MAPLE GROVE, Minn., Oct. 15, 2013 /PRNewswire/ -- Upsher-Smith Laboratories, Inc., (Upsher-Smith) announced the presentation of Phase 1 data supporting the favorable tolerability and consistent, predictable pharmacokinetic (PK) profile of its investigational drug, USL255 (extended-release topiramate) following single-dose administration to healthy subjects. USL255 is being developed by Upsher-Smith for the management of epilepsy. These findings were presented at the American Neurological Association's (ANA) Annual Meeting in New Orleans, October 13-15, 2013.
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USL255 is a once-daily, broad-spectrum antiepileptic drug specifically engineered to deliver a smooth PK profile resulting in more consistent blood concentrations of topiramate during the entire day with a lower fluctuation index compared to immediate-release (IR) topiramate administered twice-daily. Upsher-Smith previously announced the successful completion of its global Phase 3 (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 (FDA).
"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. "An important consideration in the management of patients with epilepsy is the maintenance of stable antiepileptic drug plasma concentrations to prevent seizures. Extended-release antiepileptic drug formulations aim to deliver an improved PK profile that may reduce fluctuations and maintain therapeutic drug concentrations over longer periods of time."
About the Study
The objective of this Phase 1 study was to evaluate the pharmacokinetics, maximum tolerated dose (MTD) and safety/tolerability of single-ascending doses of USL255 over a wide dose range (600-1600 mg) in healthy volunteers. The randomized, placebo-controlled, double-blind study planned to enroll 60 healthy subjects into six dose cohorts (600 mg, 800 mg, 1000 mg, 1200 mg, 1400 mg, and 1600 mg). Each cohort enrolled 10 subjects of which 8 subjects received USL255 and two subjects received matching placebo.
Blood samples were collected and tolerability was evaluated for 14 days post-dose. USL255 displayed consistent plasma exposure up to 24 hours after administration, with low inter-subject variability in total plasma exposure and maximal topiramate plasma concentrations. AUC and Cmax were dose proportional and linear from 600-1400 mg. Single doses of USL255 were generally well tolerated from 600-1200 mg, with MTD established at 1200 mg.
The data presented at ANA 2013 further support the favorable tolerability and consistent, predictable PK profile of once-daily, extended-release USL255.
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 partial-onset seizures (POS). Preliminary findings from the Phase 3 trial have been submitted for presentation at the 2013 Annual Meeting of the American Epilepsy Society (AES), 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 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.
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, 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 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.
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.
1. Epilepsy Foundation. Available at: http://www.epilepsyfoundation.org. Accessed September 6, 2013.
2. Epilepsy.com. Available at http://professionals.epilepsy.com/secondary/Refractory_Seizures.html.
Accessed on September 6, 2013.
SOURCE Upsher-Smith Laboratories, Inc.