Perampanel in real-world clinical care of adolescent and adult patients with epilepsy: Results from the retrospective Phase IV PROVE Study

Published:February 26, 2022DOI:


      • PROVE was a retrospective, non-interventional phase IV study of perampanel.
      • This analysis evaluated final data from adolescent and adult patients.
      • Perampanel was associated with favorable retention rates and sustained efficacy.
      • No new safety signals were observed with perampanel in adolescent and adult patients.



      Report final data from adolescent (12–<18 years) and adult (≥18 years) patients from PROVE (NCT03208660), a multicenter, retrospective, non-interventional, Phase IV study to assess retention, efficacy, safety, and dosing of perampanel in patients with epilepsy during routine clinical care.


      Data were retrospectively collected from medical/pharmacy records of patients in the US initiating perampanel after January 1, 2014, according to treating clinicians’ recommendation. Retention rate was the primary efficacy endpoint. Secondary endpoints included median percent changes in seizure frequency, seizure-freedom rates, investigator's impression of seizure effect, and treatment-emergent adverse events (TEAEs).


      The Safety Analysis Set (SAS) included 294 adolescents and 1157 adults (median maximum perampanel dose, 6.0 mg/day). In patients eligible for inclusion in the retention rate analysis, 24-month retention rates were 53.5% (n=91/170) in adolescents and 47.8% (n=354/741) in adults. In patients with available efficacy data during Months 10–12, median percent seizure frequency reductions were 79.3% (n=20) in adolescents and 70.8% (n=92) in adults. Most patients in the SAS with seizure-effect data experienced an improvement in seizures at the last follow-up time point (adolescents, 51.4% [n=128/249]; adults, 52.3% [n=506/967]). TEAEs occurred in 113 adolescents (38.4%; most common, aggression [6.5%]) and 512 adults (44.3%; most common, dizziness [9.2%]).


      Perampanel demonstrated favorable retention rates and sustained efficacy (up to 2 years) in adolescent and adult patients during routine clinical care; no new safety signals were observed. identifier

      Keywords (max 6)


      ASM (anti-seizure medication), FAS (Full Analysis Set), FOS (focal-onset seizures), GTC (generalized tonic-clonic), ILAE (International League Against Epilepsy), max (maximum), MedDRA (Medical Dictionary for Regulatory Activities), min (minimum), PROVE (Perampanel Real-world Evidence), SAS (Safety Analysis Set), SD (standard deviation), SMQ (standardized Medical Dictionary for Regulatory Activities query), TEAE (treatment-emergent adverse event)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Seizure - European Journal of Epilepsy
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


      1. Food and Drug Administration (FDA). Fycompa® Prescribing Information,; February 2021 [last updated February 2021; accessed August 12, 2021].

      2. European Medicines Agency (EMA). FYCOMPA® Annex I: summary of Product Characteristics,; January 2021 [last updated January 2021; accessed July 1, 2021].

