Gregory L Krauss1, Emilio Perucca2,3, Patrick Kwan4,5, Elinor Ben-Menachem6, Xue-Feng Wang7, Jerry J Shih8, Anna Patten9, Haichen Yang10, Betsy Williams11, Antonio Laurenza11. 1. Department of Neurology, Johns Hopkins University, Baltimore, MD, USA. 2. IRCCS Mondino Foundation, Pavia, Italy. 3. Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy. 4. Royal Melbourne Hospital, University of Melbourne, Parkville, Vic., Australia. 5. Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China. 6. Sahlgrenska Academy, Gothenburg, Sweden. 7. Chongqing Key Laboratory of Neurology, First Affiliated Hospital of Chongqing Medical University, Chongqing, China. 8. Department of Neurosciences, UCSD School of Medicine, La Jolla, CA, USA. 9. Department of Biostatistics, Eisai Ltd., Hatfield, UK. 10. Former Employee of Eisai Inc., Woodcliff Lake, NJ, USA. 11. Eisai Neurology Business Group, Eisai Inc., Woodcliff Lake, NJ, USA.
Abstract
OBJECTIVE: To evaluate long-term safety/tolerability and seizure outcomes in patients with focal seizures treated with adjunctive perampanel in the open-label extension (OLEx) Study 307 (ClinicalTrials.gov identifier: NCT00735397). METHODS: Patients could enter the OLEx 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 OLEx 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 OLEx. RESULTS: Of 1480 patients randomized across the double-blind studies, 1218 enrolled in the OLEx. 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 (TEAEs) leading to discontinuation in >1% of patients were dizziness, irritability, and fatigue; TEAEs 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.
RCT Entities:
OBJECTIVE: To evaluate long-term safety/tolerability and seizure outcomes in patients with focal seizures treated with adjunctive perampanel in the open-label extension (OLEx) Study 307 (ClinicalTrials.gov identifier: NCT00735397). METHODS:Patients could enter the OLEx 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 OLEx 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 OLEx. RESULTS: Of 1480 patients randomized across the double-blind studies, 1218 enrolled in the OLEx. 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 (TEAEs) leading to discontinuation in >1% of patients were dizziness, irritability, and fatigue; TEAEs 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.
Authors: Brian D Moseley; Shaloo Gupta; Nate Way; Jonathon Wright; John C Rowland; Victoria E Barghout; Feride Frech; Craig Plauschinat Journal: Patient Relat Outcome Meas Date: 2022-02-09
Authors: Jacqueline A French; Steve S Chung; Gregory L Krauss; Sang Kun Lee; Maciej Maciejowski; William E Rosenfeld; Michael R Sperling; Marc Kamin Journal: Epilepsia Date: 2021-07-13 Impact factor: 5.864