Clinical trial NCT03533114: A Multicenter Study of the Efficacy and Safety of JZP-258 in the Treatment of Idiopathic Hypersomnia (IH) With an Open-label Safety Extension
Official title: A Double-blind, Placebo-controlled, Randomized Withdrawal, Multicenter Study of the Efficacy and Safety of JZP-258 in the Treatment of Idiopathic Hypersomnia (IH) With an Open-label Safety Extension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Idiopathic Hypersomnia
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-05-22
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Male or female between 18 and 75 years of age, inclusive, at the time of consent.
2. Have a primary diagnosis of IH according to the International Classification of Sleep Disorders ICSD-2 or ICSD-3 criteria.
3. 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).
4. If currently treated with Xyrem, must have documented clinical improvement of EDS after the initiation of Xyrem per Investigator's clinical judgment.
5. 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.
6. 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.
7. 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.

Exclusion Criteria:

1. Hypersomnia due to another medical, behavioral, or psychiatric disorder condition.
2. Evidence of untreated or inadequately treated sleep-disordered breathing.
3. Clinically significant parasomnias (eg, sleep walking, rapid eye movement sleep behavior disorder, etc.).
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.

Primary outcomes:
measure: Change in Epworth Sleepiness Scale (ESS) Score
timeFrame: Change from the end of the Stable Dose Period to the end of the Double-blind Randomized Withdrawal Period (DBRW) (2 Weeks)
Secondary outcomes:
measure: Percentage of Participants Reported as Worse on the Patient Global Impression of Change (PGIc)
timeFrame: At the end of the DBRW Period (2 Weeks)
measure: Change in Total Score on the Idiopathic Hypersomnia Severity Scale (IHSS)
timeFrame: Change from the end of the Stable Dose Period to the end of the DBRW Period (2 Weeks)
measure: Percentage of Participants Reported as Worse on the Clinical Global Impression of Change (CGIc)
timeFrame: At the end of the DBRW Period (2 Weeks)
measure: Change in Total Score on the Functional Outcomes of Sleep Questionnaire (FOSQ-10)
timeFrame: Change from the end of the Stable Dose Period to the end of the DBRW Period (2 Weeks)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Sleep Disorders Center of Alabama
state: Alabama
city: Birmingham
country: United States
facility: Wright Clinical Research, LLC
state: Alabama
city: Mobile
country: United States
facility: Coastal Clinical Research
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic Building
state: Arizona
city: Los Angeles
country: United States
facility: Southern California Institute for Respiratory Diseases, Inc.
state: California
city: Redwood City
country: United States
facility: Stanford Sleep Medicine Center
state: California
city: Santa Ana
country: United States
facility: SDS Clinical Trials, Inc.
state: California
city: Boulder
country: United States
facility: Alpine Clinical Research Center
state: Colorado
city: Colorado Springs
country: United States
facility: Delta Waves, Inc.
state: Colorado
city: Brandon
country: United States
facility: PAB Clinical Research
state: Florida
city: Miami
country: United States
facility: Suncoast Research Group
state: Florida
city: Miami
country: United States
facility: Bio-Medical Research, LLC
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida, Inc.
state: Florida
city: Atlanta
country: United States
facility: NeuroTrials Research
state: Georgia
city: Macon
country: United States
facility: Sleep Practitioners, LLC
state: Georgia
city: Stockbridge
country: United States
facility: SleepCare Research Institute d/b/a Clinical Research
state: Georgia
city: Chevy Chase
country: United States
facility: Center for Sleep & Wake Disorders
state: Maryland
city: Springfield
country: United States
facility: Baystate Wesson Sleep Clinic
state: Massachusetts
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Sterling Heights
country: United States
facility: Clinical Neurophysiology Services, P.C.
state: Michigan
city: Minneapolis
country: United States
facility: Minnesota Lung Center
state: Minnesota
city: Saint Louis
country: United States
facility: Clayton Sleep Institute, LLC
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Center/Sleep-Wake Disorders Center
state: New York
city: Charlotte
country: United States
facility: American Health Research
state: North Carolina
city: Gastonia
country: United States
facility: Clinical Research of Gastonia
state: North Carolina
city: Huntersville
country: United States
facility: Research Carolina
state: North Carolina
city: Mooresville
country: United States
facility: Clinical Research of Lake Norman
state: North Carolina
city: Raleigh
country: United States
facility: Raleigh Neurology Associates
state: North Carolina
city: Cincinnati
country: United States
facility: Intrepid Research
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Dublin
country: United States
facility: Ohio Sleep Medicine and Neuroscience Institute
state: Ohio
city: Oklahoma City
country: United States
facility: Lynne Health Science Institute
state: Oklahoma
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Willow Grove
country: United States
facility: Abington Neurological Associates
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Columbia
country: United States
facility: Bogan Sleep Consultants, LLC
state: South Carolina
city: Mount Pleasant
country: United States
facility: Clinical Research of Charleston
state: South Carolina
city: Cordova
country: United States
facility: Neurology Clinic, PC
state: Tennessee
city: Austin
country: United States
facility: FutureSearch Trials of Neurology
state: Texas
city: San Antonio
country: United States
facility: Sleep Therapy & Research Center
state: Texas
city: Alken
country: Belgium
facility: Anima Research Center
city: Edegem
country: Belgium
facility: Antwerp University Hospital
city: Namur
country: Belgium
facility: CHU UCL Namur site de Sainte Elisabeth
city: Hradec Králové
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Praha
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: České Budějovice
country: Czechia
facility: Nemocnice Ceske Budejovice a.s.
city: Helsinki
country: Finland
facility: VitalMed Oy
city: Grenoble
country: France
facility: CHU de Grenoble - Hôpital Michallon
city: Lille
country: France
facility: Hopital Roger Salengro
city: Montpellier
country: France
facility: Hopital Gui de Chauliac
city: Nantes
country: France
facility: CHU Nantes - Hopital Nord Laënnec
city: Paris
country: France
facility: Hopital Pitie-Salpetriere
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Poznań
country: Poland
facility: Osrodek Badan Klinicznych CROMED
city: Warsaw
country: Poland
facility: lnstytut Psychiatrii i Neurologii, Zaklad Neurofizjologii Klinicznej
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Vithas Nuestra Señora de America
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Vitoria
country: Spain
facility: Hospital Universitario Araba
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
Study officials:
References:
citation: 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.