A Phase 3 Efficacy and Safety Study of HBS-301 in Participants With Idiopathic Hypersomnia (IH)

A Phase 3, Randomized, Double-blind, Placebo-Controlled, Efficacy and Safety Study of HBS-301 in Participants With Idiopathic Hypersomnia (IH) Followed by an Open-label Extension

This is a Phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled clinical study to assess the efficacy and safety of HBS-301 in treating idiopathic hypersomnia (IH) symptoms, including excessive daytime sleepiness (EDS), sleep inertia, and fatigue in adult participants (ages ≥18 years) with idiopathic hypersomnia (IH).

The primary objective of this study is to evaluate the efficacy of HBS-301 compared with placebo in treating IH symptoms.

Secondary objectives include evaluating the efficacy of HBS-301 compared with placebo in treating EDS, sleep inertia, and fatigue.

Study Overview

• Status: Recruiting
• Conditions: Idiopathic Hypersomnia
• Intervention / Treatment: Drug: Placebo; Drug: HBS-301 tablet

Detailed Description

This is a Phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled clinical study to assess the efficacy and safety of HBS-301 in treating IH symptoms, including EDS, sleep inertia, and fatigue in adult participants (ages ≥18 years) with IH.

Approximately 248 participants are planned for randomization in the study. The study will consist of a Screening/Baseline Period (up to 28 days), a Double-blind Treatment Period (8 weeks), an optional Open-label Extension (OLE) Period (1 year), and 30 days of safety follow-up.

• Study Type: Interventional
• Enrollment (Estimated): 248
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Katie Wilmsen; Phone Number: 443-309-5556; Email: clinicaltrials@harmonybiosciences.com
• Study Contact Backup: Name: Michelle Manuel; Phone Number: 847-903-4610; Email: clinicaltrials@harmonybiosciences.com

Study Locations

• United States
  • California
    • Santa Monica, California, United States, 90404
      • Recruiting
      • Santa Monica Clinical Trials
      • Principal Investigator: Daniel Norman, MD
      • Contact: Jualynda Smith
  • Florida
    • Miami, Florida, United States, 33176
      • Recruiting
      • PharmDev Research Institute, LLC
      • Principal Investigator: Edward Mezerhane, MD
      • Contact: Lisbet Machado Cordova, APRN
    • Winter Park, Florida, United States, 32789
      • Recruiting
      • Central Florida Pediatric Sleep Disorders Institute (Florida Pediatric Research Institute, LLC)
      • Contact: Akinyemi Ajayi, MD
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Recruiting
      • NeuroTrials Research Inc.
      • Contact: Dennis Lacey, MD
      • Contact: Melody
      • Principal Investigator: Dennis Lacey, MD
    • Stockbridge, Georgia, United States, 30281
      • Recruiting
      • Phillip Nowlin
      • Contact: Phillip Nowlin, MD
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Recruiting
      • St. Luke's Hospital, Sleep Medicine and Research Center
      • Principal Investigator: Michael McLeland, PhD
      • Contact: Michael McLeland, PhD
  • North Carolina
    • Gastonia, North Carolina, United States, 28054
      • Recruiting
      • Clinical Research of Gastonia
      • Contact: Melissa Lanham; Phone Number: 704-675-7144; Email: mlanham@crgastonia.com
      • Contact: Madeline Gibson; Phone Number: 704-675-7144; Email: mgibson@crgastonia.com
      • Principal Investigator: Anup Banerjee, MD
    • Huntersville, North Carolina, United States, 28078
      • Recruiting
      • Stern Research Partners, LLC
      • Principal Investigator: Thomas Stern, MD
      • Contact: Felix Kurniawan; Phone Number: 1012 704-248-0000; Email: felix@arsmnc.com
    • Morrisville, North Carolina, United States, 27560
      • Recruiting
      • David Kudrow, MD
      • Contact: David Kudrow, MD
  • Pennsylvania
    • Wyomissing, Pennsylvania, United States, 19610
      • Recruiting
      • Respiratory Specialists
      • Principal Investigator: Alec Platt, MD
      • Contact: Alex Platt, MD
  • Tennessee
    • Nashville, Tennessee, United States, 37204
      • Recruiting
      • K2 Medical Research
      • Contact: Auchaia Farley, PA
      • Principal Investigator: Joshua Lennon, MD
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Recruiting
      • West Virginia University
      • Contact: Mouhannad Azzouz; Phone Number: 304-598-4000; Email: mouhannad.azzouz@hsc.wvu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has a current documented diagnosis of IH per the International Classification of Sleep Disorders, Third Edition (ICSD-3) or Text Revision (ICSD-3-TR) criteria with confirmatory polysomnogram (PSG) with multiple sleep latency test (MSLT); and if applicable, an actigraphy report with sleep log on file that led to the diagnosis and was completed within the last 10 years.
• Has moderate to very severe symptoms of IH.
• If taking a permitted chronic concomitant medication or supplement, including nonprohibited antidepressants, must be on a stable dose for at least 3 months prior to Screening and agree to continue at that stable dose for the Double-blind Treatment Period of the study. Any treatment that could affect daytime sleepiness (including but not limited to stimulants, modafinil, and armodafinil) used on an as-needed basis is not permitted.
• For participants being treated for obstructive sleep apnea (OSA) or other hypoventilatory conditions, must be compliant with their medical device or oral appliance as determined by the Investigator. Participants must maintain OSA treatment compliance throughout the study.

