Study of the Efficacy and Safety of Xyrem in Pediatric Subjects with Narcolepsy with Cataplexy

• Register: EUCTR
• Last refreshed on: 16 December 2019
• Main ID: EUCTR2014-001389-93-NL
• Date of registration: 18/12/2014
• Prospective Registration: Yes
• Primary sponsor: Jazz Pharmaceuticals
• Public title: Study of the Efficacy and Safety of Xyrem in Pediatric Subjects with Narcolepsy with Cataplexy
• Scientific title: A Double-Blind, Placebo-Controlled, Randomized-Withdrawal, 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
• Date of first enrolment: 12/03/2015
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001389-93
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Finland, France, Italy, Netherlands, United States

Contacts

• Name: Mario D'Achille, Sr. CT Manager
• Affiliation: Jazz Pharmaceuticals

• Name: Mario D'Achille, Sr. CT Manager
• Affiliation: Jazz Pharmaceuticals

Key inclusion & exclusion criteria

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 Part 1)
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. Be positive for the Human Leukocyte Antigen (HLA) DQB1:0602 haplotype, determined prior to the study or as part of the study screening procedures, or have cerebrospinal fluid (CSF) hypocretin level =110 pg/mL determined prior to the study. In the absence of both, be evaluated by a panel of narcolepsy experts to confirm the diagnosis of narcolepsy with cataplexy in accordance with ICSD-3
4. Have given documented assent per local IRB/IEC requirements 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
5. Have parent(s)/guardian(s) who have given informed consent for his/her/their child’s participation in the study
6. Have a history of having at least 14 cataplexy attacks in a typical 2-week period and clinically significant symptoms of EDS prior to any narcolepsy treatment
7. Be willing to spend the required number of nights (2 to 3) in a sleep laboratory for PSG evaluations
8. 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
9. If currently treated with Xyrem, must have demonstrated clinical improvement of cataplexy per Investigator’s clinical judgment
10. Have agreed to abstain from caffeinated products during PSG and PK Nights
11. Any female subject of child-bearing potential must be willing to use a method of contraception, deemed medically acceptable by the Investigator, or agree to abstain from sexual intercourse for the duration of the study and for 30 days after study termination
12. Any male subject who is sexually active with a female partner must be willing to use a method of contraception, deemed medically acceptable by the Investigator, or agree to abstain from sexual intercourse for the duration of the study and for 30 days after study termination

In addition to the above inclusion criteria, prior to participating in the PK evaluation, subjects must meet the following inclusion criteria:
13. Be willing to spend 2 additional nights in the clinic for PK evaluation
14. This criterion was removed during Amendment 2
15. Have given additional documented assent and consent by the parent(s) or guardian(s) indicating awareness of the investigational nature of the PK evaluation and the required procedures and restrictions before participation in any PK-related activities
16. Have sufficient blood volume for PK sampling based on body weight in accordance with Seattle Children’s Hospital guideline (Appendix 4) or, for any particular investigational site, Institutional Review Board (IRB) eligibility guidelines for pediatric blood collection relevant to that site
17. D
Exclusion criteria:
Criteria 1-10 unchanged (excluded due to 5000 char limit).
11. Oxygen saturation level <95% for at least 5 minutes on room air as measured by pulse oximetry while fully awake during daytime monitoring, or subjects with known or suspected respiratory difficulty, or any condition that may compromise a subject’s breathing. If oxygen saturation values lower than 95% are observed at study sites at high geographic elevations and are acceptable to the Investigator, enrollment of the subject requires permission from the Medical Monitor
12. Past or current major thought disorder, e.g., schizophrenia, paranoia, mania, etc.
13. Recent history of clinically significant parasomnia (e.g., sleep walking, REM behavior disorder, etc.) that would negatively affect the conduct of the study
14. Current suicidal risk as determined from history or Columbia Suicide Severity Rating Scale (C-SSRS) or history of suicide attempt
15. Clinically significant depression independent of narcolepsy symptoms - If the T-score is at or above 65 on the Children’s Depression Inventory 2nd
Edition Self-Report Short Version (CDI 2:SR[S]), an evaluation of depression by the Investigator (if qualified as a mental health professional) or by the Investigator in consultation with a mental health professional must be performed to exclude a clinically significant depression
16. This criterion was removed during Amendment 2
17. Other documented clinically significant condition (including unstable medical and/or psychiatric conditions, chronic disease other than narcolepsy with cataplexy, porphyria, 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
18. An electrocardiogram (ECG) with clinically significant deviation(s) from normal, or clinically significant physical examination findings, as determined by the Investigator
19. Any clinically significant laboratory abnormality as determined by the Investigator
20. A positive pregnancy test result at screening (pregnancy tests will be performed for any female subject who has reached menarche)
21. A positive urine drug screen for benzodiazepines or drugs of abuse, a positive alcohol test, a history of substance abuse including alcohol abuse, or unwillingness to refrain from consuming alcohol during the study (if the subject takes prescribed amphetamines, a positive result for amphetamines will not exclude the subject)
22. 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)
23. 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 Part 1 Screening
24. Current treatment with oral isotretinoin
25. Inability to fast for 2 hours before the first dose through 4 hours after the last dose of Xyrem on PSG and PK nights
26. Lack of parental (or legal guardian) commitment to ensuring home situation is safe for Xyrem use, in the opinion of Investigator
27. Received any investigational drug within 30 days or 5 half-lives (whichever is

