A Multicenter Study of the Efficacy and Safety of Xyrem With an Open- Label Pharmacokinetic Evaluation and Safety Extension in Pediatric Subjects With Narcolepsy With Cataplexy

The purpose of this trial is to assess the efficacy and safety of Xyrem in pediatrics subjects with narcolepsy that includes cataplexy.

Study Overview

• Status: Completed
• Conditions: Narcolepsy With Cataplexy
• Intervention / Treatment: Drug: Xyrem

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75019
    • Hospital Robert Debre
• Italy
  • Bologna, Italy, 40139
    • Dipartimento di Scienze Biomediche e Biomotorie
• Netherlands
  • Noord Holland
    • Heemstede, Noord Holland, Netherlands, 2103 SW
      • Sleep Wake Center SEIN Heemstede
• United States
  • California
    • Long Beach, California, United States, 90806
      • Miller Children's Hospital - Long Beach
    • Orange, California, United States, 92868
      • SDS Clinical Trials, Inc.
    • Redwood City, California, United States, 94063
      • Stanford Sleep Medicine Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • The U-M Sleep Disorders Center
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Children's Hospital
    • Huntersville, North Carolina, United States, 28078
      • ARSM Research, LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • South Carolina
    • Columbia, South Carolina, United States, 29201
      • SleepMed of SC
    • Greenville, South Carolina, United States, 29615
      • Greenville Health System
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • UT/LeBonheur Neuroscience Institute
  • Texas
    • Houston, Texas, United States, 77063
      • Todd Swick, MD, PA
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Children's Hospital of The King's Daughters
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female subjects aged 7-16 years at Visit 2 for subjects on Xyrem at study entry and at Visit 1.1 for Xyrem-naïve subjects (to ensure subjects are <18 years of age at the end of the study)
2. Have a primary diagnosis of narcolepsy with cataplexy that meets International Classification of Sleep Disorders (ICSD)-2 or ICSD-3 criteria, whichever was in effect at the time of the diagnosis or, with the permission of the Medical Monitor, completes a Multiple Sleep Latency Test (MSLT) during Screening to confirm the diagnosis of Type 1 narcolepsy by ICSD-3 criteria (i.e., the subject meets all other ICSD-3 criteria for Type 1 narcolepsy)
3. Have given documented assent indicating that he/she was aware of the investigational nature of the study and the required procedures and restrictions before participation in any protocol-related activities
4. Have parent(s)/guardian(s) who have given informed consent for his/her/their child's participation in the study
5. Be willing to spend the required number of nights (2 to 3) in a sleep laboratory for PSG evaluations
6. If currently treated with Xyrem, must have been taking unchanged doses (twice nightly dosing no higher than 9 g/night) of Xyrem, and stimulants, if applicable, for the treatment of narcolepsy symptoms for at least 2 months prior to screening

In addition to the above inclusion criteria, subjects participating in the PK evaluation must meet the following inclusion criteria:

7. Be willing to spend 2 additional nights in the clinic for PK evaluation

-

Exclusion Criteria:

1. Inability to understand assent or follow study instructions for any reason, in the opinion of the Investigator
2. Parent(s) or guardian(s) unable to comply with the requirements of the study for any reason, in the opinion of the Investigator
3. Other documented clinically significant condition (including an unstable medical condition, chronic disease other than narcolepsy with cataplexy, or history or presence of another neurological disorder) that might affect the subject's safety and/or interfere with the conduct of the study in the opinion of the Investigator
4. Treatment with benzodiazepines, non-benzodiazepine anxiolytics/ hypnotics/sedatives, neuroleptics, opioids, barbiturates, diclofenac, valproate, phenytoin, ethosuximide within 2 weeks prior to enrollment (discontinuation for the purpose of study enrollment is permitted only if considered safe by the Investigator and approved by the Medical Monitor)
5. Treatment with any other medications that have anticataplectic effect (e.g., serotonin-norepinephrine reuptake inhibitors [SNRIs], selective serotonin reuptake inhibitors [SSRIs], or tricyclic antidepressants [TCAs]) within 1 month before Screening
6. Unsafe for the subject to receive placebo treatment for 2 weeks, in the opinion of the Investigator

In addition to the above exclusion criteria, subjects participating in the PK evaluation must not demonstrate the following:

-

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Xyrem; Active Xyrem at a dose ≤9 g/night	Drug: Xyrem
Placebo Comparator: Xyrem Placebo; Xyrem placebo at a volume and regimen equivalent to the stable dose of Xyrem.	Drug: Xyrem

