Prader-Willi Syndrome
Conditions
Keywords
pitolisant, excessive daytime sleepiness, irritable and disruptive behaviors, Prader-Willi syndrome
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.
Interventions
DRUGPitolisant tablet
Pitolisant tablet
OTHERPlacebo tablet
Placebo tablet
Sponsors
Harmony Biosciences Management, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in severity of EDS as measured by Patient-Reported Outcomes Measurement Information System Bank v1.0 - Sleep-Related Impairment (PROMIS-SRI) T-score | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| Percentage of patients reporting TEAEs | 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. |
| 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 score | 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. |
| Change in severity of irritable and disruptive behaviors as measured by the Aberrant Behavior Checklist-Community, Second Edition (ABC-C) Irritability domain | 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). |
| 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 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 | 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). |
| 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. |
Countries
Australia, Belgium, Canada, Denmark, France, Germany, Italy, Poland, Romania, Spain, Sweden, United Kingdom, United States
Contacts
CONTACTAnn Adee
CONTACTLinnea Ryan
STUDY_DIRECTORMedical Director
Harmony Biosciences Inc
Outcome results
None listed