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Final safety, tolerability, and seizure outcomes in patients with focal epilepsy treated with adjunctive perampanel for up to 4 years in an open‐label extension of phase III randomized trials: Study 307
Author(s) -
Krauss Gregory L.,
Perucca Emilio,
Kwan Patrick,
BenMenachem Elinor,
Wang XueFeng,
Shih Jerry J.,
Patten Anna,
Yang Haichen,
Williams Betsy,
Laurenza Antonio
Publication year - 2018
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.14044
Subject(s) - tolerability , perampanel , discontinuation , epilepsy , medicine , irritability , adverse effect , adjunctive treatment , randomized controlled trial , anesthesia , psychiatry , menopause
Summary Objective To evaluate long‐term safety/tolerability and seizure outcomes in patients with focal seizures treated with adjunctive perampanel in the open‐label extension ( OLE x) Study 307 (ClinicalTrials.gov identifier: NCT 00735397). Methods Patients could enter the OLE x after completing one of the double‐blind, phase III studies. Safety/tolerability and seizure outcomes (median percent reduction in seizure frequency per 28 days, and 50% responder and seizure freedom rates) were analyzed during the OLE x in cohorts with the same minimum perampanel exposure for all focal seizures and secondarily generalized seizures ( SGS ). An additional sensitivity analysis accounted for early dropouts from the OLE x. Results Of 1480 patients randomized across the double‐blind studies, 1218 enrolled in the OLE x. The majority of patients (65.4%‐80.9%) received a last daily dose of perampanel 12 mg and completed long‐term assessment on the same, or one fewer, concomitant antiepileptic drug compared with baseline. The long‐term safety/tolerability profile was consistent with the double‐blind studies. Treatment‐emergent adverse events ( TEAE s) leading to discontinuation in >1% of patients were dizziness, irritability, and fatigue; TEAE s of clinical interest were stable for 4 years. In all cohorts, seizure outcome improvements were sustained over time. Median percent seizure reductions per 28 days reached 62.0% and 70.6% for patients with ≥3 (n = 436) or ≥4 (n = 78) years of exposure, respectively; corresponding 50% responder rates were 59.6% and 67.9%. The largest median percent seizure reduction per 28 days occurred in SGS for patients with SGS at baseline: 88.0% and 100.0% for patients with ≥3 (n = 190) or ≥4 (n = 28) years of exposure, respectively; in these cohorts 40.0% and 53.6% of patients, respectively, attained freedom from SGS . Median percent seizure reductions per 28 days were similar when early dropouts were accounted for. Significance Long‐term (≤4 years) adjunctive perampanel treatment did not raise new safety/tolerability signals and was associated with markedly improved seizure control, particularly in patients with SGS at baseline.

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