A Phase 3 interventional study of Open-label Pitolisant and Double-blind Placebo in Idiopathic Hypersomnia, sponsored by Harmony Biosciences Management, Inc.. Completed at 58 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-25.
Sponsored by Harmony Biosciences Management, Inc. (part of Harmony Biosciences Holdings, Inc.) · Phase 3, Interventional, and Treatment
The primary objective of this study is to evaluate the safety and efficacy of pitolisant compared with placebo in treating excessive daytime sleepiness (EDS) in participants with idiopathic hypersomnia (IH) age ≥18 years.
Key secondary objectives of this study are to assess the impact of pitolisant on:
Other secondary objectives of this study are to assess the impact of pitolisant in participants with IH on:
This is a double-blind, placebo-controlled, randomized withdrawal study in adult participants (ages ≥18 years) with IH. The study will consist of a Screening Period (up to 28 days), an 8-week Open-Label Phase, and a 4-week Double-Blind Randomized Withdrawal Phase.
The Open-Label Phase of the study will be 8 weeks, which includes a 6-week Dose Optimization Period and a 2-week Stable Dose Period. In the Dose Optimization Period, all participants will be titrated to their optimal dose of open-label pitolisant (17.8 milligrams [mg] or 35.6 mg) based on Investigator assessment of tolerability and efficacy. The 3-week titration period will be followed by 3 weeks of flexible dosing (weeks 4-6) during which participants will continue to receive their optimal dose of 17.8 mg or 35.6 mg open-label pitolisant. Participants taking a strong cytochrome P450 2D6 (CYP2D6) inhibitor will be allowed in the study; however, for these participants, the maximum permitted daily dose of pitolisant will be 17.8 mg. Following completion of the 6-week Dose Optimization Period, participants will enter the 2-week Stable Dose Period. During this period, participants will remain at their optimal dose (the same dose they were taking at the end of the Dose Optimization Period [17.8 mg or 35.6 mg]) of open-label pitolisant for 2 weeks; dose adjustments are not allowed during the Stable Dose Period. At the end of the Stable Dose Period, participants will be defined as responders or non-responders. Responders will be randomized in a 1:1 ratio to receive blinded study drug (pitolisant or matching placebo) in the Double-Blind Randomized Withdrawal Phase of the study. Non-responders will not be randomized to treatment in the Double-Blind Randomized Withdrawal Phase and will complete two safety follow-up telephone contacts (TCs) at 15 (±3) days and 30 (+3) days after their final dose of open-label pitolisant.
During the Double-Blind Randomized Withdrawal Phase, participants (approximately 64 participants per treatment group) will receive blinded study drug either at the same dose they were taking in the Stable Dose Period (17.8 mg or 35.6 mg pitolisant) or matching placebo. The duration of the Double-Blind Randomized Withdrawal Phase will be 4 weeks (weeks 9-12); dose adjustments are not permitted during this phase of the study. After completion of the Double-Blind Randomized Withdrawal Phase (End-of Treatment Visit is on Day 84, the last day of blinded treatment), participants will complete two safety follow-up TCs with the site at 15 (±3) days and 30 (+3) days after their final dose of blinded study drug, which will include assessment for adverse events and concomitant medication use; alternatively, participants will have the opportunity to enroll in a long-term, open-label safety study under a separate protocol. Participants who opt to enroll into the long-term, open-label study will not complete the 15-day and 30-day follow-up TCs.
52 studies on the registry are indexed under Idiopathic Hypersomnia; 23 are open to participants now.
This study's enrollment of 214 is above the median of 82 across 40 interventional studies indexed under Idiopathic Hypersomnia.
Browse Idiopathic Hypersomnia studies →Harmony Biosciences Management, Inc. is the lead sponsor of 16 studies on the registry; 6 are open to participants now.
