A Phase 3 Efficacy and Safety Study of HBS-301 in Participants With Narcolepsy

A Phase 3, Randomized, Double-blind, Placebo-Controlled, Efficacy and Safety Study of HBS-301 in Participants With Narcolepsy 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 excessive daytime sleepiness (EDS), cataplexy, sleepiness/wakefulness, and fatigue in adult participants (ages ≥18 years) with narcolepsy.

Study Overview

• Status: Recruiting
• Conditions: Fatigue; Narcolepsy; Cataplexy; EDS
• Intervention / Treatment: Other: Placebo; Drug: HBS-301

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 EDS, cataplexy, sleepiness/wakefulness, and fatigue in adult participants (ages ≥18 years) with narcolepsy.

Approximately 258 participants are planned for randomization into 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 Period (1 year), and 30 days of safety follow-up.

• Study Type: Interventional
• Enrollment (Estimated): 258
• 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
  • Arizona
    • Peoria, Arizona, United States, 85381
      • Recruiting
      • Phoenix Medical Group, PC
      • Principal Investigator: Robert Orr, DO
  • California
    • Los Angeles, California, United States, 90025
      • Recruiting
      • Santa Monica Clinical Trials
      • Principal Investigator: Daniel Norman, MD
  • Colorado
    • Boulder, Colorado, United States, 80301
      • Recruiting
      • Alpine Clinical Research Center, Inc
      • Principal Investigator: John R Harsh, PhD
  • Florida
    • Miami, Florida, United States, 33176
      • Recruiting
      • PharmaDev Clinical Research Institute, LLC
      • Principal Investigator: Edward Mezerhane, MD
    • Winter Park, Florida, United States, 32789
      • Recruiting
      • Central Florida Pediatric Sleep Disorders Institute
      • Principal Investigator: Akinyemi O Ajayi, MD
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Recruiting
      • Neurotrials Research Inc
      • Contact: Dennis Lacey; Phone Number: 404-851-9934
    • Macon, Georgia, United States, 31210
      • Recruiting
      • Sleep Practitioners, LLC
      • Principal Investigator: Charles C Wells, Jr, MD
  • Ohio
    • Cincinnati, Ohio, United States, 45245
      • Recruiting
      • Intrepid Research, LLC
      • Principal Investigator: Bruce C Corser, MD
  • Pennsylvania
    • Wyomissing, Pennsylvania, United States, 19610
      • Recruiting
      • Respiratory Specialists
      • Principal Investigator: Alec Platt, MD
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Recruiting
      • Lowcountry Lung and Critical Care PA
      • Principal Investigator: Thomas D Kaelin Jr, DO
    • Columbia, South Carolina, United States, 29201
      • Recruiting
      • Bogan Sleep Consultants, Llc
      • Principal Investigator: Richard Bogan, MD
  • Texas
    • Dallas, Texas, United States, 75235
      • Recruiting
      • Southwest Family Medicine
      • Principal Investigator: Chrisette Dharma, MD
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • Sleep Therapy & Research Center
      • Principal Investigator: Nagwa Lamaie, MD
  • Washington
    • Spokane, Washington, United States, 99202
      • Recruiting
      • Sleep and Performance Research Center
      • Principal Investigator: Devon Hansen, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Has a current documented diagnosis of NT1 or NT2 per the International Classification of Sleep Disorders, Third Edition (ICSD-3) or the ICSD-3 Text Revision (ICSD-3-TR) within the last 10 years.
• Has EDS.
• If taking a permitted chronic concomitant medication or supplement, including nonprohibited antidepressants or wake-promoting agents, 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. As needed (PRN) use of any treatment that could affect daytime sleepiness (including but not limited to oxybates, stimulants, modafinil, and armodafinil) is not permitted.

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, including depression, that is not well controlled (i.e., symptoms and medications have not been stable for at least 3 months prior to Screening).
• Has any history of bipolar disorder or psychosis
• Has acute or chronic liver disease or a history of moderate or severe hepatic impairment.
• Has a body surface area-corrected estimated glomerular filtration rate (eGFR) <60 mL/min.
• Has a known history of long QT syndrome or 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	Drug: HBS-301; 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	Other: Placebo; Placebo tablet
Experimental: Open-Label Extension Period HBS-301; HBS-301 tablets administered once daily in the morning upon wakening	Drug: HBS-301; HBS-301 tablet; Other Names: pitolisant delayed-release

