A Long-Term Safety and Effectiveness Study to Evaluate Pitolisant in Adult Patients With Idiopathic Hypersomnia

An Open-Label Study to Evaluate the Long-Term Safety and Effectiveness of Pitolisant in Adult Patients With Idiopathic Hypersomnia Who Completed Study HBS-101-CL-010

The primary objective of this study is to assess the long-term safety and effectiveness of pitolisant in patients with idiopathic hypersomnia (IH) who completed the Double-Blind Randomized Withdrawal Phase of study HBS-101-CL-010.

Study Overview

• Status: Completed
• Conditions: Idiopathic Hypersomnia; Excessive Daytime Sleepiness
• Intervention / Treatment: Drug: Pitolisant

Detailed Description

This is a Phase 3 open-label study to evaluate the long-term safety and effectiveness of pitolisant in adult patients with IH. Patients who complete the Double-Blind Randomized Withdrawal Phase of study HBS-101-CL-010 (i.e., completed the End-of-Treatment [EOT] Visit/Visit 5 in the HBS-101-CL-010 study) and who continue to meet eligibility criteria for study HBS-101-CL-011 are eligible for enrollment.

Enrolled patients will be dispensed open-label pitolisant and may be titrated up to a maximum dose of 35.6 mg, based on the Investigator's assessment of safety/tolerability and effectiveness, during a 3-week Titration Period (Day 1 to Day 21) in accordance with the schedule:

• Week 1 (Day 1-7), 8.9 mg
• Week 2 (Day 8-14), 17.8 mg
• Week 3 (Day 15-21), 35.6 mg

The Long-Term Dosing Period will begin on Day 22 and will continue until the patient discontinues from the study or the Sponsor elects to terminate the study (i.e., End-of-Study [EOS]).

An on-site study visit will occur approximately 180 days after Visit 2 on Day 202 (Visit 3). On-site study visits will occur approximately every 6 months and telephone contacts (TCs) approximately every one month in between until the patient withdraws from the study or the study is terminated by the Sponsor. The dose of pitolisant may be adjusted (higher or lower) in increments of 4.45 mg starting at 8.9 mg up to 35.6 mg during the Long-Term Dosing Period based on Investigator assessment of safety/tolerability and effectiveness.

All patients will receive safety follow-up TCs from the study site 15 days and 30 days after their final dose of pitolisant, to assess for adverse events (AEs) and concomitant medication use.

• Study Type: Interventional
• Enrollment (Actual): 119
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Towers
    • San Ramon, California, United States, 94583
      • Sleep Medicine Specialists of California
  • Florida
    • Brandon, Florida, United States, 33511
      • Meris Clinical Research
    • Clearwater, Florida, United States, 33765
      • St. Francis Medical Institute
    • Winter Park, Florida, United States, 32789
      • Florida Pediatric Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • NeuroTrials Research Inc.
  • Illinois
    • Glenview, Illinois, United States, 60026
      • Northshore University Health System
    • Peoria, Illinois, United States, 61637
      • OSF HealthCare Saint Francis Medical Center
  • Michigan
    • Kalamazoo, Michigan, United States, 49008
      • Western Michigan University Homer Stryker MD School of Medicine
    • Sterling Heights, Michigan, United States, 48314
      • Clinical Neurophysiology Services
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • St. Luke's Sleep Medicine and Research Center
    • St Louis, Missouri, United States, 63123
      • Clayton Sleep Institute
  • Nebraska
    • North Platte, Nebraska, United States, 69101
      • Great Plains Health
  • New Jersey
    • Neptune City, New Jersey, United States, 07753
      • Sleep Dynamics
  • New York
    • New Hyde Park, New York, United States, 11042
      • Northwell Health
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University School of Medicine
    • Gastonia, North Carolina, United States, 28054
      • Clinical Research of Gastonia
    • Huntersville, North Carolina, United States, 28078
      • ARSM Research
  • Ohio
    • Canton, Ohio, United States, 44718
      • Neuroscience Research Center, LLC
    • Cincinnati, Ohio, United States, 45245
      • Intrepid Research, LLC
    • Dublin, Ohio, United States, 43017
      • Ohio Sleep Medicine and Neuroscience Institue
    • Middleburg, Ohio, United States, 44130
      • North Star Medical Research
  • Pennsylvania
    • Willow Grove, Pennsylvania, United States, 19090
      • Abington Neurological Associates
    • Wyomissing, Pennsylvania, United States, 19610
      • Respiratory Specialists
  • South Carolina
    • Columbia, South Carolina, United States, 29201
      • Bogan Sleep Consultants
    • North Charleston, South Carolina, United States, 29406
      • Lowcountry Lung Critical Care
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Neurology Clinic, P.C.
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology LP
    • Round Rock, Texas, United States, 78681
      • Central Texas Neurology Consultants, PA
    • Sugar Land, Texas, United States, 77478
      • Comprehensive Sleep Medicine Associates
    • Tomball, Texas, United States, 77375
      • Northwest Houston Neurology and Sleep
  • Wisconsin
    • Madison, Wisconsin, United States, 53719
      • University of Wisconsin-Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Is able to provide voluntary, informed consent.
2. Completed the Double-Blind Randomized Withdrawal Phase (EOT/Visit 5) from the HBS-101-CL-010 study.
3. A patient who is a female of child-bearing potential must have a negative urine pregnancy test at the Screening Visit. A patient who is a female of child-bearing potential must agree to remain abstinent or use an effective method of non-hormonal contraception to prevent pregnancy for the duration of the study and for 21 days after final dose of study drug.
4. Must have a negative result on urine drug screen at the Screening Visit, except for medications that are prescribed by a healthcare provider for medical conditions.
5. In the opinion of the Investigator, the patient is capable of understanding and complying with the protocol and administration of oral study drug.