Of its 8 completed or terminated interventional studies of FDA-regulated products, 4 (50%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
If on a treatment that could affect daytime sleepiness (including but not limited to oxybates, stimulants, modafinil, and armodafinil):
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Washout period
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Double-blind pitolisant administered once daily in the morning upon wakening for 4 weeks during the Double-Blind Randomized Withdrawal Phase
Drug: Double-blind Pitolisant
Matching placebo administered once daily in the morning upon wakening for 4 weeks during the Double-Blind Randomized Withdrawal Phase
Drug: Double-blind Placebo
Open-label pitolisant administered once daily in the morning upon wakening for 8 weeks during the Open-Label Phase
Drug: Open-label Pitolisant
Pitolisant 4.45 mg tablets: white, round, plain, biconvex film-coated tablet, 3.7 millimeters (mm) in diameter. Each tablet contains 5 mg of pitolisant hydrochloride equivalent to 4.45 mg of pitolisant. Pitolisant 17.8 mg tablets: white, round, plain, biconvex film-coated tablet, 7.5 mm in diameter. Each tablet contains 20 mg of pitolisant hydrochloride equivalent to 17.8 mg of pitolisant.
Matching placebo tablets will be provided for each strength of active pitolisant film-coated tablets.
Pitolisant 4.45 mg tablets: white, round, plain, biconvex film-coated tablet, 3.7 mm in diameter. Each tablet contains 5 mg of pitolisant hydrochloride equivalent to 4.45 mg of pitolisant. Pitolisant 17.8 mg tablets: white, round, plain, biconvex film-coated tablet, 7.5 mm in diameter. Each tablet contains 20 mg of pitolisant hydrochloride equivalent to 17.8 mg of pitolisant.
Change in Epworth Sleepiness Scale (ESS) Score From Week 8 to Week 12
The Epworth Sleepiness Scale (ESS) is an 8-item, 4-point rating scale that asks participants to rate the likelihood of falling asleep over the past week. The rating scale ranges from 0 (no chance of dozing) to 3 (high chance of dozing). The total score is calculated by summing the item level ratings. Total scores range from 0 to 24. Higher point totals represent more severe daytime sleepiness.
Time frame: Week 8 to Week 12
Change in Idiopathic Hypersomnia Severity Scale (IHSS) From Week 8 to Week 12
The Idiopathic Hypersomnia Severity Scale (IHSS) is a self-administered questionnaire with a total of 14 items that assess long sleep duration and sleep inertia (5 items), daytime functioning (7 items), and napping (2 items). All items are scored from 0 to 3 or from 0 to 4. The total score is a sum of the item scores. The total score ranges from 0 to 50. A higher score indicates more severe and frequent symptoms.
Time frame: Week 8 to Week 12
Proportion of Participants Who Worsened on the Patient Global Impression of Change for Idiopathic Hypersomnia (PGI-C [IH]) From Week 8 to Week 12
The Patient Global Impression of Change for Idiopathic Hypersomnia (PGI-C \[IH\]) is a single-item questionnaire that assesses a participant's overall impression of the change in their symptoms of IH. The scale asks participants to rate their overall impression of the change in their symptoms of IH since a specific timepoint on a 5-point verbal rating scale ranging from "much better" to "much worse."
Time frame: Week 8 to Week 12
Change in Clinical Global Impression of Severity for IH (CGI-S [IH]) From Week 8 to Week 12
The CGI-S (IH) is an investigator-rated assessment. It uses a single-item, 5-point Likert-type rating scale that ranges from: none (1); mild (2); moderate (3); severe (4); very severe (5). An assessment of less severe symptoms represents an improvement in the investigator's perception of the participant's overall clinical status related to idiopathic hypersomnia and is reflected by a decrease in score.
Time frame: Week 8 to Week 12
Change in Patient Global Impression of Severity Scale for Excessive Daytime Sleepiness (PGI-S [EDS]) From Week 8 to Week 12
The Patient Global Impression of Severity for Excessive Daytime Sleepiness (PGI-S \[EDS\]) asks participants to rate their overall impression of the severity of their EDS over the past 7 days on a 5-point verbal rating scale ranging from "none" to "very severe". Scores are: 1=None, 2=Mild, 3=Moderate, 4=Severe, and 5=Very Severe.
Time frame: Week 8 to Week 12
Change in Functional Outcomes of Sleep Questionnaire 10-Item Version (FOSQ-10) From Week 8 to Week 12
The Functional Outcomes of Sleep Questionnaire 10-Item Version (FOSQ-10) consists of 10 items assessing the impact of sleepiness on daily functioning across 5 domains: vigilance, general productivity, social outcomes, intimacy, and activity level. Each item is rated on a scale of 0 (activity not performed for other reasons), 1 (extreme difficulty), 2 (moderate difficulty), 3 (a little difficulty), and 4 (no difficulty). The FOSQ-10 total score is calculated by multiplying the mean of the subscale scores by five, with final scores ranging from 5-20. Higher scores correspond to less impairment/symptomatic severity.
