UMB Conducts First-of-a-Kind Study on Bioequivalency of Anti-Epileptic Drug

Collaborative study helps validate effectiveness of FDA’s bioequivalence standard, showing no significant differences between major brand name and generic medication used to treat patients with epilepsy.

By Malissa Carroll
August 14, 2015

A first-of-its-kind study published in Epilepsia, the official journal of the International League Against Epilepsy, by researchers from the University of Maryland School of Pharmacy and the University of Maryland School of Medicine examining the bioequivalence of generic lamotrigine versus brand-name Lamictal has found no significant differences in patients with epilepsy, reinforcing the current standard used by the Food and Drug Administration (FDA) to test bioequivalence among generic and brand name medications.

“There have been longstanding concerns among patients with epilepsy and their physicians about the safety and efficacy of generic anti-epileptic drugs,” says James Polli, PhD, the Shangraw/Noxell Endowed Chair in Industrial Pharmacy and Pharmaceutics in the Department of Pharmaceutical Sciences (PSC) at the School of Pharmacy and principal investigator for the study. “Even professional organizations such as the American Academy of Neurology and the American Epilepsy Society advise pharmacies against switching patients with epilepsy to generic medications without first notifying their physician.”

According to Polli, much of this concern stems from the FDA’s abbreviated approval process for generic drugs, which allows generic drug manufacturers to test their medications using bioequivalence tests that compare the pharmacokinetic properties of the generic medication against those found in its brand name counterpart in healthy volunteers, instead of undergoing lengthy clinical trials in patients with epilepsy, which are required for brand name drugs. He and his collaborators, including Tricia Ting, MD, associate professor of neurology at the School of Medicine and primary physician for the study, wanted to design a study that would address those concerns and help to determine whether the FDA’s current bioequivalence standard is an adequate tool to predict the safety and efficacy of generic medications.

“For years, my colleagues and I listened as patients complained about side effects or increased seizures after they were switched from a brand name to a generic medication,” says Ting. “This study offered us a great opportunity to explore questions surrounding the safety of generic drugs through an innovative randomized, double-blind, multiple-dose, steady-state, fully replicated bioequivalence study that compared a major brand name anti-epileptic drug to its generic formulation in patients with epilepsy.”

Although the FDA’s bioequivalence standard only requires generic drug manufacturers to test for bioequivalence in healthy volunteers after one dose, researchers from the Schools of Pharmacy and Medicine took their study to the next level. They compared generic lamotrigine versus brand-name Lamictal in 35 “generic-brittle” patients with epilepsy – individuals who had previously reported an increase in seizures or other adverse events after switching to a generic anti-epileptic drug. In addition, patients were switched between the brand name and generic formulations, which had been masked to ensure that patients could not differentiate between the formulations based on appearance, every two weeks for eight weeks.

“We were surprised by our patients’ enthusiasm to participate in the study, as many of these individuals had previously experienced problems after switching to a generic anti-epileptic drug,” says Ting. “Their willingness to enter a study in which they were aware that they would be repeatedly switched between a brand name and generic medication truly speaks to the high level of concern that these individuals have about the safety and efficacy of generic medication. They wanted answers.”

Created after each two-week treatment period to show how the drugs were absorbed and metabolized in the patients’ bodies, the pharmacokinetic profiles analyzed by Maureen Kane, PhD, associate professor in PSC, indicated that the brand name and generic medication were similar in almost all aspects. Researchers also examined patients’ risk for seizures as well as other adverse events, finding that 32 out of the 35 patients enrolled in the study reported no worsening of seizure control during the study, while none of the patients reported an increase in the severity of their seizures.

“By demonstrating that generic lamotrigine is bioequivalent to its brand name counterpart – Lamictal – in patients with epilepsy, our study helps validate the adequacy of the FDA’s abbreviated approval process for generic medications,” says Polli. “Our results will help to reassure both patients and physicians that the substitution of generic formulations for brand name medications is likely safe for the majority of these patients.”

“What our team has accomplished with this study is an excellent example of the great work that can be accomplished when investigators from different fields join forces to collaborate on a joint research effort,” adds Ting. “This study represents the truest form of an interdisciplinary endeavor between the Schools of Pharmacy and Medicine, and we hope that our findings help broaden patients and physicians’ understanding of the safety and efficacy of generic medications not only for individuals with epilepsy, but for all patients.”

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