A Multicenter Study of the Efficacy and Safety of JZP-258... | NCT03533114

ID	Type	Description	Link
2018-001311-79	EudraCT Number

Status Module

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
JZP-258	Drug	Participants randomized to JZP-258 will receive the dose taken at the end of the Stable Dose Period.	JZP-258

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Facility	Status	City	State	ZIP	Country	Contacts
Sleep Disorders Center of Alabama		Birmingham	Alabama	35213	United States
Wright Clinical Research, LLC

PubMed Identifier	Type	Citation	Retractions
42382222	Derived	Lin J, Lowe C, Banderas B, Chandler P, Arenson E, Shields AL, Morris S, Srivastava B, Dauvilliers Y. Content Validity and Psychometric Evaluation of the Idiopathic Hypersomnia Severity Scale (IHSS) in Adults with Idiopathic Hypersomnia. Nat Sci Sleep. 2026 Jun 26;18:571289. doi: 10.2147/NSS.S571289. eCollection 2026.
40135693	Derived

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	On Baseline IH Medication	Participants treated with medication for IH at baseline.
FG001	Treatment Naive	Participants not treated with medication for IH at baseline.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 20, 2019	Sep 3, 2021

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

Posted

Mean

Standard Deviation

score on a scale

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

ID	Title	Description
OG000	JZP-258	Participants randomized to JZP-258 will receive the dosing regimen taken during the Stable Dose Period.
OG001	Placebo	Participants randomized to placebo will receive an oral solution equivalent to the dosing regimen of JZP-258 taken during the Stable Dose Period.

Units	Counts
Participants	OG00056 OG00159

Title

Denominators

Categories

Title	Measurements
	OG0000.7± 3.22 OG0017.4± 5.16

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.

Posted

Number

participants

At the end of the DBRW Period (2 Weeks)

ID	Title	Description
OG000	JZP-258	Participants randomized to JZP-258 will receive the dosing regimen taken during the Stable Dose Period.
OG001	Placebo	Participants randomized to placebo will receive an oral solution equivalent to the dosing regimen of JZP-258 taken during the Stable Dose Period.

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.

Posted

Median

Full Range

score on a scale

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

ID	Title	Description
OG000	JZP-258	Participants randomized to JZP-258 will receive the dosing regimen taken during the Stable Dose Period.
OG001	Placebo	Participants randomized to placebo will receive an oral solution equivalent to the dosing regimen of JZP-258 taken during the Stable Dose Period.

Units	Counts
Participants

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.

Posted

Number

participants

At the end of the DBRW Period (2 Weeks)

ID	Title	Description
OG000	JZP-258	Participants randomized to JZP-258 will receive the dosing regimen taken during the Stable Dose Period.
OG001	Placebo	Participants randomized to placebo will receive an oral solution equivalent to the dosing regimen of JZP-258 taken during the Stable Dose Period.

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.

The Modified Intent to Treat (mITT) analysis set included all participants who were randomized to JZP258 or placebo, who received at least 1 dose of study drug during the DBRW and have had at least one set of post randomization assessments for ESS or IHSS, or a PGIc value at the end of the DBRW. JZP-258 overall number was 54 and placebo group overall number was 56 as fewer participants were available for this particular assessment.

Posted

Median

Full Range

score on a scale

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

ID	Title	Description
OG000	JZP-258	Participants randomized to JZP-258 will receive the dosing regimen taken during the Stable Dose Period.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	On Baseline IH Medication	Participants treated with medication for IH at baseline.	88	2	88	64	88
EG001	Treatment Naive	Participants not treated with medication for IH at baseline.	66	2	66	39	66
EG002	JZP-058	Participants randomized to JZP-258 will receive the dose taken at the end of the Stable Dose Period at the stable dose and regimen for 2 weeks.	154	4	154	97	154
EG003	Placebo	Participants randomized to placebo were administered placebo oral solution at a volume and regimen equivalent to the JZP-258 dose and regimen for 2 weeks.	59	0	59	10	59

