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

Primary Purpose

Narcolepsy With Cataplexy

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
JZP-258
Placebo
Sponsored by
Jazz Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Narcolepsy With Cataplexy

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • SDS Clinical Trials, Inc.
  • Stanford Health Services
  • Colorado Sleep Institute
  • Pulmonary Disease Specialists
  • Fort Wayne Neurological Center
  • Kentucky Research Group
  • Center for Sleep & Wake Disorders
  • Montefiore/ Sleep-Wake Disorders Center
  • Gastonia Medical Specialty Clinic
  • Research Carolina
  • Intrepid Research
  • Cleveland Clinic, Sleep Disorder Center
  • UZ Antwerpen
  • Universitair Ziekenhuis Gent
  • UZ Leuven
  • Fakultni nemocnice Ostrava
  • Vseobecna fakultni nemocnice v Praze
  • Helsingin Uniklinikka, Vitalmed Oy
  • Hôpital Gui de Chauliac
  • Hopital Roger Salengro - CHU Lille
  • Hospital Universitari Vall d'Hebron
  • Hospital Clinic i Provincial de Barcelona
  • Hospital General de Castellón
  • Instituto de Investigaciones del Sueño
  • Hospital Vithas Nuestra Señora de America

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

JZP-258

Arm Description

Placebo

JZP-258

Outcomes

Primary Outcome Measures

Change in Weekly Number of Cataplexy Attacks
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

Change in the Epworth Sleepiness Scale (ESS) Score
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'.
Number of Participants With Worsening Patient Global Impression of Change (PGIc) for Narcolepsy Overall
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).
Number of Participants With Worsening Clinical Global Impression of Change (CGIc) for Narcolepsy Overall
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.
Change in 36-Item Short Form Health Survey Version 2 (SF-36v2) Scores
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.
Change in 5-level EQ-5D (EQ-5D-5L) Crosswalk Index Score and Visual Analog Scale
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).

Full Information

First Posted
January 23, 2017
Last Updated
November 10, 2020
Sponsor
Jazz Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT03030599
Brief Title
A Study of the Efficacy and Safety of JZP-258 in Subjects With Narcolepsy With Cataplexy
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
March 14, 2017 (Actual)
Primary Completion Date
January 24, 2019 (Actual)
Study Completion Date
July 10, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jazz Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Narcolepsy With Cataplexy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
201 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Arm Title
JZP-258
Arm Type
Experimental
Arm Description
JZP-258
Intervention Type
Drug
Intervention Name(s)
JZP-258
Other Intervention Name(s)
Xyrem®
Intervention Description
JZP-258 oral solution 0.5 g/mL, which is equivalent to 0.413 g/mL of oxybate
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Matching placebo solution (aqueous solution containing sodium citrate, malic acid, and sucralose; all ingredients were compendial [United States Pharmacopeia/ National Formulary])
Primary Outcome Measure Information:
Title
Change in Weekly Number of Cataplexy Attacks
Description
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.
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)
Secondary Outcome Measure Information:
Title
Change in the Epworth Sleepiness Scale (ESS) Score
Description
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'.
Time Frame
From the end of the Stable Dose Period to the end of the Double Blind Randomized Withdrawal Period
Title
Number of Participants With Worsening Patient Global Impression of Change (PGIc) for Narcolepsy Overall
Description
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).
Time Frame
At the end of the Double Blind Randomized Withdrawal Period
Title
Number of Participants With Worsening Clinical Global Impression of Change (CGIc) for Narcolepsy Overall
Description
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.
Time Frame
At the end of the Double Blind Randomized Withdrawal Period
Title
Change in 36-Item Short Form Health Survey Version 2 (SF-36v2) Scores
Description
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.
Time Frame
At the End of the Stable Dose Period to the End of the Double Blind Randomized Withdrawal Period
Title
Change in 5-level EQ-5D (EQ-5D-5L) Crosswalk Index Score and Visual Analog Scale
Description
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).
Time Frame
At the End of the Stable Dose Period to the End of the Double Blind Randomized Withdrawal Period

