Abstracts

Rationale: Based on anecdotal reports, small retrospective case series, high switchback rates, and database studies there is a physician and patient perception that generic antiepileptic drugs (AEDs) are not always equivalent to brand products. To help determine if the concerns about potential generic inequivalence are valid and to mimic real-life circumstances, the EQUIvalence among GENeric AEDs (EQUIGEN) study group conducted a study of the brand Lamictal^® and two disparate generic products of lamotrigine in people with epilepsy with co-morbidities. Methods: We undertook a prospective, multi-center, masked, replicate, sequence-randomized, 3-sequence, 6-period, single-dose, pharmacokinetic (PK) trial in people with epilepsy on concomitant AEDs. After an extensive review process, lamotrigine was selected as the study drug based on its PK parameters and available study population. Maximum concentration and area under the curve data from the FDA abbreviated new drug applications (ANDAs) were combined with in vitro dissolution and content testing to select the two most disparate generic products available on the commercial market at the start of the study. Subjects were selected who had epilepsy with or without co-morbidities (excluding comorbidities judged to potentially affect drug absorption) and on at least one AED (including hepatic enzyme inducers, but not inhibitors (valproate) and not lamotrigine). To minimize confounds sertraline and estrogens were also excluded. 25 mg doses of lamotrigine were administered in a masked fashion to fasted subjects at the start of each 96-hour PK period. Subsequent periods were typically separated by two weeks (12-23 days) to ensure adequate washout. All concomitant medications remained at stable doses throughout the study. Results: Thus far 34 subjects have been enrolled, with 4 screen failures during the baseline phase. Subsequent study retention has been excellent with one subject dropping out after the 3^rd PK period, but no other dropouts. No study-related serious adverse events have occurred to date. Total recruitment, planned to be completed by 8/2014, is up to 54 subjects with at least 45 subjects to completion at 5 sites. Analyses will include average bioequivalence, scaled average bioequivalence and special attention to subjects with outlier data. Conclusions: In conjunction with the EQUIGEN chronic-dose study, the EQUIGEN single-dose study will inform physicians and the public about differences in variability of disparate generic AED lamotrigine products compared to the brand product as used in the real-life situation of people with epilepsy on concomitant AEDs with a spectrum of co-morbidities.