Clinical trial NCT02221869: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Narcolepsy With Cataplexy
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2014-08-21
Enrollment: 106
Sex: ALL
Minimum age (years): 7
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility 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 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

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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 exclusion criteria, subjects participating in the PK evaluation must not demonstrate the following:

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Primary outcomes:
measure: Change in Weekly Number of Cataplexy Attacks
timeFrame: From the end of the Stable Dose Period to the end of the Double-blind Treatment Period (2 weeks)
Secondary outcomes:
measure: Clinical Global Impression of Change (CGIc) for Cataplexy Severity
timeFrame: From the end of the Stable Dose Period to the end of the Double-blind Treatment Period (2 weeks)
measure: Change in the Epworth Sleepiness Scale (ESS) (CHAD) Score
timeFrame: From the end of the Stable Dose Period to the end of the Double-blind Treatment Period (2 weeks)
measure: CGIc for Narcolepsy Overall
timeFrame: From the end of the Stable Dose Period to the end of the Double-blind Treatment Period (2 weeks)
measure: 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
timeFrame: From the end of the Stable Dose Period to the end of the Double-blind Treatment Period (2 weeks)
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Miller Children's Hospital - Long Beach
state: California
city: Orange
country: United States
facility: SDS Clinical Trials, Inc.
state: California
city: Redwood City
country: United States
facility: Stanford Sleep Medicine Center
state: California
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Ann Arbor
country: United States
facility: The U-M Sleep Disorders Center
state: Michigan
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Durham
country: United States
facility: Duke Children's Hospital
state: North Carolina
city: Huntersville
country: United States
facility: ARSM Research, LLC
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Columbia
country: United States
facility: SleepMed of SC
state: South Carolina
city: Greenville
country: United States
facility: Greenville Health System
state: South Carolina
city: Memphis
country: United States
facility: UT/LeBonheur Neuroscience Institute
state: Tennessee
city: Houston
country: United States
facility: Todd Swick, MD, PA
state: Texas
city: Norfolk
country: United States
facility: Children's Hospital of The King's Daughters
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Paris
country: France
facility: Hospital Robert Debre
city: Bologna
country: Italy
facility: Dipartimento di Scienze Biomediche e Biomotorie
city: Heemstede
country: Netherlands
facility: Sleep Wake Center SEIN Heemstede
state: Noord Holland
Study officials:
References:
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.
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.
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.