A Phase 2 Study to Evaluate the Safety and Efficacy of Pitolisant in Patients With Prader-Willi Syndrome, Followed by an Open Label Extension

NCT04257929 | Active Not Recruiting Phase 2 Results FDA Drug

• 1 other identifier: HBS-101-CL-002
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 13

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 Prader Willi syndrome (PWS) ages 6 to 65 years.

Conditions

Prader-Willi Syndrome

Keywords

PWS

Outcome Measures

Primary Outcomes (1)

• Excessive Daytime Sleepiness

  Change in Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) (parent/caregiver version) score from Baseline to Week 11 for pitolisant compared with placebo. The score of the ESS-CHAD ranges from 0 to 24. A decrease in score represents an improvement in excessive daytime sleepiness.

  Baseline to Week 11

Secondary Outcomes (8)

• Excessive Daytime Sleepiness

  Baseline to Week 11

• Clinical Symptoms

  Baseline to Week 11

• Behavior

  Baseline to Week 11

• Behavioral and Cognitive Rigidity

  Baseline to Week 11

• Psychomotor Function

  Baseline to Week 11

Study Arms (4)

Double-Blind Treatment Phase Lower Dose Pitolisant

ACTIVE COMPARATOR

Pediatric patients (6 to less than 12 years of age): Week 1: 4.45 mg pitolisant administered once daily in the morning; Week 2: 8.9 mg pitolisant administered once daily in the morning; Weeks 3 through 11: 8.9 mg pitolisant administered once daily in the morning. Adolescent patients (12 to less than 18 years of age): Week 1: 4.45 mg pitolisant administered once daily in the morning; Week 2: 8.9 mg pitolisant administered once daily in the morning; Weeks 3 through 11: 13.35 mg pitolisant administered once daily in the morning. Adult patients (18 to 65 years of age): Week 1: 4.45 mg pitolisant administered once daily in the morning; Week 2: 8.9 mg pitolisant administered once daily in the morning; Weeks 3 through 11: 17.8 mg pitolisant administered once daily in the morning.

Drug: Pitolisant oral tablets

Double-Blind Treatment Phase Higher Dose Pitolisant

ACTIVE COMPARATOR

Pediatric patients (6 to less than 12 years of age): Week 1: 4.45 mg pitolisant administered once daily in the morning; Week 2: 8.9 mg pitolisant administered once daily in the morning; Weeks 3 through 11: 17.8 mg pitolisant administered once daily in the morning. Adolescent patients (12 to less than 18 years of age): Week 1: 8.9 mg pitolisant administered once daily in the morning; Week 2: 17.8 mg pitolisant administered once daily in the morning; Weeks 3 through 11: 26.7 mg pitolisant administered once daily in the morning. Adult patients (18 to 65 years of age): Week 1: 8.9 mg pitolisant administered once daily in the morning; Week 2: 17.8 mg pitolisant administered once daily in the morning; Weeks 3 through 11: 35.6 mg pitolisant administered once daily in the morning.

Drug: Pitolisant oral tablets

Double-Blind Treatment Phase Placebo

PLACEBO COMPARATOR

Pediatric patients (6 to less than 12 years of age): Week 1: Matching placebo tablets; Week 2: Matching placebo tablets; Weeks 3 through 11: Matching placebo tablets Adolescent patients (12 to less than 18 years of age): Week 1: Matching placebo tablets; Week 2: Matching placebo tablets; Weeks 3 through 11: Matching placebo tablets Adult patients (18 to 65 years of age): Week 1: Matching placebo tablets; Week 2: Matching placebo tablets; Weeks 3 through 11: Matching placebo tablets

Drug: Placebo oral tablet

Open-Label Pitolisant

OTHER

Age-based dosing (prior to implementation of amendment 6) or weight-based dosing (after implementation of amendment 6)

Drug: Pitolisant oral tablets

Interventions

Pitolisant oral tablets DRUG

Pitolisant 4.45 mg or 17.8 mg tablets

Double-Blind Treatment Phase Higher Dose Pitolisant; Double-Blind Treatment Phase Lower Dose Pitolisant; Open-Label Pitolisant

