A Study of Pitolisant in Patients With Prader-Willi Syndrome

March 13, 2026 updated by: Harmony Biosciences Management, Inc.

A Phase 3, Randomized, Double-Blind, Placebo-controlled, Efficacy and Safety Study of Pitolisant Followed by an Open-Label Extension in Patients With Prader-Willi Syndrome

This is a Phase 3, randomized, double-blind, placebo-controlled, multicenter, global clinical study to assess the efficacy and safety of pitolisant in patients living with Prader-Willi syndrome.

The primary objective of this study is to evaluate the efficacy of pitolisant in treating excessive daytime sleepiness (EDS) in patients ≥6 years of age with Prader-Willi syndrome.

Secondary objectives include assessing the impact of pitolisant on:

Irritable and disruptive behaviors Hyperphagia Other behavioral problems including social withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The study will consist of an up to 45-day Screening/Baseline Period, a Double-Blind Treatment Period, and an optional Open-Label Extension Period.

After completion of all Baseline assessments, patients who meet all eligibility criteria will be randomized 1:1 to receive once daily pitolisant or matching placebo. During the Double-Blind Treatment Period, in-person visits will be at Day 29, Day 57, and Day 77. Patients who do not elect to enter the Open-Label Extension Period will have follow-up visits 15 days and 30 days after the final dose of study drug.

During the optional Open-Label Extension Period, in-person visits will be at Day 113, Day 260, and Day 441. Patients will have follow-up visits 15 days and 30 days after the final dose of pitolisant.

Study Type

Interventional

Enrollment (Estimated)