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in severity of EDS as measured by the Epworth Sleepiness Scale (ESS)	The ESS is an 8-item, 4-point rating scale.	Baseline to end of Double-Blind Treatment Period (8 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Weekly Rate of Cataplexy (WRC) in participants with an average WRC of ≥3 over 2 consecutive weeks at Screening	The WRC is the average number of cataplexy attacks per week.	End of the Double-Blind Treatment Period (8 weeks)
Change in sleepiness/wakefulness measured by the Maintenance of Wakefulness Test (MWT)	The MWT consists of a series of 20-minute to 40-minute trials spaced 2 hours apart and is used to measure an individual's ability to stay awake.	Baseline to the end of the Double-blind Treatment Period (8 weeks)
Change in fatigue as measured by the Patient-Reported Outcomes Measurement Information System Fatigue Short Form 7a (PROMIS-Fatigue-SF-7a)	The PROMIS-Fatigue-SF-7a is a 7-question, 5-point scale used to assess fatigue.	Baseline to end of Double-Blind Treatment Period (8 weeks)
Change in severity of EDS as measured by the ESS	The ESS is an 8-item, 4-point rating scale.	Baseline through Week 1 and through Week 2 of Titration Period (1 week and 2 weeks)
Onset of efficacy of HBS-301 compared with placebo in treating cataplexy measured by WRC in participants with an average WRC of ≥3 over 2 consecutive weeks during Screening	The WRC is the average number of cataplexy attacks per week.	Baseline through Week 1 and Week 2 of the Titration Period (1 week and 2 weeks)
Change in severity of EDS as measured by the Clinical Global Impression of Change (EDS)	The Clinical Global Impression of Change (EDS) is a 7-point scale used to measure the improvement or worsening of the participant's EDS relative to a baseline.	Baseline to end of Double-blind Treatment Period (8 weeks)
Change in severity of EDS as measured by the Patient Global Impression of Severity (EDS)	The Patient Global Impression of Severity (EDS) is a participant-reported assessment that gauges the severity of a participant's EDS symptoms.	Time Frame: Baseline to the end of the Double-blind Treatment Period (8 weeks)
Improvement in the severity of EDS as measured by the Patient Global Impression of Change (EDS)	The Patient Global Impression of Change (EDS) is a participant-reported outcome used to evaluate the effectiveness of a treatment on their EDS symptoms.	Baseline to the end of the Double-blind Treatment Period (8 weeks)
Change in severity of cataplexy as measured by the Clinical Global Impression of Severity (Cataplexy) in participants with an average WRC of ≥3 over 2 consecutive weeks during Screening	The Clinical Global Impression of Severity (Cataplexy) is a 3-item observer-rated scale used to track cataplexy symptom changes.	Baseline to the end of the Double-blind Treatment Period (8 weeks)
Change in severity of cataplexy as measured by the Patient Global Impression of Severity (Cataplexy) in participants with an average WRC of ≥3 over 2 consecutive weeks during Screening	The Patient Global Impression of Severity (Cataplexy) is a participant-reported assessment that gauges the severity of cataplexy symptoms.	Baseline to the end of the Double-blind Treatment Period (8 weeks)
Improvement in severity of cataplexy as measured by the Patient Global Impression of Change (Cataplexy) in participants with an average WRC of ≥3 over 2 consecutive weeks during Screening	The Patient Global Impression of Change (Cataplexy) is a participant-reported outcome used to evaluate the effectiveness of a treatment on their cataplexy symptoms.	Baseline to the end of the Double-blind Treatment Period (8 weeks)
Change in severity of fatigue as measured by the Patient Global Impression of Severity (Fatigue)	The Patient Global Impression of Severity (Fatigue) is a participant-reported assessment that gauges the severity of a participant's fatigue symptoms.	Baseline to the end of Double-blind Treatment Period (8 weeks)
Change in severity of fatigue as measured by the Patient Global Impression of Change (Fatigue)	The Patient Global Impression of Change (Fatigue) is a participant-reported outcome used to evaluate the effectiveness of a treatment on their fatigue symptoms.	Baseline to the end of the Double-blind Treatment Period (8 weeks)
Change in severity of narcolepsy symptoms as measured by the Narcolepsy Severity Scale (for participants with NT1) or Narcolepsy Severity Scale-2 (for participants with NT2)	The Narcolepsy Severity Scale is a 15-item participant-reported questionnaire that assesses the severity and consequences of narcolepsy symptoms.	Baseline to the end of the Double-blind Treatment Period (8 weeks)
Change in cognitive complaints as measured by the British Columbia Cognitive Complaints Inventory	The British Columbia Cognitive Complaints Inventory is a participant-reported, 6-item, 4-point scale that assesses perceived cognitive difficulties.	Baseline to the end of the Double-blind Treatment Period (8 weeks)
Change in health-related quality of life as measured by the Short Form-36 physical and mental component summaries	The Short Form-36 includes 36 questions across 8 health domains to measure a participant's functional health and well-being.	Baseline to the end of the Double-blind Treatment Period (8 weeks)
Change in work productivity as measured by the Work Productivity and Activity Impairment: Narcolepsy work productivity loss score	The Work Productivity and Activity Impairment: Narcolepsy questionnaire is a 6-item scale used to measure impairments over 7 days.	Baseline to the end of the Double-blind Treatment Period (8 weeks)
Incidence of treatment-emergent adverse events	A treatment-emergent adverse event is any adverse event reported after the first dose of study drug and up to 30 days after final dose of study drug, or any worsening of a pre-existing condition reported after first dose of study drug and up to 30 days after final dose of study drug.	Throughout study (16 months, including Open-label Extension)
Evaluate the pharmacokinetic concentrations of pitolisant and major identified metabolites	Pharmacokinetics is the study of how the body interacts with administered substances for the duration of exposure.	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): June 4, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: June 22, 2026
• First Submitted That Met QC Criteria: June 25, 2026
• First Posted (Actual): June 30, 2026

Study Record Updates

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

More Information

Terms related to this study

• Keywords: fatigue; narcolepsy; EDS; pitolisant; cataplexy; HBS-301
• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Sleep Wake Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Disorders of Excessive Somnolence; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Fatigue; Narcolepsy; Cataplexy
• Other Study ID Numbers: HBS-301-CL-301; 2025-523821-17-00 (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
• product manufactured in and exported from the U.S.: No