Placebo oral tablet DRUG

Matching placebo tablets

Double-Blind Treatment Phase Placebo

Eligibility Criteria

• Age: 6 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Is able to provide voluntary, written informed consent (patient or parent\[s\]/legal guardian\[s\]) and, where applicable, voluntary, written assent (patient, as appropriate).
• Has a diagnosis of PWS confirmed by genetic testing and/or patient medical records. Genetic testing will be provided by the Sponsor, if not confirmed based on the review of the patient's medical records.
• Male or female patients ages 6 to 65 years at the time of enrollment.
• Demonstrates adequate sleep duration via patient sleep diary during Screening, defined as at least 8 hours of sleep per night for patients ages 6 to \<12 years, at least 7 hours for patients ages 12 to \<18 years, or at least 6 hours for patients ages ≥18 years, based on the mean number of hours from up to 14 nights (at least 7 nights must be recorded for evaluation).
• Has EDS as determined by Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) (parent/caregiver version) score of ≥12.
• If taking hormone treatments (including growth hormone, testosterone, and estrogen supplements) and/or allowed chronic concomitant medication or supplements, patient must be on a stable dose of these medications for 3 months prior to randomization and for the duration of the Double-Blind Treatment Phase of the study; a 10% variability in hormone dose is allowed.
• If taking a wake-promoting treatment that could affect EDS (including stimulants, modafinil, and armodafinil), must be on a stable dose for at least 28 days prior to Screening and remain on a stable dose during the Double-Blind Treatment Phase of the study (dose adjustments will be permitted in the OLE Phase) or agree to wash out of treatment for 5 half-lives or 14 days, whichever is longer.
• If taking a chronically administered sedating medication for management of behavioral manifestations (e.g., hypnotics, benzodiazepines, antipsychotics, alpha agonists, anticholinergics, and antidepressants) must be on a stable dose for at least 28 days prior to Screening and remain on a stable dose during the Double-Blind Treatment Phase of the study (dose adjustments will be permitted in the OLE Phase) or agree to wash out of treatment for 5 half-lives or 14 days, whichever is longer.
• If using cannabidiol and/or tetrahydrocannabinol, patient must be on a stable dose for 28 days prior to randomization and agree to continue the stable dose for the duration of the Double-Blind Treatment Phase of the study (dose adjustments will be permitted in the OLE Phase).
• If taking oxytocin or carbetocin, patient must be on a stable dose during the 28 days prior to randomization and agree to continue the stable dose for the duration of the Double-Blind Treatment Phase of the study (dose adjustments will be permitted in the OLE Phase) or agree to wash out of treatment for 5 half-lives or 14 days, whichever is longer.
• A patient who is a female of child-bearing potential (FCBP) must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at the Baseline Visit and agree to remain abstinent or use an effective method of nonhormonal contraception to prevent pregnancy for the duration of the study and for 21 days after final dose of study drug.
• Has a consistent caregiver (preferably the same person throughout the Double-Blind Treatment Phase of the study) who is willing and able to complete the required assessments.
• In the opinion of the Investigator, patient/parent(s)/legal guardian(s) is capable of understanding and complying with the requirements of the protocol and administration of oral study drug.

You may not qualify if:

