Pitolisant for Prader-Willi Syndrome

Recruiting at 58 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pitolisant, a medication, to determine its effectiveness for people with Prader-Willi syndrome who experience excessive daytime sleepiness. Researchers aim to discover if pitolisant can also improve irritability, disruptive behaviors, and overeating. Participants must have Prader-Willi syndrome and experience excessive daytime sleepiness. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that pitolisant is likely to be safe for humans?

Research shows that pitolisant is usually well-tolerated. In earlier studies, most patients taking pitolisant reported only mild side effects, such as anxiety, irritability, and headaches, each affecting about 12% of patients.

Although somewhat common, these side effects are generally not serious. Pitolisant is already approved for treating other conditions, like narcolepsy, so doctors understand its safety well based on its use for different health issues.

The current Phase 3 study examines pitolisant's effectiveness and safety for people with Prader-Willi syndrome, especially those with excessive daytime sleepiness. With more participants in this phase, any new safety concerns are likely to be discovered.

Overall, while pitolisant has some side effects, they are usually mild and similar to those observed in other studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Prader-Willi syndrome?

Most treatments for Prader-Willi Syndrome focus on addressing the symptoms like hormonal imbalances and behavioral challenges, often using growth hormone therapy and behavioral interventions. However, Pitolisant is unique because it targets the histamine H3 receptor in the brain, which plays a role in wakefulness and appetite regulation. This new mechanism of action offers a potential way to manage excessive daytime sleepiness and other neuropsychiatric symptoms associated with Prader-Willi Syndrome. Researchers are excited about Pitolisant because it could offer a more targeted approach to improving quality of life for individuals with this condition, addressing both sleep disturbances and behavioral issues more effectively than current options.

What evidence suggests that pitolisant might be an effective treatment for Prader-Willi syndrome?

Research has shown that pitolisant, which participants in this trial may receive, can help reduce excessive daytime sleepiness in people with Prader-Willi syndrome. A previous study found that patients who took pitolisant felt less sleepy during the day and experienced improvements in behavior problems, such as irritability and hyperactivity. Children aged 6 to 12, in particular, benefited from higher doses of the treatment. These findings suggest that pitolisant might effectively manage both sleepiness and certain behaviors in Prader-Willi syndrome. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06366464

A Study of Pitolisant in Patients 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 ...

2. ir.harmonybiosciences.com ir.harmonybiosciences.com/news-releases/news-release-details/harmony-biosciences-presents-new-secondary-outcome-data-phase-2

Release Details - Harmony Biosciences HARMONY BIOSCIENCES PRESENTS NEW SECONDARY OUTCOME DATA FROM PHASE 2 SIGNAL DETECTION STUDY IN PATIENTS WITH PRADER-WILLI SYNDROME. October 5 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12582198/

A proof-of-concept study of pitolisant for excessive daytime ... Study Impact: In this phase 2, exploratory, proof-of-concept study, treatment with pitolisant was associated with reductions in EDS and behavioral symptoms in ...

4. pwsausa.org pwsausa.org/pitolisant-shows-positive-secondary-outcomes-in-phase-2-study/

Pitolisant Shows Positive Secondary Outcomes in Phase 2 ... The study's findings highlighted significant positive effects of pitolisant, particularly in the higher-dose group. In children aged 6 to 12, ...

5. fpwr.org fpwr.org/blog/harmony-announces-phase-3-study-of-pitolisant

Harmony Biosciences Announces Phase 3 Study of Pitolisant The Phase 3 study of Pitolisant is expected to begin Q4 2023 and will include children and adults with PWS who struggle with daytime sleepiness.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40605372/

A proof-of-concept study of pitolisant for excessive daytime ... The most common adverse events in pitolisant-treated patients (doses pooled) were anxiety, irritability, and headache (11.9% each), consistent ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04257929

NCT04257929 | A Phase 2 Study to Evaluate the Safety ... The primary objective of this study is to evaluate the safety and efficacy of pitolisant compared with placebo in treating excessive daytime sleepiness (EDS)