Prader-Willi SyndromePhase 2NCT04257929
A Phase 2 Study to Evaluate the Safety and Efficacy of Pitolisant in Patients With Prader-Willi Syndrome, Followed by an Open Label Extension
A Phase 2 study testing Pitolisant oral tablets in people with Prader-Willi Syndrome, run by Harmony Biosciences Management, Inc. at 13 sites in United States.
Trial summary
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 patients with Prader Willi syndrome (PWS) ages 6 to 65 years. Read more about this study
- Who is it for?
- Ages 6 to 65 years
- Conditions the study is for
- Prader-Willi Syndrome
- What is being tested?
- Pitolisant oral tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 13 sitesUnited States
- Study dates
- 9 Dec 2020to 21 Jan 2026
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Is able to provide voluntary, written informed consent (patient or parent[s]/legal guardian[s]) and, where applicable, voluntary, written assent (patient, as appropriate).
- Has a diagnosis of PWS confirmed by genetic testing and/or patient medical records. Genetic testing will be provided by the Sponsor, if not confirmed based on the review of the patient's medical records.
- Male or female patients ages 6 to 65 years at the time of enrollment.
- Demonstrates adequate sleep duration via patient sleep diary during Screening, defined as at least 8 hours of sleep per night for patients ages 6 to <12 years, at least 7 hours for patients ages 12 to <18 years, or at least 6 hours for patients ages ≥18 years, based on the mean number of hours from up to 14 nights (at least 7 nights must be recorded for evaluation).
- Has EDS as determined by Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) (parent/caregiver version) score of ≥12.
- If taking hormone treatments (including growth hormone, testosterone, and estrogen supplements) and/or allowed chronic concomitant medication or supplements, patient must be on a stable dose of these medications for 3 months prior to randomization and for the duration of the Double-Blind Treatment Phase of the study; a 10% variability in hormone dose is allowed.
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- If taking a wake-promoting treatment that could affect EDS (including stimulants, modafinil, and armodafinil), must be on a stable dose for at least 28 days prior to Screening and remain on a stable dose during the Double-Blind Treatment Phase of the study (dose adjustments will be permitted in the OLE Phase) or agree to wash out of treatment for 5 half-lives or 14 days, whichever is longer.
- If taking a chronically administered sedating medication for management of behavioral manifestations (e.g., hypnotics, benzodiazepines, antipsychotics, alpha agonists, anticholinergics, and antidepressants) must be on a stable dose for at least 28 days prior to Screening and remain on a stable dose during the Double-Blind Treatment Phase of the study (dose adjustments will be permitted in the OLE Phase) or agree to wash out of treatment for 5 half-lives or 14 days, whichever is longer.
- If using cannabidiol and/or tetrahydrocannabinol, patient must be on a stable dose for 28 days prior to randomization and agree to continue the stable dose for the duration of the Double-Blind Treatment Phase of the study (dose adjustments will be permitted in the OLE Phase).
- If taking oxytocin or carbetocin, patient must be on a stable dose during the 28 days prior to randomization and agree to continue the stable dose for the duration of the Double-Blind Treatment Phase of the study (dose adjustments will be permitted in the OLE Phase) or agree to wash out of treatment for 5 half-lives or 14 days, whichever is longer.
- A patient who is a female of child-bearing potential (FCBP) must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at the Baseline Visit and agree to remain abstinent or use an effective method of nonhormonal contraception to prevent pregnancy for the duration of the study and for 21 days after final dose of study drug.
- Has a consistent caregiver (preferably the same person throughout the Double-Blind Treatment Phase of the study) who is willing and able to complete the required assessments.
- In the opinion of the Investigator, patient/parent(s)/legal guardian(s) is capable of understanding and complying with the requirements of the protocol and administration of oral study drug.
Who cannot join
- Has a diagnosis of another genetic or chromosomal disorder distinct from PWS.
- Has untreated obstructive sleep apnea (OSA) or is at high risk for OSA based on medical history and clinical assessment; or, has another relevant underlying sleep disorder that in the opinion of the Investigator is the primary contributing factor to the patient's EDS.
- Consistently consumes >600 mg of caffeine per day and is unable/unwilling to reduce caffeine intake to <600 mg per day for the duration of the Double-Blind Treatment Phase of the study; caffeine intake should remain consistent during Screening and throughout the Double-Blind Treatment Phase of the study.
