Bioequivalence of perampanel fine granules and tablets in healthy Japanese subjects.

ABSTRACT: OBJECTIVE:Perampanel is an approved anti-seizure drug. A new formulation of perampanel fine granules (FG; 1% perampanel) has been developed for patients who are unable to take tablets. Bioequivalence between the 4-mg FG and tablet perampanel formulations, as well as their safety and tolerability, were assessed. MATERIALS AND METHODS:In this phase I, single-center, open-label, 2-period, 2-sequence, crossover, bioequivalence study (NCT03399734), healthy Japanese subjects were randomized to receive single doses of the 4-mg FG perampanel and 4-mg perampanel tablet (separated by a ? 6-week washout period). Plasma samples for perampanel concentration analysis were collected pre-dose and at intervals up to 168 hours post-dose. The maximum observed concentration (C_max) and area under the concentration-time curve from time zero to 168 hours (AUC_(0-168h)) were used to assess the bioequivalence of the two formulations. RESULTS:The 90% confidence intervals (CIs) for the geometric mean ratio of test/reference for C_max and AUC_(0-168h) were within the bioequivalence criteria of 80 - 125% (C_max 90% CI 90.8%, 110%; AUC_(0-168h) 90% CI 98.2%, 112%; N = 21). 10/24 (41.7%) subjects with FG experienced ? 1 treatment-emergent adverse event (TEAE). The events were mild in severity and resolved within 4 hours of onset. There were no deaths, severe TEAEs, serious AEs, or TEAEs leading to study-drug withdrawal. CONCLUSION:Bioequivalence of 4-mg FG and 4-mg tablet of perampanel was demonstrated. Both perampanel formulations were generally safe and well tolerated. These data suggest that perampanel FG may be a suitable alternative formulation for patients with epilepsy who have difficulties taking perampanel tablets.

SUBMITTER: Shiba S 

PROVIDER: S-EPMC7659282 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature