CINCINNATI—University of Cincinnati (UC) clinician-researchers have received $2.6 million to study generic antiepileptic drugs as part of an effort to provide the U.S. Food and Drug Administration (FDA) with data that could lead to new regulations related to approval of new generic drugs.
The funding, from the FDA, the American Epilepsy Society and the Epilepsy Foundation, will be divided between studies of generic equivalence for the drug lamotrigine in two different populations. The studies will be phase-4 clinical trials, which are intended to gather information on an approved treatment’s risks, benefits and optimal uses.
Michael Privitera, MD, a professor in the UC Department of Neurology and Rehabilitation Medicine and a UC Health neurologist, is the principal investigator at the Cincinnati site. Privitera is director of the Epilepsy Center at the UC Neuroscience Institute, one of four institutes of UC Health and the University of Cincinnati. Michel Berg, MD, is principal investigator at the University of Rochester in Rochester, N.Y. Four other academic medical centers are also enrolling patients. Researchers expect to begin enrolling participants early in 2013.
"Many people with epilepsy and their physicians have complained about side effects or loss of seizure control when taking generic drugs, but no one knows if these complaints are truly because of problems with the generic drugs,” says Privitera. "Every day over 1 million doses of generic antiepileptic drugs are taken by people with epilepsy, and switches from one to another generic product are common. We need to be sure these switches are truly safe for our patients.
"In addition, FDA regulations are currently the same no matter what the disorder is. It may be obvious to us that a slight variability in, for example, a heartburn medicine is a lot less dangerous than the same variability in a seizure medicine. But you can’t change the regulations without data, so that’s what these studies will be providing.”
Lamotrigine is approved in the United States as a treatment for partial seizures (it is also approved for maintenance treatment of bipolar I disorder). Its brand-name form, manufactured by GlaxoSmithKline, is marketed as Lamictal. The drug is taken orally as a tablet.
Privitera points out that with generic copies of lamotrigine, the amount of the drug that actually gets into the bloodstream can be measured and is allowed by the FDA to fall within a specific range. One generic copy might be on the high end and the other on the low end of the allowable range.
One study will examine generic copies of lamotrigine from two different manufacturers, one from the "high” range and the other from the "low” range. This "chronic dose” study will test how the generics perform when administered daily over a several-week period, with the patients divided into two groups and switching copies twice over four test periods for a sequence-randomized study. (Patients will also continue their usual medications, including antiepilepsy drugs.) At the end of each two-week test period, the participants will undergo extensive blood level monitoring.
The other study will compare the two generic copies with Lamictal, the brand-name version of lamotrigine. Participants take each medicine twice during the study period. This is a "single dose” study, in which patients take a single dose of generic lamotrigine in addition to their regular antiepileptic drugs and then have rigorous blood level testing over a 96-hour period.
The estimated completion date for both studies is June 2014.
Study participants must be 18 or older, and they must have had epilepsy for at least one year and not be taking lamotrigine within 28 days pre-enrollment for the single-dose study. For the chronic dose study, participants must be on a stable dose of lamotrigine twice daily. Other criteria apply; for full details visit www.clinicaltrials.gov.
Privitera reports no conflicts of interest with GlaxoSmithKline.