- Does not agree to discontinue any prohibited medication or substance listed in the protocol.
- Participation in an interventional research study involving another investigational medication or device in the 28 days prior to enrollment and for the duration of the Double-Blind Treatment Phase of the study, unless the Investigator consults with the Medical Monitor and obtains written approval for the patient to enroll; patients who complete a washout of an investigational medication of at least 5 half-lives or 14 days (whichever is longer) may be enrolled in the Double-Blind Treatment Phase of the study. Patients considering participation in another interventional research study in the OLE Phase must consult with the Investigator who will consult with the Medical Monitor.
- Has a primary psychiatric diagnosis with current active symptoms of psychosis or schizophrenia.
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- Has a diagnosis of end-stage renal disease (estimated glomerular filtration rate [eGFR] of <15 mL/minute/1.73 m²) or severe hepatic impairment (Child-Pugh C).
- Has a diagnosis of moderate or severe renal impairment (eGFR ≥15 to ≤59 mL/minute/1.73 m²) or moderate hepatic impairment (Child-Pugh B) at Screening or during the Double-Blind Treatment Phase.
- Has abnormal laboratory values at Screening that are clinically significant as determined by the Investigator.
- Has a known history of long QT syndrome or any significant history of a serious abnormality of the electrocardiogram (ECG; e.g., recent myocardial infarction, clinically significant arrhythmia) or QT interval corrected for heart rate according to Fridericia's formula (QTcF) >442 ms for patients ages 0 to <10 years and >439 ms for patients ages 10 to <20 years, regardless of gender, and >450 ms for male patients and >470 ms for female patients ages 20 to 65 years. (ECG QTcF = QT/3√ RR) (Mason et al 2007).
- Has a family history of sudden/unexplained death, cardiac death, or death from a primary dysrhythmia potentially associated with QT prolongation in any family member.
- If receiving any new or initiating a change in allied health therapies or interventions for symptoms of PWS, must be on a stable course of therapy for at least 28 days prior to randomization.
- Has a current or recent (within one year) history of a substance use disorder or dependence disorder, including alcohol and caffeine use disorders as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V).
- Has planned surgery during the Double-Blind Treatment Phase of the study; planned surgery is permitted during the OLE Phase.
- Is receiving a concomitant medication that is known to be a strong cytochrome P450 (CYP) 2D6 inhibitor, a strong CYP3A4 inducer, or a centrally acting histamine 1 (H1) receptor antagonist; patients who complete a washout of these medications of at least 5 half-lives or 14 days (whichever is longer) can be enrolled in the Double-Blind Treatment Phase of the study. Use of strong CYP2D6 inhibitors and strong CYP3A4 inducers is allowed during the OLE Phase; however, adjustment of pitolisant dose is required. Although not prohibited during the OLE Phase of the study, use of H1 receptor antagonists should be avoided.
- Is receiving a medication known to prolong the QT interval.
- Has a significant risk of committing suicide based on history, routine psychiatric examination, Investigator's judgment, or an answer of "yes" on any question other than questions 1 to 3 on the Very Young Child/Cognitively Impaired-Lifetime Recent Columbia-Suicide Severity Rating Scale (C SSRS).
- Has a history of seizures that have recently (within 6 months) been treated with antiepileptic medications that are strong CYP3A4 inducers. Patients with a history of seizures must have a stable seizure history (e.g., frequency and severity) for at least 6 months prior to enrollment.
- Is currently breastfeeding or planning to breastfeed over the course of the study. Lactating women must agree not to breastfeed for the duration of the study (Double-Blind Treatment Phase and OLE Phase) and for 21 days after final dose of study drug.
- Based on the judgment of the Investigator, patient is unsuitable for the study for any reason, including but not limited to unstable or uncontrolled medical conditions (including psychiatric and neurological conditions) or a medical condition that might interfere with the conduct of the study, confound interpretation of study results, pose a health risk to the patient, or compromise the integrity of the study.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
Children's Hospital Colorado
Aurora, Colorado, 80045
Johns Hopkins School of Medicine
Baltimore, Maryland, 21205
Ann and Robert H Lurie Children's Hospital
Chicago, Illinois, 60611
CTI
Cincinnati, Ohio, 45212
University of Florida College of Medicine
Gainesville, Florida, 32608
Texas Children's Hospital/Baylor College of Medicine
Houston, Texas, 77030
Vanderbilt University Medical Center
Nashville, Tennessee, 37203
University of Nebraska Medical Center
Omaha, Nebraska, 68114
Road Runner Research
San Antonio, Texas, 78249
Rady Children's Hospital - San Diego
San Diego, California, 92123
Sleep Medicine Specialists of California
San Ramon, California, 94583
Santa Monica Clinical Trials
Santa Monica, California, 90404
Nemours Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate the Safety and Efficacy of Pitolisant in Patients With Prader-Willi Syndrome, Followed by an Open Label Extension
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 patients with Prader Willi syndrome (PWS) ages 6 to 65 years.
