Perampanel for adjunctive treatment of partial-onset seizures: A pooled dose-response analysis of phase III studies

Lynn D. Kramer, Andrew Satlin, Gregory L. Krauss, Jacqueline French, Emilio Perucca, Elinor Ben-Menachem, Patrick Kwan, Jerry J. Shih, Antonio Laurenza, Haichen Yang, Jin Zhu, David Squillacote

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Objective To better understand the relationship between efficacy and perampanel dose, integrated actual (last) dose data from three phase III trials and an extension study (blinded Conversion Period; open-label Maintenance Period) were analyzed. Methods Seizure frequency data were analyzed in patients who were randomized to and completed the 13-week Maintenance Period of the phase III studies on perampanel 8 mg, and who received an actual (last) dose of 12 mg during (1) the extension 16-week blinded Conversion Period or (2) weeks 1-13 of the extension Maintenance Period. Due to a treatment-by-region interaction (p = 0.042), analyses excluded patients from the Latin America region (n = 162/1,480; 10.9% of the treated cohort). Results Of 372 patients randomized to 8 mg in the phase III studies, 273 completed the Maintenance Period at 8 mg and 267 entered the extension study. In patients who then had an actual (last) dose of 12 mg during the extension blinded Conversion Period (n = 217), median percent change in seizure frequency per 28 days improved from -32.4% (8 mg, phase III Maintenance Period) to -44.2% (12 mg, extension blinded Conversion Period); 50% responder rates increased slightly from 37.3% to 42.9%. In patients who completed the phase III studies on 8 mg and had an actual (last) dose of 12 mg during weeks 1-13 of the extension Maintenance Period (n = 181), median percent change in seizure frequency per 28 days improved from -34.1% (phase III Maintenance Period) to -46.0% (weeks 1-13 extension Maintenance Period); 50% responder rates were 39.2% and 46.4%. Seizure control remained substantially unchanged in patients who completed the phase III studies at 12 mg and continued on that dose during the extension. Significance Increasing perampanel dose from 8 to 12 mg can produce additional benefits in seizure control in at least some patients who tolerate the higher dose.

Original languageEnglish (US)
Pages (from-to)423-431
Number of pages9
JournalEpilepsia
Volume55
Issue number3
DOIs
StatePublished - 2014

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Seizures
Maintenance
Therapeutics
Latin America
perampanel

Keywords

  • Actual (last) dose
  • Antiepileptic
  • Efficacy
  • Epilepsy
  • α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Kramer, L. D., Satlin, A., Krauss, G. L., French, J., Perucca, E., Ben-Menachem, E., ... Squillacote, D. (2014). Perampanel for adjunctive treatment of partial-onset seizures: A pooled dose-response analysis of phase III studies. Epilepsia, 55(3), 423-431. https://doi.org/10.1111/epi.12527

Perampanel for adjunctive treatment of partial-onset seizures : A pooled dose-response analysis of phase III studies. / Kramer, Lynn D.; Satlin, Andrew; Krauss, Gregory L.; French, Jacqueline; Perucca, Emilio; Ben-Menachem, Elinor; Kwan, Patrick; Shih, Jerry J.; Laurenza, Antonio; Yang, Haichen; Zhu, Jin; Squillacote, David.

In: Epilepsia, Vol. 55, No. 3, 2014, p. 423-431.

Research output: Contribution to journalArticle

Kramer, LD, Satlin, A, Krauss, GL, French, J, Perucca, E, Ben-Menachem, E, Kwan, P, Shih, JJ, Laurenza, A, Yang, H, Zhu, J & Squillacote, D 2014, 'Perampanel for adjunctive treatment of partial-onset seizures: A pooled dose-response analysis of phase III studies', Epilepsia, vol. 55, no. 3, pp. 423-431. https://doi.org/10.1111/epi.12527
Kramer, Lynn D. ; Satlin, Andrew ; Krauss, Gregory L. ; French, Jacqueline ; Perucca, Emilio ; Ben-Menachem, Elinor ; Kwan, Patrick ; Shih, Jerry J. ; Laurenza, Antonio ; Yang, Haichen ; Zhu, Jin ; Squillacote, David. / Perampanel for adjunctive treatment of partial-onset seizures : A pooled dose-response analysis of phase III studies. In: Epilepsia. 2014 ; Vol. 55, No. 3. pp. 423-431.
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abstract = "Objective To better understand the relationship between efficacy and perampanel dose, integrated actual (last) dose data from three phase III trials and an extension study (blinded Conversion Period; open-label Maintenance Period) were analyzed. Methods Seizure frequency data were analyzed in patients who were randomized to and completed the 13-week Maintenance Period of the phase III studies on perampanel 8 mg, and who received an actual (last) dose of 12 mg during (1) the extension 16-week blinded Conversion Period or (2) weeks 1-13 of the extension Maintenance Period. Due to a treatment-by-region interaction (p = 0.042), analyses excluded patients from the Latin America region (n = 162/1,480; 10.9{\%} of the treated cohort). Results Of 372 patients randomized to 8 mg in the phase III studies, 273 completed the Maintenance Period at 8 mg and 267 entered the extension study. In patients who then had an actual (last) dose of 12 mg during the extension blinded Conversion Period (n = 217), median percent change in seizure frequency per 28 days improved from -32.4{\%} (8 mg, phase III Maintenance Period) to -44.2{\%} (12 mg, extension blinded Conversion Period); 50{\%} responder rates increased slightly from 37.3{\%} to 42.9{\%}. In patients who completed the phase III studies on 8 mg and had an actual (last) dose of 12 mg during weeks 1-13 of the extension Maintenance Period (n = 181), median percent change in seizure frequency per 28 days improved from -34.1{\%} (phase III Maintenance Period) to -46.0{\%} (weeks 1-13 extension Maintenance Period); 50{\%} responder rates were 39.2{\%} and 46.4{\%}. Seizure control remained substantially unchanged in patients who completed the phase III studies at 12 mg and continued on that dose during the extension. Significance Increasing perampanel dose from 8 to 12 mg can produce additional benefits in seizure control in at least some patients who tolerate the higher dose.",
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AU - Krauss, Gregory L.