Exclusion Criteria:

1. Does not agree to discontinue any prohibited medication or substances listed in the protocol.
2. 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 and for 21 days after final dose of study drug.
3. Participation in an interventional research study with an investigational medication or device, other than pitolisant, for the duration of the study.
4. Has a diagnosis of end-stage renal disease (ESRD; estimated glomerular filtration rate [eGFR] of <15 mL/minute/1.73 m2) or severe hepatic impairment (Child-Pugh C).
5. Is receiving or is unable to discontinue a medication known to prolong the QT interval.
6. Has a significant risk of committing suicide or suicidality based on history; routine psychiatric examination; Investigator's judgment; or who has an answer of "yes" on any question other than questions 1 to 3 or "yes" on any question in the suicidal behavior section of the C-SSRS, Since Last Visit.
7. Based on the judgment of the Investigator, is unsuitable for the study for any reason, including but not limited to an unstable or uncontrolled medical condition or one 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Pitolisant; Week 1: 8.9 mg pitolisant administered once daily in the morning upon wakening; Week 2: 17.8 mg pitolisant administered once daily in the morning upon wakening; Weeks 3 through end of treatment: 17.8 mg to 35.6 mg pitolisant administered once daily in the morning upon wakening.	Drug: Pitolisant; Pitolisant 4.45 mg tablets Pitolisant 17.8 mg tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of pitolisant	Incidence of adverse events (AEs)	Up to approximately 3 years
Excessive daytime sleepiness	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.	Up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptoms of idiopathic hypersomnia	Change from Baseline in Idiopathic Hypersomnia Severity Scale (IHSS) The score of the IHSS ranges from 0 to 50. A decrease in score represents an improvement in symptoms of idiopathic hypersomnia.	Up to approximately 3 years
Symptoms of idiopathic hypersomnia	Change from Baseline in Clinical Global Impression of Severity (CGI-S) for IH The CGI-S is a five-item scale that ranges from none to very severe. An assessment of less severe symptoms represents an improvement in the clinician's perception of the patient's overall clinical status related to idiopathic hypersomnia.	Up to approximately 3 years
Symptoms of idiopathic hypersomnia	Change from Baseline in Patient Global Impression of Severity (PGI-S) for EDS The PGI-S is a five-item scale that ranges from none to very severe. An assessment of less severe symptoms represents an improvement in the patient's perception of the severity of their excessive daytime sleepiness.	Up to approximately 3 years
Functional outcomes of sleep	Change from Baseline in Functional Outcomes of Sleep Questionnaire 10-item version (FOSQ-10) The score of the FOSQ-10 ranges from 5 to 20. An increase in score represents an improvement in the patient's impression of the impact of hypersomnia on multiple activities of everyday living.	Up to approximately 3 years
Sleep related impairments during wakefulness	Change from Baseline in Patient-Reported Outcomes Measurement Information System Sleep-Related Impairment Item Bank v1.0-Short Form 8a (PROMIS-SRI 8a) The score of the PROMIS-SRI 8a ranges from 8-40. A decrease in score represents an improvement in the patient's impression of the impact of hypersomnia on multiple activities of everyday living.	Up to approximately 3 years
Sleep inertia	Change from Baseline in Sleep Inertia Questionnaire (SIQ) The SIQ ranges from 21 to 105. A decrease in score represents an improvement in the patient's ability to wake up after sleep.	Up to approximately 3 years

Collaborators and Investigators

• Sponsor: Harmony Biosciences Management, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2022
• Primary Completion (Actual): October 1, 2025
• Study Completion (Actual): October 1, 2025

Study Registration Dates

• First Submitted: July 11, 2022
• First Submitted That Met QC Criteria: July 11, 2022
• First Posted (Actual): July 14, 2022

Study Record Updates

• Last Update Posted (Actual): December 12, 2025
• Last Update Submitted That Met QC Criteria: December 5, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: sleepiness; pitolisant; histamine; IH
• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Sleep Wake Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Sleepiness; Disorders of Excessive Somnolence; Idiopathic Hypersomnia; pitolisant
• Other Study ID Numbers: HBS-101-CL-011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No