A Multicenter Study of the Efficacy and Safety of JZP-258 in the Treatment of Idiopathic Hypersomnia (IH) With an Open-label Safety Extension

NCT03533114 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: JZP080-3012018-001311-79
• Study Type: interventional
• Target: 154
• Locations: 8 countries
• Sites: 63

Brief Summary

This is a study of the efficacy and safety of JZP-258, an oxybate mixed-salts oral solution being developed as a low sodium alternative product for Xyrem.

Conditions

Idiopathic Hypersomnia

Outcome Measures

Primary Outcomes (1)

• Change in Epworth Sleepiness Scale (ESS) Score

  The ESS is a 8-item self reported questionnaire intended to measure daytime sleepiness. In this test, participants answer questions with regard to the level of sleepiness they experienced over approximately the 7 days prior to the assessment while performing eight common, non-stimulating activities. The ESS total score range is 1 to 24. Each activity is rated on a 4-point scale ranging from a minimum of "would never doze" to a maximum of "a high chance of dozing." Thus, the ESS scale range is as follows: 0=would never doze, 1=slight chance of dozing, 2=moderate chance of dozing, 3=high chance of dozing; 0 indicates a better outcome, and 3 indicates a worse outcome. A positive mean change value indicates an increase in score from the end of the stable dose period and worsened daytime sleepiness. A higher ESS score (above 10) reflects a greater average sleep propensity in daily life (ASP) , or daytime sleepiness.

  Change from the end of the Stable Dose Period to the end of the Double-blind Randomized Withdrawal Period (DBRW) (2 Weeks)

Secondary Outcomes (4)

• Percentage of Participants Reported as Worse on the Patient Global Impression of Change (PGIc)

  At the end of the DBRW Period (2 Weeks)

• Change in Total Score on the Idiopathic Hypersomnia Severity Scale (IHSS)

  Change from the end of the Stable Dose Period to the end of the DBRW Period (2 Weeks)

• Percentage of Participants Reported as Worse on the Clinical Global Impression of Change (CGIc)

  At the end of the DBRW Period (2 Weeks)

• Change in Total Score on the Functional Outcomes of Sleep Questionnaire (FOSQ-10)

  Change from the end of the Stable Dose Period to the end of the DBRW Period (2 Weeks)

Study Arms (2)

JZP-258

EXPERIMENTAL

JZP-258 at the stable dose and regimen for 2 weeks.

Drug: JZP-258

Placebo

PLACEBO COMPARATOR

Placebo will be administered at a volume and regimen equivalent to the JZP-258 dose and regimen for 2 weeks.

Drug: Placebo Oral Solution

Interventions

JZP-258 DRUG

Participants randomized to JZP-258 will receive the dose taken at the end of the Stable Dose Period.

JZP-258

Placebo Oral Solution DRUG

Participants randomized to Placebo will receive an oral solution at a volume and regimen equivalent to the JZP-258 dose taken at the end of the Stable Dose Period.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female between 18 and 75 years of age, inclusive, at the time of consent.
• Have a primary diagnosis of IH according to the International Classification of Sleep Disorders ICSD-2 or ICSD-3 criteria.
• At the Screening Visit and the Baseline Visit, subjects who are not on Xyrem at study entry must have ESS scores ≥ 11 (as assessed with a look-back period of 1 week).
• If currently treated with Xyrem, must have documented clinical improvement of EDS after the initiation of Xyrem per Investigator's clinical judgment.
• Average nightly total sleep time of ≥ 7 hours, per subject history. Average nightly total sleep time will be confirmed by Investigator's review of sleep diaries collected during the final 2 weeks of the Screening Period.
• If currently treated with stimulants and / or alerting agents or nicotine replacement therapy, must have been taking the same regimen and dose for at least 2 months prior to screening and must agree to take the same dose leading up to and throughout the Double-blind Randomized Withdrawal Period.
• Have used a medically acceptable method of contraception for at least 2 months prior to the first dose of study drug and consent to use a medically acceptable method of contraception from the first dose of study drug, throughout the entire study period, and for 90 days after the last dose of study drug.