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female subjects between 18 and 70 years of age, inclusive. 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. 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. Willing and able to comply with the study design schedule and other requirements. Willing and able to provide written informed consent. Exclusion Criteria: Narcolepsy secondary to another medical condition (e.g., CNS injury or lesion) 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. 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). 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. Unsafe for the subject to receive placebo treatment for 2 weeks, in the opinion of the Investigator.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Director Clinical Trial Disclosure & Transparency
Organizational Affiliation
Jazz Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
SDS Clinical Trials, Inc.
City
Orange
State/Province
California
ZIP/Postal Code
92858
Country
United States
Facility Name
Stanford Health Services
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Colorado Sleep Institute
City
Boulder
State/Province
Colorado
ZIP/Postal Code
80301
Country
United States
Facility Name
Pulmonary Disease Specialists
City
Kissimmee
State/Province
Florida
ZIP/Postal Code
34741
Country
United States
Facility Name
Fort Wayne Neurological Center
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46804
Country
United States
Facility Name
Kentucky Research Group
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40218
Country
United States
Facility Name
Center for Sleep & Wake Disorders
City
Chevy Chase
State/Province
Maryland
ZIP/Postal Code
20815
Country
United States
Facility Name
Montefiore/ Sleep-Wake Disorders Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Gastonia Medical Specialty Clinic
City
Gastonia
State/Province
North Carolina
ZIP/Postal Code
94305
Country
United States
Facility Name
Research Carolina
City
Huntersville
State/Province
North Carolina
ZIP/Postal Code
28078
Country
United States
Facility Name
Intrepid Research
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45245
Country
United States
Facility Name
Cleveland Clinic, Sleep Disorder Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
UZ Antwerpen
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
Facility Name
Universitair Ziekenhuis Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
UZ Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Fakultni nemocnice Ostrava
City
Ostrava-Poruba
ZIP/Postal Code
70800
Country
Czechia
Facility Name
Vseobecna fakultni nemocnice v Praze
City
Praha 2
ZIP/Postal Code
128 21
Country
Czechia
Facility Name
Helsingin Uniklinikka, Vitalmed Oy
City
Helsinki
ZIP/Postal Code
00380
Country
Finland
Facility Name
Hôpital Gui de Chauliac
City
Montpellier
State/Province
Herault
ZIP/Postal Code
34295
Country
France
Facility Name
Hopital Roger Salengro - CHU Lille
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clinic i Provincial de Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital General de Castellón
City
Castelló
ZIP/Postal Code
12004
Country
Spain
Facility Name
Instituto de Investigaciones del Sueño
City
Madrid
ZIP/Postal Code
28036
Country
Spain
Facility Name
Hospital Vithas Nuestra Señora de America
City
Madrid
ZIP/Postal Code
28043
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
35635687
Citation
Dauvilliers Y, Sonka K, Bogan RK, Partinen M, Del Rio Villegas R, Foldvary-Schaefer N, Skowronski R, Chen A, Black J, Skobieranda F, Thorpy MJ. Changes in Cataplexy Frequency in a Clinical Trial of Lower-Sodium Oxybate with Taper and Discontinuation of Other Anticataplectic Medications. CNS Drugs. 2022 Jun;36(6):633-647. doi: 10.1007/s40263-022-00926-0. Epub 2022 May 30. Erratum In: CNS Drugs. 2022 Jul;36(7):785-786.
Results Reference
derived
PubMed Identifier
33184650
Citation
Bogan RK, Thorpy MJ, Dauvilliers Y, Partinen M, Del Rio Villegas R, Foldvary-Schaefer N, Skowronski R, Tang L, Skobieranda F, Sonka K. Efficacy and safety of calcium, magnesium, potassium, and sodium oxybates (lower-sodium oxybate [LXB]; JZP-258) in a placebo-controlled, double-blind, randomized withdrawal study in adults with narcolepsy with cataplexy. Sleep. 2021 Mar 12;44(3):zsaa206. doi: 10.1093/sleep/zsaa206. Erratum In: Sleep. 2021 Jul 9;44(7): Sleep. 2021 Nov 12;44(11):
Results Reference
derived

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

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