A Multicenter Study of the Efficacy and Safety of Xyrem W... | NCT02221869

Status Module

Label	Type	Description	Intervention Names
Xyrem	Experimental	Active Xyrem at a dose ≤9 g/night	Drug: Xyrem
Xyrem Placebo	Placebo Comparator	Xyrem placebo at a volume and regimen equivalent to the stable dose of Xyrem.	Drug: Xyrem

Name	Type	Description	Arm Group Labels	Other Names
Xyrem	Drug		Xyrem Xyrem Placebo

Outcomes Module

Primary Outcomes

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 Outcomes

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)

Eligibility Module

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	Status	City	State	ZIP	Country	Contacts
Miller Children's Hospital - Long Beach		Long Beach	California	90806	United States
SDS Clinical Trials, Inc.

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
37942930	Derived	Dauvilliers Y, Lammers GJ, Lecendreux M, Maski K, Kansagra S, Black J, Parvataneni R, Chen A, Wang YG, Plazzi G. Effect of sodium oxybate on body mass index in pediatric patients with narcolepsy. J Clin Sleep Med. 2024 Mar 1;20(3):445-454. doi: 10.5664/jcsm.10912.
35689598	Derived	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 Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Randomized to Xyrem	Active Xyrem continued as a double-blind treatment at the stable dose taken and regimen taken in the prior 2 weeks.
FG001	Randomized to Xyrem Placebo	Xyrem placebo was initiated as a double-blind treatment at a volume and regimen equivalent to the Xyrem dose taken in the prior 2 weeks.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 23, 2017	Nov 23, 2018

Arm/Group Information

ID	Title	Description
BG000	Enrolled Population	The Enrolled Population consists of all subjects who were dispensed study drug.
BG001	Placebo (Efficacy Population)	Xyrem placebo was initiated as a double-blind treatment at a volume and regimen equivalent to the Xyrem dose taken in the prior 2 weeks in the 2-week double-blind treatment period.
BG002	Xyrem (Efficacy Population)	Active Xyrem continued as a double-blind treatment at the stable dose taken and regimen taken in the prior 2 weeks in the 2-week double-blind treatment period.
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG000106 BG00132 BG00231 BG003169

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Measure Analysis Population Description: Data analyzed separately for Enrolled and Efficacy populations

Count of Participants

Participants

Title	Denominators	Categories
Enrolled Population	ParticipantsBG000106 ParticipantsBG0010 ParticipantsBG0020 ParticipantsBG003

Sex: Female, Male

Measure Analysis Population Description: Data analyzed separately for Enrolled and Efficacy populations

Count of Participants

Participants

Title	Denominators	Categories
Enrolled Population	ParticipantsBG000106 ParticipantsBG0010 ParticipantsBG002

Ethnicity (NIH/OMB)

Measure Analysis Population Description: Data analyzed separately for Enrolled and Efficacy populations

Count of Participants

Participants

Title	Denominators	Categories
Enrolled Population	ParticipantsBG000106 ParticipantsBG0010 ParticipantsBG002

Region of Enrollment

Measure Analysis Population Description: Data reported for the Enrolled Population

Count of Participants

Participants

Title	Denominators	Categories
Netherlands	ParticipantsBG000106 ParticipantsBG0010 ParticipantsBG002

Region of Enrollment

Measure Analysis Population Description: Data reported for Efficacy Population

Number

participants

Title	Denominators	Categories
Netherlands	ParticipantsBG0000 ParticipantsBG00132 ParticipantsBG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Posted

Median

Inter-Quartile Range

number of attacks

From the end of the Stable Dose Period to the end of the Double-blind Treatment Period (2 weeks)

ID	Title	Description
OG000	Xyrem	Active Xyrem continued as a double-blind treatment at the stable dose taken and regimen used in the prior 2 weeks.
OG001	Xyrem Placebo	Xyrem placebo was initiated as a double-blind treatment at a volume and regimen equivalent to the Xyrem dose taken in the prior 2 weeks.

Units	Counts
Participants	OG00031 OG00132

Title

Denominators

Categories

Title	Measurements
	OG0000.27(-1.00 to 2.50) OG00112.71(3.44 to 19.77)

Secondary

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.

