placebo-controlled trial in patients aged 12 years and older with ongoing seizures despite prior therapy with at least two AEDs, and currently receiving 1-3 AEDs. Equal randomization to once-daily oral perampanel 8 or 12 mg, or placebo was performed. Patients entered a 19-week double-blind treatment phase comprising a 6-week titration period, with weekly 2-mg dose increments, followed by a 13-week maintenance period. Primary efficacy end points were the responder rate (proportion of patients who had a ≥50% reduction in seizure frequency during treatment per 28 days relative to baseline), and the percent change in seizure frequency per 28 days relative to pre-perampanel baseline. A secondary end point was percent change in the frequency of complex partial plus secondarily generalized seizures. Adverse events (AEs) were monitored throughout the study. Key Findings: Three hundred eighty-six patients were randomized and treated with study medication. Of these, 321 patients completed the study. The 50% responder rates (intent-to-treat analysis) were 14.7%, 33.3%, and 33.9%, respectively, for placebo, perampanel 8 mg, and perampanel 12 mg, with significant improvements over placebo for both perampanel 8 mg (p = 0.002) and 12 mg (p <0.001). The median percent change from baseline in seizure frequency per 28 days (intent-to-treat analysis) was -9.7%, -30.5%, and -17.6% for placebo, 8 mg, and 12 mg, respectively, with significant reductions compared with placebo for both 8 mg (p <0.001) and 12 mg (p = 0.011). For complex partial seizures plus partial seizures that secondarily generalized, the median percent change in frequency was -32.7% (8 mg), -21.9 (12 mg), and -8.1% (placebo), with significant reductions for both 8 mg (p <0.001) and 12 mg (p = 0.005). The most frequent (occurring in ≥10% of patients in any treatment group) treatment-emergent AEs were dizziness, somnolence, fatigue, and headache, with an apparent dose effect suggested for all except headache. Significance: This phase III trial demonstrated that adjunctive treatment with once-daily perampanel at 8 mg and 12 mg was effective in improving seizure control in patients 12 years and older with refractory partial-onset seizures. These study results also demonstrated that once-daily doses of 8 mg and 12 mg were safe and acceptably tolerated in this study. Perampanel demonstrated a favorable risk/benefit ratio in this population.

Original languageEnglish (US)
Pages (from-to)117-125
Number of pages9
JournalEpilepsia
Volume54
Issue number1
DOIs
StatePublished - Jan 2013

Fingerprint

Seizures
Placebos
Anticonvulsants
Headache
Therapeutics
perampanel
Dizziness
Random Allocation
Fatigue
Odds Ratio
Maintenance
Safety
Population

Keywords

  • Antiepileptic drugs
  • Epilepsy
  • Glutamate
  • LOCF analysis
  • Postsynaptic
  • Randomized controlled trials

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures : Results of randomized global phase III study 305. / French, Jacqueline A.; Krauss, Gregory; Steinhoff, Bernhard J.; Squillacote, David; Yang, Haichen; Kumar, Dinesh; Laurenza, Antonio.

In: Epilepsia, Vol. 54, No. 1, 01.2013, p. 117-125.

