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

Phase 3
Active, not recruiting
Conditions
Idiopathic Hypersomnia
Excessive Daytime Sleepiness
Interventions
Registration Number
NCT05458128
Lead Sponsor
Harmony Biosciences, LLC
Brief Summary

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.

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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
128
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
PitolisantPitolisantWeek 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.
Primary Outcome Measures
NameTimeMethod
Excessive daytime sleepinessUp 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.

Safety and tolerability of pitolisantUp to approximately 3 years

Incidence of adverse events (AEs)

Secondary Outcome Measures
NameTimeMethod
Functional outcomes of sleepUp to approximately 3 years

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.

Sleep related impairments during wakefulnessUp to approximately 3 years

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.

Symptoms of idiopathic hypersomniaUp to approximately 3 years

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.

Sleep inertiaUp to approximately 3 years

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.

Trial Locations

Locations (32)

Clinical Neurophysiology Services

🇺🇸

Sterling Heights, Michigan, United States

Western Michigan University Homer Stryker MD School of Medicine

🇺🇸

Kalamazoo, Michigan, United States

Sleep Dynamics

🇺🇸

Neptune City, New Jersey, United States

Cedars-Sinai Medical Towers

🇺🇸

Los Angeles, California, United States

Sleep Medicine Specialists of California

🇺🇸

San Ramon, California, United States

Meris Clinical Research

🇺🇸

Brandon, Florida, United States

St. Francis Medical Institute

🇺🇸

Clearwater, Florida, United States

Florida Pediatric Research Institute

🇺🇸

Winter Park, Florida, United States

Neurotrials Research Inc.

🇺🇸

Atlanta, Georgia, United States

NorthShore University Health System

🇺🇸

Glenview, Illinois, United States

OSF HealthCare Saint Francis Medical Center

🇺🇸

Peoria, Illinois, United States

St. Luke's Sleep Medicine and Research Center

🇺🇸

Chesterfield, Missouri, United States

Clayton Sleep Institute

🇺🇸

Saint Louis, Missouri, United States

Great Plains Health

🇺🇸

North Platte, Nebraska, United States

Northwell Health

🇺🇸

New Hyde Park, New York, United States

Duke University School of Medicine

🇺🇸

Durham, North Carolina, United States

Clinical Research of Gastonia

🇺🇸

Gastonia, North Carolina, United States

ARSM Research

🇺🇸

Huntersville, North Carolina, United States

NeuroScience Research Center, LLC

🇺🇸

Canton, Ohio, United States

Intrepid Research, LLC

🇺🇸

Cincinnati, Ohio, United States

Ohio Sleep Medicine and Neuroscience Institue

🇺🇸

Dublin, Ohio, United States

North Star Medical Research

🇺🇸

Middleburg, Ohio, United States

Abington Neurological Associates

🇺🇸

Willow Grove, Pennsylvania, United States

Respiratory Specialists

🇺🇸

Wyomissing, Pennsylvania, United States

Bogan Sleep Consultants

🇺🇸

Columbia, South Carolina, United States

Lowcountry Lung Critical Care

🇺🇸

North Charleston, South Carolina, United States

Neurology Clinic, P.C.

🇺🇸

Cordova, Tennessee, United States

FutureSearch Trials of Neurology LP

🇺🇸

Austin, Texas, United States

Central Texas Neurology Consultants, PA

🇺🇸

Round Rock, Texas, United States

Comprehensive Sleep Medicine Associates

🇺🇸

Sugar Land, Texas, United States

Northwest Houston Neurology and Sleep

🇺🇸

Tomball, Texas, United States

University of Wisconsin-Madison

🇺🇸

Madison, Wisconsin, United States

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