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

NCT ID: NCT03030599

Last Updated: 2020-11-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 201 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-14
• Study Completion Date: 2019-07-10

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.

Conditions

Narcolepsy With Cataplexy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Matching placebo solution (aqueous solution containing sodium citrate, malic acid, and sucralose; all ingredients were compendial \[United States Pharmacopeia/ National Formulary\])

JZP-258

JZP-258

Group Type: EXPERIMENTAL

JZP-258

Intervention Type: DRUG

JZP-258 oral solution 0.5 g/mL, which is equivalent to 0.413 g/mL of oxybate

Interventions

JZP-258

JZP-258 oral solution 0.5 g/mL, which is equivalent to 0.413 g/mL of oxybate

Intervention Type: DRUG

Placebo

Matching placebo solution (aqueous solution containing sodium citrate, malic acid, and sucralose; all ingredients were compendial \[United States Pharmacopeia/ National Formulary\])

Intervention Type: OTHER

Other Intervention Names

Xyrem®

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jazz Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Director Clinical Trial Disclosure & Transparency

Role: STUDY_DIRECTOR

Jazz Pharmaceuticals

Locations

SDS Clinical Trials, Inc.

Orange, California, United States

Stanford Health Services

Stanford, California, United States

Colorado Sleep Institute

Boulder, Colorado, United States

Pulmonary Disease Specialists

Kissimmee, Florida, United States

Fort Wayne Neurological Center

Fort Wayne, Indiana, United States

Kentucky Research Group

Louisville, Kentucky, United States

Center for Sleep & Wake Disorders

Chevy Chase, Maryland, United States

Montefiore/ Sleep-Wake Disorders Center

The Bronx, New York, United States

Gastonia Medical Specialty Clinic

Gastonia, North Carolina, United States

Research Carolina

Huntersville, North Carolina, United States

Intrepid Research

Cincinnati, Ohio, United States

Cleveland Clinic, Sleep Disorder Center

Cleveland, Ohio, United States

UZ Antwerpen

Edegem, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

UZ Leuven

Leuven, , Belgium

Fakultni nemocnice Ostrava

Ostrava-Poruba, , Czechia

Vseobecna fakultni nemocnice v Praze

Prague, , Czechia

Helsingin Uniklinikka, Vitalmed Oy

Helsinki, , Finland

Hôpital Gui de Chauliac

Montpellier, Herault, France

Hopital Roger Salengro - CHU Lille

Lille, , France

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Clinic i Provincial de Barcelona

Barcelona, , Spain

Hospital General de Castellón

Castelló, , Spain

Instituto de Investigaciones del Sueño

Madrid, , Spain

Hospital Vithas Nuestra Señora de America

Madrid, , Spain

Countries

Croatia; Germany; Netherlands; Poland; Switzerland; United Kingdom; United States; Belgium; Czechia; Finland; France; Spain

References

Bogan RK, Foldvary-Schaefer N, Skowronski R, Chen A, Thorpy MJ. Long-Term Safety and Tolerability During a Clinical Trial and Open-Label Extension of Low-Sodium Oxybate in Participants with Narcolepsy with Cataplexy. CNS Drugs. 2023 Apr;37(4):323-335. doi: 10.1007/s40263-023-00992-y. Epub 2023 Mar 22.

Reference Type: DERIVED

PMID: 36947322 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35635687 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33184650 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-000426-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

15-006

Identifier Type: -

Identifier Source: org_study_id