February 12, 2010 (San Antonio, Texas) — Sodium oxybate (Xyrem) continued to perform well in a second phase 3 trial, the first international study of the drug in patients with fibromyalgia, according to findings presented here at the American Academy of Pain Medicine 26th Annual Meeting.
Because of this, Jazz Pharmaceuticals has submitted an application to the US Food and Drug administration for expanded labeling of Xyrem.
Sodium oxybate is currently approved for the treatment of narcolepsy and cataplexy, but Jazz Pharmaceuticals is hoping for expanded approval that includes fibromyalgia by the end of the year.
Sodium oxybate is the sodium salt of gamma-hydroxybutyrate, a metabolite of gamma-aminobutyric acid.
An earlier phase 3 trial found that a significant number of patients experienced a 30% reduction in pain with the agent, compared with placebo, along with other favorable results. A more than 30% improvement is considered "clinically meaningful," reported Beverly Benson, PhD, director of clinical development at Jazz Pharmaceuticals, Inc.
Those results were essentially duplicated in a subsequent phase 3 trial, conducted at more than 100 centers in the United States and Europe, and presented here by Dr. Benson. A total of 376 patients completed the study.
Patients underwent a 30-day washout period and then recorded pain scores during the subsequent week to establish a baseline.
Patients were randomized to sodium oxybate 4.5 or 6 g/night, or placebo. Treatments were administered in 2 equally divided doses at bedtime and 2.5 to 4 hours later. Patients randomized to the higher dose started with 4.5 g/night for 2 weeks, and then completed the remaining 12 weeks of the trial at the full 6 g/night.
Patients began to see reductions in pain after the first week, and improvement continued steadily until week 5, when pain scores began to plateau, Dr. Benson said.
Overall, 51.4% of patients in the 6 g group experienced at least a 30% reduction in pain score, compared with 42% in the 4.5 g group. Both changes were significant compared with the placebo group, in which 26.8% of patients had a 30% reduction (P < .001 and P < .002, respectively).
A total of 37.7% of patients in the 6 g group experienced at least a 50% drop in pain score, compared with 28% in the 4.5 g group. Again, both were significant compared with the placebo group, in which 15.3% of patients showed such a reduction (P < .001 and P < .003, respectively).
At the end of treatment, 55.1% of patients in the 6 g group had at least a 30% improvement in function, according to the Fibromyalgia Impact Questionnaire, compared with 50% in the 4.5 g group and 29.8% in the placebo group (P < .001 over placebo), Dr. Benson told meeting attendees.
In addition, 39.7% of the 6 g group reported they felt "much better" or "very much better" on the Global Impression of Change scale, compared with 32.1% in the 4.5 g group and 16% in the placebo group (P < .001 over placebo).
Patients also reported significant reductions in sleep disturbance in both sodium oxybate groups (P < .001 over placebo), Dr. Benson said.
The most common adverse effects were nausea (21.2% in the 6 g group and 19.1% in the 4.5 g group), dizziness (13.2% and 11.9%, respectively), and vomiting (8.5% and 5.2%, respectively).
Researchers reported that these problems were generally mild or moderate.
"This included the European population, but we still saw repeatability between the US-only and the international trial," said Dr. Benson.
Jazz Pharmaceuticals representatives say, and some experts agree, that the drug might fill a niche that other fibromyalgia medications don't fill because it more directly addresses sleep problems.
"We know that it works by increasing slow-wave non-REM deep sleep," Dr. Benson said.
Suresh Gupta, MD, from the Dayton Outpatient Center in Ohio, said he is already pleased with the drugs that are currently on the market for fibromyalgia — pregabalin, duloxetine, and milnacipran — so it is questionable whether sodium oxybate will fit in.
But he said might be willing to try it.
"We have 3 beautiful drugs available now," he said. "There's always room for 5 more. Are they going to be better? I don't know."
"Obviously, you have to look at the side effects and side-effect profile for a new compound, and how well people tolerate it," Dr. Gupta added. "It's difficult to break into a new market, a market that's already established."
The study was funded by Jazz Pharmaceuticals. Dr. Benson is an employee with Jazz Pharmaceuticals. Dr. Gupta has disclosed no relevant financial relationships.
American Academy of Pain Medicine (AAPM) 2010 Annual Meeting: Abstract 186. Presented February 3–5, 2010.
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Cite this: Sodium Oxybate for Fibromyalgia Does Well in First International Phase 3 Trial - Medscape - Feb 12, 2010.