CHICAGO, April 17 /PRNewswire/ -- Data from the first pivotal study of XP13512/GSK1838262, a sustained-release investigational compound to treat Restless Legs Syndrome (RLS), showed that it significantly improved the symptoms of moderate-to-severe primary RLS compared to placebo, and was generally well-tolerated when administered once-daily for 12 weeks.
Data from the PIVOT RLS I (Patient Improvement in Vital Outcomes following Treatment for RLS) clinical trial, formerly designated as study XP052, were presented today at the 60th annual meeting of the American Academy of Neurology (AAN). The investigational compound is being developed by XenoPort (Nasdaq: XNPT) and GlaxoSmithKline (NYSE: GSK).
"This novel compound is the first non-dopaminergic agent to demonstrate efficacy in treating the symptoms of RLS in large controlled clinical trials," said Clete Kushida, M.D., director of the Stanford Center for Human Sleep Research and a clinical investigator in the PIVOT RLS I clinical trial.
Additional data presented at the meeting compared the pharmacokinetic profiles of an immediate-release formulation of XP13512, a sustained-release formulation of XP13512, and commercially-available gabapentin. The sustained- release formulation of XP13512, used in the PIVOT RLS I clinical trial presented at AAN, provided predictable and extended exposure in healthy volunteers compared with commercially-available gabapentin.
Absorption of commercially-available gabapentin is limited to a narrow region in the intestinal tract and can saturate at normal clinical doses. Once saturation occurs, additional gabapentin can not be absorbed. In addition, absorption rates can vary from patient to patient. In contrast, studies with both the immediate-release and the sustained-release formulations indicated that XP13512 was well-absorbed, converted rapidly to gabapentin and provided high bioavailability (>70 percent) and dose-proportional exposure.
"XP13512 is absorbed by high-capacity nutrient transporters located throughout the intestinal tract," said Ken Cundy, Ph.D., senior vice president, Preclinical Development for XenoPort. "The unique absorption mechanism of this compound overcomes the pharmacokinetic limitations of commercially-available gabapentin and allows for sustained, dose-proportional exposure to gabapentin."
About PIVOT RLS I (Study XP052)
PIVOT RLS I, a 12-week, multicenter, randomized, double-blind, placebo- controlled clinical trial of XP13512 was designed to assess efficacy and tolerability in adults with moderate-to-severe primary RLS. The study included 220 patients randomized to receive either XP13512 1200 mg (n=112) or placebo (n=108) once-daily at 5:00 p.m. with food. Co-primary endpoints in the study were mean change from baseline in the International Restless Legs Syndrome (IRLS) Scale total score and the proportion of responders (defined as ratings of 'very much improved' or 'much improved') on the investigator-rated Clinical Global Impression of Improvement (CGI-I) Scale at Week 12. Adverse events, vital signs and laboratory tests were used to assess tolerability.
Study results showed that the unadjusted mean change from baseline in IRLS Scale total score at Week 12 was significantly greater for XP13512 (-13.2) compared to placebo (-8.8) with an adjusted mean treatment difference of -4.0, 95% CI: (-6.2, -1.9) (P=0.0003). In addition, a significantly greater proportion of patients treated with XP13512 (76.1 percent) was rated as responders on the CGI-I Scale compared to placebo (38.9 percent; P<0.0001).
Sleep disturbance is often associated with RLS. In this clinical trial, patients completed the Medical Outcomes Study (MOS) Sleep Scale to assess the impact of XP13512 treatment on sleep. At Week 12, XP13512-treated patients, compared to placebo-treated patients, had statistically significant improvements in sleep quantity and sleep adequacy, as well as statistically significant reductions in sleep disturbance and daytime somnolence.
The PIVOT RLS I clinical trial used a 24-hour diary to collect the presence and severity of RLS symptoms every 30 minutes starting at 8:00 a.m. At the end of the study, more than half of patients treated with XP13512 were symptom-free for the 24-hour assessment period compared to 18 percent of placebo-treated patients.
The two most commonly reported adverse events in the study were somnolence (27 percent, XP13512 vs. 7 percent, placebo) and dizziness (20 percent, XP13512 vs. 5 percent, placebo), with the majority reported as mild-to- moderate in intensity. Nine patients (8 percent) who received XP13512 withdrew from study participation due to adverse events compared to three patients (3 percent) who received placebo. No clinically meaningful changes in vital signs or laboratory parameters were observed.
In addition, the Epworth Sleepiness Scale (ESS), a reliable tool designed to measure daytime drowsiness, was used to evaluate the likelihood of patients dozing or falling asleep in common situations of daily living, such as sitting and reading or watching TV. At Week 12, the ESS scores for patients in the XP13512 group were lower than patients in the placebo group, indicating that XP13512 treatment was associated with less daytime drowsiness. The findings on the ESS scale are consistent with the reduction in daytime somnolence associated with XP13512 treatment as assessed by the MOS Sleep scale.
According to the National Institutes of Health, up to 12 million people in the U.S. are afflicted with RLS across a range of severity from mild to severe. RLS was identified in the early 1940's by neurologist Dr. Karl Ekbom, and is characterized by a compelling urge to move the legs and by uncomfortable and unpleasant sensations in the legs often described as creeping-crawling, throbbing, pulling or tightening. Symptoms of RLS generally occur at rest, such as when sitting, lying or sleeping, and are temporarily relieved by movement. These symptoms can significantly disrupt a patient's sleep and daily activities. People with RLS often have difficulty falling asleep and can feel tired during the day. RLS symptoms can be debilitating -- published data suggest that RLS can have an impact on quality of life equivalent to, or worse than, major chronic medical disorders such as diabetes and osteoarthritis.
XenoPort, Inc. is a biopharmaceutical company focused on developing a portfolio of internally discovered product candidates that utilize the body's natural nutrient transport mechanisms to improve the therapeutic benefits of existing drugs. Its development and commercialization efforts are currently focused on potential treatments of central nervous system disorders. XenoPort's most advanced product candidate, XP13512, has successfully completed three pivotal trials in its Phase 3 clinical program for the treatment of moderate-to-severe primary RLS, and has successfully completed a Phase 2a clinical trial for the management of post-herpetic neuralgia. XenoPort has also reported positive results from a Phase 2a clinical trial of its second product candidate, XP19986, in patients with gastroesophageal reflux disease. To learn more about XenoPort, please visit the web site at www.XenoPort.com.
GlaxoSmithKline is one of the world's leading research-based pharmaceutical and healthcare companies and is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For more information, visit GlaxoSmithKline at www.gsk.com.
XenoPort Forward-Looking Statement
This press release contains "forward-looking" statements, including, without limitation, all statements related to the therapeutic and commercial potential of XP13512. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as "believes", "plans", "expected", "will", "potential" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon XenoPort's current expectations. Forward-looking statements involve risks and uncertainties. XenoPort' s actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, the ability of the company to successfully conduct the clinical trials for XP13512, and the results thereof; the uncertainty of the FDA approval process and other regulatory requirements; XenoPort' s dependence on its current and additional collaborative partners; and the therapeutic and commercial value of the company' s compounds. These and other risk factors are discussed under the heading "Risk Factors " in XenoPort' s Annual Report on Form 10-K for the year ended December 31, 2007, filed with the Securities and Exchange Commission on February 22, 2008. XenoPort expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in the company' s expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based.
GlaxoSmithKline Forward-Looking Statement
Under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect GSK' s operations are described under 'Risk Factors' in the 'Business Review' in the company' s Annual Report on Form 20-F for 2007.
XenoPort is a registered U.S. trademark.