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

Sponsor

Harmony Biosciences, LLC (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05458128

Collaborator

(none)

128

Enrollment

Locations

Arm

Anticipated Duration (Months)

2.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Hypersomnia Excessive Daytime Sleepiness	Drug: pitolisant	Phase 3

Detailed Description

This is a Phase 3 open-label, long-term 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 meet the inclusion/exclusion 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 (±3 days) 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 (±7 days; 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 (±3) days and 30 (+3) days after their final dose of pitolisant, to assess for adverse events (AEs) and concomitant medication use.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

128 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Aug 1, 2025

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Other: pitolisant Open-label: Week 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.	Drug: pitolisant Pitolisant 4.45 mg tablets: white, round, plain, biconvex film-coated tablet, 3.7 mm in diameter. The 4.45 mg strength tablet may be marked with "S" on one side and is plain on the other side. Each tablet contains 5 mg of pitolisant hydrochloride equivalent to 4.45 mg of pitolisant. Pitolisant 17.8 mg: white, round, plain, biconvex film-coated tablet, 7.5 mm in diameter. The 17.8 mg strength tablet may be marked with "H" on one side and is plain on the other side. Each tablet contains 20 mg of pitolisant hydrochloride equivalent to 17.8 mg of pitolisant.

Arm

Intervention/Treatment

Other: pitolisant

Open-label: Week 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.

Drug: pitolisant

Pitolisant 4.45 mg tablets: white, round, plain, biconvex film-coated tablet, 3.7 mm in diameter. The 4.45 mg strength tablet may be marked with "S" on one side and is plain on the other side. Each tablet contains 5 mg of pitolisant hydrochloride equivalent to 4.45 mg of pitolisant. Pitolisant 17.8 mg: white, round, plain, biconvex film-coated tablet, 7.5 mm in diameter. The 17.8 mg strength tablet may be marked with "H" on one side and is plain on the other side. Each tablet contains 20 mg of pitolisant hydrochloride equivalent to 17.8 mg of pitolisant.

Outcome Measures

Primary Outcome Measures

Safety and Tolerability of Pitolisant [Screening to 30 (+3) days after final dose]
The long term safety and tolerability of pitolisant will be evaluated via the incidence of adverse events (AEs) and changes in clinical laboratory test results, vital signs, 12-lead electrocardiograms (ECGs), and Columbia-Suicide Severity Rating Scale (C-SSRS) assessments.
Excessive Daytime Sleepiness [Baseline Visit in study HBS-101-CL-010 to month 3, 6, 9, and year 1 and then every year thereafter until End of Treatment Visit]
Change 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.
Symptoms of idiopathic hypersomnia [Baseline Visit in study HBS-101-CL-010 to month 3, 6, 9, and year 1 and then every year thereafter until End of Treatment Visit]
Change in Idiopathic Hypersomnia Severity Scale (IHSS). The score of the IHSS ranges from 0 to 50. A decrease in score represents an improvement in symptoms of idiopathic hypersomnia.
Symptoms of idiopathic hypersomnia [Baseline Visit in study HBS-101-CL-010 to month 3, 6, 9, and year 1 and then every year thereafter until End of Treatment Visit]
Change in Clinical Global Impression of Severity (CGI-S). The CGI-S is is a five item scale that ranges from none to very severe. An assessment of less severe symptoms represents an improvement in the clinician's perception of the patient's overall clinical status related to idiopathic hypersomnia.
Symptoms of idiopathic hypersomnia [Baseline Visit in study HBS-101-CL-010 to month 3, 6, 9, and year 1 and then every year thereafter until End of Treatment Visit]
Change in Patient Global Impression of Severity (PGI-S) of their excessive daytime sleepiness. 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.
Functional outcomes of sleep [Baseline Visit in study HBS-101-CL-010 to month 3, 6, 9, and year 1 and then every year thereafter until End of Treatment Visit]
Change 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 wakefulness [Baseline Visit in study HBS-101-CL-010 to month 3, 6, 9, and year 1 and then every year thereafter until End of Treatment Visit]
Change in Patient-Reported Outcomes Measurement Information System, Sleep-Related Impairment (PROMIS-SRI). The score of the PROMIS-SRI 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.
Sleep inertia [Baseline Visit in study HBS-101-CL-010 to month 3, 6, 9, and year 1 and then every year thereafter until End of Treatment Visit]
Change 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Is able to provide voluntary, informed consent.
Completed the Double-Blind Randomized Withdrawal Phase (EOT/Visit 5) from the HBS-101-CL-010 study.
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.
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.
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:

