Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Behavioral Sciences, Clinical Neurology, Psychiatry, Neurosciences & Neurology, Adolescent, Antiepileptic drug, Cognition, Development, Epilepsy, Partial seizures, PARTIAL-ONSET SEIZURES, CHILDHOOD ABSENCE EPILEPSY, RANDOMIZED PHASE-III, OPEN-LABEL EXTENSION, ANTIEPILEPTIC DRUGS, VALPROIC ACID, DOUBLE-BLIND, ZONISAMIDE MONOTHERAPY, CHILDREN, SAFETY, Anticonvulsants, Attention, Child, Cross-Over Studies, Dizziness, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Male, Memory, Short-Term, Nitriles, Pyridones, Seizures, Time Factors, Treatment Outcome, 1103 Clinical Sciences, Neurology & Neurosurgery, 3209 Neurosciences, 5202 Biological psychology, 5203 Clinical and health psychology

Abstract:

OBJECTIVE: The aim of this study was to evaluate long-term effects of adjunctive perampanel on cognition, efficacy, growth, safety, and tolerability in adolescents with inadequately controlled partial seizures. METHODS: Study 235, a multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase II study with an open-label extension phase (NCT01161524), was primarily designed to assess the effects of adjunctive perampanel on cognition. Patients (aged ≥12 to <18years) had a diagnosis of epilepsy with inadequately controlled partial seizures, with or without secondary generalization, despite receiving 1-3 antiepileptic drugs. During the double-blind phase, adjunctive perampanel or placebo was administered over a 6-week titration period and a 13-week maintenance period up to 12mg/day. During the extension phase, all patients received perampanel. Data from the extension phase are presented here. Study endpoints included change from baseline in Cognitive Drug Research (CDR) measures of cognition, seizure frequency, growth, development, the occurrence of treatment-emergent adverse events (TEAEs), and laboratory values. RESULTS: A total of 114 patients entered the extension phase (prior double-blind treatment: placebo, n=41; perampanel, n=73). Perampanel had no effect on the CDR system global cognition score, continuity of attention, quality of episodic memory, quality of working memory, or speed of memory but was associated with a significant decline in power of attention at end of treatment compared with baseline (p=0.03). There were no effects on language skills or manual dexterity from baseline to end of treatment. At Weeks 40-52, median reduction in seizure frequency was 74.1%, and 50% responder rate was 66.0%. There were no clinically relevant effects of perampanel on growth or development at end of treatment compared with baseline. Overall, 84.2% of patients experienced at least one TEAE and 70.2% experienced at least one treatment-related TEAE. The most common TEAEs were dizziness (29.8%) and somnolence (19.3%). The TEAEs resulted in the discontinuation of treatment in 6.1% of patients. CONCLUSIONS: In keeping with the 19-week double-blind phase, long-term adjunctive treatment with perampanel did not have any significant overall effects on the CDR system global cognition score in adolescent patients with inadequately controlled partial seizures. Similar trends were observed across the individual CDR system domains. Adjunctive perampanel showed sustained long-term seizure control and had a safety and tolerability profile similar to that observed in prior clinical studies.