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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 safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02221869
Recruitment Status : Completed
First Posted : August 21, 2014
Results First Posted : April 30, 2019
Last Update Posted : April 30, 2019
Sponsor:
Information provided by (Responsible Party):
Jazz Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Narcolepsy With Cataplexy
Intervention Drug: Xyrem
Enrollment 106
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.
Arm/Group Title Randomized to Xyrem Randomized to Xyrem Placebo Open-label Xyrem
Hide Arm/Group Description Active Xyrem continued as a double-blind treatment at the stable dose taken and regimen taken in the prior 2 weeks. 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. Subjects who were not randomized or continued to receive open-label Xyrem during the Double-blind Treatment Period.
Period Title: Overall Study
Started 31 32 43
Completed [1] 30 32 33
Not Completed 1 0 10
[1]
Double-blind Period
Arm/Group Title Enrolled Population Placebo (Efficacy Population) Xyrem (Efficacy Population) Total
Hide Arm/Group Description The Enrolled Population consists of all subjects who were dispensed study drug. 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 106 32 31 169
Hide Baseline Analysis Population Description
106 subjects were enrolled. 63 subjects were randomized during the Double-blind Treatment Period. 106 subjects comprised the Enrolled population, and 63 subjects comprised the Efficacy population.
Age, Categorical   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Enrolled Population Number Analyzed 106 participants 0 participants 0 participants 106 participants
<=18 years
106
 100.0%
106
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
Efficacy Population Number Analyzed 0 participants 32 participants 31 participants 63 participants
<=18 years
32
 100.0%
31
 100.0%
63
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Analysis Population Description: Measure Analysis Population Description: Data analyzed separately for Enrolled and Efficacy populations
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Enrolled Population Number Analyzed 106 participants 0 participants 0 participants 106 participants
Female
43
  40.6%
0
43
  40.6%
Male
63
  59.4%
0
63
  59.4%
Efficacy Population Number Analyzed 0 participants 32 participants 31 participants 63 participants
Female
15
  46.9%
13
  41.9%
28
  44.4%
Male
17
  53.1%
18
  58.1%
35
  55.6%
[1]
Measure Analysis Population Description: Measure Analysis Population Description: Data analyzed separately for Enrolled and Efficacy populations
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Enrolled Population Number Analyzed 106 participants 0 participants 0 participants 106 participants
Hispanic or Latino
6
   5.7%
6
   5.7%
Not Hispanic or Latino
100
  94.3%
100
  94.3%
Unknown or Not Reported
0
   0.0%
0
   0.0%
Efficacy Population Number Analyzed 0 participants 32 participants 31 participants 63 participants
Hispanic or Latino
2
   6.3%
0
   0.0%
2
   3.2%
Not Hispanic or Latino
30
  93.8%
31
 100.0%
61
  96.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Analysis Population Description: Measure Analysis Population Description: Data analyzed separately for Enrolled and Efficacy populations
Region of Enrollment   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Netherlands Number Analyzed 106 participants 0 participants 0 participants 106 participants
8
   7.5%
0 0
8
   7.5%
United States Number Analyzed 106 participants 0 participants 0 participants 106 participants
62
  58.5%
62
  58.5%
Italy Number Analyzed 106 participants 0 participants 0 participants 106 participants
25
  23.6%
25
  23.6%
France Number Analyzed 106 participants 0 participants 0 participants 106 participants
10
   9.4%
10
   9.4%
Finland Number Analyzed 106 participants 0 participants 0 participants 106 participants
1
   0.9%
1
   0.9%
[1]
Measure Analysis Population Description: Measure Analysis Population Description: Data reported for the Enrolled Population
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
Netherlands Number Analyzed 0 participants 32 participants 31 participants 63 participants
3 2 5
United States Number Analyzed 0 participants 32 participants 31 participants 63 participants
17 16 33
Italy Number Analyzed 0 participants 32 participants 31 participants 63 participants
9 9 18
France Number Analyzed 0 participants 32 participants 31 participants 63 participants
3 4 7
[1]
Measure Analysis Population Description: Measure Analysis Population Description: Data reported for Efficacy Population
1.Primary Outcome
Title Change in Weekly Number of Cataplexy Attacks
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Xyrem Xyrem Placebo
Hide Arm/Group Description:
Active Xyrem continued as a double-blind treatment at the stable dose taken and regimen used in the prior 2 weeks.
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.
Overall Number of Participants Analyzed 31 32
Median (Inter-Quartile Range)
Unit of Measure: number of attacks
0.27
(-1.00 to 2.50)
12.71
(3.44 to 19.77)
2.Secondary Outcome
Title Clinical Global Impression of Change (CGIc) for Cataplexy Severity
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Xyrem Xyrem Placebo
Hide Arm/Group Description:
Active Xyrem continued as a double-blind treatment at the stable dose taken and regimen used in the prior 2 weeks.
