Trial Outcomes & Findings for A Multicenter Study of the Efficacy and Safety of JZP-258 in the Treatment of Idiopathic Hypersomnia (IH) With an Open-label Safety Extension (NCT NCT03533114)

Last Updated: 2021-11-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

154 participants

Primary outcome timeframe

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

Results posted on

2021-11-24

Participant Flow

The safety population is categorized according to the presence or absence of medications used to treat IH symptoms at the time of study baseline.

Participant milestones

Participant milestones
Measure	On Baseline IH Medication Participants treated with medication for IH at baseline.	Treatment Naive Participants not treated with medication for IH at baseline.
Overall STARTED	88	66
Overall COMPLETED	57	38
Overall NOT COMPLETED	31	28
Open Label Titration and Optimization STARTED	88	66
Open Label Titration and Optimization COMPLETED	72	53
Open Label Titration and Optimization NOT COMPLETED	16	13
Stable Dose STARTED	71	52
Stable Dose COMPLETED	69	50
Stable Dose NOT COMPLETED	2	2
Double Blind Randomized-Withdrawal STARTED	69	47
Double Blind Randomized-Withdrawal JZP-258	57	0
Double Blind Randomized-Withdrawal Placebo	0	59
Double Blind Randomized-Withdrawal COMPLETED	67	46
Double Blind Randomized-Withdrawal NOT COMPLETED	2	1
Open-Label Safety Extension STARTED	65	41
Open-Label Safety Extension COMPLETED	57	38
Open-Label Safety Extension NOT COMPLETED	8	3

Reasons for withdrawal

Reasons for withdrawal
Measure	On Baseline IH Medication Participants treated with medication for IH at baseline.	Treatment Naive Participants not treated with medication for IH at baseline.
Overall Adverse Event	16	11
Overall Consent Withdrawal by Participant	7	6
Overall Lack of Efficacy	5	3
Overall Lost to Follow-up	1	1
Overall Physician Decision	0	2
Overall Protocol deviation	1	1
Overall Failure to meet randomization criteria	1	2
Overall Non-Compliance with study drug	0	1
Overall Other	0	1
Open Label Titration and Optimization Adverse Event	11	8
Open Label Titration and Optimization Consent Withdrawal by Participant	2	1
Open Label Titration and Optimization Lack of Efficacy	3	1
Open Label Titration and Optimization Lost to Follow-up	0	1
Open Label Titration and Optimization Protocol Deviation	0	1
Open Label Titration and Optimization Non-Compliance with Study Drug	0	1
Stable Dose Adverse Event	0	2
Stable Dose Consent Withdrawal by Participant	1	0
Stable Dose Lack of Efficacy	1	0
Double Blind Randomized-Withdrawal Adverse Event	1	1
Double Blind Randomized-Withdrawal Failure to Meet Randomization Criteria	1	0
Open-Label Safety Extension Adverse Event	3	0
Open-Label Safety Extension Consent Withdrawal by Participant	2	3
Open-Label Safety Extension Lack of Efficacy	1	0
Open-Label Safety Extension Lost to Follow-up	1	0
Open-Label Safety Extension Protocol Deviation	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	On Baseline IH Medication n=88 Participants Participants treated with medication for IH at baseline.	Treatment Naïve n=66 Participants Participants not treated with medication for IH at baseline.	Total n=154 Participants Total of all reporting groups
Age, Continuous	41.0 years STANDARD_DEVIATION 13.37 • n=5 Participants	39.4 years STANDARD_DEVIATION 14.25 • n=7 Participants	40.3 years STANDARD_DEVIATION 13.73 • n=5 Participants
Sex: Female, Male Female	65 Participants n=5 Participants	40 Participants n=7 Participants	105 Participants n=5 Participants
Sex: Female, Male Male	23 Participants n=5 Participants	26 Participants n=7 Participants	49 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) White	76 Participants n=5 Participants	53 Participants n=7 Participants	129 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Region of Enrollment North America	69 participants n=5 Participants	35 participants n=7 Participants	104 participants n=5 Participants
Region of Enrollment Europe	19 participants n=5 Participants	31 participants n=7 Participants	50 participants n=5 Participants

PRIMARY outcome

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

Outcome measures

Outcome measures
Measure	JZP-258 n=56 Participants Participants randomized to JZP-258 will receive the dosing regimen taken during the Stable Dose Period.	Placebo n=59 Participants Participants randomized to placebo will receive an oral solution equivalent to the dosing regimen of JZP-258 taken during the Stable Dose Period.
Change in Epworth Sleepiness Scale (ESS) Score	0.7 score on a scale Standard Deviation 3.22	7.4 score on a scale Standard Deviation 5.16

SECONDARY outcome

Timeframe: At the end of the DBRW Period (2 Weeks)

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.

Outcome measures

Outcome measures
Measure	JZP-258 n=56 Participants Participants randomized to JZP-258 will receive the dosing regimen taken during the Stable Dose Period.	Placebo n=59 Participants Participants randomized to placebo will receive an oral solution equivalent to the dosing regimen of JZP-258 taken during the Stable Dose Period.
Percentage of Participants Reported as Worse on the Patient Global Impression of Change (PGIc)	12 participants	52 participants

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	JZP-258 n=56 Participants Participants randomized to JZP-258 will receive the dosing regimen taken during the Stable Dose Period.	Placebo n=59 Participants Participants randomized to placebo will receive an oral solution equivalent to the dosing regimen of JZP-258 taken during the Stable Dose Period.
Change in Total Score on the Idiopathic Hypersomnia Severity Scale (IHSS)	0.0 score on a scale Interval -8.0 to 24.0	14.0 score on a scale Interval -2.0 to 38.0

SECONDARY outcome

Timeframe: At the end of the DBRW Period (2 Weeks)

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.

