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Pitolisant

Phase 3

Idiopathic Hypersomnia | Small molecule | Neurology |Harmony Biosciences Holdings, Inc.|Last Updated: Aug 25, 2026

Target and mechanism

Molecular targetHRH3
Target classInverse Agonist
ModalitySmall molecule

Also known as Pitolisant tablet

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLED
Total Trials2
Total Enrollment333

FDA Designations

No designations recorded

Clinical trial landscape

Pitolisant · 6 trials · 4 indications

Phase 3 4Phase 2 2
NCT07219485A Study of Pitolisant in Participants With Prader-Willi SyndromePrader-Willi Syndrome
ENROLLING BY_INVITATION150 Analytics
NCT06366464A Study of Pitolisant in Patients With Prader-Willi SyndromePrader-Willi Syndrome
RECRUITING134 Analytics
NCT05458128A Long-Term Safety and Effectiveness Study to Evaluate Pitolisant in Adult Patients With Idiopathic HypersomniaIdiopathic Hypersomnia
COMPLETED119 Analytics
NCT05156047A Phase 3 Study to Assess the Safety and Efficacy of Pitolisant in Adult Patients With Idiopathic HypersomniaIdiopathic Hypersomnia
COMPLETED214 Analytics
PHASE3ENROLLING BY_INVITATION
A Study of Pitolisant in Participants With Prader-Willi Syndrome
Prader-Willi SyndromeUnlock trial analytics
PHASE3RECRUITING
A Study of Pitolisant in Patients With Prader-Willi Syndrome
Prader-Willi SyndromeUnlock trial analytics
PHASE3COMPLETED
A Long-Term Safety and Effectiveness Study to Evaluate Pitolisant in Adult Patients With Idiopathic Hypersomnia
Idiopathic HypersomniaUnlock trial analytics
PHASE3COMPLETED
A Phase 3 Study to Assess the Safety and Efficacy of Pitolisant in Adult Patients With Idiopathic Hypersomnia
Idiopathic HypersomniaUnlock trial analytics

Study Endpoints

Primary Endpoints

Percentage of participants reporting Treatment-Emergent Adverse Events (TEAEs)
From the end of the EOT visit of the parent study through 30 days after the final dose of study drug.

A treatment-emergent adverse event (TEAE) is any adverse event reported during treatment with study drug in this study and up to 30 days after final dose of study drug, or any worsening of a pre-existing condition reported during treatment with study drug and up to 30 days after final dose of study drug.

Change in severity of EDS as measured by Patient-Reported Outcomes Measurement Information System Bank v1.0 - Sleep-Related Impairment (PROMIS-SRI) T-score
Baseline and end of the Double Blind Treatment Period (Day 77)

The PROMIS-SRI item bank consists of 13 items with a 5-point rating scale.

Safety and tolerability of pitolisant
Up to approximately 3 years

Incidence of adverse events (AEs)

Excessive daytime sleepiness
Up to approximately 3 years

Change from Baseline in Epworth Sleepiness Scale (ESS) score The score of the Epworth Sleepiness Scale ranges from 0 to 24. A decrease in score represents an improvement in excessive daytime sleepiness.

Change in Excessive Daytime Sleepiness (EDS) Based on Change in Daytime Sleepiness Scale (DSS) Score
Baseline to Week 11

The score of the DSS ranges from 0 to 15. A decrease in the DSS score represents an improvement in EDS.

Secondary Endpoints

Change in severity of irritable and disruptive behaviors as measured by the Aberrant Behavior Checklist-Community, Second Edition (ABC-C) Irritability domain
Baseline and end of the Double Blind Treatment Period (Day 77)
Change in overall severity of EDS as measured by the Caregiver Global Impression of Severity for Excessive Daytime Sleepiness (CaGI-S for EDS)
Baseline and end of the Double Blind Treatment Period (Day 77)
Change in overall severity of EDS as measured by the Clinical Global Impression of Severity for Excessive Daytime Sleepiness (CGI-S for EDS)
Baseline and end of the Double Blind Treatment Period (Day 77)
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Study Design & Arms

AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
PitolisantEXPERIMENTALAll participants receive pitolisant administered orally once daily in the morning upon awakening.
Double-Blind Treatment Period PitolisantEXPERIMENTALPitolisant tablets administered once daily in the morning upon wakening
Double-Blind Treatment Period PlaceboPLACEBO_COMPARATORMatching placebo administered tablets once daily in the morning upon wakening
Open-Label Extension Period PitolisantOTHERPitolisant tablets administered once daily in the morning upon wakening
Double-blind pitolisantACTIVE_COMPARATORDouble-blind pitolisant administered once daily in the morning upon wakening for 4 weeks during the Double-Blind Randomized Withdrawal Phase
Double-blind placeboPLACEBO_COMPARATORMatching placebo administered once daily in the morning upon wakening for 4 weeks during the Double-Blind Randomized Withdrawal Phase
Open-label pitolisantEXPERIMENTALOpen-label pitolisant administered once daily in the morning upon wakening for 8 weeks during the Open-Label Phase
Higher dose pitolisantACTIVE_COMPARATORDouble-Blind Treatment Phase: 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.
Lower dose pitolisantACTIVE_COMPARATORDouble-Blind Treatment Phase: 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
PlaceboPLACEBO_COMPARATORDouble-Blind Treatment Phase: Week 1: Matching placebo tablets; Week 2: Matching placebo tablets; Weeks 3 through 11: Matching placebo tablets
Double-Blind Treatment Phase Lower Dose PitolisantACTIVE_COMPARATORPediatric 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 PitolisantACTIVE_COMPARATORPediatric 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 PlaceboPLACEBO_COMPARATORPediatric 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

Interventions

NameTypeDescription
PitolisantDRUG* Pitolisant 4.45 mg tablets * Pitolisant 17.8 mg tablets
Pitolisant tabletDRUGPitolisant tablet
Placebo tabletOTHERPlacebo tablet
Open-label pitolisantDRUGPitolisant 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.
Double-blind placeboDRUGMatching placebo tablets will be provided for each strength of active pitolisant film-coated tablets.
Double-blind pitolisantDRUGPitolisant 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.
Pitolisant Oral TabletDRUGPitolisant 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.
Placebo oral tabletDRUGMatching placebo tablets will be provided for each strength of active pitolisant film-coated tablets.
Pitolisant oral tabletsDRUGPitolisant 4.45 mg or 17.8 mg tablets
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Eligibility Criteria

Age Range7 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites1

Inclusion Criteria: Each participant must meet the following criteria to be enrolled in this study: 1. Ability to provide voluntary, written informed consent (participant, if applicable, or parent\[s\]/legal guardian\[s\]) and, where applicable, voluntary, written assent (participant, as appropria...

Countries:United StatesAustraliaBelgiumCanadaDenmarkFranceGermanyItalyPolandRomaniaSpainSwedenUnited Kingdom
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Recent Changes (Last 90 Days)

MEDIUMAug 25, 2026NCT06366464primaryCompletionDate: changed
MEDIUMAug 25, 2026NCT06366464primaryCompletionDate: changed
MEDIUMJun 12, 2026NCT04257929TRIAL_REMOVED: changed
MEDIUMJun 12, 2026NCT04257929TRIAL_REMOVED: changed
MEDIUMJun 12, 2026NCT04257929TRIAL_REMOVED: changed

Frequently asked questions about Pitolisant

What is Pitolisant used for?

Pitolisant is an investigational small molecule being developed for myotonic dystrophy type 1, idiopathic hypersomnia, and Prader-Willi syndrome. It is in Phase 3 clinical development for these neurologic conditions. The drug is being studied to address excessive daytime sleepiness and other symptoms associated with these disorders.

Who makes Pitolisant?

Pitolisant is being developed by Harmony Biosciences Holdings, Inc., a biopharmaceutical company traded on NASDAQ under the ticker HRMY. The company is conducting clinical trials to evaluate the drug's safety and efficacy across multiple neurologic indications.

What phase is Pitolisant in?

Pitolisant is in Phase 3 clinical development. It has completed Phase 2 trials in Prader-Willi syndrome and myotonic dystrophy type 1, and is currently being evaluated in Phase 3 studies for Prader-Willi syndrome. The drug remains investigational and has not been approved by regulatory authorities.

What clinical trials is Pitolisant in?

Pitolisant is being studied in several clinical trials. NCT06366464 is a Phase 3 recruiting study in Prader-Willi syndrome with 134 participants. NCT07219485 is a Phase 3 study enrolling by invitation in the same condition. Completed trials include NCT04257929 in Prader-Willi syndrome and NCT04886518 in myotonic dystrophy type 1.

Is Pitolisant the same as Pitolisant tablet?

Yes, Pitolisant tablet is the same drug as Pitolisant. The tablet formulation is the oral dosage form being evaluated in clinical trials. Both names refer to the same investigational small molecule developed by Harmony Biosciences for neurologic conditions.

How does Pitolisant work?

Pitolisant is a small molecule that targets the histamine H3 receptor, acting as an inverse agonist. By modulating this receptor, it increases histamine release in the brain, which promotes wakefulness and may address excessive daytime sleepiness associated with conditions like Prader-Willi syndrome and myotonic dystrophy type 1.