Exclusion Criteria:

• Has hypersomnia due to another medical disorder.
• Has a history of pitolisant use within 5 half-lives prior to Screening.
• Has a primary diagnosis of psychiatric illness that is not well controlled.
• Has a history of moderate or severe hepatic impairment.
• Has a body surface area (BSA)-corrected estimated glomerular filtration rate (eGFR) <60 mL/min.
• Has a known history of long QT syndrome or any significant history of a serious abnormality of the electrocardiogram (ECG).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Double-Blind Treatment Period HBS-301; HBS-301 tablets administered once daily in the morning upon wakening at least 1 hour before meals	Drug: HBS-301 tablet; HBS-301 tablet; Other Names: pitolisant delayed-release
Placebo Comparator: Double-blind Treatment Period Placebo; Matching placebo tablets administered once daily in the morning upon wakening at least 1 hour before meals	Drug: Placebo; Placebo tablet
Experimental: Open-label Extension Period HBS-301; HBS-301 tablets administered once daily in the morning upon wakening at least 1 hour before meals	Drug: HBS-301 tablet; HBS-301 tablet; Other Names: pitolisant delayed-release

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the efficacy of HBS-301 compared with placebo in treating IH symptoms	Change in severity of IH symptoms as measured by the Idiopathic Hypersomnia Severity Scale	Baseline to the end of the Double-blind Treatment Period (8 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the efficacy of HBS-301 compared with placebo in treating EDS	Change in severity of EDS as measured by the Epworth Sleepiness Scale	Baseline to the end of the Double-blind Treatment Period (8 weeks)
To evaluate the efficacy of HBS-301 compared with placebo in treating sleep inertia	Change in sleep inertia as measured by the Sleep Inertia Questionnaire	Baseline to the end of the Double-blind Treatment Period (8 weeks)
To evaluate the efficacy of HBS-301 compared with placebo on fatigue	Change in fatigue as measured by the Patient-Reported Outcomes Measurement Information System Fatigue Short Form 7a	Baseline to the end of the Double-blind Treatment Period (8 weeks)
To evaluate the onset of efficacy of HBS-301 compared with placebo in treating EDS	Change in severity of EDS as measured by the Epworth Sleepiness Scale	Baseline through Week 1 and Week 2 of the Titration Period (1 week and 2 weeks)
To evaluate the onset of efficacy of HBS-301 compared to placebo in treating IH symptoms	Change in severity of IH symptoms as measured by the Idiopathic Hypersomnia Severity Scale	Baseline through Week 1 and Week 2 of the Titration Period (1 week and 2 weeks)
To evaluate the efficacy of HBS-301 compared with placebo in treating IH symptoms	Change in severity of IH symptoms as measured by the Clinical Global Impression of Severity (IH)	Baseline to end of Double-blind Treatment Period (8 weeks)
To evaluate the efficacy of HBS-301 compared with placebo in treating IH symptoms	Change in severity of IH symptoms as measured by the Patient Global Impression of Severity (IH)	Baseline to end of Double-blind Treatment Period (8 weeks)
To evaluate the efficacy of HBS-301 compared with placebo in treating sleep-related impairment	Change in severity of sleep-related impairment as measured by the PROMIS Custom Form v1.0 Sleep-Related Impairment-Harmony Biosciences	Baseline to the end of the Double-blind Treatment Period (8 weeks)
To evaluate the efficacy of HBS-301 compared with placebo on severity of fatigue	Change in severity of fatigue as measured by the Patient Global Impression of Severity (Fatigue)	Baseline of the end of the Double-blind Treatment Period (8 weeks)
To evaluate the efficacy of HBS-301 compared with placebo on overall severity of EDS	Change in severity of EDS as measured by the Patient Global Impression of Severity (EDS)	Baseline to the end of the Double-blind Treatment Period (8 weeks)
To evaluate the efficacy of HBS-301 compared with placebo on severity of sleep inertia	Change in severity of sleep inertia as measured by the Patient Global Impression of Severity (Sleep Inertia)	Baseline to end of Double-blind Treatment Period (8 weeks)
To evaluate the efficacy of HBS-301 compared with placebo on cognitive complaints	Change in cognitive complaints as measured by the British Columbia Cognitive Complaints Inventory	Baseline to the end of the Double-blind Treatment Period (8 weeks)
To evaluate the efficacy of HBS-301 compared with placebo on overall health-related quality of life	Change in health-related quality of life as measured by the Short Form Health Survey-36	Baseline to the end of the Double-blind Treatment Period (8 weeks)
To evaluate the efficacy of HBS-301 compared with placebo on work productivity	Change in work productivity as measured by the Work Productivity and Activity Impairment: Idiopathic Hypersomnia	Baseline to the end of the Double-blind Treatment Period (8 weeks)
To evaluate the safety of HBS-301	Incidence of treatment-emergent adverse events	Throughout study (16 months including OLE)
To evaluate the pharmacokinetic concentrations of pitolisant and major identified metabolites	Concentrations of pitolisant and major identified metabolites	Throughout study (16 weeks)

Collaborators and Investigators

• Sponsor: Harmony Biosciences Management, Inc.
• Investigators: Study Director: David Seiden, MD, Harmony Biosciences Management, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: March 21, 2026
• First Submitted That Met QC Criteria: March 25, 2026
• First Posted (Actual): March 30, 2026

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: excessive daytime sleepiness; idiopathic hypersomnia; pitolisant; sleep inertia; HBS-301
• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Sleep Wake Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Disorders of Excessive Somnolence; Idiopathic Hypersomnia
• Other Study ID Numbers: HBS-301-CL-302; 2025-523822-42-00 (Ctis)

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