You may not qualify if:

• Hypersomnia due to another medical, behavioral, or psychiatric disorder condition.
• Evidence of untreated or inadequately treated sleep-disordered breathing.
• Clinically significant parasomnias (eg, sleep walking, rapid eye movement sleep behavior disorder, etc.).
• Current or past (within 1 year) major depressive episode according to DSM-5 criteria. Patients with depression under control are allowed per the judgment of the Investigator or the treating physician and the anti-depressant treatment has to be stable for at least 6 months prior to Screening and remain stable for the duration of the study.
• Current suicidal risk as determined from history by presence of active suicidal ideation as indicated by positive response to item #4 or #5 on C-SSRS, or any history of suicide attempt.
• Occupation requiring nighttime shift work or variable shift work with early work start times or other occupations that could affect the safety of the subject per the judgment of the Investigator.
• Treatment or planned treatment with any CNS sedating agents, including but not limited to benzodiazepines or other sedating anxiolytics, sedating antidepressants, hypnotics, sedatives, neuroleptics, opoids, barbiturates, phenytoin, melatonin, ethosuximide, medications containing valproic acid or its sodium salt, or any other medication in which the subject experiences sedation are prohibited during the study. Treatment must have been discontinued within 2 weeks or 5 half-lives, whichever is longer, prior to enrollment. The Investigator must ensure that discontinuation from these medications is medically supervised. Subjects must abstain from these medications during the study.
• Current or past substance use disorder (including alcohol) according to DSM-5 criteria, or the subject is unwilling to refrain from consuming alcohol, cannabinoids, or prohibited medications during the study.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (63)

Sleep Disorders Center of Alabama

Birmingham, Alabama, 35213, United States

Location

Wright Clinical Research, LLC

Birmingham, Alabama, 35243, United States

Location

Coastal Clinical Research

Mobile, Alabama, 36608, United States

Location

Mayo Clinic Building

Phoenix, Arizona, 85054, United States

Location

Southern California Institute for Respiratory Diseases, Inc.

Los Angeles, California, 90048, United States

Location

Stanford Sleep Medicine Center

Redwood City, California, 94063, United States

Location

SDS Clinical Trials, Inc.

Santa Ana, California, 92705, United States

Location

Alpine Clinical Research Center

Boulder, Colorado, 80301, United States

Location

Delta Waves, Inc.

Colorado Springs, Colorado, 80918, United States

Location

PAB Clinical Research

Brandon, Florida, 33511, United States

Location

Suncoast Research Group

Miami, Florida, 33135, United States

Location

Bio-Medical Research, LLC

Miami, Florida, 33184, United States

Location

Clinical Research of West Florida, Inc.

Tampa, Florida, 33603, United States

Location

NeuroTrials Research

Atlanta, Georgia, 30342, United States

Location

Sleep Practitioners, LLC

Macon, Georgia, 31210, United States

Location

SleepCare Research Institute d/b/a Clinical Research

Stockbridge, Georgia, 30281, United States

Location

Center for Sleep & Wake Disorders

Chevy Chase, Maryland, 20815, United States

Location

Baystate Wesson Sleep Clinic

Springfield, Massachusetts, 01199, United States

Location

Bronson Methodist Hospital

Kalamazoo, Michigan, 49007, United States

Location

Clinical Neurophysiology Services, P.C.

Sterling Heights, Michigan, 48314, United States

Location

Minnesota Lung Center

Minneapolis, Minnesota, 55435, United States

Location

Clayton Sleep Institute, LLC

St Louis, Missouri, 63146, United States

Location

Montefiore Medical Center/Sleep-Wake Disorders Center

The Bronx, New York, 10467, United States

Location

American Health Research

Charlotte, North Carolina, 28207, United States

Location

Clinical Research of Gastonia

Gastonia, North Carolina, 28054, United States

Location

Research Carolina

Huntersville, North Carolina, 28078, United States

Location

Clinical Research of Lake Norman

Mooresville, North Carolina, 28117, United States

Location

Raleigh Neurology Associates

Raleigh, North Carolina, 27607, United States

Location

Intrepid Research

Cincinnati, Ohio, 45245, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio Sleep Medicine and Neuroscience Institute

