Study Shows Xyrem Effectiveness

Minneapolis, MN - February 1, 2002

People with narcolepsy, a sleep disorder which afflicts about 1 in 2,000 people, suffer sleep attacks throughout the day. But a new drug, sodium oxybate (Xyrem), reduced sleep attacks by 70 percent when given in 9-gram doses upon retiring and 2.5 to 4 hours later, according to the findings of the U.S. Xyrem Multicenter Study Group, a consortium of university sleep researchers as reported in the American Academy of Sleep Medicine and Sleep Research Society's February issue of the journal "Sleep". Xyrem is a product of Orphan Medical and is currently in process of approval by the Food and Drug Administration.

A randomized, double blind, placebo-controlled multicenter trial was conducted comparing the effects of 3 doses of orally administered sodium oxybate with placebo for the treatment of cataplexy associated with Narcolepsy. Cataplexy is a temporary decrease or complete loss of muscle control triggered by an emotional response that is often seen in narcoleptics.

The objective of the study was to evaluate and compare the efficacy and safety of three doses of sodium oxybate and placebo for the treatment of narcolepsy symptoms. The study participants consisted of 136 narcolepsy patients with 3 to 249 cataplexy attacks weekly. The average number of cataplexy attacks per patient was 21 per week.

Prior to baseline measures, subjects discontinued anticataplectic medications. Stable doses of stimulants were permitted. Subjects were randomized in blinded fashion to receive 3, 6, or 9 g doses of sodium oxybate or placebo taken in equally divided doses upon retiring to bed and 2.5-4 hours later for 4 weeks.

Measurements and Results

The following description of study methodology and results is quoted from the abstract published by the American Academy of Sleep Medicine and Sleep Research Society.

"Disease symptoms and adverse events were recorded in daily diaries. The primary measure of efficacy was the change from baseline in weekly cataplexy attacks. Secondary measures included daytime sleepiness using the Epworth Sleepiness Scale (ESS), inadvertent daytime naps/sleep attacks and nighttime awakenings. Investigators assessed changes in disease severity using Clinical Global Impression of Change (CGI-c). Compared to placebo, weekly cataplexy attacks were decreased by sodium oxybate at the 6 g dose (p=0.0529) and significantly at the 9 g dose (p=0.0008). The ESS was reduced at all doses, becoming significant at the 9 g dose (p=0.0001). The CGI-c demonstrated a dose-related improvement, significant at the 9 g dose (p=0.0002). The frequency of inadvertent naps/sleep attacks and the nighttime awakenings showed similar dose-response trends, becoming significant at the 9 g dose (p=0.0122 and p=0.0035, respectively). Sodium oxybate was generally well-tolerated at all three doses. Nausea, headache, dizziness and enuresis were the most commonly reported adverse events."

The researchers concluded that odium oxybate significantly improved symptoms in patients with narcolepsy and was well tolerated. In addition to the 70% reduction in sleep attacks at the 9 g dose, the study found that lower doses of 6 and 3 grams reduced sleep attacks by 50 percent and that an inactive placebo used as a control reduced the attacks by 28 percent, the group reported in the journal Sleep. "These data support and extend previous findings that demonstrate sodium oxybate is an effective treatment for the symptoms of narcolepsy," the scientists said.

Full text of this article can be found in the February 2002 edition of the journal "Sleep", the official publication of the American Academy of Sleep Medicine.