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A Study of Pitolisant in Patients with Prader-Willi Syndrome

Phase 3
Recruiting
Conditions
Prader-Willi Syndrome
Interventions
Other: Placebo tablet
Registration Number
NCT06366464
Lead Sponsor
Harmony Biosciences Management, Inc.
Brief Summary

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

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
134
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Double-Blind Treatment Period PitolisantPitolisant tabletPitolisant tablets administered once daily in the morning upon wakening
Double-Blind Treatment Period PlaceboPlacebo tabletMatching placebo administered tablets once daily in the morning upon wakening
Open-Label Extension Period PitolisantPitolisant tabletPitolisant tablets administered once daily in the morning upon wakening
Primary Outcome Measures
NameTimeMethod
Change in severity of EDS as measured by Patient-Reported Outcomes Measurement Information System Bank v1.0 - Sleep-Related Impairment (PROMIS-SRI) T-scoreBaseline 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.

Secondary Outcome Measures
NameTimeMethod
Change in severity of irritable and disruptive behaviors as measured by the Aberrant Behavior Checklist-Community, Second Edition (ABC-C) Irritability domainBaseline 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).

Change in overall severity of EDS as measured by the Caregiver Global Impression of Severity for Excessive Daytime Sleepiness (CaGI-S for EDS)Baseline and end of the Double Blind Treatment Period (Day 77)

The CaGI-S for EDS is a 1-item, 5-point rating scale.

Change in overall severity of EDS as measured by the Clinical Global Impression of Severity for Excessive Daytime Sleepiness (CGI-S for EDS)Baseline and end of the Double Blind Treatment Period (Day 77)

The CGI-S for EDS is a 1-item, 5-point rating scale.

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 BehaviorsBaseline 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.

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)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.

Change in severity of EDS as measured by the Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD [parent/caregiver version]) total scoreBaseline and end of the Double Blind Treatment Period (Day 77)

The ESS-CHAD (parent/caregiver version) is an 8-item, 4-point rating scale.

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 DomainsBaseline 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).

Percentage of patients reporting TEAEsBaseline 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.

Trial Locations

Locations (22)

Santa Monica Clinical Trials

🇺🇸

Los Angeles, California, United States

Center of Excellence in Diabetes and Endocrinology

🇺🇸

Sacramento, California, United States

Colorado Children's Hospital

🇺🇸

Aurora, Colorado, United States

Nemours Children's Hospital

🇺🇸

Wilmington, Delaware, United States

Atlanta Diabetes Associates

🇺🇸

Atlanta, Georgia, United States

Rady Children's Hospital - Scan Diego

🇺🇸

San Diego, California, United States

Tri-Valley Sleep Center

🇺🇸

San Ramon, California, United States

Emory University School of Medicine

🇺🇸

Atlanta, Georgia, United States

Rare Disease Research

🇺🇸

Atlanta, Georgia, United States

Ann And Robert H Lurie Children's Hospital of Chicago

🇺🇸

Chicago, Illinois, United States

Riley Children's Hospital

🇺🇸

Indianapolis, Indiana, United States

Johns Hopkins Hospital

🇺🇸

Baltimore, Maryland, United States

Mayo Clinic-PPDS

🇺🇸

Rochester, Minnesota, United States

Montefiore Medical Center

🇺🇸

Bronx, New York, United States

Maimonides Medical Center

🇺🇸

Brooklyn, New York, United States

CTI Clinical Research Center

🇺🇸

Cincinnati, Ohio, United States

Center for Human Genetics

🇺🇸

Cleveland, Ohio, United States

Texas Children's Hospital

🇺🇸

Houston, Texas, United States

Road Runner Research

🇺🇸

San Antonio, Texas, United States

Texas Valley Clinical Research

🇺🇸

Weslaco, Texas, United States

Childrens Hospital of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

Queensland Children's Hospital

🇦🇺

Brisbane, Queensland, Australia

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