Upsher-Smith Presents Favorable Pharmacokinetic Data On Once-Daily USL255 (Extended-Release Topiramate)

  Upsher-Smith Presents Favorable Pharmacokinetic Data On Once-Daily USL255
                        (Extended-Release Topiramate)

Findings Presented at 30th International Epilepsy Congress

PR Newswire

MAPLE GROVE, Minn., June 24, 2013

MAPLE GROVE, Minn., June 24, 2013 /PRNewswire/ -- Upsher-Smith Laboratories,
Inc., (Upsher-Smith) today announced the presentation of Phase I data
supporting dose-proportional pharmacokinetics, consistent drug levels, and
favorable tolerability of its investigational drug, USL255 (extended-release
topiramate), across a wide range of doses in healthy subjects. USL255 is
specifically engineered to provide convenient once-daily dosing and reduce
fluctuations in plasma topiramate levels observed with currently available
treatment options. These findings were presented at the 30^th International
Epilepsy Congress (IEC) in Montreal, Canada, June 23-27, 2013.

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USL255 is a proprietary, extended-release formulation of topiramate being
developed by Upsher-Smith for the management of epilepsy in adults.

"Maintenance of stable antiepileptic drug plasma concentrations to prevent
seizures is an important consideration in the management of patients with
epilepsy," said James Cloyd, PharmD, Professor and Lawrence C. Weaver Endowed
Chair-Orphan Drug Development, Department of Experimental and Clinical
Pharmacology, College of Pharmacy, University of Minnesota.
"Second-generation, extended-release antiepileptic drug formulations aim to
reduce the frequency of dosing, thereby increasing patient compliance, while
at the same time lowering the risk of adverse events related to peak drug

The abstract of the poster presentation, USL255, Extended-Release Topiramate,
Demonstrates Dose-Proportional Pharmacokinetics and Tolerability over a Wide
Dosing Range in Healthy Subjects, can be found online at

About the Study
The data presented at IEC 2013 evaluated USL255 in two single-dose, Phase 1
studies in healthy subjects: 1) an open-label, 5-way crossover study of USL255
at dosage strengths of 25 - 400 mg in 30 subjects; 2) a randomized,
placebo-controlled, double-blind, ascending, maximum tolerated dose study
where 40 subjects received 600, 800, 1000, 1200, or 1400 mg of USL255.
Post-hoc analyses evaluated dose proportionality and variability of AUC and
C[max] across the entire dosing range (25 – 1400 mg). USL255 demonstrated
dose proportionality in AUC from 25 - 1400 mg; C[max] was proportional to dose
from 50 – 1400 mg. Across the dosing range, consistent plasma topiramate
exposure was observed with low inter-subject variability.

In healthy subjects, single doses of USL255 were reported to be well
tolerated, as measured by investigator-reported adverse events,
electrocardiograms, and evaluation of clinical laboratory tests and vital sign
measurements obtained throughout the studies. 

Upsher-Smith recently announced the successful completion of its global Phase
III (PREVAIL) clinical trial for USL255 and that its New Drug Application for
USL255 has been accepted for review by the U.S. Food and Drug Administration

The PREVAIL trial was a randomized, multicenter, double-blind,
placebo-controlled, parallel-group study designed to evaluate the efficacy and
safety of USL255 as adjunctive therapy in patients with refractory
partial-onset seizures (POS). Preliminary findings from the Phase III trial
will be submitted for presentation at the 2013 Annual Meeting of the American
Epilepsy Society, December 6-10 in Washington, D.C.

PREVAIL was conducted under a Special Protocol Assessment (SPA) agreement with
the FDA. More information about the trial is available at (NCT01142193).

An open-label extension study to evaluate the safety of USL255 as adjunctive
therapy in patients with refractory POS who had participated in PREVAIL is
ongoing. The open-label extension study can be found by searching NCT01191086

About Epilepsy
Epilepsy is a medical condition that causes seizures affecting a variety of
cognitive andphysical functions. More than two million people in the U.S.
are estimated to be affected by epilepsy with about 200,000 new cases of
epilepsy diagnosed each year.^1 For many people with epilepsy, medication
will prevent seizures if taken regularly, but some people continue to have
seizures.^1 As many as two out of three patients treated for epilepsy have
seizures that are refractory to therapy, either because they have incomplete
control of their seizures or they experience treatment-related side effects
that interfere with their quality of life.^2

Upsher-Smith's Epilepsy Pipeline
Upsher-Smith's clinical development pipeline includes three investigational
drugs that are being studied for the management of epilepsy. USL255 is an
investigational once-daily, extended-release topiramate for the management of
epilepsy. The pipeline also includes USL261, an investigational intranasal
midazolam for the rescue treatment of seizures in patients who require control
of intermittent bouts of increased seizure activity, often called seizure
clusters, which is the subject of an ongoing international Phase III clinical
trial (ARTEMIS1) with an open-label safety extension study. In addition,
USL260 (tonabersat) is in early clinical development as a potential
first-in-class neuronal gap junction modulator.

About Upsher-Smith
Upsher-Smith, founded in 1919, is an independent and privately-owned specialty
pharmaceutical company headquartered in Maple Grove, Minnesota that focuses on
product growth and innovation for branded and generic pharmaceuticals.
Upsher-Smith has a particular focus on developing therapies to assist people
suffering from central nervous system diseases, and also markets products
relating to cardiology, dermatology, and women's health. For more
information, visit


1. Epilepsy Foundation. Available at:
Accessed May 30, 2013.
2. Available at Accessed
on May 30, 2013.

SOURCE Upsher-Smith Laboratories, Inc.

Contact: Daina Basile, Kovak-Likly Communications, 203-762-8833,
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