AU - French, Jacqueline

AU - Perucca, Emilio

AU - Ben-Menachem, Elinor

AU - Kwan, Patrick

AU - Shih, Jerry J.

AU - Laurenza, Antonio

AU - Yang, Haichen

AU - Zhu, Jin

AU - Squillacote, David

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N2 - Objective To better understand the relationship between efficacy and perampanel dose, integrated actual (last) dose data from three phase III trials and an extension study (blinded Conversion Period; open-label Maintenance Period) were analyzed. Methods Seizure frequency data were analyzed in patients who were randomized to and completed the 13-week Maintenance Period of the phase III studies on perampanel 8 mg, and who received an actual (last) dose of 12 mg during (1) the extension 16-week blinded Conversion Period or (2) weeks 1-13 of the extension Maintenance Period. Due to a treatment-by-region interaction (p = 0.042), analyses excluded patients from the Latin America region (n = 162/1,480; 10.9% of the treated cohort). Results Of 372 patients randomized to 8 mg in the phase III studies, 273 completed the Maintenance Period at 8 mg and 267 entered the extension study. In patients who then had an actual (last) dose of 12 mg during the extension blinded Conversion Period (n = 217), median percent change in seizure frequency per 28 days improved from -32.4% (8 mg, phase III Maintenance Period) to -44.2% (12 mg, extension blinded Conversion Period); 50% responder rates increased slightly from 37.3% to 42.9%. In patients who completed the phase III studies on 8 mg and had an actual (last) dose of 12 mg during weeks 1-13 of the extension Maintenance Period (n = 181), median percent change in seizure frequency per 28 days improved from -34.1% (phase III Maintenance Period) to -46.0% (weeks 1-13 extension Maintenance Period); 50% responder rates were 39.2% and 46.4%. Seizure control remained substantially unchanged in patients who completed the phase III studies at 12 mg and continued on that dose during the extension. Significance Increasing perampanel dose from 8 to 12 mg can produce additional benefits in seizure control in at least some patients who tolerate the higher dose.

AB - Objective To better understand the relationship between efficacy and perampanel dose, integrated actual (last) dose data from three phase III trials and an extension study (blinded Conversion Period; open-label Maintenance Period) were analyzed. Methods Seizure frequency data were analyzed in patients who were randomized to and completed the 13-week Maintenance Period of the phase III studies on perampanel 8 mg, and who received an actual (last) dose of 12 mg during (1) the extension 16-week blinded Conversion Period or (2) weeks 1-13 of the extension Maintenance Period. Due to a treatment-by-region interaction (p = 0.042), analyses excluded patients from the Latin America region (n = 162/1,480; 10.9% of the treated cohort). Results Of 372 patients randomized to 8 mg in the phase III studies, 273 completed the Maintenance Period at 8 mg and 267 entered the extension study. In patients who then had an actual (last) dose of 12 mg during the extension blinded Conversion Period (n = 217), median percent change in seizure frequency per 28 days improved from -32.4% (8 mg, phase III Maintenance Period) to -44.2% (12 mg, extension blinded Conversion Period); 50% responder rates increased slightly from 37.3% to 42.9%. In patients who completed the phase III studies on 8 mg and had an actual (last) dose of 12 mg during weeks 1-13 of the extension Maintenance Period (n = 181), median percent change in seizure frequency per 28 days improved from -34.1% (phase III Maintenance Period) to -46.0% (weeks 1-13 extension Maintenance Period); 50% responder rates were 39.2% and 46.4%. Seizure control remained substantially unchanged in patients who completed the phase III studies at 12 mg and continued on that dose during the extension. Significance Increasing perampanel dose from 8 to 12 mg can produce additional benefits in seizure control in at least some patients who tolerate the higher dose.

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