Efficacy and safety of perampanel in adolescent patients with drug-resistant
partial seizures in three double-blind, placebo-controlled, phase III randomized
clinical studies and a combined extension study.
Author(s): Rosenfeld W(1), Conry J(2), Lagae L(3), Rozentals G(4), Yang H(5), Fain R(6),
Williams B(7), Kumar D(8), Zhu J(9), Laurenza A(10).
Affiliation(s): Author information:
(1)Comprehensive Epilepsy Care Center for Children and Adults, St Louis, MO, USA.
Electronic address: werosenfeld@msn.com. (2)Children's National Medical Center,
Washington, DC, USA. Electronic address: jconry@childrensnational.org.
(3)University Hospitals KULeuven, Leuven, Belgium. Electronic address:
lieven.lagae@uzleuven.be. (4)Children's Clinical University Hospital, Riga,
Latvia. Electronic address: dr.rozentals@inbox.lv. (5)Eisai Neuroscience Product
Creation Unit, Woodcliff Lake, NJ, USA. Electronic address:
Haichen_Yang@eisai.com. (6)Eisai Medical and Scientific Affairs, Woodcliff Lake,
NJ, USA. Electronic address: Randi_Fain@eisai.com. (7)Eisai Medical and
Scientific Affairs, Woodcliff Lake, NJ, USA. Electronic address:
Betsy_Williams@eisai.com. (8)Eisai Neuroscience Product Creation Unit, Woodcliff
Lake, NJ, USA. Electronic address: Dinesh_Kumar@eisai.com. (9)Formerly Eisai
Inc., Woodcliff Lake, NJ, USA. Electronic address: vgo329@yahoo.com. (10)Eisai
Neuroscience Product Creation Unit, Woodcliff Lake, NJ, USA. Electronic address:
Antonio_Laurenza@eisai.com.
Publication date & source: 2015, Eur J Paediatr Neurol. , 19(4):435-45
OBJECTIVE: Assess perampanel's efficacy and safety as adjunctive therapy in
adolescents (ages 12-17) with drug-resistant partial seizures.
METHODS: Adolescent patients enrolled in multinational, double-blind,
placebo-controlled, phase III core studies (studies 304, 305, or 306) completed
19-week, double-blind phase (6-week titration/13-week maintenance) with
once-daily perampanel or placebo. Upon completion, patients were eligible for the
extension (study 307), beginning with 16-week, blinded conversion, during which
placebo patients switched to perampanel. Patients then entered the open-label
treatment.
RESULTS: Of 1480 patients from the core studies, 143 were adolescents. Pooled
adolescent data from these core studies demonstrated median percent decreases in
seizure frequency for perampanel 8 mg (34.8%) and 12 mg (35.6%) were
approximately twice that of placebo (18.0%). Responder rates increased with
perampanel 8 mg (40.9%) and 12 mg (45.0%) versus placebo (22.2%). Adolescents
receiving concomitant enzyme-inducing antiepileptic drugs (AEDs) had smaller
reductions in seizure frequency (8 mg:31.6%; 12 mg:26.8%) than those taking
non-inducing AEDs (8 mg:54.6%; 12 mg:52.7%). Relative to pre-perampanel baseline,
seizure frequency and responder rates during the extension (Weeks 1-52) improved
with perampanel. Most commonly reported adverse events in adolescents during the
core studies were dizziness (20.4%), somnolence (15.3%), aggression (8.2%),
decreased appetite (6.1%), and rhinitis (5.1%). Dizziness (13.2%), somnolence
(11.6%), and aggression (6.6%) most often led to perampanel interruption/dose
adjustment during the extension.
SIGNIFICANCE: Data demonstrated adjunctive perampanel treatment in adolescents
with drug-resistant partial seizures produced better seizure control versus
placebo, sustained seizure frequency improvements, and a generally favorable
safety profile. Results were comparable to the overall study population.
CLINICAL TRIAL REGISTRATION: clinicaltrials.gov Identifiers: Study 304:
NCT00699972; 305: NCT00699582; 306: NCT00700310; Study 307: NCT00735397.
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