A Phase 3 Study to Assess the Safety and Efficacy of Pitolisant in Adult Patients With Idiopathic Hypersomnia
- Conditions
- Idiopathic Hypersomnia
- Interventions
- Registration Number
- NCT05156047
- Lead Sponsor
- Harmony Biosciences, LLC
- 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
- Detailed Description
This is a double-blind, placebo-controlled, randomized withdrawal study in adult patients (ages ≥18 years) with IH. The study will consist of a Screening Period (up to 28 days), an 8-week Open-Label Phase, and a 4-week Double-Blind Randomized Withdrawal Phase.
The Open-Label Phase of the study will be 8 weeks, which includes a 6-week Dose Optimization Period and a 2-week Stable Dose Period. In the Dose Optimization Period, all patients will be titrated to their optimal dose of open-label pitolisant (17.8 mg or 35.6 mg) based on Investigator assessment of tolerability and efficacy. The 3-week titration period will be followed by 3 weeks of flexible dosing (weeks 4-6) during which patients will continue to receive their optimal dose of 17.8 mg or 35.6 mg open-label pitolisant. Patients taking a strong CYP2D6 inhibitor will be allowed in the study; however, for these patients, the maximum permitted daily dose of pitolisant will be 17.8 mg. Following completion of the 6-week Dose Optimization Period, patients will enter the 2-week Stable Dose Period. During this period, patients will remain at their optimal dose (the same dose they were taking at the end of the Dose Optimization Period \[17.8 mg or 35.6 mg\]) of open-label pitolisant for 2 weeks; dose adjustments are not allowed during the Stable Dose Period. At the end of the Stable Dose Period, patients will be defined as responders or non-responders. Responders will be randomized in a 1:1 ratio to receive blinded study drug (pitolisant or matching placebo) in the Double-Blind Randomized Withdrawal Phase of the study. Non-responders will not be randomized to treatment in the Double-Blind Randomized Withdrawal Phase and will complete two safety follow-up telephone contacts (TCs) at 15 (±3) days and 30 (+3) days after their final dose of open-label pitolisant.
During the Double-Blind Randomized Withdrawal Phase, patients (approximately 64 patients per treatment group) will receive blinded study drug either at the same dose they were taking in the Stable Dose Period (17.8 mg or 35.6 mg pitolisant) or matching placebo. The duration of the Double-Blind Randomized Withdrawal Phase will be 4 weeks (weeks 9-12); dose adjustments are not permitted during this phase of the study. After completion of the Double-Blind Randomized Withdrawal Phase (End-of Treatment \[EOT\] Visit is on Day 84, the last day of blinded treatment), patients will complete two safety follow-up TCs with the site at 15 (±3) days and 30 (+3) days after their final dose of blinded study drug, which will include assessment for AEs and concomitant medication use; alternatively, patients will have the opportunity to enroll in a long-term, open-label safety study under a separate protocol. Patients who opt to enroll into the long-term, open-label study will not complete the 15 day and 30 day follow-up TCs.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 214
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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.
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Has an ESS score of ≥12 at Screening and at Baseline (Visit 2).
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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.
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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.
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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.
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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.
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In the opinion of the Investigator, the patient is capable of understanding and complying with the protocol and administration of oral study drug.
- 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.
- Is receiving a concomitant medication that is known to be a strong CYP3A4 inducer, or a centrally acting histamine 1 (H1) receptor antagonist; patients who undergo a washout of these medications of at least 5 half-lives or one week (whichever is longer) may be enrolled in the study. Use of strong CYP2D6 inhibitors is allowed; however, for these patients the maximum permitted daily dose of pitolisant is 17.8 mg.
- Is a known CYP2D6 poor metabolizer (PM).
- Has abnormal laboratory values at Screening that are clinically significant as determined by the Investigator.
- Has initiated any new or change in allied health therapies or interventions that can interfere with the study outcomes within 28 days prior to Screening and at any time during the study, based on the Investigator's judgment.
- Has a current or recent (within 1 year) history of a substance use disorder or dependence disorder, including alcohol, tobacco, and caffeine use disorders as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5).
- Has planned surgery during the study.
- Has a significant risk of committing suicide or suicidality based on history; routine psychiatric examination; Investigator's judgment; or an answer of "yes" on any question other than questions 1 to 3 (for the previous month) or "yes" on any question in the suicidal behavior section (for the past year) of the Columbia-Suicide Severity Scale (C-SSRS), Baseline/Screening.
- 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. This exclusion criterion applies not only to entry into the study, but also to continuation in the study, should such an unstable, uncontrolled, or serious medical condition arise.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Double-blind pitolisant Double-blind pitolisant Double-blind pitolisant administered once daily in the morning upon wakening for 4 weeks during the Double-Blind Randomized Withdrawal Phase Double-blind placebo Double-blind placebo Matching placebo administered once daily in the morning upon wakening for 4 weeks during the Double-Blind Randomized Withdrawal Phase Open-label pitolisant Open-label pitolisant Open-label pitolisant administered once daily in the morning upon wakening for 8 weeks during the Open-Label Phase
- Primary Outcome Measures
Name Time Method Excessive Daytime Sleepiness Week 8 to Week 12 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.
- Secondary Outcome Measures
Name Time Method Attention Week 8 to Week 12 Change in Cogstate Identification Test.
The Cogstate Identification Test is a computerized test. A faster speed represents an improvement in attention test performance.Sleep related impairments during wakefulness Week 8 to Week 12 Change in Patient-Reported Outcomes Measurement Information System, Sleep-Related Impairment.
