Clinical trials

Trial N1: Efficacy for Cataplexy in Narcolepsy

XYREM significantly decreased the frequency of cataplexy attacks at week 41,2

Study results

  • The 3 g per night dose had little effect1

Dosing and administration

  • Recommended starting dosage1:
    4.5 g per night administered orally in 2 equal, divided doses
    • 2.25 g at bedtime and 2.25 g taken 2.5 to 4 hours later
  • Increase the dose by 1.5 g per night at weekly intervals (additional 0.75 g at bedtime and 0.75 g taken 2.5 to 4 hours later) to the effective dose range of 6 g to 9 g per night1
  • Dosage higher than 9 g per night has not been studied and should not ordinarily be administered1

Study description

Trial N1 was a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial comparing the effects of orally administered XYREM with placebo for the treatment of narcolepsy symptoms. The study enrolled 136 patients with narcolepsy with moderate to severe cataplexy who had 3 to 249 (median, 21) cataplexy attacks weekly at baseline. Prior to randomization, anticataplectic agents (eg, SSRIs and tricyclic antidepressants) were gradually withdrawn over a period of 4 weeks followed by a washout period of 5 days or 5 times the half-life of the discontinued anticataplectic medication, up to 28 days (whichever option was longer). Each patient was randomized to receive 3 g, 6 g, or 9 g of sodium oxybate or placebo per night without titration. Stable doses of stimulants were permitted. 85% of patients were also being treated with CNS stimulants. The treatment period was 4 weeks. The primary efficacy measure was the frequency of cataplexy attacks.1-3

Trial N2: Continued Efficacy for Cataplexy in Narcolepsy After Long-term Use

XYREM demonstrated continued efficacy in treating cataplexy after long-term use1,4

Study results

  • After a mean of 21 months of use, patients maintained on XYREM during the 2-week double-blind treatment phase experienced no median change in number of cataplexy attacks from the 2-week single-blind baseline phase1,4
  • Patients who switched to placebo experienced a median increase of 21 cataplexy attacks during the same 2-week double-blind period1,4

Study description

Trial N2 was a randomized, double-blind, placebo-controlled, multicenter trial to assess the continued efficacy of orally administered XYREM after long-term use when compared to placebo in 55 patients with narcolepsy. To be included, patients had to have had a history of 5 or more cataplexy attacks per week prior to receiving any treatment for cataplexy, and had to have undergone continuous treatment with sodium oxybate for at least 6 months prior to study entry. Patients had been on an established dose of open-label sodium oxybate, ranging from 3 g to 9 g per night, for 7 to 44 months (mean, 21 months) at study entry. Patients using anticataplectic medications other than sodium oxybate during the 30-day period prior to trial entry were excluded. Patients were allowed to continue stable dosages of stimulants for the treatment of daytime sleepiness associated with narcolepsy. The primary efficacy measure was the change in the number of cataplexy attacks from baseline (2-week, single-blind, lead-in phase) to the end point (2-week, double-blind treatment phase).1,3,4

Trial N3: Efficacy for Excessive Daytime Sleepiness (EDS) in Narcolepsy

XYREM significantly improved EDS at week 81,5

Study results

  • XYREM at the 6 g and 9 g per night dosages significantly reduced ESS scores at week 81,5
  • XYREM at the 6 g and 9 g per night dosages significantly improved CGI-c scores at week 81,5

Study description

Trial N3 was a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial that compared the effects of orally administered XYREM with placebo for the treatment of narcolepsy in 228 patients with moderate to severe symptoms at study entry. Patients were randomized to 1 of 4 treatment groups: placebo, XYREM 4.5 g/night, XYREM 6 g/night, or XYREM 9 g/night. The 8-week double-blind treatment phase consisted of 4 weeks of dose titration and 4 weeks of stable dosing. Patients were either maintained at 4.5 g/night or titrated up (1.5 g per week) after 1 week to either 6 g/night or 9 g/night. Antidepressants were withdrawn prior to randomization; stimulants were continued at stable doses. 78% of patients were also being treated with central nervous system stimulants. The Epworth Sleepiness Scale (ESS), as a measure of EDS, and the Clinical Global Impression of Change (CGI-c) were the primary efficacy measures in this trial.1,3,5

Trial N4: Efficacy for Excessive Daytime Sleepiness (EDS) in Narcolepsy

XYREM significantly reduced daytime sleepiness in narcolepsy1,8

Study results

  • XYREM, with or without modafinil, significantly reduced daytime sleepiness as measured by MWT at week 81,8

Study description

Trial N4 was a randomized, double-blind, double-dummy, placebo-controlled, parallel-group, multicenter trial comparing the effects of orally administered XYREM and modafinil with placebo in the treatment of daytime sleepiness in narcolepsy. 222 adult patients with narcolepsy were evaluated. To be included, patients had to have been taking a stimulant medication for the treatment of EDS for at least 3 months and were taking stable doses of modafinil (200 to 600 mg/day) for at least 1 month immediately prior to the trial or were taking stable doses of modafinil for at least 6 weeks prior to trial entry. Patients were permitted to remain on antidepressant medications at unchanged doses throughout the trial. Patients were not allowed to have used sodium oxybate or any investigational therapy within the 30-day period prior to enrollment. This trial was designed to assess the efficacy of sodium oxybate as a monotherapy and as a combination therapy when used with modafinil as compared with placebo in the treatment of EDS in narcolepsy. This trial was not designed to compare the effects of XYREM to modafinil because patients receiving modafinil were not titrated to a maximally effective dose. Daytime sleepiness as measured by the mean average daytime sleep latency on the 20-minute Maintenance of Wakefulness Test (MWT) was the primary efficacy measure.1,3,8


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