Evaluation of Reproducibility of Pharmacokinetics and Clinical Outcome Differences with Brand and Generic Lamotrigine Switching in Epilepsy Patients (BEEP FU Study) (P2.033)

Objective:Three generic-brittle epilepsy patients from a previously completed BEEP study in which generic lamotrigine was shown to be bioequivalent to brand Lamictal in a double-blind, multiple-dose, full replicate design, pharmacokinetic study were identified to be of interest due to exhibiting either a clinical or individual pharmacokinetic difference between generic and brand. A fourth patient from the BEEP study was included as “control”. Methods:The entire study was repeated in these four epilepsy patients, with the addition of an 8-week assessment of baseline seizure frequency and an alternative treatment sequence, to evaluate the reproducibility of the clinical and PK differences seen in the original study. Results: The primary outcome were pharmacokinetic profiles, which by inspection were similar between generic and brand, in each patient. The prior BEEP subject who previously showed a 20[percnt] lower generic pharmacokinetic profile do not show a material difference on this occasion. However, the prior BEEP subject who showed many more seizures on generic than brand, with essentially no difference in PK profiles, again showed a similar pattern, despite blinded treatment arms in a different sequence from the original study, being now generic, brand, brand, generic, coinciding with an average frequency of G 16.1, B 2.1, B 2.9, and G 6.6 seizures/day, respectively, a 2-to-5 fold increase on generic from baseline average frequency of 3.6 seizures/day on brand. The prior BEEP subject who discontinued because of an apparent nocebo effect, with worsened seizures and side effects that he attributed to generic and brand switching, completed this time. The control subject again showed similar generic and brand outcomes as in the original bioequivalent study. Conclusions: Results of this reproducibility study support prior BEEP findings. It is difficult to fully explain the subject who showed very similar generic and brand profiles but differences in seizure frequency between generic and brand. Disclosure: Dr. Ting has nothing to disclose. Dr. Jiang has nothing to disclose. Dr. Kane has nothing to disclose. Dr. Polli has nothing to disclose.