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Non-cardiac chest pain	General disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected88 at risk EG0010 events0 affected66 at risk EG0021 events1 affected154 at risk EG0030 events0 affected59 at risk
Pyelonephritis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected88 at risk EG0011 events1 affected66 at risk EG0021 events1 affected154 at risk EG003
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected88 at risk EG0010 events0 affected66 at risk EG0021 events1 affected154 at risk EG003
Syncope	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected88 at risk EG0011 events1 affected66 at risk EG0021 events1 affected154 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected88 at risk EG0015 events1 affected66 at risk EG0025 events1 affected154 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG00015 events11 affected88 at risk EG0014 events3 affected66 at risk EG00217 events12 affected154 at risk EG0032 events2 affected59 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0008 events8 affected88 at risk EG0012 events2 affected66 at risk EG00210 events10 affected154 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG00031 events21 affected88 at risk EG00114 events13 affected66 at risk EG00244 events34 affected154 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG00018 events15 affected88 at risk EG0013 events3 affected66 at risk EG00219 events17 affected154 at risk EG003
Fatigue	General disorders	MedDRA 19.1	Systematic Assessment	EG00010 events8 affected88 at risk EG0015 events4 affected66 at risk EG00214 events11 affected154 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0006 events6 affected88 at risk EG0017 events6 affected66 at risk EG00213 events12 affected154 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0007 events7 affected88 at risk EG0016 events5 affected66 at risk EG00213 events12 affected154 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0007 events6 affected88 at risk EG0017 events6 affected66 at risk EG00214 events12 affected154 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0007 events7 affected88 at risk EG0017 events7 affected66 at risk EG00214 events14 affected154 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0009 events7 affected88 at risk EG0011 events1 affected66 at risk EG00210 events8 affected154 at risk EG003
Dizziness	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0008 events8 affected88 at risk EG00111 events11 affected66 at risk EG00219 events19 affected154 at risk EG003
Headache	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG00026 events15 affected88 at risk EG00116 events12 affected66 at risk EG00240 events27 affected154 at risk EG003
Tremor	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG00011 events9 affected88 at risk EG0010 events0 affected66 at risk EG00211 events9 affected154 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG00011 events10 affected88 at risk EG0018 events8 affected66 at risk EG00218 events17 affected154 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG00015 events13 affected88 at risk EG0014 events4 affected66 at risk EG00213 events11 affected154 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG00010 events7 affected88 at risk EG0012 events2 affected66 at risk EG00212 events9 affected154 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0005 events5 affected88 at risk EG0011 events1 affected66 at risk EG0020 events0 affected154 at risk EG003
Sinusitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected88 at risk EG0015 events4 affected66 at risk EG0020 events0 affected154 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0005 events5 affected88 at risk EG0011 events1 affected66 at risk EG0020 events0 affected154 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0006 events5 affected88 at risk EG0013 events2 affected66 at risk EG0020 events0 affected154 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0006 events6 affected88 at risk EG0010 events0 affected66 at risk EG0020 events0 affected154 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0005 events5 affected88 at risk EG0010 events0 affected66 at risk EG0020 events0 affected154 at risk EG003
Somnolence	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0006 events5 affected88 at risk EG0015 events4 affected66 at risk EG0020 events0 affected154 at risk EG003
Snoring	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected88 at risk EG0015 events4 affected66 at risk EG0020 events0 affected154 at risk EG003

ID	Term
D006970	Disorders of Excessive Somnolence
D020919	Sleep Disorders, Intrinsic
D020920	Dyssomnias
D012893	Sleep Wake Disorders
D009422	Nervous System Diseases
D001523	Mental Disorders

ID	Title	Description
BG000	On Baseline IH Medication	Participants treated with medication for IH at baseline.
BG001	Treatment Naïve	Participants not treated with medication for IH at baseline.
BG002	Total	Total of all reporting groups