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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02221869

Enrollment

106

Registered

2014-08-21

Start date

2014-10-01

Completion date

2019-01-25

Last updated

2019-04-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Narcolepsy With Cataplexy

Brief summary

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

Interventions

DRUGXyrem

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

7 Years to 17 Years

Healthy volunteers

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

Design outcomes

Primary

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

Measure	Time frame	Description
Clinical Global Impression of Change (CGIc) for Cataplexy Severity	From the end of the Stable Dose Period to the end of the Double-blind Treatment Period (2 weeks)	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	From the end of the Stable Dose Period to the end of the Double-blind Treatment Period (2 weeks)	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	From the end of the Stable Dose Period to the end of the Double-blind Treatment Period (2 weeks)	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	From the end of the Stable Dose Period to the end of the Double-blind Treatment Period (2 weeks)	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

Countries

France, Italy, Netherlands, United States

Participant flow

Recruitment details

106 subjects were enrolled. Xyrem-naïve subjects (n=74) entered the Dose Titration Period (3 to 10 weeks). Xyrem-naïve and on Xyrem subjects (n= 99) entered the Stable Dose Period (2 to 3 weeks). 96 subjects then entered the Double-Blind Randomized Withdrawal Period (2 weeks). 95 subjects then entered the Open-label Safety Period (38 to 47 weeks).

Pre-assignment details

Subjects aged 7-17 who were being treated with Xyrem or Xyrem naïve were eligible for the study. 63 subjects were randomized and 33 received open-label Xyrem during the Double-blind Treatment Period. 106 and 63 subjects comprised the Enrolled population and the Efficacy population respectively.

Participants by arm

Arm	Count
Enrolled Population The Enrolled Population consists of all subjects who were dispensed study drug.	106
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.	32
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.	31
Total	169

Baseline characteristics

Characteristic	Placebo (Efficacy Population)	Total	Xyrem (Efficacy Population)	Enrolled Population
Age, Categorical Efficacy Population <=18 years	32 Participants	63 Participants	31 Participants	—
Age, Categorical Efficacy Population >=65 years	0 Participants	0 Participants	0 Participants	—
Age, Categorical Efficacy Population Between 18 and 65 years	0 Participants	0 Participants	0 Participants	—
Age, Categorical Enrolled Population <=18 years	—	106 Participants	—	106 Participants
Age, Categorical Enrolled Population >=65 years	—	0 Participants	—	0 Participants
Age, Categorical Enrolled Population Between 18 and 65 years	—	0 Participants	—	0 Participants
Ethnicity (NIH/OMB) Efficacy Population Hispanic or Latino	2 Participants	2 Participants	0 Participants	—
Ethnicity (NIH/OMB) Efficacy Population Not Hispanic or Latino	30 Participants	61 Participants	31 Participants	—
Ethnicity (NIH/OMB) Efficacy Population Unknown or Not Reported	0 Participants	0 Participants	0 Participants	—
Ethnicity (NIH/OMB) Enrolled Population Hispanic or Latino	—	6 Participants	—	6 Participants
Ethnicity (NIH/OMB) Enrolled Population Not Hispanic or Latino	—	100 Participants	—	100 Participants
Ethnicity (NIH/OMB) Enrolled Population Unknown or Not Reported	—	0 Participants	—	0 Participants
Region of Enrollment Finland	—	1 Participants	—	1 Participants
Region of Enrollment France	3 participants	10 Participants	4 participants	10 Participants
Region of Enrollment Italy	9 participants	18 participants	9 participants	25 Participants
Region of Enrollment Netherlands	3 participants	5 participants	0 Participants	8 Participants
Region of Enrollment United States	17 participants	62 Participants	16 participants	62 Participants
Sex: Female, Male Efficacy Population Female	15 Participants	28 Participants	13 Participants	—
Sex: Female, Male Efficacy Population Male	17 Participants	35 Participants	18 Participants	—
Sex: Female, Male Enrolled Population Female	0 Participants	43 Participants	—	43 Participants
Sex: Female, Male Enrolled Population Male	0 Participants	63 Participants	—	63 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 104	0 / 32
other Total, other adverse events	80 / 104	10 / 32
serious Total, serious adverse events	2 / 104	0 / 32

Outcome results

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.