Abstracts

Rationale: Previous studies have shown that reducing the pill burden to patients can not only improve the Quality of Life for the patient, but can also decrease health care costs (Velez et al. Neurology. 2015;84:SUPPL.14). The objective of this analysis was to determine the bioequivalence of 1 dose of a new formulation Levetiracetam (LEV) 1500 mg Extended-Release (XR) tablet compared with 2 doses of existing LEV 750 mg XR tablets (reference product) in healthy subjects under fed and fasting conditions. Methods: In 2 separate open label, 2 treatment, 2 period, 2 sequence, single dose, crossover, bioequivalence studies a total of 42 healthy volunteers were randomized to receive either a single oral dose of LEV 1500 mg XR tablet or two doses of the reference product, under either fasting (n=18, 20?"46 years, BMI 19.0?"24.4 kg/m2) or fed (n=24, 23?"43 years, BMI 18.8?"24.5 kg/m2) conditions. Study periods were separated by a washout period of 7 days. To study bioavailability in consecutive fasting and fed states, 36 healthy volunteers (21?"44 years, BMI 18.8?"25.0 kg/m2) received a single oral dose of LEV 1500 mg XR tablet or two doses of the reference product in alternating fasted and fed states for 4 consecutive days in a crossover study with a washout period of 16 days. Blood samples were collected before dosing and at regular intervals post-dose. Pharmacokinetic parameters (AUC0-t, Cmax, Tmax) were determined. A 90% geometric confidence interval (CI) of the relative geometric means of AUC0-t and Cmax, between 80% and 125% for Ln-transformed data was set to define bioequivalence. Furthermore, adverse events were recorded throughout the studies. Results: The 90% CI calculated from the Ln-transformed data on the least square means ratios (test/reference) for AUC0-t and Cmax values were within the defined limits for both fasted and fed states. Bioequivalence was also confirmed when switching from fasted to fed state, with all 90% CI calculated from the Ln-transformed data falling within to 80%?"125% bounds (TABLE). When switched from fasted/fed or fed/fasted state, 5 subjects showed an altered PK profile with prolonged absorption on Days 2 and 4 (fed dosing), similar for both products (Figure). However, this delay did not result in sub-therapeutic concentrations or increased overall exposure and therefore was judged to not be clinically meaningful. There was one treatment-related safety event with the new formulation LEV 1500 mg XR in the fasting-fed switch study; this event was of mild to moderate intensity. Conclusions: Based on these assessments, the new formulation LEV 1500 mg XR exhibits bioequivalence compared with 2x existing LEV 750 mg XR. There were no additional safety issues with the new formulation. Funding: This study was funded by Sun Pharmaceutical Industries Ltd.