Posted

Mean

Standard Deviation

score on a scale

From the end of the Stable Dose Period to the end of the Double-blind Treatment Period (2 weeks)

ID	Title	Description
OG000	Xyrem	Active Xyrem continued as a double-blind treatment at the stable dose taken and regimen used in the prior 2 weeks.
OG001	Xyrem Placebo	Xyrem placebo was initiated as a double-blind treatment at a volume and regimen equivalent to the Xyrem dose taken in the prior 2 weeks.

Units	Counts
Participants	OG000

Secondary

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.

Posted

Median

Inter-Quartile Range

score on a scale

From the end of the Stable Dose Period to the end of the Double-blind Treatment Period (2 weeks)

ID	Title	Description
OG000	Xyrem	Active Xyrem continued as a double-blind treatment at the stable dose taken and regimen used in the prior 2 weeks.
OG001	Xyrem Placebo	Xyrem placebo was initiated as a double-blind treatment at a volume and regimen equivalent to the Xyrem dose taken in the prior 2 weeks.

Units	Counts
Participants

Secondary

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.

Posted

Mean

Standard Deviation

score on a scale

From the end of the Stable Dose Period to the end of the Double-blind Treatment Period (2 weeks)

ID	Title	Description
OG000	Xyrem	Active Xyrem continued as a double-blind treatment at the stable dose taken and regimen used in the prior 2 weeks.
OG001	Xyrem Placebo	Xyrem placebo was initiated as a double-blind treatment at a volume and regimen equivalent to the Xyrem dose taken in the prior 2 weeks.

Units	Counts
Participants	OG000

Secondary

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

Posted

Median

Inter-Quartile Range

score on a scale

From the end of the Stable Dose Period to the end of the Double-blind Treatment Period (2 weeks)

ID	Title	Description
OG000	Xyrem	Active Xyrem continued as a double-blind treatment at the stable dose taken and regimen used in the prior 2 weeks.
OG001	Xyrem Placebo	Xyrem placebo was initiated as a double-blind treatment at a volume and regimen equivalent to the Xyrem dose taken in the prior 2 weeks.

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Enuresis	Renal and urinary disorders	Systematic Assessment	EG00020 affected104 at risk EG0011 affected32 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG00020 affected104 at risk EG0010 affected32 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG00019 affected104 at risk EG0010 affected32 at risk
Headache	Nervous system disorders	Systematic Assessment	EG00018 affected104 at risk EG0010 affected32 at risk
Weight decreased	Investigations	Systematic Assessment	EG00012 affected104 at risk EG0011 affected32 at risk
Decreased appetite	Metabolism and nutrition disorders	Systematic Assessment	EG0009 affected104 at risk EG0010 affected32 at risk
Nasopharyngitis	Infections and infestations	Systematic Assessment	EG0009 affected104 at risk EG0010 affected32 at risk
Upper respiratory tract infection	Infections and infestations	Systematic Assessment	EG0009 affected104 at risk EG0010 affected32 at risk
Dizziness	Nervous system disorders	Systematic Assessment	EG0008 affected104 at risk EG0010 affected32 at risk
Somnolence	Nervous system disorders	Systematic Assessment	EG0002 affected104 at risk EG0017 affected32 at risk
Cataplexy	Nervous system disorders	Systematic Assessment	EG0002 affected104 at risk EG0016 affected32 at risk
Sleep disorder	Psychiatric disorders	Systematic Assessment	EG0001 affected104 at risk EG0012 affected32 at risk

ID	Term
D006970	Disorders of Excessive Somnolence
D020919	Sleep Disorders, Intrinsic
D020920	Dyssomnias
D012893	Sleep Wake Disorders
D009422	Nervous System Diseases
D001523	Mental Disorders

ID	Term
D006885	Hydroxybutyrates
D002087	Butyrates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D006880	Hydroxy Acids

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Safety Population	Safety population who took study drug	0	104	2	104	80	104
EG001	Randomized Placebo	Subjects assigned to the Randomized Placebo group during the Double-blind Treatment Period. Adverse events with onset on or after the first dose in the Double-blind Treatment Period and prior to the date of first dose in the Open-label Safety Period are presented.	0	32	0	32	10	32

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Acute Psychosis	Psychiatric disorders		Systematic Assessment		EG0001 affected104 at risk EG0010 affected32 at risk
Suicidal Ideation	Psychiatric disorders		Systematic Assessment		EG0001 affected104 at risk EG0010 affected32 at risk