Time frame: Week 8 to Week 12
Change in Patient-Reported Outcomes Measurement Information System Sleep-Related Impairment Short Form 8a (PROMIS-SRI SF 8a) From Week 8 to Week 12
The PROMIS-SRI SF 8a is a self-report measure that includes 8 questions designed to assess a participant's perceptions of their waking alertness, sleepiness, and tiredness during usual waking hours, and the perceived functional impairments during wakefulness associated with sleep problems or impaired alertness over the past week. Responses are rated using a 5-point scale, with responses ranging from: 1=not at all; 2=a little bit; 3=somewhat; 4=quite a bit; 5=very much, with average scores ranging from 8 to 40. Raw scores are converted to a T-score using the conversion table from the PROMIS-SRI Scoring Manual. Raw score ranges from 8 to 40; T-score ranges from 30 to 80.1. Higher scores represent greater impairment.
Time frame: Week 8 to Week 12
Change in Sleep Inertia Questionnaire (SIQ) From Week 8 to Week 12
The Sleep Inertia Questionnaire (SIQ) consists of 21 questions that assess sleep inertia. Each question is rated on a scale of 1 to 5, where: 1=not at all; 2=a little; 3=somewhat; 4=often; 5=all the time. Total scores range from 21 to 105. Higher scores represent greater sleep inertia.
Time frame: Week 8 to Week 12
Change in Cogstate One Back Test (ONB) From Week 8 to Week 12
Cognition was assessed using the Cogstate Computerized Cognitive Battery tests. The cognitive domain of working memory was assessed specifically with the One Back Test (ONB), which measures the speed of the participant's response. Results are reported as the mean of the common logarithm (log 10) transformed reaction time (in milliseconds \[msec\]) for correct responses. A decrease in score represents an increase in working memory performance.
Time frame: Week 8 to Week 12
Change in Cogstate Identification Test (IDN) From Week 8 to Week 12
Cognition was assessed using the Cogstate Computerized Cognitive Battery tests. The cognitive domain of visual attention was assessed using the Identification Test (IDN). Results reported as the mean of the log 10 transformed reaction time for correct responses. A decrease in score represents an increase in visual attention performance.
Time frame: Week 8 to Week 12
Change in Cogstate Detection Test (DET) From Week 8 to Week 12
Cognition was assessed using the Cogstate Computerized Cognitive Battery tests. The cognitive domain of psychomotor function was assessed specifically using the Detection Test (DET). The test measures the speed of the participant's response. Results reported as the mean of the log 10 transformed reaction time (msec) for the correct responses. A decrease in score represents an increase in psychomotor function performance.
Time frame: Week 8 to Week 12
Change in ESS Score From Week 1 to Week 8
The Epworth Sleepiness Scale (ESS) is an 8-item, 4-point rating scale that asks participants to rate the likelihood of falling asleep over the past week. The rating scale ranges from 0 (no chance of dozing) to 3 (high chance of dozing). The total score is calculated by summing the item level ratings. Total scores range from 0 to 24. Higher point totals represent more severe daytime sleepiness.
Time frame: Week 1 to Week 8
Change in Idiopathic Hypersomnia Severity Scale (IHSS) Score From Week 1 to Week 8
The Idiopathic Hypersomnia Severity Scale (IHSS) is a self-administered questionnaire with a total of 14 items that assess long sleep duration and sleep inertia (5 items), daytime functioning (7 items), and napping (2 items). All items are scored from 0 to 3 or from 0 to 4. The total score is a sum of the item scores. The total score ranges from 0 to 50. A higher score indicates more severe and frequent symptoms.