Read the detailed description
The study will consist of a Screening Period, an 11-week Double-Blind Treatment Phase (including a 3-week Titration Period and an 8-week Stable Dose Period), and an optional Open Label Extension (OLE) Phase. The OLE Phase will be multi-year in duration and will continue until the Sponsor elects to terminate the study.
Approximately 60 patients ages 6 to 65 years who meet all eligibility criteria will be randomized at the Baseline Visit in a 1:1:1 ratio to lower dose pitolisant, higher dose pitolisant, or matching placebo. In the Double-Blind Treatment Phase, patients will be titrated to their randomized stable dose of study drug during the 3-week Titration Period.
After completion of the 3-week Titration Period, patients will continue to take study drug at their randomized stable dose once daily in the morning upon wakening for an additional 8 weeks of blinded treatment (Stable Dose Period). The duration of the Double-Blind Treatment Phase will be 11 weeks.
Following the 11-week Double-Blind Treatment Phase, eligible patients will be given the opportunity to participate in an optional OLE Phase. During the OLE Phase, all eligible patients will receive treatment with open-label pitolisant and will undergo titration during a 3-week Titration Period to a maximum target dose as specified in the protocol. At the end of the 3-week Titration Period, patients will continue to take their target dose of pitolisant once daily in the morning upon wakening until the end of the study.
- Conditions
- Prader-Willi Syndrome
- Being tested
- Pitolisant oral tablets, Placebo oral tablet
- Keywords
- PWS
- Medical subject headings
- Prader-Willi Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pitolisant oral tabletsDrug
Pitolisant 4.45 mg or 17.8 mg tablets
Placebo oral tabletDrug
Matching placebo tablets
| Study group | Role | What they receive |
|---|---|---|
| Double-Blind Treatment Phase Lower Dose Pitolisant | Active comparator | Pediatric patients (6 to less than 12 years of age):
Week 1: 4.45 mg pitolisant administered once daily in the morning; Week 2: 8.9 mg pitolisant administered once daily in the morning; Weeks 3 through 11: 8.9 mg pitolisant administered once daily in the morning.
Adolescent patients (12 to less than 18 years of age):
Week 1: 4.45 mg pitolisant administered once daily in the morning; Week 2: 8.9 mg pitolisant administered once daily in the morning; Weeks 3 through 11: 13.35 mg pitolisant administered once daily in the morning.
Adult patients (18 to 65 years of age):
Week 1: 4.45 mg pitolisant administered once daily in the morning; Week 2: 8.9 mg pitolisant administered once daily in the morning; Weeks 3 through 11: 17.8 mg pitolisant administered once daily in the morning. Receives: Drug: Pitolisant oral tablets |
| Double-Blind Treatment Phase Higher Dose Pitolisant | Active comparator | Pediatric patients (6 to less than 12 years of age):
Week 1: 4.45 mg pitolisant administered once daily in the morning; Week 2: 8.9 mg pitolisant administered once daily in the morning; Weeks 3 through 11: 17.8 mg pitolisant administered once daily in the morning.
Adolescent patients (12 to less than 18 years of age):
Week 1: 8.9 mg pitolisant administered once daily in the morning; Week 2: 17.8 mg pitolisant administered once daily in the morning; Weeks 3 through 11: 26.7 mg pitolisant administered once daily in the morning.
