Upsher-Smith Presents New Data On The PK Equivalence Of USL255 (Extended-Release Topiramate) When Sprinkled On Food Or Swallowed Intact

MAPLE GROVE, Minn., Dec. 10, 2013 /PRNewswire/ -- Upsher-Smith Laboratories, Inc. (Upsher-Smith), today announced the presentation of new Phase 1 data showing that USL255 (extended-release topiramate) may provide a beneficial treatment option for individuals with difficulty swallowing whole capsules or tablets.  Additionally, simulations of data from another Phase 1 study demonstrated a return to steady-state topiramate levels within one 24-hour dosing interval, suggesting, for USL255 doses delayed up to 18 hours, the risk of dropping to sub-therapeutic concentrations is minimized.  The data were presented for the first time at the American Epilepsy Society's (AES) 67^th Annual Meeting in Washington, DC, December 6-10, 2013. 

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Upsher-Smith presented two abstracts with Phase 1 data on USL255, a once-daily, broad-spectrum antiepileptic drug specifically engineered to deliver a smooth pharmacokinetic (PK) profile.  It is being developed by Upsher-Smith for the treatment of seizure disorders. Upsher-Smith's New Drug Application for USL255 has been accepted for review by the U.S. Food and Drug Administration (FDA). When approved, USL255 may offer dosing flexibility because it can be swallowed whole or the capsule contents of all strengths may be sprinkled onto soft food.

Phase 1 data presented at AES came from a single-dose study (N=36) that evaluated the PK profile of 200 mg of USL255 administered to healthy volunteers. Subjects were randomized to receive both an intact USL255 200 mg capsule taken under fasting conditions and three weeks later a 200 mg capsule of USL255 opened and sprinkled onto one tablespoonful of applesauce after an overnight fast. Researchers found that USL255 when sprinkled on soft food or given intact demonstrated PK equivalence for both AUC and C_max. The findings indicated that USL255 may provide a beneficial option for individuals with difficulty swallowing whole capsules or tablets.

"The positive results of the Phase 1 study demonstrate that USL255 may help address a common issue facing many patients with seizure disorders: challenges swallowing capsules or tablets," said Barry Gidal, Pharm.D., R.Ph., Division Chair, School of Pharmacy, University of Wisconsin. "This specifically designed formulation with the flexibility of once-daily dosing and the option of sprinkle administration may provide added benefits to patients living with the challenge of seizures."

The second presentation evaluated the pharmacokinetic effects of delayed administration of USL255.  Simulations were conducted to assess the effects of taking USL255 6, 12, 18 and 24 hours later than scheduled.  The data demonstrated a return to near steady-state topiramate plasma concentration within one 24-hour dosing interval after the delayed dose was administered. Administration of USL255 up to 18 hours after a missed dose will minimize the duration of decreased topiramate concentrations without significant risk of increased maximal plasma concentrations.

At the AES conference, Upsher-Smith also presented seven abstracts on its recently completed global Phase 3 study, PREVAIL, which enrolled more than 200 patients at 66 centers to evaluate the safety and efficacy of USL255.

Abstracts of the poster presentations can be found online at www.aesnet.org.  To schedule an interview with an investigator, please contact Jessica Orr at [email protected].  

About Upsher-Smith's Phase 3 (PREVAIL) Clinical Trial
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 POS. 

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

Upsher-Smith's Epilepsy Pipeline
Upsher-Smith's clinical development pipeline includes three investigational drugs that are being studied for the management of seizure disorders.  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 3 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 www.upsher-smith.com.

SOURCE Upsher-Smith Laboratories, Inc.