Clinical trial NCT05458128: A Long-Term Safety and Effectiveness Study to Evaluate Pitolisant in Adult Patients with Idiopathic Hypersomnia
Official title: An Open-Label Study to Evaluate the Long-Term Safety and Effectiveness of Pitolisant in Adult Patients with Idiopathic Hypersomnia Who Completed Study HBS-101-CL-010
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Idiopathic Hypersomnia
Excessive Daytime Sleepiness
Keywords: pitolisant
histamine
sleepiness
IH
Lead sponsor: Harmony Biosciences Management, Inc.
Sponsor class: INDUSTRY
First posted: 2022-07-14
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety and tolerability of pitolisant
timeFrame: Up to approximately 3 years
measure: Excessive daytime sleepiness
timeFrame: Up to approximately 3 years
Secondary outcomes:
measure: Symptoms of idiopathic hypersomnia
timeFrame: Up to approximately 3 years
measure: Symptoms of idiopathic hypersomnia
timeFrame: Up to approximately 3 years
measure: Symptoms of idiopathic hypersomnia
timeFrame: Up to approximately 3 years
measure: Functional outcomes of sleep
timeFrame: Up to approximately 3 years
measure: Sleep related impairments during wakefulness
timeFrame: Up to approximately 3 years
measure: Sleep inertia
timeFrame: Up to approximately 3 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Towers
state: California
city: San Ramon
country: United States
facility: Sleep Medicine Specialists of California
state: California
city: Brandon
country: United States
facility: Meris Clinical Research
state: Florida
city: Clearwater
country: United States
facility: St. Francis Medical Institute
state: Florida
city: Winter Park
country: United States
facility: Florida Pediatric Research Institute
state: Florida
city: Atlanta
country: United States
facility: Neurotrials Research Inc.
state: Georgia
city: Glenview
country: United States
facility: NorthShore University Health System
state: Illinois
city: Peoria
country: United States
facility: OSF HealthCare Saint Francis Medical Center
state: Illinois
city: Kalamazoo
country: United States
facility: Western Michigan University Homer Stryker MD School of Medicine
state: Michigan
city: Sterling Heights
country: United States
facility: Clinical Neurophysiology Services
state: Michigan
city: Chesterfield
country: United States
facility: St. Luke's Sleep Medicine and Research Center
state: Missouri
city: Saint Louis
country: United States
facility: Clayton Sleep Institute
state: Missouri
city: North Platte
country: United States
facility: Great Plains Health
state: Nebraska
city: Neptune City
country: United States
facility: Sleep Dynamics
state: New Jersey
city: New Hyde Park
country: United States
facility: Northwell Health
state: New York
city: Durham
country: United States
facility: Duke University School of Medicine
state: North Carolina
city: Gastonia
country: United States
facility: Clinical Research of Gastonia
state: North Carolina
city: Huntersville
country: United States
facility: ARSM Research
state: North Carolina
city: Canton
country: United States
facility: NeuroScience Research Center, LLC
state: Ohio
city: Cincinnati
country: United States
facility: Intrepid Research, LLC
state: Ohio
city: Dublin
country: United States
facility: Ohio Sleep Medicine and Neuroscience Institue
state: Ohio
city: Middleburg
country: United States
facility: North Star Medical Research
state: Ohio
city: Willow Grove
country: United States
facility: Abington Neurological Associates
state: Pennsylvania
city: Wyomissing
country: United States
facility: Respiratory Specialists
state: Pennsylvania
city: Columbia
country: United States
facility: Bogan Sleep Consultants
state: South Carolina
city: North Charleston
country: United States
facility: Lowcountry Lung Critical Care
state: South Carolina
city: Cordova
country: United States
facility: Neurology Clinic, P.C.
state: Tennessee
city: Austin
country: United States
facility: FutureSearch Trials of Neurology LP
state: Texas
city: Round Rock
country: United States
facility: Central Texas Neurology Consultants, PA
state: Texas
city: Sugar Land
country: United States
facility: Comprehensive Sleep Medicine Associates
state: Texas
city: Tomball
country: United States
facility: Northwest Houston Neurology and Sleep
state: Texas
city: Madison
country: United States
facility: University of Wisconsin-Madison
state: Wisconsin
Study officials:
References: