Back to resultsA 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
Primary Purpose
Narcolepsy With Cataplexy
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Xyrem
Sponsored by
About this trial
This is an interventional treatment trial for Narcolepsy With Cataplexy
Eligibility Criteria
Inclusion Criteria:
- 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)
- 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)
- 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
- Have parent(s)/guardian(s) who have given informed consent for his/her/their child's participation in the study
- Be willing to spend the required number of nights (2 to 3) in a sleep laboratory for PSG evaluations
- 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:
- Inability to understand assent or follow study instructions for any reason, in the opinion of the Investigator
- Parent(s) or guardian(s) unable to comply with the requirements of the study for any reason, in the opinion of the Investigator
- 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
- 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)
- 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
- 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:
-
Sites / Locations
- Miller Children's Hospital - Long Beach
- SDS Clinical Trials, Inc.
- Stanford Sleep Medicine Center
- Ann & Robert H. Lurie Children's Hospital of Chicago
- The U-M Sleep Disorders Center
- Montefiore Medical Center
- Duke Children's Hospital
- ARSM Research, LLC
- Cincinnati Children's Hospital Medical Center
- University Hospitals Cleveland Medical Center
- Nationwide Children's Hospital
- SleepMed of SC
- Greenville Health System
- UT/LeBonheur Neuroscience Institute
- Todd Swick, MD, PA
- Children's Hospital of The King's Daughters
- Seattle Children's Hospital
- Hospital Robert Debre
- Dipartimento di Scienze Biomediche e Biomotorie
- Sleep Wake Center SEIN Heemstede
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Xyrem
Xyrem Placebo
Arm Description
Active Xyrem at a dose ≤9 g/night
Xyrem placebo at a volume and regimen equivalent to the stable dose of Xyrem.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02221869
Brief Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
October 1, 2014 (Actual)
Primary Completion Date
February 2017 (Actual)
Study Completion Date
January 25, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jazz Pharmaceuticals
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this trial is to assess the efficacy and safety of Xyrem in pediatrics subjects with narcolepsy that includes cataplexy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Narcolepsy With Cataplexy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
106 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Xyrem
Arm Type
Experimental
Arm Description
Active Xyrem at a dose ≤9 g/night
Arm Title
Xyrem Placebo
Arm Type
Placebo Comparator
Arm Description
Xyrem placebo at a volume and regimen equivalent to the stable dose of Xyrem.
Intervention Type
Drug
Intervention Name(s)
Xyrem
Primary Outcome Measure Information:
Title
Change in Weekly Number of Cataplexy Attacks
Description
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.
Time Frame
From the end of the Stable Dose Period to the end of the Double-blind Treatment Period (2 weeks)
Secondary Outcome Measure Information:
Title
Clinical Global Impression of Change (CGIc) for Cataplexy Severity
Description
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.
Time Frame
From the end of the Stable Dose Period to the end of the Double-blind Treatment Period (2 weeks)
Title
Change in the Epworth Sleepiness Scale (ESS) (CHAD) Score
Description
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.
Time Frame
From the end of the Stable Dose Period to the end of the Double-blind Treatment Period (2 weeks)
Title
CGIc for Narcolepsy Overall
Description
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.
Time Frame
From the end of the Stable Dose Period to the end of the Double-blind Treatment Period (2 weeks)
Title
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
Description
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
Time Frame
From the end of the Stable Dose Period to the end of the Double-blind Treatment Period (2 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
7 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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)
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)
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
Have parent(s)/guardian(s) who have given informed consent for his/her/their child's participation in the study
Be willing to spend the required number of nights (2 to 3) in a sleep laboratory for PSG evaluations
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:
Inability to understand assent or follow study instructions for any reason, in the opinion of the Investigator
Parent(s) or guardian(s) unable to comply with the requirements of the study for any reason, in the opinion of the Investigator
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
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)
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
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:
-
Facility Information:
Facility Name
Miller Children's Hospital - Long Beach
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
Facility Name
SDS Clinical Trials, Inc.
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Stanford Sleep Medicine Center
City
Redwood City
State/Province
California
ZIP/Postal Code
94063
Country
United States
Facility Name
Ann & Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
The U-M Sleep Disorders Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Duke Children's Hospital
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
ARSM Research, LLC
City
Huntersville
State/Province
North Carolina
ZIP/Postal Code
28078
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
University Hospitals Cleveland Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
SleepMed of SC
City
Columbia
State/Province
South Carolina
ZIP/Postal Code
29201
Country
United States
Facility Name
Greenville Health System
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29615
Country
United States
Facility Name
UT/LeBonheur Neuroscience Institute
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Facility Name
Todd Swick, MD, PA
City
Houston
State/Province
Texas
ZIP/Postal Code
77063
Country
United States
Facility Name
Children's Hospital of The King's Daughters
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Hospital Robert Debre
City
Paris
ZIP/Postal Code
75019
Country
France
Facility Name
Dipartimento di Scienze Biomediche e Biomotorie
City
Bologna
ZIP/Postal Code
40139
Country
Italy
Facility Name
Sleep Wake Center SEIN Heemstede
City
Heemstede
State/Province
Noord Holland
ZIP/Postal Code
2103 SW
Country
Netherlands
12. IPD Sharing Statement
Citations:
PubMed Identifier
35689598
Citation
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.
Results Reference
derived
PubMed Identifier
34920345
Citation
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.
Results Reference
derived
PubMed Identifier
30169321
Citation
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.
Results Reference
derived
Learn more about this trial
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
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