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

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ClinicalTrials.gov Identifier: NCT03533114
Recruitment Status : Completed
First Posted : May 22, 2018
Results First Posted : November 24, 2021
Last Update Posted : November 24, 2021
Sponsor:
Information provided by (Responsible Party):
Jazz Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Idiopathic Hypersomnia
Interventions Drug: JZP-258
Drug: Placebo Oral Solution
Enrollment 154
Recruitment Details The safety population is categorized according to the presence or absence of medications used to treat IH symptoms at the time of study baseline.
Pre-assignment Details  
Arm/Group Title On Baseline IH Medication Treatment Naive
Hide Arm/Group Description Participants treated with medication for IH at baseline. Participants not treated with medication for IH at baseline.
Period Title: Overall
Started 88 66
Completed 57 38
Not Completed 31 28
Reason Not Completed
Adverse Event             16             11
Consent Withdrawal by Participant             7             6
Lack of Efficacy             5             3
Lost to Follow-up             1             1
Physician Decision             0             2
Protocol deviation             1             1
Failure to meet randomization criteria             1             2
Non-Compliance with study drug             0             1
Other             0             1
Period Title: Open Label Titration and Optimization
Started 88 66
Completed 72 53
Not Completed 16 13
Reason Not Completed
Adverse Event             11             8
Consent Withdrawal by Participant             2             1
Lack of Efficacy             3             1
Lost to Follow-up             0             1
Protocol Deviation             0             1
Non-Compliance with Study Drug             0             1
Period Title: Stable Dose
Started 71 52
Completed 69 50
Not Completed 2 2
Reason Not Completed
Adverse Event             0             2
Consent Withdrawal by Participant             1             0
Lack of Efficacy             1             0
Period Title: Double Blind Randomized-Withdrawal
Started 69 47
JZP-258 57 0
Placebo 0 59
Completed 67 46
Not Completed 2 1
Reason Not Completed
Adverse Event             1             1
Failure to Meet Randomization Criteria             1             0
Period Title: Open-Label Safety Extension
Started 65 41
Completed 57 38
Not Completed 8 3
Reason Not Completed
Adverse Event             3             0
Consent Withdrawal by Participant             2             3
Lack of Efficacy             1             0
Lost to Follow-up             1             0
Protocol Deviation             1             0
Arm/Group Title On Baseline IH Medication Treatment Naïve Total
Hide Arm/Group Description Participants treated with medication for IH at baseline. Participants not treated with medication for IH at baseline. Total of all reporting groups
Overall Number of Baseline Participants 88 66 154
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 88 participants 66 participants 154 participants
41.0  (13.37) 39.4  (14.25) 40.3  (13.73)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 88 participants 66 participants 154 participants
Female
65
  73.9%
40
  60.6%
105
  68.2%
Male
23
  26.1%
26
  39.4%
49
  31.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 88 participants 66 participants 154 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   1.5%
1
   0.6%
Black or African American
5
   5.7%
4
   6.1%
9
   5.8%
White
76
  86.4%
53
  80.3%
129
  83.8%
More than one race
0
   0.0%
1
   1.5%
1
   0.6%
Unknown or Not Reported
7
   8.0%
7
  10.6%
14
   9.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 88 participants 66 participants 154 participants
North America 69 35 104
Europe 19 31 50
1.Primary Outcome
Title Change in Epworth Sleepiness Scale (ESS) Score
Hide Description 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.
Time Frame Change from the end of the Stable Dose Period to the end of the Double-blind Randomized Withdrawal Period (DBRW) (2 Weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title JZP-258 Placebo
Hide Arm/Group Description:
Participants randomized to JZP-258 will receive the dosing regimen taken during the Stable Dose Period.
Participants randomized to placebo will receive an oral solution equivalent to the dosing regimen of JZP-258 taken during the Stable Dose Period.
Overall Number of Participants Analyzed 56 59
Mean (Standard Deviation)
Unit of Measure: score on a scale
0.7  (3.22) 7.4  (5.16)
2.Secondary Outcome
Title Percentage of Participants Reported as Worse on the Patient Global Impression of Change (PGIc)
Hide Description 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.
Time Frame At the end of the DBRW Period (2 Weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title JZP-258 Placebo
Hide Arm/Group Description:
Participants randomized to JZP-258 will receive the dosing regimen taken during the Stable Dose Period.