Time frame: Week 1 to Week 8
This study included an 8-week Open-Label Phase (OLP) followed by a 4-week Double-Blind Randomized Withdrawal Phase (DBRWP).
| Milestone | Open-Label Pitolisant | Double-Blind Pitolisant | Double-Blind Placebo |
|---|---|---|---|
| Started | 214 | 0 | 0 |
| Open-label safety population | 213 | 0 | 0 |
| Responder | 143 | 0 | 0 |
| Responders not randomized in dbrwp | 4 | 0 | 0 |
| Non-responder | 30 | 0 | 0 |
| Pharmacokinetic population | 192 | 0 | 0 |
| Completed | 173 | 0 | 0 |
| Not completed | 41 | 0 | 0 |
| Withdrew: Adverse event | 22 | 0 | 0 |
| Withdrew: Lack of efficacy | 8 | 0 | 0 |
| Withdrew: Failure to meet continuation criteria | 3 | 0 | 0 |
| Withdrew: Protocol violation | 2 | 0 | 0 |
| Withdrew: Lost to follow-up | 1 | 0 | 0 |
| Withdrew: Pregnancy | 1 | 0 | 0 |
| Withdrew: Withdrawal by subject | 1 | 0 | 0 |
| Withdrew: Non-compliance with study treatment | 1 | 0 | 0 |
| Withdrew: Withdrawal of consent | 1 | 0 | 0 |
| Withdrew: Non-compliance with study schedule | 1 | 0 | 0 |
| Milestone | Open-Label Pitolisant | Double-Blind Pitolisant | Double-Blind Placebo |
|---|---|---|---|
| Started | 0 | 69 | 70 |
| Intent-to-treat population | 0 | 69 | 70 |
| Double-blind safety population | 0 | 69 | 70 |
| Completed | 0 | 67 | 69 |
| Not completed | 0 | 2 | 1 |
| Withdrew: Adverse event | 0 | 1 | 0 |
| Withdrew: Failure to meet continuation criteria | 0 | 0 | 1 |
| Withdrew: Withdrawal of consent | 0 | 1 | 0 |
The Epworth Sleepiness Scale (ESS) is an 8-item, 4-point rating scale that asks participants to rate the likelihood of falling asleep over the past week. The rating scale ranges from 0 (no chance of dozing) to 3 (high chance of dozing). The total score is calculated by summing the item level ratings. Total scores range from 0 to 24. Higher point totals represent more severe daytime sleepiness.
| score on a scale | Double-Blind Pitolisant | Double-Blind Placebo |
|---|---|---|
| Change in Epworth Sleepiness Scale (ESS) Score From Week 8 to Week 12 | 3.41 ± 0.499 | 4.26 ± 0.494 |
The Idiopathic Hypersomnia Severity Scale (IHSS) is a self-administered questionnaire with a total of 14 items that assess long sleep duration and sleep inertia (5 items), daytime functioning (7 items), and napping (2 items). All items are scored from 0 to 3 or from 0 to 4. The total score is a sum of the item scores. The total score ranges from 0 to 50. A higher score indicates more severe and frequent symptoms.
| score on a scale | Double-Blind Pitolisant | Double-Blind Placebo |
|---|---|---|
| Change in Idiopathic Hypersomnia Severity Scale (IHSS) From Week 8 to Week 12 | 2.2 ± 7.63 | 5.4 ± 7.93 |
The Patient Global Impression of Change for Idiopathic Hypersomnia (PGI-C \[IH\]) is a single-item questionnaire that assesses a participant's overall impression of the change in their symptoms of IH. The scale asks participants to rate their overall impression of the change in their symptoms of IH since a specific timepoint on a 5-point verbal rating scale ranging from "much better" to "much worse."
| proportion of participants | Double-Blind Pitolisant | Double-Blind Placebo |
|---|---|---|
| Proportion of Participants Who Worsened on the Patient Global Impression of Change for Idiopathic Hypersomnia (PGI-C [IH]) From Week 8 to Week 12 | 0.47 | 0.60 |
The CGI-S (IH) is an investigator-rated assessment. It uses a single-item, 5-point Likert-type rating scale that ranges from: none (1); mild (2); moderate (3); severe (4); very severe (5). An assessment of less severe symptoms represents an improvement in the investigator's perception of the participant's overall clinical status related to idiopathic hypersomnia and is reflected by a decrease in score.
| score on a scale | Double-Blind Pitolisant | Double-Blind Placebo |
|---|---|---|
| Change in Clinical Global Impression of Severity for IH (CGI-S [IH]) From Week 8 to Week 12 | 0.6 ± 0.95 | 0.8 ± 0.99 |
The Patient Global Impression of Severity for Excessive Daytime Sleepiness (PGI-S \[EDS\]) asks participants to rate their overall impression of the severity of their EDS over the past 7 days on a 5-point verbal rating scale ranging from "none" to "very severe". Scores are: 1=None, 2=Mild, 3=Moderate, 4=Severe, and 5=Very Severe.
