XenoPort Reports Positive Results from Its Initial Phase I Study of XP13512, a Next Generation Gabapentin
SANTA CLARA, Calif., Jan. 12 /PRNewswire/ -- XenoPort, Inc., a privately held biopharmaceutical company, announced today the successful completion of the company's first Phase I clinical study of XP13512, a Transported Prodrug of gabapentin. The objective of the study was to assess safety, tolerability and pharmacokinetics of XP13512 in healthy adult volunteers.
The Phase I study was a randomized, placebo-controlled, double-blind study with five ascending single doses of an immediate-release formulation of XP13512. One week after the XP13512 dose, subjects were given an approximately equimolar dose of Neurontin® to allow for pharmacokinetic comparison in the same subject. Subjects were monitored for adverse events, and blood and urine were sampled to determine gabapentin pharmacokinetic profiles and bioavailability from both XP13512 and Neurontin.
The Phase I study indicated that XP13512 was well tolerated at all doses. All reported adverse effects were mild and consistent with those previously reported for Neurontin.
Additionally, the study demonstrated that XP13512 was rapidly absorbed and converted to gabapentin. Exposure to the intact prodrug was low and transient at all XP13512 doses. Exposure to gabapentin (AUC of gabapentin in blood) after oral XP13512 was dose proportional whereas exposure after oral Neurontin was not dose proportional. At the highest dose tested, mean gabapentin exposure after XP13512 administration was approximately 2.5 times higher than from an equivalent dose of Neurontin. Gabapentin exposure after oral XP13512 was less variable between individuals than after Neurontin, particularly at higher doses. At the four highest doses, XP13512 provided substantially higher gabapentin exposure than equimolar Neurontin in all subjects. Biovailability as gabapentin (measure by urinary recovery) after oral XP13512 was approximately 70% or better across the entire dose range while bioavailability after oral Neurontin decreased with increasing dose.
"We are thrilled by these results and are gratified that the safety and improved pharmacokinetic performance that we demonstrated in preclinical studies were borne out in this first human study," said Daniel M. Canafax, Pharm.D., vice president clinical development. "These results support continued clinical development of XP13512. We look forward to completing additional ongoing Phase I studies with XP13512, including a study with sustained-release formulations. We also plan to assess the potential of XP13512 to provide meaningful benefit to patients in Phase II studies during 2004."
"We are excited by these initial clinical results with XP13512," said Ronald W, Barrett , Ph.D, president and chief executive officer. "These Phase I results not only show XP13512's potential to address unmet medical needs, but also validate the utility of our Engineered Drug Transport technology in humans for the first time. We look forward to advancing additional XenoPort product candidates from our Transported Prodrug platform into clinical development in 2004."
About XP13512
XP13512 is a Transported Prodrug of gabapentin that has been engineered to utilize high capacity transport mechanisms located in both the small and large intestine and to rapidly convert to gabapentin once in the body. In contrast to gabapentin itself, XP13512 was shown in preclinical and clinical studies to produce dose proportional blood levels of gabapentin across a broad range of oral doses, and to be absorbed efficiently from the large intestine. This is a critical requirement for the successful development of a sustained release formulation with reduced dosing frequency.
Pfizer, Inc. currently sells gabapentin under the trade name Neurontin®. Worldwide sales for Neurontin in 2002 were $2.3 billion. Neurontin is approved for marketing in the United States as adjunctive therapy for partial seizures and for management of post-herpetic neuralgia. In addition, physicians prescribe the drug for treatment of other neuropathic pain disorders and a variety of other conditions. Almost 10 million patients have been prescribed Neurontin in the U.S. since its approval in 1994.
About Transported Prodrugs
A Transported Prodrug is a chemically modified version of an active drug molecule that is designed to engage natural transport mechanisms found on intestinal cell membranes, thereby gaining efficient entrance into the bloodstream. The Transported Prodrug is then converted to the parent drug by enzymes in the appropriate tissue. XenoPort's Transported Prodrugs are intended to offer significant benefits over existing drugs by improving efficacy, expanding indications, lowering side effects, improving ease of use and increasing patient compliance.
About XenoPort, Inc.
XenoPort, Inc., based in Santa Clara, California, is a privately held biopharmaceutical company focused on harnessing the body's intrinsic cellular transport systems to improve the oral absorption, distribution and pharmacokinetics of drugs. The company applies an integrated technology platform, consisting of transporter genomics, assay technology, and proprietary chemistries, to engineer drug molecules for active transport. XenoPort is currently applying its technology to off-patent drugs to create new patentable Transported Prodrugs with improved medicinal properties. XP13512 is the first of several product candidates in XenoPort's portfolio to enter human testing. XenoPort intends to develop its product candidates through clinical proof of concept prior to establishing partnerships for further development and commercialization. |
