A Phase 3 Study to Assess the Safety and Efficacy of Pitolisant in Adult Patients With Idiopathic Hypersomnia

NCT05156047 | Completed Phase 3 FDA Drug

• 1 other identifier: HBS-101-CL-010
• Study Type: interventional
• Target: 214
• Locations: 1 country
• Sites: 58

Brief 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 idiopathic hypersomnia (IH) age ≥18 years. Key secondary objectives of this study are to assess the impact of pitolisant on:

• Overall symptoms of IH
• Patient impression of overall change in their symptoms of IH
• Investigator assessment of overall disease severity of IH Other secondary objectives of this study are to assess the impact of pitolisant in patients with IH on:
• Patient impression of overall severity of their EDS
• Functional status and activities of daily living
• Sleep-related impairment
• Sleep inertia
• Cognitive function

Conditions

Idiopathic Hypersomnia

Keywords

pitolisant; histamine; sleepiness

Outcome Measures

Primary Outcomes (1)

• Excessive Daytime Sleepiness

  Change in Epworth Sleepiness Scale score from the end of the Stable Dose Period to the end of the 4-week Double-Blind Randomized Withdrawal Phase for pitolisant compared with placebo. The score of the Epworth Sleepiness Scale ranges from 0 to 24. A decrease in score represents an improvement in excessive daytime sleepiness.

  Week 8 to Week 12

Secondary Outcomes (10)

• Symptoms of idiopathic hypersomnia

  Week 8 to Week 12

• Symptoms of idiopathic hypersomnia

  Week 8 to Week 12

• Symptoms of idiopathic hypersomnia

  Week 8 to Week 12

• Symptoms of idiopathic hypersomnia

  Week 8 to Week 12

• Functional outcomes of sleep

  Week 8 to Week 12

Study Arms (3)

Double-blind pitolisant

ACTIVE COMPARATOR

Double-blind pitolisant administered once daily in the morning upon wakening for 4 weeks during the Double-Blind Randomized Withdrawal Phase

Drug: Double-blind pitolisant

Double-blind placebo

PLACEBO COMPARATOR

Matching placebo administered once daily in the morning upon wakening for 4 weeks during the Double-Blind Randomized Withdrawal Phase

Drug: Double-blind placebo

Open-label pitolisant

EXPERIMENTAL

Open-label pitolisant administered once daily in the morning upon wakening for 8 weeks during the Open-Label Phase

Drug: Open-label pitolisant

Interventions

Open-label pitolisant DRUG

Pitolisant 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.

Open-label pitolisant

Double-blind placebo DRUG

Matching placebo tablets will be provided for each strength of active pitolisant film-coated tablets.

Double-blind placebo

Double-blind pitolisant DRUG

Pitolisant 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 pitolisant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is able to provide voluntary, written informed consent.
• Has a current diagnosis of IH per International Classification of Sleep Disorders Third Edition (ICSD 3) criteria.
• Male or female patient age ≥18 years at the time of Screening.
• Has an ESS score of ≥12 at Screening and at Baseline (Visit 2).
• Has a PGI-S score of moderate, severe, or very severe at Screening and at Baseline (Visit 2).
• For patients being treated for OSA or other hypoventilatory conditions, patients must be compliant as demonstrated by BiPAP/CPAP therapy with 30 days of data showing ≥4 hours of BiPAP/CPAP therapy per night for ≥70% of nights. If not on BiPAP/CPAP therapy, patients being treated for OSA must be compliant as determined by the Investigator with their medical device or oral appliance. Data must be from within 90 days prior to the Screening visit. Patients must agree to maintain compliance with their treatment for OSA throughout the duration of the study.
• If on a treatment that could affect daytime sleepiness (including but not limited to oxybates, stimulants, modafinil, and armodafinil):
• Must be on a stable dose for at least 2 months prior to Screening and agree to continue the stable dose for the duration of the study.
• If not on a stable dose for 2 months prior to Screening, washout for 5 half-lives or 14 days, whichever is longer, prior to Day 1 and agree to remain off these treatments until completion of the study.
• A patient who is a female of child-bearing potential (FCBP) must have a negative serum pregnancy test at the Screening Visit and negative urine pregnancy test at the Baseline Visit (Visit 2) and at the end of the Stable Dose Period (Visit 4) and 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.
• Must have a negative result on urine drug screen at the Screening Visit, Baseline Visit (Visit 2) and at the end of the Stable Dose Period (Visit 4), except for medications that are prescribed by a healthcare provider for medical conditions.
• In the opinion of the Investigator, the patient is capable of understanding and complying with the protocol and administration of oral study drug.

You may not qualify if:

• Has hypersomnia due to another medical disorder (e.g., narcolepsy).
• Has an AHI of ≥10 as determined by the most recent sleep study or BiPAP/CPAP device readout.
• Has a clinically significant hypoventilatory condition as determined by the Investigator.
• Has a primary diagnosis of a psychiatric illness that is not well controlled.
• Patients taking antidepressants who have not been on a stable dose of their antidepressant for at least 12 weeks prior to Screening; patients on a stable dose of their antidepressant for at least 12 weeks prior to Screening must agree to continue their stable dose for the duration of the study.
• Experiences a mean of \<6 hours of sleep per night based on sleep diary during Screening (patients need to record at least 7 nights within a 10-day period in their sleep diary within 14-days prior to the Baseline Visit \[Visit 2\]).
• 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 study.
• Does not agree to discontinue any prohibited medication or substance listed in the protocol.
• Is currently or has previously used pitolisant.
• 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.
• Participation in an interventional research study involving another investigational medication, device, or behavioral treatment within 28 days or within 5 half-lives of the investigational medication (whichever is longer) prior to Screening.
• Has a diagnosis of ESRD (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 at any time during the study.
• Has a history of long corrected QT interval (QTc) syndrome or corrected QT interval using Fridericia's formula (QTcF) \>450 msec for males or \>470 msec for females (QTcF = QT / 3√ RR) at Screening.
• Is receiving and is unable to discontinue a medication known to prolong the QT interval.

