Bioequivalence of Two Perampanel 12mg Tablets in Healthy, Adult, Human Subjects under Fed Conditions-An Open Label, Cross Over Study - Abstract
Background: Perampanel is a glutamate non-competitive receptor antagonist that is effective as adjunctive therapy for epilepsy. The main objective of the present research is to compare the bioavailability and to evaluate the bioequivalence between the test and reference product. The secondary objective is to assess the safety and tolerability of the drug. Methods and findings: The study design was an open label, randomized, two treatment, two sequence, two period, single dose, cross over, oral bioequivalence study of the two formulations in single dose of 12mg. The study was conducted in 28 healthy, adult, human subjects, aged between 22 to 44 years, under fed conditions with a washout period of 42 days in between doses. Blood samples were collected up to 72 hours post-dose for measurement of pharmacokinetic parameters in each period. Safety evaluation was done by assessing clinical examinations, vital signs assessment, clinical laboratory parameters and monitoring subject’s well-being, symptoms and signs for adverse events. A validated LC-MS/MS method was used to determine the plasma concentrations of Perampanel. Bioequivalence between both the products was established by calculating 90% confidence intervals for the ratio of Cmax and AUC0-72 values for the test and reference products. The 90% confidence intervals found for the relation of Test/Reference were Cmax 90.23% - 107.9% and AUC0-72 92.02% - 104.12%. Conclusion: According to FDA’s guidelines for Bioequivalence research, the confidence intervals for Cmax and AUC0-72 ranged between 80.00-125.00%. The above limits obtained for Perampanel were within the accepted bio-equivalence limits. Thus, bio-equivalence was demonstrated between Perampanel 12mg Tablets of Abbott Laboratories de Colombia and Fycompa® (Perampanel 12mg) tablets of Eisai Europe Limited in healthy, adult, human subjects under fed conditions.