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A Study of the Efficacy and Safety of JZP-258 in Subjects With Narcolepsy With Cataplexy

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ClinicalTrials.gov Identifier: NCT03030599
Recruitment Status : Completed
First Posted : January 25, 2017
Results First Posted : November 12, 2020
Last Update Posted : November 12, 2020
Sponsor:
Information provided by (Responsible Party):
Jazz Pharmaceuticals

Brief Summary:
This is a double-blind, placebo-controlled, randomized-withdrawal, multicenter study of the efficacy and safety of JZP-258.

Condition or disease Intervention/treatment Phase
Narcolepsy With Cataplexy Drug: JZP-258 Other: Placebo Phase 3

Detailed Description:
Subjects will be transitioned to JZP-258 based on their treatment status at study entry. All subjects will begin JZP-258 treatment at the beginning of this period and continue through Week 12. They will be treated with JZP-258 alone for the final two weeks of this 12-week period. Once the JZP-258 dose has been optimized per the Investigator's judgment, these subjects may enter the 2-week Stable-Dose Period with that dose. Subjects are eligible to enter the Double-Blind Randomized-Withdrawal Period if the dose of JZP-258 remains unchanged during the Stable-Dose Period and, in the judgment of the Investigator, no clinically significant worsening in narcolepsy symptoms or clinically significant adverse events due to JZP-258 treatment have occurred. Subjects will return for a Safety Follow-up visit 2 weeks after the Double-Blind Randomized-Withdrawal Period. Subjects who complete the double-blind treatment period during the Main Study are eligible to enter a 24-week Open-Label Extension. During this period subjects will receive open label JZP-258. Subjects will return for a Safety Follow-up visit 2 weeks after the Open-Label Extension Period.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 201 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Double-Blind, Placebo-Controlled, Randomized-Withdrawal, Multicenter Study of the Efficacy and Safety of JZP-258 in Subjects With Narcolepsy With Cataplexy
Actual Study Start Date : March 14, 2017
Actual Primary Completion Date : January 24, 2019
Actual Study Completion Date : July 10, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo
Other: Placebo
Matching placebo solution (aqueous solution containing sodium citrate, malic acid, and sucralose; all ingredients were compendial [United States Pharmacopeia/ National Formulary])

Experimental: JZP-258
JZP-258
Drug: JZP-258
JZP-258 oral solution 0.5 g/mL, which is equivalent to 0.413 g/mL of oxybate
Other Name: Xyrem®




Primary Outcome Measures :
  1. Change in Weekly Number of Cataplexy Attacks [ Time Frame: Change from baseline (2 weeks of the Stable Dose Period) to the 2 weeks of the Double Blind Randomized Withdrawal Period (DB RWP) ]
    Participants completed a daily Cataplexy Frequency Diary each night prior to bedtime. Participants were to record the number of cataplexy attacks that they had each day.


Secondary Outcome Measures :
  1. Change in the Epworth Sleepiness Scale (ESS) Score [ Time Frame: From the end of the Stable Dose Period to the end of the Double Blind Randomized Withdrawal Period ]
    This is the key secondary endpoint. The Epworth Sleepiness Scale (ESS) was a self-administered questionnaire with 8 questions. Participants were asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. Most participants engaged in those activities at least occasionally, although not necessarily every day. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that participants average sleep propensity in daily life (ASP), or their 'daytime sleepiness'.

  2. Number of Participants With Worsening Patient Global Impression of Change (PGIc) for Narcolepsy Overall [ Time Frame: At the end of the Double Blind Randomized Withdrawal Period ]
    At the end of the Double Blind Randomized Withdrawal Period (DB RWP), participants rated the change in their condition on a 7-point scale ranging from 1 = "very much improved" to 7 = "very much worse" since the last visit. This endpoint measures the percentage of participants with worsening PGIc scores for narcolepsy overall (defined as scores of Much Worse or Very Much Worse).

  3. Number of Participants With Worsening Clinical Global Impression of Change (CGIc) for Narcolepsy Overall [ Time Frame: At the end of the Double Blind Randomized Withdrawal Period ]
    At the end of the Double Blind Randomized Withdrawal Period, Investigators rated their impression of any change in the severity of the participant's narcolepsy overall condition since the start of the Double Blind Randomized Withdrawal Period on a 7-point scale ranging from 1 = "very much improved" to 7 = "very much worse". This endpoint measures the percentage of participants with worsening CGIc scores for narcolepsy overall, defined as scores of Much Worse or Very Much Worse.

