Upsher-Smith Presents Data Supporting Favorable Tolerability And Consistent Pharmacokinetic Profile Of Once-Daily USL255 (Extended-Release Topiramate)

MAPLE GROVE, Minn., March 20, 2013 /PRNewswire/ -- Upsher-Smith Laboratories, Inc., (Upsher-Smith) today announced the presentation of data supporting favorable tolerability and a predictable, consistent pharmacokinetic (PK) profile of USL255 at high doses following single-dose administration to healthy subjects.  USL255, an investigational once-daily, extended-release (ER) topiramate formulation is in development for the management of epilepsy in adults.  This data was presented at the 65^th Annual American Academy of Neurology (AAN) Meeting in San Diego, CA (http://www.aan.com), March 16-23, 2013.

"Epilepsy drug therapy often must be carefully titrated in order to optimize benefit while minimizing adverse effects," 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.  "The introduction of extended-release formulations for a number of antiepileptic drugs offers the potential for management of seizures by decreasing the number of doses patients take on a daily basis and reducing the risk of adverse effects related to peak drug concentrations."

"At Upsher-Smith, we are committed to researching new treatment options for people living with challenging central nervous system conditions like epilepsy," added William Pullman, MB BS, BMedSc, PhD, FRACP, Chief Scientific Officer, Upsher-Smith.  "The data presented at AAN from the development program for USL255 adds to the existing body of evidence supporting the further development of USL255 for the once-daily management of epilepsy."

The abstract of the poster presentation can be found online at http://www.aan.com:

• Single, High Doses of USL255, an Extended-Release Topiramate Formulation, are Well Tolerated and Demonstrate a Dose-Proportional Pharmacokinetic Profile in Healthy Subjects 
  P04.212. Session P04:  Epilepsy:  Antiepileptic Medications:  Special Populations and Pharmacokinetics

USL255 (Extended-Release Topiramate) Data

The objective of the single-dose, Phase I study was to determine the maximum tolerated dose (MTD), safety/tolerability, and pharmacokinetics (PK) of ascending doses of USL255 in healthy volunteers.  The study planned for sixty subjects to be randomized (4:1) to USL255 (600, 800, 1000, 1200, 1400 or 1600 mg) versus placebo.  PK samples were drawn, and tolerability and vital signs assessed, out to 14 days post-dose.  Escalation to the next dose level was done only after USL255 demonstrated suitable tolerability four days post-dose, assessed by a priori tolerability criteria.  Dose proportionality and linearity of topiramate exposure was determined using statistical models.  The study results showed single-ascending doses of USL255 were generally well tolerated from 600 – 1200 mg, with 1200 mg established as the MTD.  AUC and C_max were dose proportional and linear over the entire 600 – 1400 mg dose range.

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://www.clinicaltrials.gov (NCT01142193).

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 Epilepsy

Epilepsy is a medical condition that causes seizures affecting a variety of cognitive and physical 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.²    

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, branded-generic and generic pharmaceuticals.  Upsher-Smith has a particular focus on providing therapies to assist people suffering from central nervous system diseases (including epilepsy, Parkinson's disease and Alzheimer's disease) and also markets products relating to cardiology, dermatology, and women's health.  For more information, visit www.upsher-smith.com.

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SOURCE Upsher-Smith Laboratories, Inc.