XP13512 Update

XP13512 is an experimental new drug currently href="http://clinicaltrials.gov/ct2/results?term=XP13512">in
phase III trials for the treatment of href="http://www.merck.com/mmpe/sec16/ch215/ch215f.html"
rel="tag">restless legs syndrome.  I was
reminded about this after seeing a post at href="http://sleepdoctor.blogspot.com/2008/03/restless-legs-syndrome-and.html">sleepdoctor,
and following the link to Sleep Expert, and browsing from there.
 The author, Dr. Poceta, wrote about href="http://www.revolutionhealth.com/blogs/stevepocetamd/new-medicine-for-rls--12134"
rel="tag">XP13512.  He appropriately discloses
that he was involved in clinical trials of the drug.



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:

href="http://03530.com/2008/03/03/xenoport-and-glaxosmithkline-report-positive-top-line-results-of-final-pivotal-trial-of-xp13512gsk1838262-for-restless-legs-syndrome.html">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 href="http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a694007.html"
rel="tag">gabapentin ( href="http://www.pdrhealth.com/drugs/rx/rx-mono.aspx?contentFileName=Neu1289.html&contentName=Neurontin&contentId=379"
rel="tag">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 href="http://jpet.aspetjournals.org/cgi/content/short/jpet.104.067959v1">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.