134

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
    • Queensland
      • Brisbane, Queensland, Australia
  • Belgium
  • Canada
    • Ontario
      • Thornhill, Ontario, Canada
        • Recruiting
        • AMNDX Inc.
        • Contact:
        • Principal Investigator:
          • Alan Lowe, MD
      • Toronto, Ontario, Canada
  • Denmark
      • Aarhus, Denmark
        • Recruiting
        • Aarhus University Hospital
        • Contact:
        • Principal Investigator:
          • Cecilie Ejerskov
      • Copenhagen, Denmark
        • Recruiting
        • Rigshospitalet
        • Contact:
        • Principal Investigator:
          • Stense Farholt, MD
  • France
      • Angers, France
        • Recruiting
        • CHU d'Angers
        • Principal Investigator:
          • Frederic Illouz, MD
        • Contact:
      • Toulouse, France
        • Recruiting
        • CHU de Toulouse-Hôpital Des Enfants
        • Principal Investigator:
          • Gwenaëlle Diene
        • Contact:
  • Germany
      • Essen, Germany
        • Recruiting
        • University Hospital Essen
        • Contact:
        • Principal Investigator:
          • Cordula Kiewert, MD
  • Italy
      • Florence, Italy
        • Recruiting
        • Azienda Ospedaliero Universitaria A Meyer
        • Principal Investigator:
          • Stefano Stagi
        • Contact:
      • Genova, Italy
        • Recruiting
        • Istituto G Gaslini Ospedale Pediatrico IRCCS - INCIPIT - PIN
        • Contact:
        • Principal Investigator:
          • Mohamad Maghnie, MD
      • Milan, Italy
        • Recruiting
        • Ospedale San Raffaele S.r.l. - PPDS
        • Contact:
        • Principal Investigator:
          • Roberta Pajno, MD
      • Padua, Italy
        • Recruiting
        • Azienda Ospedale Università Padova - Dipartimento Salute della Donna e del Bambino - INCIPIT - PIN
        • Contact:
        • Principal Investigator:
          • Laura Guazzarotti, MD
      • Roma, Italy
        • Recruiting
        • Ospedale Pediatrico Bambino Gesu Irccs
        • Principal Investigator:
          • Danilo Fintini, MD
        • Contact:
      • Trieste, Italy
        • Recruiting
        • IRCCS Materno Infantile Burlo Garofolo - INCIPIT - PIN
        • Contact:
        • Principal Investigator:
          • Gianluca Tornese, MD
  • Poland
      • Szczecin, Poland
        • Recruiting
        • Samodzielny Publiczny Szpital Kliniczny
        • Contact:
        • Principal Investigator:
          • Elzbieta Petriczko
      • Wroclaw, Poland
        • Recruiting
        • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu-Chalubinskiego 2-2a
        • Principal Investigator:
          • Beata Wikiera, MD
        • Contact:
  • Romania
      • Bucharest, Romania
        • Recruiting
        • Institutul National de Endocrinologie C. I. Parhon
        • Contact:
        • Principal Investigator:
          • Iuliana Gherlan
      • Bucharest, Romania
        • Recruiting
        • National Clinical Center for Children Neurorehabilitation "Dr. Nicolae Robanescu"
        • Contact:
        • Principal Investigator:
          • Madalina Leanca, MD
      • Timișoara, Romania
        • Recruiting
        • Louis Turcanu Emergency Clinical Hospital for Children
        • Contact:
        • Principal Investigator:
          • Otilia Marginean, MD
  • Spain
      • Barcelona, Spain
        • Recruiting
        • Hospital Sant Joan de Déu
        • Contact:
        • Principal Investigator:
          • Oscar Sans Capdevila
      • Barcelona, Spain
        • Recruiting
        • Corporacio Sanitaria Parc Tauli, Sabadell
        • Contact:
        • Principal Investigator:
          • Raquel Corripio Collado
      • Madrid, Spain
        • Recruiting
        • Hospital Universitario 12 De Octubre
        • Contact:
        • Principal Investigator:
          • Irene Lazaro Rodriguez
      • Málaga, Spain
        • Recruiting
        • Universitario Virgen de la Victoria
        • Contact:
        • Principal Investigator:
          • Francisco Madueno Tinahones
  • Sweden
      • Solna, Sweden
  • United Kingdom
    • England
      • Cambridge, England, United Kingdom
        • Recruiting
        • Fulbourn Hospital
        • Contact:
        • Principal Investigator:
          • Shahid Zaman, MD
      • Hull, England, United Kingdom
        • Recruiting
        • Hull Royal Infirmary
        • Contact:
        • Principal Investigator:
          • Thozhukat Sathyapalan, MBBS, MD
    • Scotland
      • Dundee, Scotland, United Kingdom
        • Recruiting
        • Ninewells Hospital - PPDS
        • Contact:
        • Principal Investigator:
          • Clare Webster, MD
      • Edinburgh, Scotland, United Kingdom
  • United States
    • California
      • Los Angeles, California, United States, 90025
        • Recruiting
        • Santa Monica Clinical Trials
        • Principal Investigator:
          • Daniel Norman, MD
        • Contact:
      • Sacramento, California, United States, 95821-2123
        • Recruiting
        • Center Of Excellence in Diabetes and Endocrinology
        • Principal Investigator:
          • Gnanagurudasan Prakasam, MD
        • Contact:
      • San Diego, California, United States, 92123
        • Recruiting
        • Rady Children's Hospital - Scan Diego
        • Contact:
        • Principal Investigator:
          • Rakesh Bhattacharjee, MD
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • Colorado Children's Hospital
        • Principal Investigator:
          • Shawn McCandless, MD
        • Contact:
    • Delaware
      • Wilmington, Delaware, United States, 19803-3607
        • Recruiting
        • Nemours Children's Hospital
        • Contact:
        • Principal Investigator:
          • Aaron Chidekel, MD
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University School of Medicine
        • Principal Investigator:
          • Michael Gambello, MD, PhD
        • Contact:
      • Atlanta, Georgia, United States, 30318
        • Withdrawn
        • Atlanta Diabetes Associates
      • Atlanta, Georgia, United States, 30329
        • Withdrawn
        • Rare Disease Research
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Ann and Robert H Lurie Children's Hospital of Chicago
        • Principal Investigator:
          • Priya Khanna, MD
        • Contact:
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Riley Children's Hospital
        • Principal Investigator:
          • Hasnaa Jalou, MD
        • Contact:
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Recruiting
        • Johns Hopkins Hospital
        • Principal Investigator:
          • Ann Scheimann, MD
        • Contact:
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic-PPDS
        • Contact:
        • Principal Investigator:
          • Brendan Lanpher, MD
    • New York
      • Brooklyn, New York, United States, 11219
        • Recruiting
        • Maimonides Medical Center
        • Contact:
        • Principal Investigator:
          • Edward Yi, MD
      • The Bronx, New York, United States, 10467
        • Recruiting
        • Montefiore Medical Center
        • Principal Investigator:
          • Eric Hollander, MD
        • Contact:
    • North Carolina
      • Morrisville, North Carolina, United States, 27560
        • Recruiting
        • Science 37 (at-home option)
        • Principal Investigator:
          • Dr. Sara Trepanier
        • Contact:
    • Ohio
      • Cincinnati, Ohio, United States, 45212
        • Withdrawn
        • CTI Clinical Research Center
      • Cleveland, Ohio, United States, 441016
        • Recruiting
        • Center for Human Genetics
        • Contact:
        • Principal Investigator:
          • Anna Mitchell, MD
    • Texas
      • Houston, Texas, United States, 77030
      • San Antonio, Texas, United States, 78249-3539
        • Recruiting
        • Road Runner Research
        • Contact:
        • Principal Investigator:
          • Tarak Patel, MD
      • Weslaco, Texas, United States, 78596
        • Terminated
        • Texas Valley Clinical Research
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Childrens Hospital of Wisconsin
        • Contact:
        • Principal Investigator:
          • Donald Basel, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Genetically confirmed diagnosis of PWS
  • Excessive daytime sleepiness
  • Has a consistent parent/caregiver (preferably the same person throughout the study) who is willing and able to complete the required study assessments.
  • In the opinion of the Investigator, the patient/parent(s)/caregiver(s)/legal guardian(s) are capable of understanding and complying with the requirements of the protocol and administration of oral study drug.