Participants randomized to placebo will receive an oral solution equivalent to the dosing regimen of JZP-258 taken during the Stable Dose Period.
Overall Number of Participants Analyzed 56 59
Measure Type: Number
Unit of Measure: participants
12 52
3.Secondary Outcome
Title Change in Total Score on the Idiopathic Hypersomnia Severity Scale (IHSS)
Hide Description 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.
Time Frame Change from the end of the Stable Dose Period to the end of the DBRW Period (2 Weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title JZP-258 Placebo
Hide Arm/Group Description:
Participants randomized to JZP-258 will receive the dosing regimen taken during the Stable Dose Period.
Participants randomized to placebo will receive an oral solution equivalent to the dosing regimen of JZP-258 taken during the Stable Dose Period.
Overall Number of Participants Analyzed 56 59
Median (Full Range)
Unit of Measure: score on a scale
0.0
(-8 to 24)
14.0
(-2 to 38)
4.Secondary Outcome
Title Percentage of Participants Reported as Worse on the Clinical Global Impression of Change (CGIc)
Hide Description 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.
Time Frame At the end of the DBRW Period (2 Weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title JZP-258 Placebo
Hide Arm/Group Description:
Participants randomized to JZP-258 will receive the dosing regimen taken during the Stable Dose Period.
Participants randomized to placebo will receive an oral solution equivalent to the dosing regimen of JZP-258 taken during the Stable Dose Period.
Overall Number of Participants Analyzed 56 59
Measure Type: Number
Unit of Measure: participants
12 52
5.Secondary Outcome
Title Change in Total Score on the Functional Outcomes of Sleep Questionnaire (FOSQ-10)
Hide Description 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.
Time Frame Change from the end of the Stable Dose Period to the end of the DBRW Period (2 Weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title JZP-258 Placebo
Hide Arm/Group Description:
Participants randomized to JZP-258 will receive the dosing regimen taken during the Stable Dose Period.
Participants randomized to placebo will receive an oral solution equivalent to the dosing regimen of JZP-258 taken during the Stable Dose Period.
Overall Number of Participants Analyzed 54 56
Median (Full Range)
Unit of Measure: score on a scale
-0.08
(-8.5 to 4.5)
-4.17
(-12.5 to 1.3)
Time Frame 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.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title On Baseline IH Medication Treatment Naive JZP-058 Placebo
Hide Arm/Group Description Participants treated with medication for IH at baseline. Participants not treated with medication for IH at baseline. 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. 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.
All-Cause Mortality
On Baseline IH Medication Treatment Naive JZP-058 Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/88 (0.00%)      0/66 (0.00%)      0/154 (0.00%)      0/59 (0.00%)    
Hide Serious Adverse Events
On Baseline IH Medication Treatment Naive JZP-058 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/88 (2.27%)      2/66 (3.03%)      4/154 (2.60%)      0/59 (0.00%)    
General disorders         
Non-cardiac chest pain  1  1/88 (1.14%)  1 0/66 (0.00%)  0 1/154 (0.65%)  1 0/59 (0.00%)  0
Infections and infestations         
Pyelonephritis  1  0/88 (0.00%)  0 1/66 (1.52%)  1 1/154 (0.65%)  1 0/59 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Rhabdomyolysis  1  1/88 (1.14%)  1 0/66 (0.00%)  0 1/154 (0.65%)  1 0/59 (0.00%)  0