| score on a scale | Double-Blind Pitolisant | Double-Blind Placebo |
|---|---|---|
| Change in Patient Global Impression of Severity Scale for Excessive Daytime Sleepiness (PGI-S [EDS]) From Week 8 to Week 12 | 0.6 ± 1.12 | 0.9 ± 1.22 |
The Functional Outcomes of Sleep Questionnaire 10-Item Version (FOSQ-10) consists of 10 items assessing the impact of sleepiness on daily functioning across 5 domains: vigilance, general productivity, social outcomes, intimacy, and activity level. Each item is rated on a scale of 0 (activity not performed for other reasons), 1 (extreme difficulty), 2 (moderate difficulty), 3 (a little difficulty), and 4 (no difficulty). The FOSQ-10 total score is calculated by multiplying the mean of the subscale scores by five, with final scores ranging from 5-20. Higher scores correspond to less impairment/symptomatic severity.
| score on a scale | Double-Blind Pitolisant | Double-Blind Placebo |
|---|---|---|
| Change in Functional Outcomes of Sleep Questionnaire 10-Item Version (FOSQ-10) From Week 8 to Week 12 | -0.882 ± 3.1456 | -2.068 ± 2.4539 |
The PROMIS-SRI SF 8a is a self-report measure that includes 8 questions designed to assess a participant's perceptions of their waking alertness, sleepiness, and tiredness during usual waking hours, and the perceived functional impairments during wakefulness associated with sleep problems or impaired alertness over the past week. Responses are rated using a 5-point scale, with responses ranging from: 1=not at all; 2=a little bit; 3=somewhat; 4=quite a bit; 5=very much, with average scores ranging from 8 to 40. Raw scores are converted to a T-score using the conversion table from the PROMIS-SRI Scoring Manual. Raw score ranges from 8 to 40; T-score ranges from 30 to 80.1. Higher scores represent greater impairment.
| score on a scale | Double-Blind Pitolisant | Double-Blind Placebo |
|---|---|---|
| Change in Patient-Reported Outcomes Measurement Information System Sleep-Related Impairment Short Form 8a (PROMIS-SRI SF 8a) From Week 8 to Week 12 | 3.6 ± 6.46 | 5.8 ± 6.51 |
The Sleep Inertia Questionnaire (SIQ) consists of 21 questions that assess sleep inertia. Each question is rated on a scale of 1 to 5, where: 1=not at all; 2=a little; 3=somewhat; 4=often; 5=all the time. Total scores range from 21 to 105. Higher scores represent greater sleep inertia.
| score on a scale | Double-Blind Pitolisant | Double-Blind Placebo |
|---|---|---|
| Change in Sleep Inertia Questionnaire (SIQ) From Week 8 to Week 12 | 8.2 ± 16.00 | 13.6 ± 16.32 |
Cognition was assessed using the Cogstate Computerized Cognitive Battery tests. The cognitive domain of working memory was assessed specifically with the One Back Test (ONB), which measures the speed of the participant's response. Results are reported as the mean of the common logarithm (log 10) transformed reaction time (in milliseconds \[msec\]) for correct responses. A decrease in score represents an increase in working memory performance.
| log 10 msec | Double-Blind Pitolisant | Double-Blind Placebo |
|---|---|---|
| Change in Cogstate One Back Test (ONB) From Week 8 to Week 12 | -0.01 ± 0.054 | 0.02 ± 0.060 |
Cognition was assessed using the Cogstate Computerized Cognitive Battery tests. The cognitive domain of visual attention was assessed using the Identification Test (IDN). Results reported as the mean of the log 10 transformed reaction time for correct responses. A decrease in score represents an increase in visual attention performance.
| log 10 msec | Double-Blind Pitolisant | Double-Blind Placebo |
|---|---|---|
| Change in Cogstate Identification Test (IDN) From Week 8 to Week 12 | -0.01 ± 0.046 | 0.00 ± 0.046 |
Cognition was assessed using the Cogstate Computerized Cognitive Battery tests. The cognitive domain of psychomotor function was assessed specifically using the Detection Test (DET). The test measures the speed of the participant's response. Results reported as the mean of the log 10 transformed reaction time (msec) for the correct responses. A decrease in score represents an increase in psychomotor function performance.
