SEATTLE, WA—Sodium oxybate (Xyrem; Jazz), alone or in combination with modafinil, improved excessive sleepiness in patients with narcolepsy both with and without cataplexy, results of a retrospective analysis of Phase 3 randomized trial data presented at SLEEP 2015 has found.
The effects of sodium oxybate on patients with narcolepsy without cataplexy have not been evaluated in clinical trials, noted Jed Black, MD, Jazz Pharmaceuticals, Inc, Palo Alto, CA, and Stanford Sleep Medicine Center, Redwood City, CA.
The placebo-controlled trial randomized patients to eight weeks of treatment with placebo, sodium oxybate (6g/nightly for four weeks increased to 9g/nightly for four weeks), modafinil 200– 600mg/day, or sodium oxybate plus modafinil. The patients were adults with narcolepsy with cataplexy (n=95) or without cataplexy (n=127).
Patients with cataplexy “were identified based on medical history, concomitant medications, and sleep-onset rapid eye movement (REM) periods on the nocturnal polysomnogram,” Dr. Black said.
The study assessed change from baseline at eight weeks on the Epworth Sleepiness Scale (ESS), Maintenance of Wakefulness Test (MWT) sleep latency, and percentage of patients with improvement on the Clinical Global Impression of Change (CGI-C).
In patients with narcolepsy and cataplexy, ESS improvement was significantly greater with sodium oxybate (-2.9; P=0.011) and sodium oxybate plus modafinil (-3.8; P=0.002) vs. placebo (+0.8).
Similarly, in patients with narcolepsy alone, ESS improvement was significantly greater with sodium oxybate (-3.0; P=0.021) and sodium oxybate plus modafinil (-2.8; P=0.015) vs. placebo (0.8). In the patients with narcolepsy and cataplexy, sleep latency was significantly increased with sodium oxybate plus modafinil (3.34 minutes; P<0.001), and tended to be increased with sodium oxybate (0.90 minutes; P=0.096) vs placebo (-2.58 minutes).
In the patients with narcolepsy without cataplexy, sleep latency was significantly increased for both the sodium oxybate (P=0.007) and sodium oxybate plus modafinil group (P<0.001). Significantly more patients with narcolepsy with cataplexy treated with sodium oxybate (69.2%; P=0.004) and sodium oxybate +modafinil (59.1%; P=0.001) achieved “very much improved” or “much improved” on the CGI-C vs. placebo (18.8%).
More patients with narcolepsy without cataplexy treated with sodium oxybate (44.1%) and sodium oxybate +modafinil (41.4%) achieved “very much improved” or “much improved” on the CGI-C vs placebo (28.6%), but these differences were not statistically significant, Dr. Black added.