Adult patients (18 to 65 years of age):
Week 1: 8.9 mg pitolisant administered once daily in the morning; Week 2: 17.8 mg pitolisant administered once daily in the morning; Weeks 3 through 11: 35.6 mg pitolisant administered once daily in the morning. Receives: Drug: Pitolisant oral tablets |
| Double-Blind Treatment Phase Placebo | Placebo comparator | Pediatric patients (6 to less than 12 years of age):
Week 1: Matching placebo tablets; Week 2: Matching placebo tablets; Weeks 3 through 11: Matching placebo tablets
Adolescent patients (12 to less than 18 years of age):
Week 1: Matching placebo tablets; Week 2: Matching placebo tablets; Weeks 3 through 11: Matching placebo tablets
Adult patients (18 to 65 years of age):
Week 1: Matching placebo tablets; Week 2: Matching placebo tablets; Weeks 3 through 11: Matching placebo tablets Receives: Drug: Placebo oral tablet |
| Open-Label Pitolisant | Other | Age-based dosing (prior to implementation of amendment 6) or weight-based dosing (after implementation of amendment 6) Receives: Drug: Pitolisant oral tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Excessive Daytime Sleepiness
Change in Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) (parent/caregiver version) score from Baseline to Week 11 for pitolisant compared with placebo.
The score of the ESS-CHAD ranges from 0 to 24. A decrease in score represents an improvement in excessive daytime sleepiness.
Measured: Baseline to Week 11
Secondary outcomes (8)
Excessive Daytime Sleepiness
Change in Caregiver Global Impression of Severity for Excessive Daytime Sleepiness.
The Caregiver Global Impression of Severity for Excessive Daytime Sleepiness is a five-item scale that ranges from "not at all" to "very high likelihood." An assessment of being less likely to fall asleep represents an improvement in the caregiver's overall impression of the patient's excessive daytime sleepiness.
Measured: Baseline to Week 11
Clinical Symptoms
Change in Clinical Global Impression of Severity of Overall Clinical Status.
The Clinical Global Impression of Severity of Overall Clinical Status is a four-item scale that ranges from "normal" to "severely symptomatic." An assessment of less severe symptoms represents an improvement in the clinician's perception of the overall clinical status related to PWS.
Measured: Baseline to Week 11
Behavior
Change in Aberrant Behavior Checklist, Second Edition.
The Aberrant Behavior Checklist-Community, Second Edition, rates 58 specific symptoms on a four-item scale ranging from "not at all a problem" to "the problem is severe in degree." A decrease in score represents an improvement in the caregiver's impression in the patient's problematic behavior.
Measured: Baseline to Week 11
Behavioral and Cognitive Rigidity
Change in Montefiore-Einstein Rigidity Scale - Prader-Willi Syndrome (MERS-R-PWS).
The MERS-R-PWS is a clinician-rated, semi-structured interview conducted with both the patient with PWS and caregiver present. The MERS-R-PWS measures three domains of rigid behavior - behavior, cognitive, and protest. Within each domain, four items are rated on a scale ranging from 0 to 4. A decrease in score represents an improvement in rigid behavior.
Measured: Baseline to Week 11
Psychomotor Function
Change in Cogstate Detection Test.
The Cogstate Detection Test is a computerized test. Accuracy with a faster speed represents an improvement in psychomotor test performance.
Measured: Baseline to Week 11
Attention
Change in Cogstate Identification Test.
The Cogstate Identification Test is a computerized test. Accuracy with a faster speed represents an improvement in attention test performance.
Measured: Baseline to Week 11
Working Memory
Change in Cogstate One Back Test.
The Cogstate One Back Test is a computerized test. Accuracy with a faster speed represents a better working memory test performance.
Measured: Baseline to Week 11
Caregiver Burden
Change in 22-Item Zarit Burden Interview.
The Zarit Burden Interview is a self-reported questionnaire in which caregivers are asked to rate their experience on a five-item scale (0 = "never" and 4 = "nearly always") for 22 questions related to caregiver health and psychological well-being, finances, impact on social life, and relationship with the patient with PWS. A decrease in score represents an improvement in the caregiver's perceived burden.
Measured: Baseline to Week 11
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2020
- Study start9 Dec 2020
- Primary completion17 Aug 2022
- Study completion21 Jan 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Prader-Willi SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- Harmony Biosciences Management, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04257929
- Sponsor's protocol ID
- HBS-101-CL-002
- Status last verified
- Apr 2026
- First submitted
- 29 Jan 2020
- Last updated
- 12 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Revana A, Bhattacharjee R, Miller JL, Chidekel A, Khanna P, Ratnam S, Runyan G, Bauer E, Davis Rapchak K, Seiden D, Budur K, Dayno JM. A proof-of-concept study of pitolisant for excessive daytime sleepiness in patients with Prader-Willi syndrome. J Clin Sleep Med. 2025 Nov 1;21(11):1893-1902. doi: 10.5664/jcsm.11800.