Exclusion Criteria:

  • Has a diagnosis of sleep apnea (OSA, CSA) that is not adequately controlled
  • Has a diagnosis of hypersomnia due to another sleep/medical disorder
  • Participation in an interventional research study involving another investigational medication, device, or behavioral treatment within 30 days or 5 half-lives (whichever is longer) of the investigational medication prior to Screening

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Double-Blind Treatment Period Pitolisant
Pitolisant tablets administered once daily in the morning upon wakening
Drug: Pitolisant tablet
Pitolisant tablet
Other Names:
  • pitolisant
Placebo Comparator: Double-Blind Treatment Period Placebo
Matching placebo administered tablets once daily in the morning upon wakening
Other: Placebo tablet
Placebo tablet
Other Names:
  • placebo
Other: Open-Label Extension Period Pitolisant
Pitolisant tablets administered once daily in the morning upon wakening
Drug: Pitolisant tablet
Pitolisant tablet
Other Names:
  • pitolisant

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in severity of EDS as measured by Patient-Reported Outcomes Measurement Information System Bank v1.0 - Sleep-Related Impairment (PROMIS-SRI) T-score
Time Frame: Baseline and end of the Double Blind Treatment Period (Day 77)
The PROMIS-SRI item bank consists of 13 items with a 5-point rating scale.
Baseline and end of the Double Blind Treatment Period (Day 77)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in severity of irritable and disruptive behaviors as measured by the Aberrant Behavior Checklist-Community, Second Edition (ABC-C) Irritability domain
Time Frame: Baseline and end of the Double Blind Treatment Period (Day 77)
The ABC-C is a 58-item questionnaire, divided into 5 subscales (Irritability, Social Withdrawal, Stereotypic Behavior, Hyperactive/Noncompliance, and Inappropriate Speech).
Baseline and end of the Double Blind Treatment Period (Day 77)
Change in overall severity of EDS as measured by the Caregiver Global Impression of Severity for Excessive Daytime Sleepiness (CaGI-S for EDS)
Time Frame: Baseline and end of the Double Blind Treatment Period (Day 77)
The CaGI-S for EDS is a 1-item, 5-point rating scale.
Baseline and end of the Double Blind Treatment Period (Day 77)
Change in overall severity of EDS as measured by the Clinical Global Impression of Severity for Excessive Daytime Sleepiness (CGI-S for EDS)
Time Frame: Baseline and end of the Double Blind Treatment Period (Day 77)
The CGI-S for EDS is a 1-item, 5-point rating scale.
Baseline and end of the Double Blind Treatment Period (Day 77)
Change in overall severity of irritable and disruptive behaviors as measured by the Caregiver Global Impression of Severity (CaGI-S) for Irritable and/or Disruptive Behaviors
Time Frame: Baseline and end of the Double Blind Treatment Period (Day 77)
The CaGI-S for Irritable and/or Disruptive Behaviors is a 1-item, 5-point rating scale.
Baseline and end of the Double Blind Treatment Period (Day 77)
Change in severity of hyperphagia as measured by the Hyperphagia Questionnaire for Clinical Trials (HQ-CT), in conjunction with the Food Safe Zone Questionnaire (FSZQ)
Time Frame: Baseline and end of the Double Blind Treatment Period (Day 77)

The HQ-CT is a 9-item measure of food-related preoccupations and problems.

The FSZQ is a 20-item measure of environmental controls to manage hyperphagia.
Baseline and end of the Double Blind Treatment Period (Day 77)
Change in severity of EDS as measured by the Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD [parent/caregiver version]) total score
Time Frame: Baseline and end of the Double Blind Treatment Period (Day 77)
The ESS-CHAD (parent/caregiver version) is an 8-item, 4-point rating scale.
Baseline and end of the Double Blind Treatment Period (Day 77)
Change in severity of other behavioral problems as measured by the Aberrant Behavior Checklist-Community, Second Edition (ABC-C) Hyperactivity/Noncompliance, Inappropriate Speech, Social Withdrawal, and Stereotypic Behavior Domains
Time Frame: Baseline and end of the Double Blind Treatment Period (Day 77)
The ABC-C is a 58-item questionnaire, divided into 5 subscales (Irritability, Social Withdrawal, Stereotypic Behavior, Hyperactive/Noncompliance, and Inappropriate Speech).
Baseline and end of the Double Blind Treatment Period (Day 77)
Percentage of patients reporting TEAEs
Time Frame: Baseline up to Day 441
A treatment-emergent adverse events is any adverse event reported after the first dose of study drug and up to 30 days after final dose of study drug, or any worsening of a pre-existing condition reported after first dose of study drug and up to 30 days after final dose of study drug.
Baseline up to Day 441

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Harmony Biosciences Management, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 28, 2024

Primary Completion (Estimated)

July 1, 2026

Study Completion (Estimated)

July 1, 2027

Study Registration Dates

First Submitted

October 9, 2023

First Submitted That Met QC Criteria

April 12, 2024

First Posted (Actual)

April 16, 2024

Study Record Updates

Last Update Posted (Actual)

March 17, 2026

Last Update Submitted That Met QC Criteria

March 13, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HBS-101-CL-312

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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