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Narcolepsy with Cataplexy
MedDRA version: 20.0 Level: LLT Classification code 10007738 Term: Cataplexy and narcolepsy System Organ Class: 100000004852

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: Xyrem
Product Name: Xyrem (sodium oxybate) oral solution
Pharmaceutical Form: Oral solution
INN or Proposed INN: NA
CAS Number: 502-85-2
Current Sponsor code: NA
Other descriptive name: SODIUM OXYBATE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

Main Objective: Primary objectives are:
1) To evaluate the efficacy of Xyrem (sodium oxybate) oral solution in the treatment of cataplexy in pediatric subjects with narcolepsy
2) To evaluate the safety of Xyrem in the treatment of cataplexy in pediatric subjects with narcolepsy for up to one year (and potentially more than one year in some subjects participating in a continuation of the open-label safety evaluation)

Primary end point(s): Primary efficacy endpoints:
- Change in weekly number of cataplexy attacks.

Secondary Objective: Secondary objectives are:
1) To evaluate the efficacy of Xyrem in the treatment of excessive daytime sleepiness (EDS) in pediatric subjects with narcolepsy with cataplexy
2) To characterize the pharmacokinetics (PK) of Xyrem in pediatric subjects (ages 7-17 years) with narcolepsy with cataplexy
3) To evaluate the safety of titrating Xyrem in pediatric subjects to an effective and tolerable dose

Timepoint(s) of evaluation of this end point: From the last 2 weeks of the Stable-Dose Period to the 2 weeks of the Double-Blind Treatment Period

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: - 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
- Change in the Epworth Sleepiness Scale for Children and Adolescents (ESS [CHAD]) score: from the end of the Stable-Dose Period to the end of the Double-Blind Treatment Period
- CGIc for narcolepsy overall: from the end of the Stable-Dose Period to the end of the Double-Blind Treatment Period
- Change in Quality of Life (QoL) (SF-10): from the end of the Stable-Dose Period to the end of the Double-Blind Treatment Period

Secondary end point(s): Secondary efficacy endpoints:
- Clinical Global Impression of Change (CGIc) for cataplexy severity
- Change in the Epworth Sleepiness Scale for Children and Adolescents (ESS [CHAD]) score
- CGIc for narcolepsy overall
- Change in Quality of Life (QoL) (SF-10)

Secondary ID(s)

2014-001389-93-FI

13-005

Source(s) of Monetary Support

Jazz Pharmaceuticals

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 16/08/2019
• Date Completed: 25/01/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-001389-93/results