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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Idiopathic Hypersomnia, Excessive Daytime Sleepiness

Intervention / Treatment
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* Drug: pitolisant


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: pitolisant<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability of Pitolisant | 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. | Screening to 30 (+3) days after final dose | 
| Excessive Daytime Sleepiness | 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. | 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 | 
| Symptoms of idiopathic hypersomnia | 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. | 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 | 
| Symptoms of idiopathic hypersomnia | 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. | 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 | 
| Symptoms of idiopathic hypersomnia | 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. | 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 | 
| Functional outcomes of sleep | 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. | 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 | 
| Sleep related impairments during wakefulness | 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. | 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 | 
| Sleep inertia | 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. | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pitolisant, histamine, sleepiness, IH