child narcolepsy 3

“What clinical effects were seen in pediatric patients with narcolepsy?”

XYREM demonstrated efficacy vs placebo for both cataplexy and excessive daytime sleepiness (EDS) in pediatric patients ages 7 and older with narcolepsy.1,2

The results of the pediatric XYREM Trial N5 showed...

  • Compared with patients randomized to receive placebo and withdrawn from XYREM, patients who continued on XYREM had1:
    • Significantly fewer weekly cataplexy attacks vs placebo
    • Significantly lower percentage of patients with scores of "much worse" or "very much worse" on the Clinical Global Impression of Change (CGI-c) for cataplexy severity and narcolepsy overall
    • Significantly less median change from baseline in EDS as measured by ESS-CHAD scores

Study results

Number of Weekly Cataplexy Attacks and Epworth Sleepiness Scale for Children and Adolescents Score1

Median Number of Cataplexy Attacks (attacks/week)

Treatment Group

Placebo (n=32)

Baseline*†

4.7

Double-Blind Treatment Period‡§

21.3

Median Change From Baseline

12.7

Treatment Group

XYREM (n=31)

Baseline*†

3.5

Double-Blind Treatment Period‡§

3.8

Median Change From Baseline

0.3

Comparison to Placebo (P Value||)

<0.0001

Median Epworth Sleepiness Scale (Child and Adolescent) Score

Treatment Group

Placebo (n=31**)

Baseline*†

11

Double-Blind Treatment Period‡§

12

Median Change From Baseline

3

Treatment Group

XYREM (n=30**)

Baseline*†

8

Double-Blind Treatment Period‡§

9

Median Change From Baseline

0

Comparison to Placebo (P Value||)

0.0004

*For weekly number of cataplexy attacks, baseline value is calculated from the last days of the stable-dose period.

For Epworth Sleepiness Scale score, baseline value is collected at the end of stable-dose period.

Weekly number of cataplexy attacks is calculated from all days within the double-blind treatment period.

§For Epworth Sleepiness Scale, value is collected at the end of the double-blind treatment period.

||P value from rank-based analysis of covariance (ANCOVA) with treatment as a factor and rank baseline value as a covariate.

**One patient in each of the treatment groups did not have baseline ESS-CHAD score available and were not included in this analysis.

Secondary Endpoints: Clinical Global Impression of Change (CGI-c) for Cataplexy Severity and for Narcolepsy Overall Completed at the End of the 2-Week Double-Blind Treatment Period1,2*

pediatric xyrem trial n5 cataplexy cgi-c graph
pediatric xyrem trial n5 narcolepsy graph

*Responses indicate change of severity or symptoms relative to receiving XYREM treatment at baseline.

Percentages based on total number of observed values.

P value from Pearson’s chi-square test.

§Two patients randomized to XYREM did not have the CGI-c assessments completed and were excluded from the analysis.

Trial N5 Study Description

Study Design
  • Double-blind, placebo-controlled, randomized-withdrawal, multicenter study1,2
  • Followed by an open-label safety period, for a total study duration of up to 1 year2
Patients Studied
  • 106 children and adolescents with narcolepsy type 1 aged 7-17 years1,2
  • 2 patients did not receive study drug (safety population, n=104), and 63 patients entered the double-blind treatment period before the protocol amendment (efficacy population)2
Baseline Characteristics
  • Median age: 12 years; range: 7-16 years1,2
  • Cataplexy frequency of ≥14 attacks in a typical 2-week period prior to any treatment for narcolepsy symptoms1,2
  • Either on a stable dose of XYREM or XYREM-naïve1,2
  • ~50% of patients used concomitant stimulants throughout the stable-dose and double-blind periods1,2
  • Concomitant use of medications with anticataplectic effects (eg, serotonin-norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, and tricyclic antidepressants) was not allowed (none of these medications is indicated for cataplexy in narcolepsy)2,3
Objective
  • Evaluate the safety and efficacy of XYREM for the treatment of narcolepsy symptoms in children and adolescents1,2
Primary Efficacy Measure
  • Change in weekly number of cataplexy attacks from the last 2 weeks of the stable dose period to the 2 weeks of the double-blind treatment period1,2

Study Design Flowchart

pediatric Xyrem trial n5 study design flowchart
THE NARCOLEPSY SCREENER APP
The recommended initial total nightly pediatric dose and recommended total nightly dose are based on patient weight.1
Cataplexy
The pediatric dosage may be gradually titrated based on efficacy and tolerability.1