  4. Change in 36-Item Short Form Health Survey Version 2 (SF-36v2) Scores [ Time Frame: At the End of the Stable Dose Period to the End of the Double Blind Randomized Withdrawal Period ]
    The SF-36v2 is a multi-purpose, short-form health survey with 36 questions/ items. It yields an 8-scale profile of functional health and well-being scores as well as a psychometrically-based physical and mental overall component summary measures. Two summary scores were derived using the SF-36v2. Physical Component Summary measures dimensions of functional health that are meaningful to respondents, including the impact of health and health-related changes on physical function, pain, and the ability to carry out daily roles. The Mental Component Summary component scale measures the impact of health and health-related changes on well-being, including vitality, social function, and emotional well-being. Participants self-report on items in a summary that have between 2-6 choices per item (e.g. none of the time, some of the time, etc.). Summations of item scores were transformed into a range from 0 to 100; zero= worst HRQL, 100=best HRQL. Higher scores indicate better health status.

  5. Change in 5-level EQ-5D (EQ-5D-5L) Crosswalk Index Score and Visual Analog Scale [ Time Frame: At the End of the Stable Dose Period to the End of the Double Blind Randomized Withdrawal Period ]
    The EQ-5D-5L is a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/ discomfort, and anxiety/ depression). The EQ-5D-5L includes 5 levels of severity for each of the 5 dimensions of the descriptive system (1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems) that reflect increasing levels of difficulty. The 5 digit health states for each dimension are converted into a single value per country (0= equivalent to death, 1= equivalent to best imaginable health and values below 0= health states rated worse than death capped at -1), using the EQ-5D-5L crosswalk index value calculator as recommended by EuroQol group. A visual analogue scale (VAS) used within this scale recorded the participants self-rated health on a VAS and the endpoints resulted in a numeric value set ranging from 0 (= worst imaginable health state) up to 100 (= best imaginable health state).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female subjects between 18 and 70 years of age, inclusive.
  2. Have a primary diagnosis of narcolepsy with cataplexy that meets ICSD-3 criteria or DSM-5 criteria, and currently untreated or treated with or without anticataplectics.
  3. If applicable, treated with a stimulant or alerting agent at unchanged doses for at least 2 months prior to dosing or not treated with a stimulant or alerting agent.
  4. Willing and able to comply with the study design schedule and other requirements.
  5. Willing and able to provide written informed consent.

Exclusion Criteria:

  1. Narcolepsy secondary to another medical condition (e.g., CNS injury or lesion)
  2. History or presence of any unstable or clinically significant medical condition, behavioral or psychiatric disorder (including active suicidal ideation), or history or presence of another neurological disorder or surgical history that might affect the subject's safety and/or interfere with the conduct of the study in the opinion of the Investigator.
  3. Treatment with any central nervous system sedating agents, including but not limited to benzodiazepines, nonbenzodiazepine anxiolytics/ hypnotics/sedatives, neuroleptics, opioids, barbiturates, phenytoin, ethosuximide, or MCT inhibitors, e.g. diclofenac, valproate, ibuprofen, 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).
  4. Treatment with an antidepressant for cataplexy, if the withdrawal of the antidepressant during cross-titration with JZP-258 might be unsafe due to prior history of depression.
  5. Unsafe for the subject to receive placebo treatment for 2 weeks, in the opinion of the Investigator.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03030599


Locations
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Sponsors and Collaborators
Jazz Pharmaceuticals
Investigators
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Study Director: Director Clinical Trial Disclosure & Transparency Jazz Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Jazz Pharmaceuticals:
Study Protocol  [PDF] May 15, 2018
Statistical Analysis Plan  [PDF] February 25, 2019

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Jazz Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03030599    
Other Study ID Numbers: 15-006
2016-000426-20 ( EudraCT Number )
First Posted: January 25, 2017    Key Record Dates
Results First Posted: November 12, 2020
Last Update Posted: November 12, 2020
Last Verified: November 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Narcolepsy
Cataplexy
Disorders of Excessive Somnolence
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Mental Disorders