MAPLE GROVE, Minn., Dec. 5, 2011 /PRNewswire/ -- Upsher-Smith Laboratories, Inc. [http://www.upsher-smith.com] today announced the presentation of Phase 1 data showing that once-daily administration of USL255, a proprietary, extended-release (ER) formulation of the epilepsy medication topiramate, demonstrated linear dose-proportionality and, when compared to immediate-release (IR) topiramate administered twice-daily, an improved pharmacokinetic (PK) profile by demonstrating less topiramate fluctuation over 24 hours at steady state in healthy volunteers.
These data and other findings were presented Sunday, December 4th, at the American Epilepsy Society's (AES) 2011 Annual Meeting in Baltimore, MD [http://www.aesnet.org].
"Fluctuations in plasma levels of certain anti-epileptic drugs can cause concern for patients and their physicians, as fluctuating levels have the potential to contribute to increased side effects or break-through seizures. A once-daily, extended-release topiramate formulation that could reduce fluctuations in plasma topiramate levels may help address these concerns," said Wesley Mark Todd, M.D., Senior Director, Medical Affairs at Upsher-Smith. "We are excited to share new Phase I data with the clinicians at this year's AES Annual Meeting."
Abstracts of these posters can be found online at www.aesnet.org.
About The Studies
The first study assessed dose-proportionality, linearity and tolerability of USL255. In this Phase I, single-dose, open-label, 5-way crossover study, 30 healthy subjects were randomized into one of five treatment sequences with six subjects per sequence. Subjects were given each dose of USL255 (25, 50, 100, 200 and 400 mg) in varying order depending on their assigned treatment sequence. Following each treatment, subjects entered a three week washout period with blood samples being collected throughout the first 14 days. The investigators concluded that USL255's topiramate exposure was linear and dose-proportional from 25 mg up to 400 mg. Subsequent analyses compared dose-normalized Cmax values of USL255 400 mg to 200 mg, and 200 mg to 100 mg. All 90% confidence intervals were between 0.80 – 1.25 which indicates that Cmax changed dose-proportionally within double dose increases between 100 mg and 400 mg. As expected, the number of subjects who experienced a treatment-emergent adverse event generally increased with ascending doses, and all were mild to moderate in severity.
The second study compared the steady-state PK profile of once-daily USL255 to the twice-daily IR formulation. In this Phase I, open-label, 2-way crossover study, healthy subjects were up-titrated to 200 mg of topiramate (either USL255 or twice daily IR topiramate) over 12 days and maintained on 200 mg for 14 days. On day 15, subjects were crossed over, without washout, to the other topiramate formulation through day 28. Subjects were then down-titrated off the study drug over eight days. The study results confirmed that USL255 administered once-daily provided an improved PK profile as determined by an equivalent AUC, lower Cmax, higher Cmin and a reduced fluctuation index at steady-state when compared to twice-daily IR topiramate. All treatment-emergent adverse events were mild in severity.
USL255 is an investigational treatment being developed for the management of epilepsy in adults and is also the subject of a global Phase III clinical trial (PREVAIL). Information about the trial can be found at: http://clinicaltrials.gov/ct2/show/NCT01142193?term=upsher+smith&rank=4
Upsher-Smith's Expanding CNS Pipeline
Upsher-Smith's central nervous system (CNS) pipeline includes a number of investigational drug programs. In addition to USL255 (extended-release topiramate), USL is developing an intranasal midazolam (USL261), for the rescue treatment of seizures in patients on stable anti-epileptic drug regimens who require control of intermittent bouts of increased seizure activity, frequently referred to as seizure clusters. Another program is USL260 (tonabersat), an investigational drug and first-in-class neuronal gap junction modulator which is also a potential treatment for epilepsy.
Epilepsy is a medical condition that produces seizures affecting a variety of mental and physical functions. Almost three million people in the U.S. have some form of epilepsy with about 200,000 new cases of epilepsy diagnosed each year.(1)
Upsher-Smith Laboratories, Inc., founded in 1919, is a rapidly growing, privately held pharmaceutical company that develops, manufactures, and markets prescription and consumer products. Upsher-Smith's product portfolio focuses in the areas of women's health, dermatology, cardiology, and CNS diseases. The company's focus is growing a CNS pipeline for diseases with significant unmet need, including epilepsy and Parkinson's disease. To expand its CNS pipeline, Upsher-Smith seeks alliances and co-development programs, pursues licensing and acquisitions, and leverages its core competency in formulation development. For more information, visit http://www.upsher-smith.com.
(1) Epilepsy Foundation. Available at: http://www.epilepsyfoundation.org/. Accessed on March 18, 2011.
|SOURCE Upsher-Smith Laboratories, Inc.|
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