| log 10 msec | Double-Blind Pitolisant | Double-Blind Placebo |
|---|---|---|
| Change in Cogstate Detection Test (DET) From Week 8 to Week 12 | -0.02 ± 0.047 | 0.00 ± 0.051 |
The Epworth Sleepiness Scale (ESS) is an 8-item, 4-point rating scale that asks participants to rate the likelihood of falling asleep over the past week. The rating scale ranges from 0 (no chance of dozing) to 3 (high chance of dozing). The total score is calculated by summing the item level ratings. Total scores range from 0 to 24. Higher point totals represent more severe daytime sleepiness.
| score on a scale | Open-Label Pitolisant |
|---|---|
| Change in ESS Score From Week 1 to Week 8 | -9.4 ± 4.08 |
The Idiopathic Hypersomnia Severity Scale (IHSS) is a self-administered questionnaire with a total of 14 items that assess long sleep duration and sleep inertia (5 items), daytime functioning (7 items), and napping (2 items). All items are scored from 0 to 3 or from 0 to 4. The total score is a sum of the item scores. The total score ranges from 0 to 50. A higher score indicates more severe and frequent symptoms.
| score on a scale | Open-Label Pitolisant |
|---|---|
| Change in Idiopathic Hypersomnia Severity Scale (IHSS) Score From Week 1 to Week 8 | -10.0 ± 7.46 |
Collected over Day 1 through Day 114. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Open-Label Pitolisant | 0/213 (0%) | 2/213 (0.9%) | 142/213 (66.7%) |
| Double-Blind Pitolisant | 0/69 (0%) | 2/69 (2.9%) | 23/69 (33.3%) |
| Double-Blind Placebo | 0/70 (0%) | 1/70 (1.4%) | 18/70 (25.7%) |
| Event | Open-Label Pitolisant | Double-Blind Pitolisant | Double-Blind Placebo |
|---|---|---|---|
| CholelithiasisHepatobiliary disorders | 0/213 | 1/69 | 0/70 |
| Cerebral venous sinus thrombosisNervous system disorders | 0/213 | 1/69 | 0/70 |
| Venomous biteInjury, poisoning and procedural complications | 0/213 | 0/69 | 1/70 |
| Suicidal ideationPsychiatric disorders | 1/213 | 0/69 | 0/70 |
| Suicide attemptPsychiatric disorders | 1/213 | 0/69 | 0/70 |
| Event | Open-Label Pitolisant | Double-Blind Pitolisant | Double-Blind Placebo |
|---|---|---|---|
| HeadacheNervous system disorders | 48/213 | 2/69 | 1/70 |
| InsomniaPsychiatric disorders | 31/213 | 0/69 | 2/70 |
| NasopharyngitisInfections and infestations | 14/213 | 4/69 | 0/70 |
| Abnormal dreamsPsychiatric disorders | 12/213 | 0/69 | 0/70 |
| NauseaGastrointestinal disorders | 9/213 | 0/69 | 0/70 |
| COVID-19Infections and infestations | 9/213 | 2/69 | 0/70 |
| AnxietyPsychiatric disorders | 9/213 | 1/69 | 0/70 |
| SinusitisInfections and infestations | 3/213 | 0/69 | 2/70 |
| Alanine aminotransferase increasedInvestigations | 2/213 | 0/69 | 2/70 |
| DizzinessNervous system disorders | 6/213 | 0/69 | 0/70 |
Open-label Safety Population: all participants who received at least 1 dose of study drug during the OLP.
| Age, Continuous(years) | Open-Label Pitolisant |
|---|---|
| Mean | 39.7 ± 12.85 |
| Sex: Female, Male(Participants) | Open-Label Pitolisant |
|---|---|
| Female | 169 |
| Male | 44 |
| Ethnicity (NIH/OMB)(Participants) | Open-Label Pitolisant |
|---|---|
| Hispanic or Latino | 10 |
| Not Hispanic or Latino | 203 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Open-Label Pitolisant |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 8 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 16 |
| White | 187 |
| More than one race | 0 |
| Unknown or Not Reported | 2 |
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from May 2022 to primary completion in Sep 2023, 15 months.
Results were first posted in Sep 2026, 3 years after primary completion. A results delay was requested in Aug 2024.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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