Clinical trial NCT03030599: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Narcolepsy With Cataplexy
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2017-01-25
Enrollment: 201
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in Weekly Number of Cataplexy Attacks
timeFrame: Change from baseline (2 weeks of the Stable Dose Period) to the 2 weeks of the Double Blind Randomized Withdrawal Period (DB RWP)
Secondary outcomes:
measure: Change in the Epworth Sleepiness Scale (ESS) Score
timeFrame: From the end of the Stable Dose Period to the end of the Double Blind Randomized Withdrawal Period
measure: Number of Participants With Worsening Patient Global Impression of Change (PGIc) for Narcolepsy Overall
timeFrame: At the end of the Double Blind Randomized Withdrawal Period
measure: Number of Participants With Worsening Clinical Global Impression of Change (CGIc) for Narcolepsy Overall
timeFrame: At the end of the Double Blind Randomized Withdrawal Period
measure: Change in 36-Item Short Form Health Survey Version 2 (SF-36v2) Scores
timeFrame: At the End of the Stable Dose Period to the End of the Double Blind Randomized Withdrawal Period
measure: Change in 5-level EQ-5D (EQ-5D-5L) Crosswalk Index Score and Visual Analog Scale
timeFrame: At the End of the Stable Dose Period to the End of the Double Blind Randomized Withdrawal Period
Other outcomes:
Locations:
city: Orange
country: United States
facility: SDS Clinical Trials, Inc.
state: California
city: Stanford
country: United States
facility: Stanford Health Services
state: California
city: Boulder
country: United States
facility: Colorado Sleep Institute
state: Colorado
city: Kissimmee
country: United States
facility: Pulmonary Disease Specialists
state: Florida
city: Fort Wayne
country: United States
facility: Fort Wayne Neurological Center
state: Indiana
city: Louisville
country: United States
facility: Kentucky Research Group
state: Kentucky
city: Chevy Chase
country: United States
facility: Center for Sleep & Wake Disorders
state: Maryland
city: Bronx
country: United States
facility: Montefiore/ Sleep-Wake Disorders Center
state: New York
city: Gastonia
country: United States
facility: Gastonia Medical Specialty Clinic
state: North Carolina
city: Huntersville
country: United States
facility: Research Carolina
state: North Carolina
city: Cincinnati
country: United States
facility: Intrepid Research
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic, Sleep Disorder Center
state: Ohio
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Ostrava-Poruba
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Helsinki
country: Finland
facility: Helsingin Uniklinikka, Vitalmed Oy
city: Montpellier
country: France
facility: Hôpital Gui de Chauliac
state: Herault
city: Lille
country: France
facility: Hopital Roger Salengro - CHU Lille
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Castelló
country: Spain
facility: Hospital General de Castellón
city: Madrid
country: Spain
facility: Instituto de Investigaciones del Sueño
city: Madrid
country: Spain
facility: Hospital Vithas Nuestra Señora de America
Study officials:
affiliation: Jazz Pharmaceuticals
name: Director Clinical Trial Disclosure & Transparency
role: STUDY_DIRECTOR
References:
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.
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.