Does not agree to discontinue any prohibited medication or substances listed in the protocol.
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 with an investigational medication or device, other than pitolisant, for the duration of the study.
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).
Is receiving or is unable to discontinue a medication known to prolong the QT interval.
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.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Scottsdale	Arizona	United States	85259
2	Cedars-Sinai Medical Towers	Los Angeles	California	United States	90048
3	Stanford Center for Sleep Sciences and Medicine	Redwood City	California	United States	94063
4	Sleep Medicine Specialists of California	San Ramon	California	United States	94583
5	SDS Clinical Trials Inc.	Santa Ana	California	United States	92705
6	Santa Monica Clinical Trials	Santa Monica	California	United States	90404
7	Alpine Clinical Research Center	Boulder	Colorado	United States	80301
8	Nuvance Health	Norwalk	Connecticut	United States	06850
9	Meris Clinical Research	Brandon	Florida	United States	33511
10	Sleep Medicine Specialists of South Florida, PA	Miami	Florida	United States	33126
11	Florida Pediatric Research Institute	Winter Park	Florida	United States	32789
12	Neurotrials Research Inc.	Atlanta	Georgia	United States	30328
13	The Neurological Center of North GA	Gainesville	Georgia	United States	30501
14	Northwestern University	Chicago	Illinois	United States	60611
15	Northshore Sleep Medicine	Chicago	Illinois	United States	60612
16	NorthShore Uni HealthSys-Glenbrook Hospital	Glenview	Illinois	United States	60026
17	OSF HealthCare Saint Francis Medical Center	Peoria	Illinois	United States	61637
18	Helene A. Emsellem MD PC	Chevy Chase	Maryland	United States	20815
19	The Center for Sleep and Wake Disorders	Chevy Chase	Maryland	United States	20815
20	Boston Children's Hospital	Boston	Massachusetts	United States	02115
21	Beth Israel Deaconess Medical Center	Newton	Massachusetts	United States	02459
22	Henry Ford Health System	Novi	Michigan	United States	48377
23	Bronson Sleep Health	Portage	Michigan	United States	49024
24	Clinical Neurophysiology Services	Sterling Heights	Michigan	United States	48314
25	Minnesota Lung Center	Edina	Minnesota	United States	55125
26	St. Luke's Sleep Medicine and Research Center	Chesterfield	Missouri	United States	63017
27	Clayton Sleep Institute	Saint Louis	Missouri	United States	63123
28	Great Plains Health	North Platte	Nebraska	United States	69101
29	Neurology Specialists of Monmouth County, PA	West Long Branch	New Jersey	United States	07764
30	Northwell Health	New Hyde Park	New York	United States	11042
31	Research Carolina Elite LLC	Denver	North Carolina	United States	28037
32	Duke University School of Medicine	Durham	North Carolina	United States	27705
33	Clinical Research of Gastonia	Gastonia	North Carolina	United States	28054
34	ARSM Research	Huntersville	North Carolina	United States	28078
35	Raleigh Neurology Associates	Raleigh	North Carolina	United States	27607
36	Intrepid Research, LLC	Cincinnati	Ohio	United States	45245
37	Rainbow Babies Children's Hospital	Cleveland	Ohio	United States	44106
38	Cleveland Clinc	Cleveland	Ohio	United States	44195
39	Ohio Sleep Medicine and Neuroscience Institue	Dublin	Ohio	United States	43017
40	North Star Medical Research	Middleburg	Ohio	United States	44130
41	Brian Abaluck, LLC	Paoli	Pennsylvania	United States	19301
42	Respiratory Specialists	Wyomissing	Pennsylvania	United States	19610
43	Medical University of South Carolina- Institute of Psychiatry	Charleston	South Carolina	United States	29425
44	Bogan Sleep Consultants	Columbia	South Carolina	United States	29201
45	Lowcountry Lung Critical Care	North Charleston	South Carolina	United States	29406
46	Neurology Clinic, P.C.	Cordova	Tennessee	United States	38018
47	FutureSearch Trials of Neurology LP	Austin	Texas	United States	78731
48	Comprehensive Sleep Medicine Associates	Sugar Land	Texas	United States	77478
49	Northwest Houston Neurology and Sleep	Tomball	Texas	United States	77375
50	Children's Specialty Group, PLLC	Norfolk	Virginia	United States	23507
51	University of Wisconsin-Madison	Madison	Wisconsin	United States	53719