• Has a diagnosis of another genetic or chromosomal disorder distinct from PWS.
• Has untreated obstructive sleep apnea (OSA) or is at high risk for OSA based on medical history and clinical assessment; or, has another relevant underlying sleep disorder that in the opinion of the Investigator is the primary contributing factor to the patient's EDS.
• 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 Double-Blind Treatment Phase of the study; caffeine intake should remain consistent during Screening and throughout the Double-Blind Treatment Phase of the study.
• Does not agree to discontinue any prohibited medication or substance listed in the protocol.
• Participation in an interventional research study involving another investigational medication or device in the 28 days prior to enrollment and for the duration of the Double-Blind Treatment Phase of the study, unless the Investigator consults with the Medical Monitor and obtains written approval for the patient to enroll; patients who complete a washout of an investigational medication of at least 5 half-lives or 14 days (whichever is longer) may be enrolled in the Double-Blind Treatment Phase of the study. Patients considering participation in another interventional research study in the OLE Phase must consult with the Investigator who will consult with the Medical Monitor.
• Has a primary psychiatric diagnosis with current active symptoms of psychosis or schizophrenia.
• Has a diagnosis of end-stage renal disease (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 during the Double-Blind Treatment Phase.
• Has abnormal laboratory values at Screening that are clinically significant as determined by the Investigator.
• Has a known history of long QT syndrome or any significant history of a serious abnormality of the electrocardiogram (ECG; e.g., recent myocardial infarction, clinically significant arrhythmia) or QT interval corrected for heart rate according to Fridericia's formula (QTcF) \>442 ms for patients ages 0 to \<10 years and \>439 ms for patients ages 10 to \<20 years, regardless of gender, and \>450 ms for male patients and \>470 ms for female patients ages 20 to 65 years. (ECG QTcF = QT/3√ RR) (Mason et al 2007).
• Has a family history of sudden/unexplained death, cardiac death, or death from a primary dysrhythmia potentially associated with QT prolongation in any family member.
• If receiving any new or initiating a change in allied health therapies or interventions for symptoms of PWS, must be on a stable course of therapy for at least 28 days prior to randomization.
• Has a current or recent (within one year) history of a substance use disorder or dependence disorder, including alcohol and caffeine use disorders as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V).
• Has planned surgery during the Double-Blind Treatment Phase of the study; planned surgery is permitted during the OLE Phase.
• Is receiving a concomitant medication that is known to be a strong cytochrome P450 (CYP) 2D6 inhibitor, a strong CYP3A4 inducer, or a centrally acting histamine 1 (H1) receptor antagonist; patients who complete a washout of these medications of at least 5 half-lives or 14 days (whichever is longer) can be enrolled in the Double-Blind Treatment Phase of the study. Use of strong CYP2D6 inhibitors and strong CYP3A4 inducers is allowed during the OLE Phase; however, adjustment of pitolisant dose is required. Although not prohibited during the OLE Phase of the study, use of H1 receptor antagonists should be avoided.

Sponsors & Collaborators

• Harmony Biosciences Management, Inc.: lead

Study Sites (13)

Rady Children's Hospital - San Diego

San Diego, California, 92123, United States

Location

Sleep Medicine Specialists of California

San Ramon, California, 94583, United States

Location

Santa Monica Clinical Trials

Santa Monica, California, 90404, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Nemours Alfred I duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

University of Florida College of Medicine

Gainesville, Florida, 32608, United States

Location

Ann and Robert H Lurie Children's Hospital

Chicago, Illinois, 60611, United States

Location

Johns Hopkins School of Medicine

Baltimore, Maryland, 21205, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68114, United States

Location

CTI

Cincinnati, Ohio, 45212, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37203, United States

Location

Texas Children's Hospital/Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Road Runner Research

San Antonio, Texas, 78249, United States

Location

Related Publications (1)

• Revana A, Bhattacharjee R, Miller JL, Chidekel A, Khanna P, Ratnam S, Runyan G, Bauer E, Davis Rapchak K, Seiden D, Budur K, Dayno JM. A proof-of-concept study of pitolisant for excessive daytime sleepiness in patients with Prader-Willi syndrome. J Clin Sleep Med. 2025 Nov 1;21(11):1893-1902. doi: 10.5664/jcsm.11800.

  PMID: 40605372 DERIVED

MeSH Terms

Conditions

Prader-Willi Syndrome

Interventions

pitolisant

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Imprinting Disorders; Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Sharon Wolfe-Schwartz, Executive Director, Medical and RegulatoryWriting
• Organization: Harmony Biosciences

swolfe-schwartz@harmonybiosciences.com

267-965-0270

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2020
• First Posted: February 6, 2020
• Study Start: December 9, 2020
• Primary Completion: August 17, 2022
• Study Completion (Estimated): September 7, 2028
• Last Updated: February 20, 2026
• Results First Posted: October 22, 2025

Record last verified: 2026-02

Locations

US (13)