He conveys the impression that XP13512 works pretty well.
The results in some were dramatic. Of course, the study in the recent press release was "double-blinded," so I didn't know what the patients were on, but now I have several patients in the "open-label" portion of the study in which the patient and I both know they are on the real drug. As the summary press report says, this could be the first non-dopamine medication approved for RLS, and will give patients with RLS another well-studied and safe option for treatment.
From the company press release:
XenoPort And GlaxoSmithKline Report Positive Top-line Results Of Final Pivotal Trial Of XP13512/GSK1838262 For Restless Legs Syndrome
“This novel compound is the first non-dopaminergic agent to demonstrate efficacy in controlled clinical trials for the treatment of primary RLS and may offer patients a new treatment option,” said Atul Pande, M.D., senior vice president, GlaxoSmithKline Neurosciences Medicines Development Center. “With the completion of this third Phase 3 clinical trial, we look forward to filing the NDA for primary RLS in the third quarter of 2008.”...
Results from the pre-specified analysis indicate that treatment with 1200 mg of XP13512 was associated with statistically significant improvements in the co-primary endpoints compared to placebo. Improvements in the IRLS scale score were significantly greater for 1200 mg XP13512 than for placebo (unadjusted mean values: -13.0 for 1200 mg XP13512; -9.8 for placebo; p=0.0015). At the end of treatment, significantly more patients treated with 1200 mg of XP13512 were reported as “much improved” or “very much improved” on the CGI-I scale compared to those treated with placebo (78% for 1200 mg XP13512; 45% for placebo...
These adverse events were generally mild or moderate in intensity. Withdrawals due to adverse events were 7% in the 1200 mg XP13512 group, 6% in the 600 mg XP13512 group and 6% in the placebo group...
(Dr. Pande was one of my professors.)
XP13512 is like gabapentin (Neurontin), but it is chemically modified to improve absorption. A 1.2g dose of Neurontin provides as much as what most people can absorb at one time. Of that 1.2g, only 30-40% is absorbed, with a great deal of variability from person to person. That obviously limits the efficacy of the drug. I don't have good human data for the kinetics of XP13512 to share. In monkeys, though, it is much better: 84.2% compared to 25.4%.
RLS is a tricky thing to treat sometimes. Sometimes, you get lucky and have good results from the first drug you try. But sometimes you hav3e to try several. Other times, a given drug might work for a while, then inexplicably stop working. I was glad to see that they included a 9-month study in their phase III trials. Perhaps that was Dr. Pande's idea. He's always had a practical inclination like that.
I'm also glad to see that they are doing studies to see if XP13512 will work for post-herpetic neuralgia. We could use another good non-opioid pain medication. In fact, that might turn out to be more important than the RLS indication.
Medicine & Health
Brain & Behavior
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