Outcome measures

Outcome measures
Measure	JZP-258 n=56 Participants Participants randomized to JZP-258 will receive the dosing regimen taken during the Stable Dose Period.	Placebo n=59 Participants Participants randomized to placebo will receive an oral solution equivalent to the dosing regimen of JZP-258 taken during the Stable Dose Period.
Percentage of Participants Reported as Worse on the Clinical Global Impression of Change (CGIc)	12 participants	52 participants

SECONDARY outcome

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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	JZP-258 n=54 Participants Participants randomized to JZP-258 will receive the dosing regimen taken during the Stable Dose Period.	Placebo n=56 Participants Participants randomized to placebo will receive an oral solution equivalent to the dosing regimen of JZP-258 taken during the Stable Dose Period.
Change in Total Score on the Functional Outcomes of Sleep Questionnaire (FOSQ-10)	-0.08 score on a scale Interval -8.5 to 4.5	-4.17 score on a scale Interval -12.5 to 1.3

Adverse Events

On Baseline IH Medication

Serious events: 2 serious events

Other events: 64 other events

Deaths: 0 deaths

Treatment Naive

Serious events: 2 serious events

Other events: 39 other events

Deaths: 0 deaths

JZP-058

Serious events: 4 serious events

Other events: 97 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	On Baseline IH Medication n=88 participants at risk Participants treated with medication for IH at baseline.	Treatment Naive n=66 participants at risk Participants not treated with medication for IH at baseline.	JZP-058 n=154 participants at risk 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.	Placebo n=59 participants at risk 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.
General disorders Non-cardiac chest pain	1.1% 1/88 • Number of events 1 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were recorded from the time on or after the first dose of study drug, including adverse events that occurred until 30 days after the last dose date up to 42 weeks.	0.00% 0/66 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were recorded from the time on or after the first dose of study drug, including adverse events that occurred until 30 days after the last dose date up to 42 weeks.	0.65% 1/154 • Number of events 1 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were recorded from the time on or after the first dose of study drug, including adverse events that occurred until 30 days after the last dose date up to 42 weeks.	0.00% 0/59 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were recorded from the time on or after the first dose of study drug, including adverse events that occurred until 30 days after the last dose date up to 42 weeks.
Infections and infestations Pyelonephritis	0.00% 0/88 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were recorded from the time on or after the first dose of study drug, including adverse events that occurred until 30 days after the last dose date up to 42 weeks.	1.5% 1/66 • Number of events 1 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were recorded from the time on or after the first dose of study drug, including adverse events that occurred until 30 days after the last dose date up to 42 weeks.	0.65% 1/154 • Number of events 1 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were recorded from the time on or after the first dose of study drug, including adverse events that occurred until 30 days after the last dose date up to 42 weeks.	0.00% 0/59 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were recorded from the time on or after the first dose of study drug, including adverse events that occurred until 30 days after the last dose date up to 42 weeks.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	1.1% 1/88 • Number of events 1 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were recorded from the time on or after the first dose of study drug, including adverse events that occurred until 30 days after the last dose date up to 42 weeks.	0.00% 0/66 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were recorded from the time on or after the first dose of study drug, including adverse events that occurred until 30 days after the last dose date up to 42 weeks.	0.65% 1/154 • Number of events 1 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were recorded from the time on or after the first dose of study drug, including adverse events that occurred until 30 days after the last dose date up to 42 weeks.	0.00% 0/59 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were recorded from the time on or after the first dose of study drug, including adverse events that occurred until 30 days after the last dose date up to 42 weeks.
Nervous system disorders Syncope	0.00% 0/88 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were recorded from the time on or after the first dose of study drug, including adverse events that occurred until 30 days after the last dose date up to 42 weeks.	1.5% 1/66 • Number of events 1 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were recorded from the time on or after the first dose of study drug, including adverse events that occurred until 30 days after the last dose date up to 42 weeks.	0.65% 1/154 • Number of events 1 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were recorded from the time on or after the first dose of study drug, including adverse events that occurred until 30 days after the last dose date up to 42 weeks.	0.00% 0/59 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were recorded from the time on or after the first dose of study drug, including adverse events that occurred until 30 days after the last dose date up to 42 weeks.
Renal and urinary disorders Nephrolithiasis	0.00% 0/88 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were recorded from the time on or after the first dose of study drug, including adverse events that occurred until 30 days after the last dose date up to 42 weeks.	1.5% 1/66 • Number of events 5 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were recorded from the time on or after the first dose of study drug, including adverse events that occurred until 30 days after the last dose date up to 42 weeks.	0.65% 1/154 • Number of events 5 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were recorded from the time on or after the first dose of study drug, including adverse events that occurred until 30 days after the last dose date up to 42 weeks.	0.00% 0/59 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were recorded from the time on or after the first dose of study drug, including adverse events that occurred until 30 days after the last dose date up to 42 weeks.

Other adverse events

Additional Information

Director, Disclosure & Transparency

Jazz Pharmaceuticals

Phone: 2158709177

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor can review trial results communications prior to public release and can embargo such communications for a period of at least 60 days from the time submitted to sponsor for review. If requested by sponsor, the PI will withhold publication for up to an additional 30 days. Furthermore, the first publication of study results must be a joint publication of all study sites unless a joint manuscript has not been submitted for publication within 12 months of completion of the study.
Publication restrictions are in place

Restriction type: OTHER