MAPLE GROVE, Minn., Aug. 13, 2013 /PRNewswire/ -- Upsher-Smith Laboratories, Inc.'s, USL255 (extended-release topiramate), an investigational once-daily formulation for the management of epilepsy, demonstrated equivalent systemic exposure with an improved topiramate (TPM) pharmacokinetic (PK) profile at steady-state, as measured by a significantly lower Cmax (Pmin (PEpilepsia. (The Journal of the International League Against Epilepsy-ILAE).
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"The goal of therapy with antiepileptic drugs is freedom from seizures and absence of side effects. While many individuals with epilepsy are successfully treated with one or more of the currently available AEDs, a substantial number still live with uncontrolled seizures or intolerable side effects," said Meir Bialer, PharmD, lead study investigator. "The results from this study suggest that USL255's improved PK profile, reduced fluctuations in topiramate steady-state plasma concentrations and favorable tolerability findings may offer patients a once-daily alternative to twice-daily commercially availableimmediate-release topiramate."
About the Study
The comparative study, published in Epilepsia, was designed to compare the steady-state PK profile of USL255 (200 mg QD) to TPM-IR (100 mg Q12h) in the same healthy subjects. The randomized, open-label, single-center, two-way crossover, multiple-dose study consisted of a 12-day up-titration, two 14-day maintenance periods with an immediate crossover between periods, followed by an 8-day down-titration.
Thirty-eight healthy adult subjects between the ages of 18 and 65 were randomized 1:1 to receive either USL255 or TPM-IR during up-titration and Period 1, and were switched to the alternate formulation (without washout) for Period 2, followed by down-titration.
At steady state, USL255 exhibited a smaller fluctuation in topiramate plasma concentration and significantly lower variability in topiramate concentrations over 24 hours compared to TPM-IR.
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Because switching from one formulation of an AED to another can lead to potential problems such as varied treatment response, breakthrough seizures, and/or increased adverse events, the study also evaluated the effects of switching TPM formulations on PK parameters. Steady-state topiramate concentrations were maintained after switching topiramate formulations (TPM-IR to USL255 or USL255 to TPM-IR), and the PK parameters of Cmin, AUC and Cmax met criteria for bioequivalence for the two formulations.
USL255 was observed to be generally well tolerated in healthy subjects. The treatment-emergent adverse events (TEAEs) seen in this study were mild in intensity. Although the most common TEAEs occurred with similar frequency in both groups, subjects receiving USL255 were observed to have fewer side effects related to cognition and memory impairment than those receiving TPM-IR.
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Study Published in Epilepsia Demonstrated Improved PK Profile for USL255 (Extended-Release Topiramate) vs Immediate ...