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

Idiopathic Hypersomnia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03533114
• Other study ID #: JZP080-301
• Secondary ID: 2018-001311-79
• Status: Completed
• Phase: Phase 3
• Start date: November 27, 2018
• Est. completion date: December 18, 2020

Study information

• Verified date: November 2021
• Source: Jazz Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 154
• Est. completion date: December 18, 2020
• Est. primary completion date: June 12, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Disorders of Excessive Somnolence
• Idiopathic Hypersomnia

Intervention

Drug:
• JZP-258
Participants randomized to JZP-258 will receive the dose taken at the end of the Stable Dose Period.
• Placebo Oral Solution
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.

Locations

Country	Name	City	State
Belgium	Anima Research Center	Alken
Belgium	Antwerp University Hospital	Edegem
Belgium	CHU UCL Namur site de Sainte Elisabeth	Namur
Czechia	Nemocnice Ceske Budejovice a.s.	Ceské Budejovice
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Králové
Czechia	Vseobecna fakultni nemocnice v Praze	Praha
Finland	VitalMed Oy	Helsinki
France	CHU de Grenoble - Hôpital Michallon	Grenoble
France	Hopital Roger Salengro	Lille
France	Hopital Gui de Chauliac	Montpellier
France	CHU Nantes - Hopital Nord Laënnec	Nantes
France	Hopital Pitie-Salpetriere	Paris
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Osrodek Badan Klinicznych CROMED	Poznan
Poland	lnstytut Psychiatrii i Neurologii, Zaklad Neurofizjologii Klinicznej	Warsaw
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario Clinico San Carlos	Madrid
Spain	Hospital Vithas Nuestra Señora de America	Madrid
Spain	Hospital Universitari i Politecnic La Fe	Valencia
Spain	Hospital Universitario Araba	Vitoria
United Kingdom	Royal Infirmary of Edinburgh	Edinburgh
United States	NeuroTrials Research	Atlanta	Georgia
United States	FutureSearch Trials of Neurology	Austin	Texas
United States	Sleep Disorders Center of Alabama	Birmingham	Alabama
United States	Wright Clinical Research, LLC	Birmingham	Alabama
United States	Alpine Clinical Research Center	Boulder	Colorado
United States	PAB Clinical Research	Brandon	Florida
United States	Montefiore Medical Center/Sleep-Wake Disorders Center	Bronx	New York
United States	Medical University of South Carolina	Charleston	South Carolina
United States	American Health Research	Charlotte	North Carolina
United States	Center for Sleep & Wake Disorders	Chevy Chase	Maryland
United States	Intrepid Research	Cincinnati	Ohio
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	Delta Waves, Inc.	Colorado Springs	Colorado
United States	Bogan Sleep Consultants, LLC	Columbia	South Carolina
United States	Neurology Clinic, PC	Cordova	Tennessee
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Ohio Sleep Medicine and Neuroscience Institute	Dublin	Ohio
United States	Clinical Research of Gastonia	Gastonia	North Carolina
United States	Research Carolina	Huntersville	North Carolina
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	Southern California Institute for Respiratory Diseases, Inc.	Los Angeles	California
United States	Sleep Practitioners, LLC	Macon	Georgia
United States	Bio-Medical Research, LLC	Miami	Florida
United States	Suncoast Research Group	Miami	Florida
United States	Minnesota Lung Center	Minneapolis	Minnesota
United States	Coastal Clinical Research	Mobile	Alabama
United States	Clinical Research of Lake Norman	Mooresville	North Carolina
United States	Clinical Research of Charleston	Mount Pleasant	South Carolina
United States	Lynne Health Science Institute	Oklahoma City	Oklahoma
United States	Mayo Clinic Building	Phoenix	Arizona
United States	Raleigh Neurology Associates	Raleigh	North Carolina
United States	Stanford Sleep Medicine Center	Redwood City	California
United States	Clayton Sleep Institute, LLC	Saint Louis	Missouri
United States	Sleep Therapy & Research Center	San Antonio	Texas
United States	SDS Clinical Trials, Inc.	Santa Ana	California
United States	Baystate Wesson Sleep Clinic	Springfield	Massachusetts
United States	Clinical Neurophysiology Services, P.C.	Sterling Heights	Michigan
United States	SleepCare Research Institute d/b/a Clinical Research	Stockbridge	Georgia
United States	Clinical Research of West Florida, Inc.	Tampa	Florida
United States	Abington Neurological Associates	Willow Grove	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Jazz Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Czechia,  Finland,  France,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percentage of Participants Reported as Worse on the Patient Global Impression of Change (PGIc)	The Patient Global Impression - Change (PGIc) scale was completed by the participant. The PGI-C scale rated the participant's condition at a specified time point on a 7-point scale ranging from a minimum of "Very much improved" to a maximum of "Very much worse." The PGIc scale consists of the following ratings: 1-Very Much improved, 2-Much improved, 3-Minimally improved, 4-No change, 5-Minimally worse, 6-Much worse, 7-Very much worse; a rating of 1 indicates a better outcome, and a rating of 7 indicates a worse outcome. Worsened condition was defined as a PGIc rating of 5, 6, or 7.	At the end of the DBRW Period (2 Weeks)
Secondary	Change in Total Score on the Idiopathic Hypersomnia Severity Scale (IHSS)	The IHSS is a 14-item self-reported questionnaire assessing the severity of IH symptoms of excessive sleepiness, prolonged sleep duration, cognitive impairment and sleep inertia. Total scores can range from 0 to 50, with higher scores indicating a greater severity or frequency of symptoms.	Change from the end of the Stable Dose Period to the end of the DBRW Period (2 Weeks)
Secondary	Percentage of Participants Reported as Worse on the Clinical Global Impression of Change (CGIc)	The CGIc scale is a 7-point Likert-type scale that rates the Investigator's impression of any change in the severity of the participant's condition at a specified time point. The participant was rated on a 7-point scale ranging from a minimum of "Very much improved" to a maximum of "Very much worse." The CGIc scale consists of the following ratings: 1-Very Much improved, 2-Much improved, 3-Minimally improved, 4-No change, 5-Minimally worse, 6-Much worse, 7-Very much worse; a rating of 1 indicates a better outcome, and a rating of 7 indicates a worse outcome. Worsened condition was defined as a CGIc rating of 5, 6, or 7.	At the end of the DBRW Period (2 Weeks)
Secondary	Change in Total Score on the Functional Outcomes of Sleep Questionnaire (FOSQ-10)	The FOSQ-10 is a short version of the original FOSQ-30 instrument, which is a disease specific quality of life questionnaire to determine functional status in adults. Measures are designed to assess the impact of disorders of excessive sleepiness on multiple activities of everyday living and the extent to which these activities are improved by effective treatment. The questionnaire has a 4-point Likert response format (e.g., 1= extreme difficulty, 2= moderate difficulty, 3=a little difficulty, and 4 =no difficulty). FOSQ-10 total score is calculated by first taking the mean of the items for each subscale with more than 1 item completed and then taking the mean across the non-missing 5 subscales (General Productivity, Activity Level, Vigilance, Social Outcomes, Intimacy and Sexual Relationship) multiplied by 5. The score ranges from a minimum of 5 points to a maximum of 20 points, with higher scores indicating better functional status.	Change from the end of the Stable Dose Period to the end of the DBRW Period (2 Weeks)