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Weekly Number of Cataplexy Attacks	Double-blind comparison of the 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 Period.	From the end of the Stable Dose Period to the end of the Double-blind Treatment Period (2 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impression of Change (CGIc) for Cataplexy Severity	CGIc for cataplexy severity from the end of the Stable Dose Period to the end of the Double-blind Treatment Period. The CGIc is a 7-point scale ranging from "very much improved" to "very much worse." A score of 0 = no change, a score of 3 = very much improved, and a score of -3 = very much worse.	From the end of the Stable Dose Period to the end of the Double-blind Treatment Period (2 weeks)
Change in the Epworth Sleepiness Scale (ESS) (CHAD) Score	Change in the ESS (CHAD) score from the end of the Stable Dose Period to the end of the Double-blind Treatment Period. The ESS is a self-administered questionnaire with 8 questions. It provides a measure of a person's general level of daytime sleepiness, or their average sleep propensity in daily life. In the ESS for children and adolescents (CHAD), certain activities were modified. Each activity is scored on a scale ranging from 0-3, with 0 = would never fall asleep, and 3 = high chance of falling asleep. The total score ranges from 0-24, with a higher number representing an increased propensity for sleepiness.	From the end of the Stable Dose Period to the end of the Double-blind Treatment Period (2 weeks)
CGIc for Narcolepsy Overall	CGIc for narcolepsy overall from the end of the Stable Dose Period to the end of the Double-blind Treatment Period. The CGIc is a 7-point scale ranging from "very much improved" to "very much worse." A score of 0 = no change, a score of 3 = very much improved, and a score of -3 = very much worse.	From the end of the Stable Dose Period to the end of the Double-blind Treatment Period (2 weeks)
Change in Quality of Life (QoL; SF-10 Physical and Psychosocial Summary Score) From the End of the Stable Dose Period to the End of the Double-blind Treatment Period	The SF-10 Health Survey for Children is a parent-completed survey that contains 10 questions adapted from the Child Health Questionnaire. The SF-10 is intended to produce physical and psychosocial health summary measures. Each of the 10 questions responses is scored with a point value from 1 to 6 (1 is the worst possible condition and 6 is the best possible condition). The SF-10 physical and psychosocial measures are scored such that higher scores indicate more favorable functioning. The questions and associated point values are separated into the Physical Health (PHS-10 domain) and Psychosocial Health (PSS-10 domain). The sums of the scores in each domain are standardized using the mean and standard deviation from a normal population (2006 sample). The standardized scores are transformed to norm based scoring (NBS) metric. Through NBS, scale scores are standardized to a mean of 50 and SD of 10 in the combined U.S. general population and clinical samples. NBS scores are reported	From the end of the Stable Dose Period to the end of the Double-blind Treatment Period (2 weeks)

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals

Publications and helpful links

General Publications

• Lecendreux M, Plazzi G, Dauvilliers Y, Rosen CL, Ruoff C, Black J, Parvataneni R, Guinta D, Wang YG, Mignot E. Long-term safety and maintenance of efficacy of sodium oxybate in the treatment of narcolepsy with cataplexy in pediatric patients. J Clin Sleep Med. 2022 Sep 1;18(9):2217-2227. doi: 10.5664/jcsm.10090.
• Wang YG, Menno D, Chen A, Steininger TL, Morris S, Black J, Profant J, Johns MW. Validation of the Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) questionnaire in pediatric patients with narcolepsy with cataplexy aged 7-16 years. Sleep Med. 2022 Jan;89:78-84. doi: 10.1016/j.sleep.2021.11.003. Epub 2021 Nov 11.
• Plazzi G, Ruoff C, Lecendreux M, Dauvilliers Y, Rosen CL, Black J, Parvataneni R, Guinta D, Wang YG, Mignot E. Treatment of paediatric narcolepsy with sodium oxybate: a double-blind, placebo-controlled, randomised-withdrawal multicentre study and open-label investigation. Lancet Child Adolesc Health. 2018 Jul;2(7):483-494. doi: 10.1016/S2352-4642(18)30133-0. Epub 2018 May 21.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2014
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): January 25, 2019

Study Registration Dates

• First Submitted: July 28, 2014
• First Submitted That Met QC Criteria: August 19, 2014
• First Posted (Estimate): August 21, 2014

Study Record Updates

• Last Update Posted (Actual): April 30, 2019
• Last Update Submitted That Met QC Criteria: April 26, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Disorders of Excessive Somnolence; Narcolepsy; Cataplexy
• Other Study ID Numbers: 13-005