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.
Overall Number of Participants Analyzed 29 32
Mean (Standard Deviation)
Unit of Measure: score on a scale
-0.4  (1.12) -1.5  (1.19)
3.Secondary Outcome
Title Change in the Epworth Sleepiness Scale (ESS) (CHAD) Score
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Xyrem Xyrem Placebo
Hide Arm/Group Description:
Active Xyrem continued as a double-blind treatment at the stable dose taken and regimen used in the prior 2 weeks.
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.
Overall Number of Participants Analyzed 30 31
Median (Inter-Quartile Range)
Unit of Measure: score on a scale
0.0
(-1.0 to 2.0)
3.0
(1.0 to 5.0)
4.Secondary Outcome
Title CGIc for Narcolepsy Overall
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Xyrem Xyrem Placebo
Hide Arm/Group Description:
Active Xyrem continued as a double-blind treatment at the stable dose taken and regimen used in the prior 2 weeks.
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.
Overall Number of Participants Analyzed 29 32
Mean (Standard Deviation)
Unit of Measure: score on a scale
-0.4  (0.95) -1.4  (1.13)
5.Secondary Outcome
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
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Xyrem Xyrem Placebo
Hide Arm/Group Description:
Active Xyrem continued as a double-blind treatment at the stable dose taken and regimen used in the prior 2 weeks.
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.
Overall Number of Participants Analyzed 30 30
Median (Inter-Quartile Range)
Unit of Measure: score on a scale
SF-10 Physical Summary Score
0
(-2.730 to 2.500)
0
(-8.420 to 2.730)
SF-10 Psychosocial Summary Score
0
(-6.240 to 2.680)
-2.670
(-8.020 to 2.670)
Time Frame Safety data are provided through the 120 day update.
Adverse Event Reporting Description The Safety Population included all subjects who took study drug, and consisted of 104 subjects. There are 2 subjects included in the Enrolled Population who were dispensed study drug, but did not take the medication and were subsequently discontinued. As a result, safety analyses focused on the 104 subjects in the Safety Population. Adverse events are reported by the Safety Population in order to capture adverse events occurring across all treatment periods.
 
Arm/Group Title Safety Population Randomized Placebo
Hide Arm/Group Description Safety population who took study drug 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.
All-Cause Mortality
Safety Population Randomized Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/104 (0.00%)   0/32 (0.00%) 
Hide Serious Adverse Events
Safety Population Randomized Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   2/104 (1.92%)   0/32 (0.00%) 
Psychiatric disorders     
Acute Psychosis   1/104 (0.96%)  0/32 (0.00%) 
Suicidal Ideation   1/104 (0.96%)  0/32 (0.00%) 
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Safety Population Randomized Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   80/104 (76.92%)   10/32 (31.25%) 
Gastrointestinal disorders     
Nausea   20/104 (19.23%)  0/32 (0.00%) 
Vomiting   19/104 (18.27%)  0/32 (0.00%) 
Infections and infestations     
Nasopharyngitis   9/104 (8.65%)  0/32 (0.00%) 
Upper respiratory tract infection   9/104 (8.65%)  0/32 (0.00%) 
Investigations     
Weight decreased   12/104 (11.54%)  1/32 (3.13%) 
Metabolism and nutrition disorders     
Decreased appetite   9/104 (8.65%)  0/32 (0.00%) 
Nervous system disorders     
Headache   18/104 (17.31%)  0/32 (0.00%) 
Dizziness   8/104 (7.69%)  0/32 (0.00%) 
Somnolence   2/104 (1.92%)  7/32 (21.88%) 
Cataplexy   2/104 (1.92%)  6/32 (18.75%) 
Psychiatric disorders     
Sleep disorder   1/104 (0.96%)  2/32 (6.25%) 
Renal and urinary disorders     
Enuresis   20/104 (19.23%)  1/32 (3.13%) 
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The sponsor can review trial results communications prior to public release and can embargo such communications for a period of at least 60 days from the time submitted to sponsor for review. If requested by sponsor, the PI will withhold publication for up to an additional 30 days. Furthermore, the first publication of study results must be a joint publication of all study sites unless a joint manuscript has not been submitted for publication within 12 months of completion of the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Director, Disclosure & Transparency
Organization: Jazz Pharmaceuticals
Phone: 215-970-7145
EMail: ClinicalTrialDisclosure@JazzPharma.com
Layout table for additonal information
Responsible Party: Jazz Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02221869    
Other Study ID Numbers: 13-005
First Submitted: July 28, 2014
First Posted: August 21, 2014
Results First Submitted: November 23, 2018
Results First Posted: April 30, 2019
Last Update Posted: April 30, 2019