Nervous system disorders         
Syncope  1  0/88 (0.00%)  0 1/66 (1.52%)  1 1/154 (0.65%)  1 0/59 (0.00%)  0
Renal and urinary disorders         
Nephrolithiasis  1  0/88 (0.00%)  0 1/66 (1.52%)  5 1/154 (0.65%)  5 0/59 (0.00%)  0
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
On Baseline IH Medication Treatment Naive JZP-058 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   64/88 (72.73%)      39/66 (59.09%)      97/154 (62.99%)      10/59 (16.95%)    
Gastrointestinal disorders         
Diarrhoea  1  11/88 (12.50%)  15 3/66 (4.55%)  4 12/154 (7.79%)  17 2/59 (3.39%)  2
Dry mouth  1  8/88 (9.09%)  8 2/66 (3.03%)  2 10/154 (6.49%)  10 0/59 (0.00%)  0
Nausea  1  21/88 (23.86%)  31 13/66 (19.70%)  14 34/154 (22.08%)  44 1/59 (1.69%)  1
Vomiting  1  15/88 (17.05%)  18 3/66 (4.55%)  3 17/154 (11.04%)  19 2/59 (3.39%)  2
Constipation  1  5/88 (5.68%)  5 1/66 (1.52%)  1 0/154 (0.00%)  0 0/59 (0.00%)  0
General disorders         
Fatigue  1  8/88 (9.09%)  10 4/66 (6.06%)  5 11/154 (7.14%)  14 1/59 (1.69%)  1
Infections and infestations         
Nasopharyngitis  1  6/88 (6.82%)  6 6/66 (9.09%)  7 12/154 (7.79%)  13 0/59 (0.00%)  0
Upper respiratory tract infection  1  7/88 (7.95%)  7 5/66 (7.58%)  6 12/154 (7.79%)  13 0/59 (0.00%)  0
Urinary tract infection  1  6/88 (6.82%)  7 6/66 (9.09%)  7 12/154 (7.79%)  14 0/59 (0.00%)  0
Sinusitis  1  1/88 (1.14%)  1 4/66 (6.06%)  5 0/154 (0.00%)  0 0/59 (0.00%)  0
Injury, poisoning and procedural complications         
Fall  1  5/88 (5.68%)  5 1/66 (1.52%)  1 0/154 (0.00%)  0 0/59 (0.00%)  0
Metabolism and nutrition disorders         
Decreased appetite  1  7/88 (7.95%)  7 7/66 (10.61%)  7 14/154 (9.09%)  14 0/59 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Muscle spasms  1  7/88 (7.95%)  9 1/66 (1.52%)  1 8/154 (5.19%)  10 0/59 (0.00%)  0
Back pain  1  5/88 (5.68%)  6 2/66 (3.03%)  3 0/154 (0.00%)  0 0/59 (0.00%)  0
Pain in extremity  1  6/88 (6.82%)  6 0/66 (0.00%)  0 0/154 (0.00%)  0 0/59 (0.00%)  0
Nervous system disorders         
Dizziness  1  8/88 (9.09%)  8 11/66 (16.67%)  11 19/154 (12.34%)  19 0/59 (0.00%)  0
Headache  1  15/88 (17.05%)  26 12/66 (18.18%)  16 27/154 (17.53%)  40 2/59 (3.39%)  2
Tremor  1  9/88 (10.23%)  11 0/66 (0.00%)  0 9/154 (5.84%)  11 0/59 (0.00%)  0
Paraesthesia  1  5/88 (5.68%)  5 0/66 (0.00%)  0 0/154 (0.00%)  0 0/59 (0.00%)  0
Somnolence  1  5/88 (5.68%)  6 4/66 (6.06%)  5 0/154 (0.00%)  0 0/59 (0.00%)  0
Psychiatric disorders         
Anxiety  1  10/88 (11.36%)  11 8/66 (12.12%)  8 17/154 (11.04%)  18 1/59 (1.69%)  1
Insomnia  1  13/88 (14.77%)  15 4/66 (6.06%)  4 11/154 (7.14%)  13 6/59 (10.17%)  6
Respiratory, thoracic and mediastinal disorders         
Snoring  1  1/88 (1.14%)  1 4/66 (6.06%)  5 0/154 (0.00%)  0 0/59 (0.00%)  0
Skin and subcutaneous tissue disorders         
Night sweats  1  7/88 (7.95%)  10 2/66 (3.03%)  2 9/154 (5.84%)  12 0/59 (0.00%)  0
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Director, Disclosure & Transparency
Organization: Jazz Pharmaceuticals
Phone: 2158709177
EMail: ClinicalTrialDisclosure@JazzPharma.com
Layout table for additonal information
Responsible Party: Jazz Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03533114    
Other Study ID Numbers: JZP080-301
2018-001311-79 ( EudraCT Number )
First Submitted: May 10, 2018
First Posted: May 22, 2018
Results First Submitted: September 7, 2021
Results First Posted: November 24, 2021
Last Update Posted: November 24, 2021