Pitolisant for Prader-Willi Syndrome

Recruiting at 20 trial locations

Overseen By Linnea Ryan

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Harmony Biosciences, LLC

Disqualifiers: Sleep apnea, Hypersomnia, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

134 Participants Needed

Trial Summary

What is the purpose of this trial?

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

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are participating in another study with an investigational medication, you must wait 30 days or 5 half-lives before joining this trial.

What data supports the effectiveness of the drug Pitolisant for Prader-Willi Syndrome?

Research shows that Pitolisant, a drug used for narcolepsy, may help children with Prader-Willi Syndrome by reducing daytime sleepiness and improving cognitive functions like mental clarity and processing speed. ^{1 2 3 4 5}

How is the drug pitolisant unique for treating Prader-Willi Syndrome?

Pitolisant is unique for treating Prader-Willi Syndrome because it is a first-in-class drug that targets the histamine H3 receptor, which helps improve alertness and cognitive function, addressing symptoms like excessive daytime sleepiness and cognitive difficulties that are common in this condition. ^{1 2 3 6 7}

Eligibility Criteria

This trial is for patients aged 6 and older with Prader-Willi Syndrome, specifically to address excessive daytime sleepiness. Details about who can join or reasons for exclusion are not provided.

Inclusion Criteria

I often feel very sleepy during the day.

I have a caregiver willing to help with my study needs.

My condition is genetically confirmed Prader-Willi Syndrome.

Exclusion Criteria

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

My sleep apnea is not well-managed.

I have been diagnosed with excessive sleepiness due to another sleep or medical condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

6 weeks

Double-Blind Treatment

Participants receive either pitolisant or placebo once daily in a double-blind manner

11 weeks

3 visits (in-person) at Day 29, Day 57, and Day 77

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person) 15 days and 30 days after the final dose

Open-Label Extension (optional)

Participants may opt into continuation of treatment with pitolisant long-term

52 weeks

3 visits (in-person) at Day 113, Day 260, and Day 441

Treatment Details

Interventions

• Pitolisant

Trial Overview The study tests the effectiveness of a drug called Pitolisant compared to a placebo in reducing excessive daytime sleepiness in Prader-Willi Syndrome patients. It's randomized and double-blind, meaning neither participants nor researchers know who gets the real drug versus the placebo.

Participant Groups

Group I: Open-Label Extension Period Pitolisant Experimental Treatment 1 Intervention

Pitolisant tablets administered once daily in the morning upon wakening

Group II: Double-Blind Treatment Period Pitolisant Experimental Treatment 1 Intervention

Pitolisant tablets administered once daily in the morning upon wakening

Group III: Double-Blind Treatment Period Placebo Placebo Group 1 Intervention

Matching placebo administered tablets once daily in the morning upon wakening

Pitolisant is already approved in European Union, United States for the following indications:

Approved in European Union as Wakix for:

• Narcolepsy with or without cataplexy

Approved in United States as Wakix for:

• Excessive daytime sleepiness (EDS) associated with narcolepsy
• Cataplexy in adults with narcolepsy

Who Is Running the Clinical Trial?

Harmony Biosciences, LLC

Lead Sponsor

Trials

9

Recruited

2,000+

Harmony Biosciences Management, Inc.

Lead Sponsor

Trials

9

Recruited

2,000+

Findings from Research

In a case series of 3 children with Prader-Willi Syndrome (PWS), treatment with pitolisant, a histamine 3 receptor inverse agonist, led to decreased daytime sleepiness and improved cognitive function.

Pitolisant may offer a new therapeutic option for managing symptoms of PWS, potentially alleviating cognitive disabilities and enhancing overall quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive Improvements in Children with Prader-Willi Syndrome Following Pitolisant Treatment-Patient Reports. Pullen, LC., Picone, M., Tan, L., et al.[2020]

Pitolisant, a medication that enhances histaminergic neuron activity, may improve symptoms in a 15-year-old girl with Prader-Willi syndrome and other conditions, showing promise for this population.

The treatment was well tolerated with minimal side effects, suggesting it could be a safe option for patients with Prader-Willi syndrome who do not respond to traditional psychostimulants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pitolisant in an Adolescent with Prader-Willi Syndrome. Pennington, S., Stutzman, D., Sannar, E.[2021]

Pitolisant, a histamine H3 receptor antagonist/inverse agonist, is approved for treating narcolepsy in adults and has recently received approval for use in children aged 6 and older in the EU, marking a significant milestone in its development.

The approval for pediatric use is based on clinical data demonstrating its efficacy in treating narcolepsy with or without cataplexy, expanding treatment options for younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pitolisant: Pediatric First Approval. Keam, SJ.[2023]

Topiramate has shown promising effects in reducing self-injury and impulsive/aggressive behaviors in patients with Prader-Willi syndrome, based on a systematic review of 102 patients across various studies.

Risperidone is effective for managing psychotic symptoms related to uniparental disomy, while N-acetyl cysteine appears beneficial for skin picking, highlighting the need for further research into pharmacological treatments for behavioral issues in Prader-Willi syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychotropic treatments in Prader-Willi syndrome: a critical review of published literature. Bonnot, O., Cohen, D., Thuilleaux, D., et al.[2022]

In a study of 24 patients with Prader-Willi Syndrome (PWS), those with uniparental disomy (UPD) exhibited a more severe clinical phenotype compared to those with deletion, indicating that the type of genetic anomaly influences the severity of symptoms.

Topiramate, a medication used to manage compulsive behaviors, was found to be less effective and less tolerated in patients with UPD compared to those with deletion, suggesting the need for personalized treatment approaches based on genetic differences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prader-Willi syndrome: Symptoms and topiramate response in light of genetics. Louveau, C., Turtuluci, MC., Consoli, A., et al.[2023]

In a phase II trial involving 23 patients with partial seizures who were already on other antiepileptic medications, pitolisant was well tolerated and showed a clinical response in about one third of participants after 3 months.

However, the study did not provide strong evidence for the efficacy of pitolisant due to the small sample size and lack of a placebo control, indicating that further research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploratory Phase II Trial to Evaluate the Safety and the Antiepileptic Effect of Pitolisant (BF2.649) in Refractory Partial Seizures, Given as Adjunctive Treatment During 3 Months. Collart Dutilleul, P., Ryvlin, P., Kahane, P., et al.[2019]

Pitolisant (Wakix™) is an approved treatment in the EU for narcolepsy, effectively reducing excessive daytime sleepiness and cataplexy in adults, as demonstrated in the pivotal HARMONY I trial.

The drug works as an inverse agonist of the histamine H3 receptor and has received special designations, including orphan drug status, highlighting its importance for patients with narcolepsy who have not responded to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pitolisant: First Global Approval. Syed, YY.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Cognitive Improvements in Children with Prader-Willi Syndrome Following Pitolisant Treatment-Patient Reports. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Pitolisant in an Adolescent with Prader-Willi Syndrome. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Pitolisant: Pediatric First Approval. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

Psychotropic treatments in Prader-Willi syndrome: a critical review of published literature. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Prader-Willi syndrome: Symptoms and topiramate response in light of genetics. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Exploratory Phase II Trial to Evaluate the Safety and the Antiepileptic Effect of Pitolisant (BF2.649) in Refractory Partial Seizures, Given as Adjunctive Treatment During 3 Months. [2019]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Pitolisant: First Global Approval. [2019]