Research output: Contribution to journalArticle

French, Jacqueline A. ; Krauss, Gregory ; Steinhoff, Bernhard J. ; Squillacote, David ; Yang, Haichen ; Kumar, Dinesh ; Laurenza, Antonio. / Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures : Results of randomized global phase III study 305. In: Epilepsia. 2013 ; Vol. 54, No. 1. pp. 117-125.
@article{1c7933ff870741a2a0f4a5a4bc851aae,
title = "Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: Results of randomized global phase III study 305",
abstract = "Purpose: To assess the efficacy and safety of once-daily doses of perampanel 8 and 12 mg when added to 1-3 concomitantly administered, approved antiepileptic drugs (AEDs) in patients with uncontrolled partial-onset seizures. Methods: Study 305 was a multicenter, double-blind, placebo-controlled trial in patients aged 12 years and older with ongoing seizures despite prior therapy with at least two AEDs, and currently receiving 1-3 AEDs. Equal randomization to once-daily oral perampanel 8 or 12 mg, or placebo was performed. Patients entered a 19-week double-blind treatment phase comprising a 6-week titration period, with weekly 2-mg dose increments, followed by a 13-week maintenance period. Primary efficacy end points were the responder rate (proportion of patients who had a ≥50{\%} reduction in seizure frequency during treatment per 28 days relative to baseline), and the percent change in seizure frequency per 28 days relative to pre-perampanel baseline. A secondary end point was percent change in the frequency of complex partial plus secondarily generalized seizures. Adverse events (AEs) were monitored throughout the study. Key Findings: Three hundred eighty-six patients were randomized and treated with study medication. Of these, 321 patients completed the study. The 50{\%} responder rates (intent-to-treat analysis) were 14.7{\%}, 33.3{\%}, and 33.9{\%}, respectively, for placebo, perampanel 8 mg, and perampanel 12 mg, with significant improvements over placebo for both perampanel 8 mg (p = 0.002) and 12 mg (p <0.001). The median percent change from baseline in seizure frequency per 28 days (intent-to-treat analysis) was -9.7{\%}, -30.5{\%}, and -17.6{\%} for placebo, 8 mg, and 12 mg, respectively, with significant reductions compared with placebo for both 8 mg (p <0.001) and 12 mg (p = 0.011). For complex partial seizures plus partial seizures that secondarily generalized, the median percent change in frequency was -32.7{\%} (8 mg), -21.9 (12 mg), and -8.1{\%} (placebo), with significant reductions for both 8 mg (p <0.001) and 12 mg (p = 0.005). The most frequent (occurring in ≥10{\%} of patients in any treatment group) treatment-emergent AEs were dizziness, somnolence, fatigue, and headache, with an apparent dose effect suggested for all except headache. Significance: This phase III trial demonstrated that adjunctive treatment with once-daily perampanel at 8 mg and 12 mg was effective in improving seizure control in patients 12 years and older with refractory partial-onset seizures. These study results also demonstrated that once-daily doses of 8 mg and 12 mg were safe and acceptably tolerated in this study. Perampanel demonstrated a favorable risk/benefit ratio in this population.",
keywords = "Antiepileptic drugs, Epilepsy, Glutamate, LOCF analysis, Postsynaptic, Randomized controlled trials",
author = "French, {Jacqueline A.} and Gregory Krauss and Steinhoff, {Bernhard J.} and David Squillacote and Haichen Yang and Dinesh Kumar and Antonio Laurenza",
year = "2013",
month = "1",
doi = "10.1111/j.1528-1167.2012.03638.x",
language = "English (US)",
volume = "54",
pages = "117--125",
journal = "Epilepsia",
issn = "0013-9580",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures

T2 - Results of randomized global phase III study 305

AU - French, Jacqueline A.

AU - Krauss, Gregory

AU - Steinhoff, Bernhard J.

AU - Squillacote, David

AU - Yang, Haichen

AU - Kumar, Dinesh

AU - Laurenza, Antonio

PY - 2013/1

Y1 - 2013/1

N2 - Purpose: To assess the efficacy and safety of once-daily doses of perampanel 8 and 12 mg when added to 1-3 concomitantly administered, approved antiepileptic drugs (AEDs) in patients with uncontrolled partial-onset seizures. Methods: Study 305 was a multicenter, double-blind, placebo-controlled trial in patients aged 12 years and older with ongoing seizures despite prior therapy with at least two AEDs, and currently receiving 1-3 AEDs. Equal randomization to once-daily oral perampanel 8 or 12 mg, or placebo was performed. Patients entered a 19-week double-blind treatment phase comprising a 6-week titration period, with weekly 2-mg dose increments, followed by a 13-week maintenance period. Primary efficacy end points were the responder rate (proportion of patients who had a ≥50% reduction in seizure frequency during treatment per 28 days relative to baseline), and the percent change in seizure frequency per 28 days relative to pre-perampanel baseline. A secondary end point was percent change in the frequency of complex partial plus secondarily generalized seizures. Adverse events (AEs) were monitored throughout the study. Key Findings: Three hundred eighty-six patients were randomized and treated with study medication. Of these, 321 patients completed the study. The 50% responder rates (intent-to-treat analysis) were 14.7%, 33.3%, and 33.9%, respectively, for placebo, perampanel 8 mg, and perampanel 12 mg, with significant improvements over placebo for both perampanel 8 mg (p = 0.002) and 12 mg (p <0.001). The median percent change from baseline in seizure frequency per 28 days (intent-to-treat analysis) was -9.7%, -30.5%, and -17.6% for placebo, 8 mg, and 12 mg, respectively, with significant reductions compared with placebo for both 8 mg (p <0.001) and 12 mg (p = 0.011). For complex partial seizures plus partial seizures that secondarily generalized, the median percent change in frequency was -32.7% (8 mg), -21.9 (12 mg), and -8.1% (placebo), with significant reductions for both 8 mg (p <0.001) and 12 mg (p = 0.005). The most frequent (occurring in ≥10% of patients in any treatment group) treatment-emergent AEs were dizziness, somnolence, fatigue, and headache, with an apparent dose effect suggested for all except headache. Significance: This phase III trial demonstrated that adjunctive treatment with once-daily perampanel at 8 mg and 12 mg was effective in improving seizure control in patients 12 years and older with refractory partial-onset seizures. These study results also demonstrated that once-daily doses of 8 mg and 12 mg were safe and acceptably tolerated in this study. Perampanel demonstrated a favorable risk/benefit ratio in this population.