PubMed 40605372
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate the Safety and Efficacy of Pitolisant in Patients With Prader-Willi Syndrome, Followed by an Open Label Extension
- ClinicalTrials.gov ID
- NCT04257929
- Acronym / sponsor ID
- HBS-101-CL-002
- Conditions
- Prader-Willi Syndrome
- Keywords
- PWS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- Harmony Biosciences Management, Inc.Industry (pharma, biotech, devices)
- Study start
- 9 Dec 2020 (actual)
- Primary completion
- 17 Aug 2022 (actual)
- Study completion
- 21 Jan 2026 (actual)
- First posted
- 6 Feb 2020 (actual)
- Results
- Posted 22 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 patients with Prader Willi syndrome (PWS) ages 6 to 65 years.
Detailed description
The study will consist of a Screening Period, an 11-week Double-Blind Treatment Phase (including a 3-week Titration Period and an 8-week Stable Dose Period), and an optional Open Label Extension (OLE) Phase. The OLE Phase will be multi-year in duration and will continue until the Sponsor elects to terminate the study.
Approximately 60 patients ages 6 to 65 years who meet all eligibility criteria will be randomized at the Baseline Visit in a 1:1:1 ratio to lower dose pitolisant, higher dose pitolisant, or matching placebo. In the Double-Blind Treatment Phase, patients will be titrated to their randomized stable dose of study drug during the 3-week Titration Period.
After completion of the 3-week Titration Period, patients will continue to take study drug at their randomized stable dose once daily in the morning upon wakening for an additional 8 weeks of blinded treatment (Stable Dose Period). The duration of the Double-Blind Treatment Phase will be 11 weeks.
Following the 11-week Double-Blind Treatment Phase, eligible patients will be given the opportunity to participate in an optional OLE Phase. During the OLE Phase, all eligible patients will receive treatment with open-label pitolisant and will undergo titration during a 3-week Titration Period to a maximum target dose as specified in the protocol. At the end of the 3-week Titration Period, patients will continue to take their target dose of pitolisant once daily in the morning upon wakening until the end of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Double-Blind Treatment Phase Lower Dose Pitolisant | Active comparator | Drug: Pitolisant oral tabletsPediatric patients (6 to less than 12 years of age): Week 1: 4.45 mg pitolisant administered once daily in the morning; Week 2: 8.9 mg pitolisant administered once daily in the morning; Weeks 3 through 11: 8.9 mg pitolisant administered once daily in the morning. Adolescent patients (12 to less than 18 years of age): Week 1: 4.45 mg pitolisant administered once daily in the morning; Week 2: 8.9 mg pitolisant administered once daily in the morning; Weeks 3 through 11: 13.35 mg pitolisant administered once daily in the morning. Adult patients (18 to 65 years of age): Week 1: 4.45 mg pitolisant administered once daily in the morning; Week 2: 8.9 mg pitolisant administered once daily in the morning; Weeks 3 through 11: 17.8 mg pitolisant administered once daily in the morning. |
| Double-Blind Treatment Phase Higher Dose Pitolisant | Active comparator | Drug: Pitolisant oral tabletsPediatric patients (6 to less than 12 years of age): Week 1: 4.45 mg pitolisant administered once daily in the morning; Week 2: 8.9 mg pitolisant administered once daily in the morning; Weeks 3 through 11: 17.8 mg pitolisant administered once daily in the morning. Adolescent patients (12 to less than 18 years of age): Week 1: 8.9 mg pitolisant administered once daily in the morning; Week 2: 17.8 mg pitolisant administered once daily in the morning; Weeks 3 through 11: 26.7 mg pitolisant administered once daily in the morning. Adult patients (18 to 65 years of age): Week 1: 8.9 mg pitolisant administered once daily in the morning; Week 2: 17.8 mg pitolisant administered once daily in the morning; Weeks 3 through 11: 35.6 mg pitolisant administered once daily in the morning. |
| Double-Blind Treatment Phase Placebo | Placebo comparator | Drug: Placebo oral tabletPediatric patients (6 to less than 12 years of age): Week 1: Matching placebo tablets; Week 2: Matching placebo tablets; Weeks 3 through 11: Matching placebo tablets Adolescent patients (12 to less than 18 years of age): Week 1: Matching placebo tablets; Week 2: Matching placebo tablets; Weeks 3 through 11: Matching placebo tablets Adult patients (18 to 65 years of age): Week 1: Matching placebo tablets; Week 2: Matching placebo tablets; Weeks 3 through 11: Matching placebo tablets |
| Open-Label Pitolisant | Other | Drug: Pitolisant oral tabletsAge-based dosing (prior to implementation of amendment 6) or weight-based dosing (after implementation of amendment 6) |
Who may qualify
- Ages
- 6 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- Is able to provide voluntary, written informed consent (patient or parent[s]/legal guardian[s]) and, where applicable, voluntary, written assent (patient, as appropriate).