Sponsors & Collaborators

• Harmony Biosciences Management, Inc.: lead

Study Sites (58)

Phoenix Medical Group

Peoria, Arizona, 85381, United States

Location

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

Cedars-Sinai Medical Towers

Los Angeles, California, 90048, United States

Location

University of California- Los Angeles

Los Angeles, California, 90095, United States

Location

Sleep Medicine Specialists of California

San Ramon, California, 94583, United States

Location

SDS Clinical Trials Inc.

Santa Ana, California, 92705, United States

Location

Santa Monica Clinical Trials

Santa Monica, California, 90404, United States

Location

Alpine Clinical Research Center

Boulder, Colorado, 80301, United States

Location

Norwalk Hospital Sleep Center

Norwalk, Connecticut, 06850, United States

Location

Meris Clinical Research

Brandon, Florida, 33511, United States

Location

St. Francis Medical Institute

Clearwater, Florida, 33765, United States

Location

Sleep Medicine Specialists of South Florida, PA

Miami, Florida, 33126, United States

Location

Pasadena Center For Medical Research, LLC

St. Petersburg, Florida, 33763, United States

Location

Florida Pediatric Research Institute

Winter Park, Florida, 32789, United States

Location

Neurotrials Research Inc.

Atlanta, Georgia, 30328, United States

Location

The Neurological Center of North GA

Gainesville, Georgia, 30501, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

NorthShore Uni HealthSys-Glenbrook Hospital

Glenview, Illinois, 60026, United States

Location

OSF HealthCare Saint Francis Medical Center

Peoria, Illinois, 61637, United States

Location

Helene A. Emsellem MD PC

Chevy Chase, Maryland, 20815, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Neurocare, INC

Newton, Massachusetts, 02459, United States

Location

Henry Ford Health System

Novi, Michigan, 48377, United States

Location

Bronson Sleep Health

Portage, Michigan, 49024, United States

Location

Clinical Neurophysiology Services

Sterling Heights, Michigan, 48314, United States

Location

Minnesota Lung Center

Edina, Minnesota, 55125, United States

Location

Minnesota Lung Center

Woodbury, Minnesota, 55125, United States

Location

St. Luke's Sleep Medicine and Research Center

Chesterfield, Missouri, 63017, United States

Location

Clayton Sleep Institute

St Louis, Missouri, 63123, United States

Location

Great Plains Health

North Platte, Nebraska, 69101, United States

Location

Neurology Specialists of Monmouth County, PA

West Long Branch, New Jersey, 07764, United States

Location

Northwell Health

New Hyde Park, New York, 11042, United States

Location

Research Carolina Elite LLC

Denver, North Carolina, 28037, United States

Location

Duke University School of Medicine

Durham, North Carolina, 27705, United States

Location

Clinical Research of Gastonia

Gastonia, North Carolina, 28054, United States

Location

ARSM Research

Huntersville, North Carolina, 28078, United States

Location

NeuroScience Research Center, LLC

Canton, Ohio, 44718, United States

Location

Intrepid Research, LLC

Cincinnati, Ohio, 45245, United States

Location

Rainbow Babies Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinc

Cleveland, Ohio, 44195, United States

Location

Ohio Sleep Medicine and Neuroscience Institue

Dublin, Ohio, 43017, United States

Location

North Star Medical Research

Middleburg, Ohio, 44130, United States

Location

CardioVoyage

Ardmore, Oklahoma, 73401, United States

Location

Brian Abaluck, LLC

Paoli, Pennsylvania, 19301, United States

Location

Abington Neurological Associates

Willow Grove, Pennsylvania, 19090, United States

Location

Respiratory Specialists

Wyomissing, Pennsylvania, 19610, United States

Location

Medical University of South Carolina- Institute of Psychiatry

Charleston, South Carolina, 29425, United States

Location

Bogan Sleep Consultants

Columbia, South Carolina, 29201, United States

Location

Lowcountry Lung Critical Care

North Charleston, South Carolina, 29406, United States

Location

Advanced Center for Sleep Disorders

Chattanooga, Tennessee, 37421, United States

Location

Neurology Clinic, P.C.

Cordova, Tennessee, 38018, United States

Location

FutureSearch Trials of Neurology LP

Austin, Texas, 78731, United States

Location

Central Texas Neurology Consultants, PA

Round Rock, Texas, 78681, United States

Location

Comprehensive Sleep Medicine Associates

Sugar Land, Texas, 77478, United States

Location

Northwest Houston Neurology and Sleep

Tomball, Texas, 77375, United States

Location

Children's Hospital of the King's Daughter

Norfolk, Virginia, 23507, United States

Location

West Virginia University - Department of Neurology

Morgantown, West Virginia, 26506, United States

Location

University of Wisconsin-Madison

Madison, Wisconsin, 53719, United States

Location

MeSH Terms

Conditions

Idiopathic Hypersomnia; Sleepiness

Condition Hierarchy (Ancestors)

Disorders of Excessive Somnolence; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Double-blind, randomized withdrawal

Study Record Dates

• First Submitted: December 1, 2021
• First Posted: December 14, 2021
• Study Start: May 25, 2022
• Primary Completion: September 8, 2023
• Study Completion: September 8, 2023
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

US (58)