Time to prerandomization monthly seizure count in perampanel trials: A novel
epilepsy endpoint.
Author(s): French JA(1), Gil-Nagel A(2), Malerba S(2), Kramer L(2), Kumar D(2), Bagiella
E(2).
Affiliation(s): Author information:
(1)From the NYU Comprehensive Epilepsy Center (J.A.F.), New York; Hospital Ruber
Internacional (A.G.-N.), Madrid, Spain; Mount Sinai Hospital (S.M., E.B.), New
York; and the Eisai Neuroscience Product Creation Unit (L.K., D.K.), Woodcliff
Lake, NJ. jacqueline.french@nyumc.org. (2)From the NYU Comprehensive Epilepsy
Center (J.A.F.), New York; Hospital Ruber Internacional (A.G.-N.), Madrid, Spain;
Mount Sinai Hospital (S.M., E.B.), New York; and the Eisai Neuroscience Product
Creation Unit (L.K., D.K.), Woodcliff Lake, NJ.
Publication date & source: 2015, Neurology. , 84(20):2014-20
OBJECTIVE: To determine whether a novel endpoint of time to prerandomization
monthly seizure count could be used to differentiate efficacious and
nonefficacious therapies in clinical trials of new add-on antiepileptic drugs
(AEDs).
METHODS: This analysis used data from 3 randomized, double-blind,
placebo-controlled phase III trials of perampanel as an add-on therapy in
patients with epilepsy who were experiencing refractory partial seizures: studies
304 (ClinicalTrials.gov identifier NCT00699972), 305 (NCT00699582), and 306
(NCT00700310). Time to prerandomization monthly seizure count was evaluated post
hoc for each trial, and findings were compared with the original primary outcomes
(median percent change in seizure frequency and 50% responder rate). Outcomes
were assessed for all partial-onset seizures, secondarily generalized (SG)
tonic-clonic seizures only, and complex partial plus SG (CP + SG) seizures.
RESULTS: Perampanel 4-12 mg significantly prolonged median time to
prerandomization monthly seizure count, generally by more than 1 week, compared
with placebo, across all 3 studies, consistent with the original primary
outcomes. Analysis of SG seizures only, and CP + SG seizures, also indicated a
significantly prolonged median time to prerandomization monthly seizure count
with perampanel 8 mg and 12 mg compared with placebo.
CONCLUSIONS: Time to prerandomization monthly seizure count is a promising novel
alternative to the standard endpoints of median percent change in seizure
frequency and 50% responder rates used in trials of add-on AEDs. Use of this
endpoint could reduce exposure to placebo or ineffective treatments, thereby
facilitating trial recruitment and improving safety.
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