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Levetiracetam Coated Tablet: A Randomized, Single-Dose, Two-Sequence, TwoPeriod, Crossover Study to Assess the Bioequivalence between Two Formulations

Marcelo Gomes Davanco, Jessica Meulman, Fernando Costa, Leonardo de Souza Teixeira, Iram Moreira Mundim, Karini Bruno Bellorio, Carina Pimentel, Itapema Alves, Celso Francisco Pimentel Vespasiano

Levetiracetam is an antiseizure medication prescribed to treat epilepsy. This study aimed to evaluate the bioequivalence between two formulations of levetiracetam coated tablets in order to meet regulatory requirements for marketing in Brazil. An open-label, randomized, single-dose, two-period, two-sequence, two-treatment crossover study was conducted in Brazilian healthy subjects of both genders. Subjects received a single dose of Levetiracetam 1000 mg test tablet (Zodiac Produtos Farmacêuticos S.A) and reference product (Etira^®, Aché Laboratórios Farmacêuticos S.A.) under fasting conditions according to a randomly assigned order with a 7-day washout period. Serial blood samples were collected up to 36 h post-dose. Plasma concentrations of levetiracetam were obtained by a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were calculated using non-compartmental methods. A total of 32 healthy subjects were enrolled and 31 subjects completed the study. There were no serious adverse events during the study. Geometric mean ratios (90% confidence intervals) for C_max, AUC_0-t and AUC_0-inf were 99.06% (90.61%-108.28%), 101.57% (99.75%-103.42%) and 101.02% (98.90%- 103.18%), respectively. The test formulation of levetiracetam 1000 mg coated tablet (Zodiac Produtos Farmacêuticos S.A.) was considered bioequivalent to reference product Etira^® (Aché Laboratórios Farmacêuticos S.A.) according to regulatory requirements. Both formulations were safe and well tolerated during the study. Levetiracetam 500 mg strength was waived of in vivo testing based on proportional similarity of the formulations and similar in vitro dissolution profiles between the strengths.