Dublin, Ohio, 43017, United States

Location

Lynne Health Science Institute

Oklahoma City, Oklahoma, 73112, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

Location

Abington Neurological Associates

Willow Grove, Pennsylvania, 19090, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Bogan Sleep Consultants, LLC

Columbia, South Carolina, 29201, United States

Location

Clinical Research of Charleston

Mt. Pleasant, South Carolina, 29464, United States

Location

Neurology Clinic, PC

Cordova, Tennessee, 38018, United States

Location

FutureSearch Trials of Neurology

Austin, Texas, 78731, United States

Location

Sleep Therapy & Research Center

San Antonio, Texas, 78229, United States

Location

Anima Research Center

Alken, 3570, Belgium

Location

Antwerp University Hospital

Edegem, 2650, Belgium

Location

CHU UCL Namur site de Sainte Elisabeth

Namur, 5000, Belgium

Location

Nemocnice Ceske Budejovice a.s.

České Budějovice, 370 01, Czechia

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 50333, Czechia

Location

Vseobecna fakultni nemocnice v Praze

Prague, 128 21, Czechia

Location

VitalMed Oy

Helsinki, 00240, Finland

Location

CHU de Grenoble - Hôpital Michallon

Grenoble, 38043, France

Location

Hopital Roger Salengro

Lille, 59037, France

Location

Hopital Gui de Chauliac

Montpellier, 34295, France

Location

CHU Nantes - Hopital Nord Laënnec

Nantes, 44093, France

Location

Hopital Pitie-Salpetriere

Paris, 75651, France

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-952, Poland

Location

Osrodek Badan Klinicznych CROMED

Poznan, 61-505, Poland

Location

lnstytut Psychiatrii i Neurologii, Zaklad Neurofizjologii Klinicznej

Warsaw, 02-957, Poland

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Vithas Nuestra Señora de America

Madrid, 28043, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Hospital Universitario Araba

Vitoria-Gasteiz, 01009, Spain

Location

Royal Infirmary of Edinburgh

Edinburgh, EH16 4SA, United Kingdom

Location

Related Publications (3)

• Bogan RK, Fuller DS, Whalen M, Casstevens C, Schneider LD. A minimal clinically important difference for the sleep inertia visual analog scale in idiopathic hypersomnia. J Clin Sleep Med. 2025 Jul 1;21(7):1209-1216. doi: 10.5664/jcsm.11662.

  PMID: 40135693 DERIVED

• Morse AM, Dauvilliers Y, Arnulf I, Thorpy MJ, Foldvary-Schaefer N, Chandler P, Chen A, Hickey L, Black J, Bogan RK. Long-term efficacy and safety of low-sodium oxybate in an open-label extension period of a placebo-controlled, double-blind, randomized withdrawal study in adults with idiopathic hypersomnia. J Clin Sleep Med. 2023 Oct 1;19(10):1811-1822. doi: 10.5664/jcsm.10698.

  PMID: 37409509 DERIVED

• Dauvilliers Y, Arnulf I, Foldvary-Schaefer N, Morse AM, Sonka K, Thorpy MJ, Mignot E, Chandler P, Parvataneni R, Black J, Sterkel A, Chen D, Skobieranda F, Bogan RK. Safety and efficacy of lower-sodium oxybate in adults with idiopathic hypersomnia: a phase 3, placebo-controlled, double-blind, randomised withdrawal study. Lancet Neurol. 2022 Jan;21(1):53-65. doi: 10.1016/S1474-4422(21)00368-9.

  PMID: 34942138 DERIVED

MeSH Terms

Conditions

Idiopathic Hypersomnia

Condition Hierarchy (Ancestors)

Disorders of Excessive Somnolence; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Results Point of Contact

• Title: Director, Disclosure & Transparency
• Organization: Jazz Pharmaceuticals

ClinicalTrialDisclosure@JazzPharma.com

2158709177

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2018
• First Posted: May 22, 2018
• Study Start: November 27, 2018
• Primary Completion: June 12, 2020
• Study Completion: December 18, 2020
• Last Updated: November 24, 2021
• Results First Posted: November 24, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

BE (3); FI (1); FR (5); PL (3); ES (7); US (40); GB (1); CZ (3)