FEASIBILITY OF ASSESSING ANTIEPILEPTIC DRUG BIOEQUIVALENCE IN PATIENTS WITH EPILEPSY UNDER CLINICAL USE CONDITIONS
Abstract number :
3.216
Submission category :
7. Antiepileptic Drugs
Year :
2013
Submission ID :
1749806
Source :
www.aesnet.org
Presentation date :
12/7/2013 12:00:00 AM
Published date :
Dec 5, 2013, 06:00 AM
Authors :
T. Ting, W. Jiang, A. Krumholz, J. Polli
Rationale: A prototypic test was designed in 2011 under the Food and Drug Administration (FDA) s Generic Program to assess generic and brand AED bioequivalence in epilepsy patients to more closely approximate clinical use conditions than the standard bioequivalence study (i.e. a single-dose pharmacokinetic trial in healthy volunteers). The study design considered, with input from the FDA, the National Institutes of Health, and the Epilepsy Foundation, not only the unique pharmacologic aspects of performing a phase 4 bioequivalence study in patients already taking lamotrigine (LTG) for epilepsy (i.e. type of cross-over design, product dose, drug interactions, steady-state assessment), but also potentially important clinical influences on variability introduced by type of patients enrolled and subject adherence. Our experience in this study, currently ongoing at our institution, allows us to assess the feasibility of implementing this novel bioequivalence study design in patients with epilepsy.Methods: A double-blind, multiple-dose, full replicated design, pharmacokinetic study of LTG 100mg tablets in patients with epilepsy initiated subject enrollment in June 2012 (goal N=32) at the University of Maryland, with all study visits held in the medical center Clinical Research Center. Inclusion criteria require subjects to be generic-brittle in terms of potential sensitivity to switching drug products. Over-encapsulation was the method for blinding to reduce potential negative placebo, or nocebo, effect with product switching during the study in order to optimize study retention. The design includes patient education and scheduled telephone contacts for dosing adherence, and patient diaries and pill counting for drug reconciliation. Overnight accommodation has been made available to aid adherence to early morning study visits.Results: A majority of subjects have completed this study to date, with one withdrawal due to subject report of worsened seizures with switching of blinded drug. Subjects adherence to study drug dosing was excellent as confirmed by diary review and pill counting. All trough and 12-hour PK levels were drawn according to schedule, with all but one subject choosing to use the offered overnight accommodations. This study is ongoing, and pharmacokinetic data are pending.Conclusions: A study design to evaluate the bioequivalence of generic and brand name LTG tablets in patients with epilepsy has been implemented with the vast majority of enrolled subjects completing successfully, to date. Although the study is on-going, in-study metrics of patient completion and medication adherence indicates this innovative design to be a feasible method to assess bioequivalence in patients under clinical use conditions, and thus serve as a prototype for brand and generic equivalence assessment.
Antiepileptic Drugs