wHAT CLINICAL EFFECTS wERE SEEN FOR EXCESSIVE DAYTIME SLEEPINESS (EDS) IN NARCOLEPSY?

wHAT CLINICAL EFFECTS wERE SEEN FOR EXCESSIVE DAYTIME SLEEPINESS (EDS) IN NARCOLEPSY?

XYREM, at the 6 g and 9 g per night dosages, significantly reduced EDS.1,2

The results of the XYREM Trial N3 showed...

  • Both the 6 g and 9 g per night dosages significantly reduced EDS as measured by ESS scores at week 8.1,2
  • The 4.5 g per night dosage did not produce a significant reduction in EDS as measured by ESS scores at week 8 compared with placebo.2
  • In addition, both the 6 g and 9 g per night dosages significantly improved CGI-c scores at week 8 compared with placebo.1,2

Study results

Change From Baseline in Median ESS Scores at Week 81,2

Change From Baseline in Median ESS Scores at Week 8
BL = Baseline
EP = End Point

Median change from
baseline at week 8:
Placebo = -0.5
XYREM 6 g per night = -2.0
XYREM 9 g per night = -5.0

*P<0.001 vs placebo.

Interpreting Epworth Sleepiness Scores3,4

Interpreting Epworth Sleepiness Scores

“Much Improved” or “Very Much Improved” on the CGI-c at Week 81,2

“Much Improved” or “Very Much Improved” on the CGI-c at Week 8

Trial N3 Study Description

Study Design1,2
  • Randomized, double-blind, placebo-controlled, parallel-group, multicenter trial
  • Compared effects of orally administered XYREM (4.5 g, 6 g, or 9 g per night) with placebo for the treatment of EDS in narcolepsy
Patients Studied1,2
  • 228 adult patients with narcolepsy with cataplexy and with exclusion criteria featuring:
    • No use of XYREM or any investigational therapy within 30 days prior to trial entry
Baseline Characteristics1,2
  • Mean age: 40.5 years
  • Moderate to severe symptoms at study entry:
    • Median Epworth Sleepiness Scale (ESS) score of 18
  • 78% were taking concomitant stimulant medications
Objective1,2
  • Evaluate the efficacy and safety of XYREM compared with placebo in the treatment of EDS in narcolepsy
Primary Efficacy Measures1,2
  • The ESS, as a measure of EDS, and the Clinical Global Impression of Change (CGI-c)

Trial N3 Study Design Flowchart1,2,6

Trial N3 Study Design

*Titrated up (1.5 g per week) from 4.5 g after 1 week.

  • Patients were gradually tapered from antidepressant medications or any other medication used for the treatment of cataplexy during a withdrawal period of up to 21 days, followed by a washout period that:
    • Lasted either 5 days or 5 times the half-life of the discontinued drug (whichever was longer, but never lasting longer than 18 days).
    • Withdrawal was initiated earlier in the study if patients were using fluoxetine due to the very long elimination half-life of the drug and its active metabolite.
  • Patients were allowed to continue the use of concomitant stimulant medications.
  • The 8-week, double-blind treatment phase consisted of 4 weeks of dose titration and 4 weeks of stable dosing.

The American Academy of Sleep Medicine (AASM) recommends sodium oxybate as a standard of care for the treatment of EDS in narcolepsy.5