AB - Purpose: To assess the efficacy and safety of once-daily doses of perampanel 8 and 12 mg when added to 1-3 concomitantly administered, approved antiepileptic drugs (AEDs) in patients with uncontrolled partial-onset seizures. Methods: Study 305 was a multicenter, double-blind, placebo-controlled trial in patients aged 12 years and older with ongoing seizures despite prior therapy with at least two AEDs, and currently receiving 1-3 AEDs. Equal randomization to once-daily oral perampanel 8 or 12 mg, or placebo was performed. Patients entered a 19-week double-blind treatment phase comprising a 6-week titration period, with weekly 2-mg dose increments, followed by a 13-week maintenance period. Primary efficacy end points were the responder rate (proportion of patients who had a ≥50% reduction in seizure frequency during treatment per 28 days relative to baseline), and the percent change in seizure frequency per 28 days relative to pre-perampanel baseline. A secondary end point was percent change in the frequency of complex partial plus secondarily generalized seizures. Adverse events (AEs) were monitored throughout the study. Key Findings: Three hundred eighty-six patients were randomized and treated with study medication. Of these, 321 patients completed the study. The 50% responder rates (intent-to-treat analysis) were 14.7%, 33.3%, and 33.9%, respectively, for placebo, perampanel 8 mg, and perampanel 12 mg, with significant improvements over placebo for both perampanel 8 mg (p = 0.002) and 12 mg (p <0.001). The median percent change from baseline in seizure frequency per 28 days (intent-to-treat analysis) was -9.7%, -30.5%, and -17.6% for placebo, 8 mg, and 12 mg, respectively, with significant reductions compared with placebo for both 8 mg (p <0.001) and 12 mg (p = 0.011). For complex partial seizures plus partial seizures that secondarily generalized, the median percent change in frequency was -32.7% (8 mg), -21.9 (12 mg), and -8.1% (placebo), with significant reductions for both 8 mg (p <0.001) and 12 mg (p = 0.005). The most frequent (occurring in ≥10% of patients in any treatment group) treatment-emergent AEs were dizziness, somnolence, fatigue, and headache, with an apparent dose effect suggested for all except headache. Significance: This phase III trial demonstrated that adjunctive treatment with once-daily perampanel at 8 mg and 12 mg was effective in improving seizure control in patients 12 years and older with refractory partial-onset seizures. These study results also demonstrated that once-daily doses of 8 mg and 12 mg were safe and acceptably tolerated in this study. Perampanel demonstrated a favorable risk/benefit ratio in this population.

KW - Antiepileptic drugs

KW - Epilepsy

KW - Glutamate

KW - LOCF analysis

KW - Postsynaptic

KW - Randomized controlled trials

UR - http://www.scopus.com/inward/record.url?scp=84872090913&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84872090913&partnerID=8YFLogxK

U2 - 10.1111/j.1528-1167.2012.03638.x

DO - 10.1111/j.1528-1167.2012.03638.x

M3 - Article

VL - 54

SP - 117

EP - 125

JO - Epilepsia

JF - Epilepsia

SN - 0013-9580

IS - 1

ER -