Equivalence Among Antiepileptic Drug Generic and Brand Products in People With Epilepsy: Chronic-Dose 4-Period Replicate Design — Chronic Dose  

Epilepsy Clinical Trial

Official title: Equivalence Among Antiepileptic Drug Generic and Brand Products in People With Epilepsy: Chronic-Dose 4-Period Replicate Design (EQUIGEN Chronic-Dose Study)

Status Completed

Clinical Trial Summary

The United States Food and Drug Administration (FDA) has specific rules generic drug companies must follow to get a generic copy of a seizure medication approved. Currently, the FDA approves generic drugs by requiring studies on normal volunteers who don't have epilepsy and who take just one dose of the generic drug followed by a series of blood tests. Some 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.

When the FDA tests generic copies of lamotrigine (LTG), the blood levels measured after volunteers receive the generic lamotrigine tablets are allowed to fall within a specific range. This research will test whether two different manufacturer's generic lamotrigine, that fall in different parts of that range, perform in a similar way when given to people with epilepsy every day over a several week period. The two products will be called GENERIC A and GENERIC B.

The generic forms of the study drug lamotrigine to be tested in this study are approved by the FDA for the treatment of seizures.

Clinical Trial Description

Qualified subjects will be screened and upon fulfilling inclusion/exclusion criteria and signing the informed consent will be enrolled into the study and enter the randomization phase (2-30 days). Subjects will be randomized according to a sealed allocation list that will be balanced for sequence and provided to each site prior to the first subject enrollment. Subjects that withdraw prior to completing the second period will be replaced in a randomized manner. The randomization list will be generated by the study statistical group. There are four test periods in two sequences for a sequence-randomized study. During two test periods subjects will receive twice daily dosing of the "low" generic product and during the other two periods subjects will receive twice daily dosing of the "high" generic product. Each subject will return at the end of the 14+/-1 day stable dosing period for an in-facility 12-hour pharmacokinetic (PK) session to collect samples to determine Cmax and AUCs (area under curve). Each in-facility pharmacokinetic testing will be separated by a 14+/-1 day stable dosing period. A final follow-up phone evaluation will be conducted 12-16 days (target 14 days) after the last dose of study medication. A single make-up period will be permitted if there are issues during any single period. During the study the subjects will continue their usual concomitant medications, including AEDs (anti epilepsy drugs), without change.

Investigators will compare the AED levels as measured by Cmax and AUC in each group using average bioequivalence (ABE) and individual bioequivalence (IBE) criteria. Average bioequivalence will be established if the 90% confidence intervals of the geometric mean of Cmax and AUCs for the most disparate generic products compared to each other are entirely within the 80%-125% range (the FDA criteria for bioequivalence) using the two one-sided standard analyses. Otherwise the products will be considered to not be bioequivalent.

Study Population: Approximately 36 subjects (30 subjects to completion).

Number of centers: 3 sites enrolling approximately 12 subjects each.

Duration of study: Approximately 1 year. ;

Related Conditions & MeSH terms

• Epilepsy

• NCT number: NCT01713777
• Study type: Interventional
• Source: University of Cincinnati
• Status: Completed
• Phase: Phase 4
• Start date: April 2013
• Completion date: September 2015