Excessive Daytime Sleepiness (EDS)

Daytime sleepiness significantly decreased, as assessed by the Epworth Sleepiness Scale (ESS)^[1][2]

Trial 3 was an 8-week trial that assessed the efficacy of XYREM for the treatment of EDS at nightly doses of 4.5, 6, and 9 g in 228 patients with moderate-to-severe symptoms of narcolepsy. The primary efficacy measures were subjective changes in EDS measured by the ESS and changes in disease severity measured by the CGI-c.

During the baseline period, ESS scores in the 4 treatment groups ranged from 17.5 to 19.0, indicative of severe sleepiness^[1][2]. After 8 weeks of treatment, XYREM produced a dose-related median decrease in ESS scores from baseline of -2.0, and -5.0 with XYREM doses of 6, and 9 g, respectively. These changes were statistically significant (P<0.001 vs placebo) at the 6- and 9-g doses compared with placebo (-0.5)^[1].

A quartile analysis (not shown) indicated that more than 25% of patients in the 9-g group had normal scores (ESS <10) following treatment with XYREM^[1]

It is important to note that XYREM treatment significantly decreased EDS at 6 and 9 g/night, even though most of these patients continued to receive stable doses of stimulant medications throughout the trial^[1]. In XYREM clinical trials, ≈80% of patients maintained concomitant stimulant use^[2].

The ESS is a subjective patient questionnaire that evaluates the extent of daytime sleepiness in everyday situations.
Scale: 0-8 normal, 9-12 mild, 13-16 moderate, ≥17 severe
4.5 g/night is the recommended starting dose. The effective dosing range is 6-9 g/night.

Source: ^[1][2]

• XYREM is indicated for the treatment of EDS in patients with narcolepsy
• XYREM is indicated for the treatment of cataplexy in patients with narcolepsy
• In XYREM clinical trials, ≈80% of patients maintained concomitant stimulant use
  • The most commonly reported adverse events (≥5%) in placebo-controlled trials (n=655) associated with the use of XYREM and occurring more frequently than seen in placebo–treated patients were: nausea (19%), dizziness (18%), headache (18%), vomiting (8%), somnolence (6%), urinary incontinence (6%), and nasopharyngitis (6%).
  • In clinical trials in narcolepsy (n=717), 10% of patients discontinued because of adverse events. The most frequent reasons for discontinuation (>1%) were: nausea (2%), dizziness (2%), and vomiting (1%)

XYREM Significantly Increased the Ability to Stay Awake^[2][3]

Trial 4 was an 8-week, randomized, double-blind, double-dummy, placebo-controlled, parallel-group, multicenter trial that compared the effects of XYREM, alone or with modafinil, vs placebo in 222 patients with narcolepsy. The primary efficacy measure was the objective change in EDS as measured by the MWT. Cataplexy was not required for enrollment^[3].

The trial was not designed to compare XYREM and modafinil. As patients receiving modafinil were not necessarily titrated to an optimal dose, the efficacy of modafinil and XYREM should not be compared^[3].

Baseline MWT sleep latencies ranged from 9.7 to 11.3 minutes among the different treatment groups while on modafinil, indicating moderate-to-severe sleepiness^[3].
Withdrawal of modafinil in the placebo-treated group resulted in a mean decrease in MWT sleep latency of 2.7 minutes, indicating a worsening of EDS^[3].

The sleep latency in the XYREM group was significantly (P<0.001) longer than in the placebo group at the end of the trial^[3].
When XYREM and modafinil were combined, the MWT sleep latency increased by a mean change from baseline value of 2.7 minutes, which was significantly greater compared with placebo (P<0.001)^[3].

Note: The MWT measures the ability of a patient to remain awake during a series of 20-minute periods while reclining in a quiet, dimly lit room. The point at which the patient falls asleep is determined by PSG. The inability to stay awake for more than 12 minutes is suggestive of narcolepsy.

In XYREM clinical trials, ≈80% of patients maintained concomitant stimulant use^[2].

© 2012 Jazz Pharmaceuticals Inc.