CHICAGO — The investigational drug XP13512 has been shown in a large, randomized, double-blind, placebo-controlled clinical trial to successfully control symptoms of restless legs syndrome and to improve sleep quantity and adequacy.
“This is the first nondopaminergic agent studied in a large trial for [restless legs syndrome], and it was developed to overcome pharmacokinetic deficiencies of gabapentin,” said Dr. Clete A. Kushida, describing the agent that is converted to gabapentin after absorption in the intestine.
In this multicenter trial, 220 patients with RLS received either 1,200 mg XP13512 (n = 112) or placebo at 5 p.m. daily. About 60% were female in both groups and the average age was 50. Participants typically had symptoms for 13 years or more.
Using the International Restless Legs Syndrome (IRLS) scale, the mean change from baseline was significantly greater in the treated group than in those on placebo (−13.2 vs. −8.8; P = .0003).
More patients treated with XP13512 were rated as “much improved” or “very much improved” by the investigator using the Clinical Global Impression-Improvement scale than were those receiving placebo (76.1% vs. 38.9%; P less than .0001). By the end of the 12-week trial, 50% of XP13512-treated patients were symptom free over a 24-hour period, compared with 17.7% of placebo-treated patients.
Treatment also resulted in better subjective sleep quality and quantity, and beneficial effects were detected within 1 week.
One serious adverse event occurred in the placebo group. Somnolence and dizziness, the two most frequently reported treatment-linked events, were mild to moderate and generally transient, said Dr. Kushida, director of the center for human sleep research at Stanford (Calif.) University, who presented the results at the annual meeting of the American Academy of Neurology.
Gabapentin is approved for the management of postherpetic neuralgia and the treatment of partial seizures. It is also helpful for the treatment of neuropathic pain. Although early testing showed it controls RLS symptoms, it has shortfalls that limit its therapeutic potential, including unpredictable absorption and a short half-life, says Dr. Kushida.
XP13512, a gabapentin prodrug with extended release, is absorbed by transporter proteins located throughout the GI tract and is rapidly converted to gabapentin. Pharmacokinetic studies show this results in higher peak concentration with longer duration of exposure.
Dr. Kushida disclosed relationships to numerous companies, including XenoPort Inc., the maker of XP13512.