Effects of age, gender and genetic polymorphism Based on a population pharmacokinetic analysis of patients receiving up to 24 mg lenvatinib once daily, age, sex, weight, or race (Japanese versus other, Caucasian versus other) had no significant effects on clearance Paediatric patients have not been studied. Effects of food Food does not affect the extent of absorption, but slows the rate of absorption. When given with food to healthy subjects, peak plasma concentrations are delayed by 2 h. Summary of bioavailability and bioequivalence studies Three biopharmaceutic/bioavailability/bioequivalence studies have been presented in the dossier. Table 1 summarises the studies performed, and indicates which studies have been fully evaluated or summarised. Table 1. Summary of bioavailability and bioequivalence studies. Primary objectives Formulations Evaluation Number To compare the E7080 10-mg Summary bioavailability of a 10-mg capsule only capsule formulation with E7080 10-mg the 10-mg tablet tablet formulation of To determine the effect E7080 10-mg Full of food on the capsule evaluation bioavailability of Trial following administration of E7080 with and without a high fat meal To determine whether E7080 10-mg Summary two test lots of 10-mg capsules with low, only capsules that vary by the medium and high of lenvatinib crystal crystal form form were bioequivalent to a reference lot of capsules. The different formulations and their relation to the final proposed commercial formulation and the clinical study phases are summarised below in Table 2. Table 2. Different formulations and clinical study phases. E7080-A001-003 has been fully evaluated as it provides an estimate of the food effect for the capsules. Evaluation of crossover multiple dose PK Study E7080-E044-101 which included a food effect arm was not required as it was performed on tablets, which have had very limited use and were not used in pivotal studies.
Effects of age, gender and genetic polymorphism Based on a population pharmacokinetic analysis of patients receiving up to 24 mg lenvatinib once daily, age, sex, weight, or race (Japanese versus other, Caucasian versus other) had no significant effects on clearance Paediatric patients have not been studied. Effects of food Food does not affect the extent of absorption, but slows the rate of absorption. When given with food to healthy subjects, peak plasma concentrations are delayed by 2 h. Summary of bioavailability and bioequivalence studies Three biopharmaceutic/bioavailability/bioequivalence studies have been presented in the dossier. Table 1 summarises the studies performed, and indicates which studies have been fully evaluated or summarised. Table 1. Summary of bioavailability and bioequivalence studies. Number Primary objectives Formulations Evaluation To compare the bioavailability of a 10-mg capsule formulation with the 10-mg tablet formulation of E7080 10-mg capsule E7080 10-mg tablet Summary only To determine the effect of food on the bioavailability of following administration of E7080 with and without a high fat meal E7080 10-mg capsule Full evaluation To determine whether two test lots of 10-mg capsules that vary by the of lenvatinib crystal form were bioequivalent to a reference lot of capsules. E7080 10-mg capsules with low, medium and high crystal form Summary only The different formulations and their relation to the final proposed commercial formulation and the clinical study phases are summarised below in Table 2. Table 2. Different formulations and clinical study phases. E7080-A001-003 has been fully evaluated as it provides an estimate of the food effect for the capsules. Evaluation of crossover multiple dose PK Study E7080-E044-101 which included a food effect arm was not required as it was performed on tablets, which have had very limited use and were not used in pivotal studies. Trial
auspar-lenvatinib-mesilate-160830.docx