Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
Register:
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EUCTR |
Last refreshed on:
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25 November 2019 |
Main ID: |
EUCTR2014-001389-93-FI |
Date of registration:
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10/12/2014 |
Prospective Registration:
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Yes |
Primary sponsor: |
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Public title:
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Study of the Efficacy and Safety of Xyrem in Pediatric Subjects with Narcolepsy with Cataplexy
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Scientific title:
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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
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Date of first enrolment:
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27/08/2015 |
Target sample size:
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100 |
Recruitment status: |
Not Recruiting |
URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001389-93 |
Study type:
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Interventional clinical trial of medicinal product |
Study design:
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Controlled: no Randomised: yes 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
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): yes
Therapeutic confirmatory - (Phase III): yes
Therapeutic use (Phase IV): no
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Countries of recruitment
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Finland
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France
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Italy
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Netherlands
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United States
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Contacts
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Name:
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Mario D'Achille, Sr. CT Manager
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Address:
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1818 Market Street
PA 19103
Philadelphia
United States |
Telephone:
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+12157108317 |
Email:
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mario.dachille@jazzpharma.com |
Affiliation:
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Jazz Pharmaceuticals |
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Name:
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Mario D'Achille, Sr. CT Manager
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Address:
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1818 Market Street
PA 19103
Philadelphia
United States |
Telephone:
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+12157108317 |
Email:
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mario.dachille@jazzpharma.com |
Affiliation:
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Jazz Pharmaceuticals |
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Key inclusion & exclusion criteria
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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 confimr the diagnosis of Type 1 narcolepsy by ICSD-3 criteria (ie., 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 8CSF) 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 indicating that he/she was aware of the investigational nature of the study and the required procedures and restrictions efore 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. 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 15. Have sufficient blood volume for PK sampling based on body weight in accordance with Seattle Children’s Hospital guideline (Appendix 4) or
Exclusion criteria: 1. Not able to understand assent or follow study instructions, in the Investigator's opinion 2. Parent(s)/guardian(s) unable to comply with the study requirements, in the Investigator's opinion 3. Previously treated with Xyrem and discontinued because of lack of efficacy and/or tolerability issues 4. Narcolepsy secondary to another medical condition, e.g., CNS injury or lesion 5. Restless leg syndrome requiring treatment other than iron supplements 6. Succinic semi-aldehyde dehydrogenase deficiency 7. Uncontrolled hypothyroidism 8. History of seizure disorders 9. History of head trauma associated with loss of consciousness 10. Evidence of sleep-disordered breathing including: a. Presence of clinically significant obstructive or central sleep apnea as determined by the Inv. or documented previously; or b. Obstructive AHI >5 for subjects 7-11 years of age or obstructive AHI >10 for subjects 12-17 years of age; or c. Oxygen saturation nadir =85% at night; or d. Clinically significant hypoventilation 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 or history of suicide attempt 15.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 qulaified 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. 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 Inv.'s opinion 17. An ECG with clinically significant deviation(s) from normal, or clinically significant physical examination findings, as determined by the Inv. 18. Any clinically significant lab abnormality as determined by the Inv. 19. A positive pregnancy test result at screening (pregnancy tests will be performed for any female subject who has reached menarche) 20. A positive urine drug screen for benzodiazepines or drugs of abuse, a positive alcohol test, a history of substance abuse including alcohol abuse, or unwilling
Age minimum:
Age maximum:
Gender:
Female: yes Male: yes
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Health Condition(s) or Problem(s) studied
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Narcolepsy with Cataplexy
MedDRA version: 19.0
Level: LLT
Classification code 10007738
Term: Cataplexy and narcolepsy
System Organ Class: 100000004852
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Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
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Intervention(s)
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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- Pharmaceutical form of the placebo: Oral solution Route of administration of the placebo: Oral use
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Primary Outcome(s)
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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
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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
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Primary end point(s): Primary efficacy endpoints: - Change in weekly number of cataplexy attacks.
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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
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Secondary Outcome(s)
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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
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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)
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Source(s) of Monetary Support
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Jazz Pharmaceuticals
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Ethics review
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Status: Approved
Approval date:
Contact:
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