The score of the Patient-Reported Outcomes Measurement Information System, Sleep-Related Impairment ranges from 8 to 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 hypersomnia Week 8 to Week 12 Change in Patient Global Impression of Severity of their excessive daytime sleepiness.
The Patient Global Impression of Severity 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 inertia Week 8 to Week 12 Change in Sleep Inertia Questionnaire.
The Sleep Inertia Questionnaire ranges from 21 to 105. A decrease in score represents an improvement in the patient's ability to wake up after sleep.Working Memory Week 8 to Week 12 Change in Cogstate One Back Test.
The Cogstate One Back Test is a computerized test. A faster speed represents a better working memory test performance.Functional outcomes of sleep Week 8 to Week 12 Change in Functional Outcomes of Sleep Questionnaire 10-item Version.
The score of the Functional Outcomes of Sleep Questionnaire 10-item Version 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.Psychomotor Function Week 8 to Week 12 Change in Cogstate Detection Test.
The Cogstate Detection Test is a computerized test. A faster speed represents an improvement in psychomotor test performance.
Trial Locations
- Locations (57)
Santa Monica Clinical Trials
🇺🇸Santa Monica, California, United States
Lowcountry Lung Critical Care
🇺🇸North Charleston, South Carolina, United States
NorthShore Uni HealthSys-Glenbrook Hospital
🇺🇸Glenview, Illinois, United States
Clinical Neurophysiology Services
🇺🇸Sterling Heights, Michigan, United States
University of California- Los Angeles
🇺🇸Los Angeles, California, United States
Central Texas Neurology Consultants, PA
🇺🇸Round Rock, Texas, United States
Comprehensive Sleep Medicine Associates
🇺🇸Sugar Land, Texas, United States
Florida Pediatric Research Institute
🇺🇸Winter Park, Florida, United States
Henry Ford Health System
🇺🇸Novi, Michigan, United States
St. Francis Medical Institute
🇺🇸Clearwater, Florida, United States
Neurotrials Research Inc.
🇺🇸Atlanta, Georgia, United States
Minnesota Lung Center
🇺🇸Woodbury, Minnesota, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Cleveland Clinc
🇺🇸Cleveland, Ohio, United States
Sleep Medicine Specialists of South Florida, PA
🇺🇸Miami, Florida, United States
Duke University School of Medicine
🇺🇸Durham, North Carolina, United States
Intrepid Research, LLC
🇺🇸Cincinnati, Ohio, United States
Bogan Sleep Consultants
🇺🇸Columbia, South Carolina, United States
Great Plains Health
🇺🇸North Platte, Nebraska, United States
Phoenix Medical Group
🇺🇸Peoria, Arizona, United States
Advanced Center for Sleep Disorders
🇺🇸Chattanooga, Tennessee, United States
West Virginia University - Department of Neurology
🇺🇸Morgantown, West Virginia, United States
Neurology Clinic, P.C.
🇺🇸Cordova, Tennessee, United States
University of Wisconsin-Madison
🇺🇸Madison, Wisconsin, United States
Cedars-Sinai Medical Towers
🇺🇸Los Angeles, California, United States
Sleep Medicine Specialists of California
🇺🇸San Ramon, California, United States
SDS Clinical Trials Inc.
🇺🇸Santa Ana, California, United States
Norwalk Hospital Sleep Center
🇺🇸Norwalk, Connecticut, United States
Alpine Clinical Research Center
🇺🇸Boulder, Colorado, United States
Meris Clinical Research
🇺🇸Brandon, Florida, United States
Pasadena Center For Medical Research, LLC
🇺🇸Saint Petersburg, Florida, United States
The Neurological Center of North GA
🇺🇸Gainesville, Georgia, United States
OSF HealthCare Saint Francis Medical Center
🇺🇸Peoria, Illinois, United States
Helene A. Emsellem MD PC
🇺🇸Chevy Chase, Maryland, United States
Neurocare, INC
🇺🇸Newton, Massachusetts, United States
Bronson Sleep Health
🇺🇸Portage, Michigan, United States
St. Luke's Sleep Medicine and Research Center
🇺🇸Chesterfield, Missouri, United States
Clayton Sleep Institute
🇺🇸Saint Louis, Missouri, United States
Neurology Specialists of Monmouth County, PA
🇺🇸West Long Branch, New Jersey, United States
Northwell Health
🇺🇸New Hyde Park, New York, United States
Research Carolina Elite LLC
🇺🇸Denver, North Carolina, United States
Clinical Research of Gastonia
🇺🇸Gastonia, North Carolina, United States
ARSM Research
🇺🇸Huntersville, North Carolina, United States
Ohio Sleep Medicine and Neuroscience Institue
🇺🇸Dublin, Ohio, United States
Rainbow Babies Children's Hospital
🇺🇸Cleveland, Ohio, United States
NeuroScience Research Center, LLC
🇺🇸Canton, Ohio, United States
CardioVoyage
🇺🇸Ardmore, Oklahoma, United States
North Star Medical Research
🇺🇸Middleburg, Ohio, United States
Brian Abaluck, LLC
🇺🇸Paoli, Pennsylvania, United States
Abington Neurological Associates
🇺🇸Willow Grove, Pennsylvania, United States
Respiratory Specialists
🇺🇸Wyomissing, Pennsylvania, United States
Children's Hospital of the King's Daughter
🇺🇸Norfolk, Virginia, United States
Northwest Houston Neurology and Sleep
🇺🇸Tomball, Texas, United States
Medical University of South Carolina- Institute of Psychiatry
🇺🇸Charleston, South Carolina, United States
FutureSearch Trials of Neurology LP
🇺🇸Austin, Texas, United States
Mayo Clinic
🇺🇸Scottsdale, Arizona, United States