        • French J.A.
        • Krauss G.L.
        • Biton V.
        • Squillacote D.
        • Yang H.
        • Laurenza A.
        • et al.
        Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304.
        Neurology. 2012; 79: 589-596
        • French J.A.
        • Krauss G.L.
        • Steinhoff B.J.
        • Squillacote D.
        • Yang H.
        • Kumar D.
        • et al.
        Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: results of randomized global phase III study 305.
        Epilepsia. 2013; 54: 117-125
        • Krauss G.L.
        • Serratosa J.M.
        • Villanueva V.
        • Endziniene M.
        • Hong Z.
        • French J.
        • et al.
        Randomized phase III study 306: adjunctive perampanel for refractory partial-onset seizures.
        Neurology. 2012; 78: 1408-1415
        • Nishida T.
        • Lee S.K.
        • Inoue Y.
        • Saeki K.
        • Ishikawa K.
        • Kaneko S
        Adjunctive perampanel in partial-onset seizures: Asia-Pacific, randomized phase III study.
        Acta Neurol Scand. 2018; 137: 392-399
        • French J.A.
        • Krauss G.L.
        • Wechsler R.T.
        • Wang X.-.F.
        • DiVentura B.
        • Brandt C.
        • et al.
        Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy: a randomized trial.
        Neurology. 2015; 85: 950-957
        • Piña-Garza J.E.
        • Lagae L.
        • Villanueva V.
        • Renfroe J.B.
        • Laurenza A.
        • Williams B.
        • et al.
        Long-term effects of adjunctive perampanel on cognition in adolescents with partial seizures.
        Epilepsy Behav. 2018; 83: 50-58
        • Makady A.
        • de Boer A.
        • Hillege H.
        • Klungel O.
        • Goettsch W
        What Is Real-World Data? A Review of Definitions Based on Literature and Stakeholder Interviews.
        Value Health. 2017; 20: 858-865
        • Wheless J.
        • Wechsler R.T.
        • Lancman M.
        • Aboumatar S.
        • Patten A.
        • Malhotra M
        Perampanel in real-world clinical care of patients with epilepsy: interim analysis of a phase IV study.
        Epilepsia Open. 2020; 6: 79-89
        • Krauss G.L.
        • Perucca E.
        • Ben-Menachem E.
        • Kwan P.
        • Shih J.J.
        • Clement J.F.
        • et al.
        Long-term safety of perampanel and seizure outcomes in refractory partial-onset seizures and secondarily generalized seizures: results from phase III extension study 307.
        Epilepsia. 2014; 55: 1058-1068
        • Villanueva V.
        • Montoya J.
        • Castillo A.
        • Mauri-Llerda J.Á.
        • Giner P.
        • López-González F.J.
        • et al.
        Perampanel in routine clinical use in idiopathic generalized epilepsy: the 12-month GENERAL study.
        Epilepsia. 2018; 59: 1740-1752
        • Villanueva V.
        • Garces M.
        • Lopez-Gonzalez F.J.
        • Rodriguez-Osorio X.
        • Toledo M.
        • Salas-Puig J.
        • et al.
        Safety, efficacy and outcome-related factors of perampanel over 12 months in a real-world setting: the FYDATA study.
        Epilepsy Res. 2016; 126: 201-210
        • Gil-Nagel A.
        • Burd S.
        • Toledo M.
        • Sander J.W.
        • Lebedeva A.
        • Patten A.
        • et al.
        A retrospective, multicentre study of perampanel given as monotherapy in routine clinical care in people with epilepsy.
        Seizure. 2018; 54: 61-66
        • Rohracher A.
        • Zimmermann G.
        • Villanueva V.
        • Garamendi I.
        • Sander J.W.
        • Wehner T.
        • et al.
        Perampanel in routine clinical use across Europe: pooled, multicenter, observational data.
        Epilepsia. 2018; 59: 1727-1739
        • Singh K.
        • Shah Y.D.
        • Luciano D.
        • Friedman D.
        • Devinsky O.
        • Kothare S.V
        Safety and efficacy of perampanel in children and adults with various epilepsy syndromes: a single-center postmarketing study.
        Epilepsy Behav. 2016; 61: 41-45
        • Villanueva V.
        • Montoya J.
        • Castillo A.
        • Mauri-Llerda J.A.
        • Giner P.
        • Lopez-Gonzalez F.J.
        • et al.
        Perampanel in routine clinical use in idiopathic generalized epilepsy: the 12-month GENERAL study.
        Epilepsia. 2018; 59: 1740-1752
        • Lin K.L.
        • Lin J.J.
        • Chou M.L.
        • Hung P.C.
        • Hsieh M.Y.
        • Chou I.J.
        • et al.
        Efficacy and tolerability of perampanel in children and adolescents with pharmacoresistant epilepsy: the first real-world evaluation in Asian pediatric neurology clinics.
        Epilepsy Behav. 2018; 85: 188-194
        • Rohracher A.
        • Kalss G.
        • Neuray C.
        • Hofler J.
        • Dobesberger J.
        • Kuchukhidze G.
        • et al.
        Perampanel in patients with refractory and super-refractory status epilepticus in a neurological intensive care unit: a single-center audit of 30 patients.
        Epilepsia. 2018; 59: 234-242
        • Garrison L.P.
        • Neumann P.J.
        • Erickson P.
        • Marshall D.
        • Mullins C.D
        Using real-world data for coverage and payment decisions: the ISPOR real-world data task force report.
        Value Health. 2007; 10 (Jr.): 326-335
        • Blonde L.
        • Khunti K.
        • Harris S.B.
        • Meizinger C.
        • Skolnik N.S
        Interpretation and impact of real-world clinical data for the practicing clinician.
        Adv Ther. 2018; 35: 1763-1774