- Has a diagnosis of PWS confirmed by genetic testing and/or patient medical records. Genetic testing will be provided by the Sponsor, if not confirmed based on the review of the patient's medical records.
- Male or female patients ages 6 to 65 years at the time of enrollment.
- Demonstrates adequate sleep duration via patient sleep diary during Screening, defined as at least 8 hours of sleep per night for patients ages 6 to <12 years, at least 7 hours for patients ages 12 to <18 years, or at least 6 hours for patients ages ≥18 years, based on the mean number of hours from up to 14 nights (at least 7 nights must be recorded for evaluation).
- Has EDS as determined by Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) (parent/caregiver version) score of ≥12.
Key exclusion criteria (20 listed)
- Has a diagnosis of another genetic or chromosomal disorder distinct from PWS.
- Has untreated obstructive sleep apnea (OSA) or is at high risk for OSA based on medical history and clinical assessment; or, has another relevant underlying sleep disorder that in the opinion of the Investigator is the primary contributing factor to the patient's EDS.
- Consistently consumes >600 mg of caffeine per day and is unable/unwilling to reduce caffeine intake to <600 mg per day for the duration of the Double-Blind Treatment Phase of the study; caffeine intake should remain consistent during Screening and throughout the Double-Blind Treatment Phase of the study.
- Does not agree to discontinue any prohibited medication or substance listed in the protocol.
- Participation in an interventional research study involving another investigational medication or device in the 28 days prior to enrollment and for the duration of the Double-Blind Treatment Phase of the study, unless the Investigator consults with the Medical Monitor and obtains written approval for the patient to enroll; patients who complete a washout of an investigational medication of at least 5 half-lives or 14 days (whichever is longer) may be enrolled in the Double-Blind Treatment Phase of the study. Patients considering participation in another interventional research study in the OLE Phase must consult with the Investigator who will consult with the Medical Monitor.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pitolisant oral tabletsPitolisant 4.45 mg or 17.8 mg tablets | Drug | Double-Blind Treatment Phase Higher Dose Pitolisant, Double-Blind Treatment Phase Lower Dose Pitolisant, Open-Label Pitolisant |
| Placebo oral tabletMatching placebo tablets | Drug | Double-Blind Treatment Phase Placebo |
Primary outcome
Excessive Daytime Sleepiness
Time frame: Baseline to Week 11
Change in Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) (parent/caregiver version) score from Baseline to Week 11 for pitolisant compared with placebo. The score of the ESS-CHAD ranges from 0 to 24. A decrease in score represents an improvement in excessive daytime sleepiness.
8 secondary outcomes
Excessive Daytime Sleepiness
Time frame: Baseline to Week 11
Clinical Symptoms
Time frame: Baseline to Week 11
Behavior
Time frame: Baseline to Week 11
Behavioral and Cognitive Rigidity
Time frame: Baseline to Week 11
Psychomotor Function
Time frame: Baseline to Week 11
Attention
Time frame: Baseline to Week 11
Working Memory
Time frame: Baseline to Week 11
Caregiver Burden
Time frame: Baseline to Week 11
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40605372Revana A, Bhattacharjee R, Miller JL, Chidekel A, Khanna P, Ratnam S, Runyan G, Bauer E, Davis Rapchak K, Seiden D, Budur K, Dayno JM. A proof-of-concept study of pitolisant for excessive daytime sleepiness in patients with Prader-Willi syndrome. J Clin Sleep Med. 2025 Nov 1;21(11):1893-1902. doi: 10.5664/jcsm.11800.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pitolisant oral tablets in people with Prader-Willi Syndrome, run by Harmony Biosciences Management, Inc. at 13 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Excessive Daytime Sleepiness (time frame: Baseline to Week 11). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04257929, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2026.