Pitolisant for Prader-Willi Syndrome

Not currently recruiting at 14 trial locations

Overseen By Krystle Davis, MS

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Harmony Biosciences Management, Inc.

Must not be taking: Strong CYP2D6 inhibitors

Disqualifiers: Other genetic disorders, Untreated OSA, Psychosis, Renal disease, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether pitolisant, a medication, can alleviate excessive daytime sleepiness in individuals with Prader-Willi syndrome. Prader-Willi syndrome is a genetic condition that can lead to constant hunger and sleep issues. The study includes groups receiving either pitolisant or a placebo (a pill with no active medication) to compare results. Individuals diagnosed with Prader-Willi syndrome who experience significant daytime sleepiness might be suitable candidates for this trial. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important early findings.

Do I have to stop taking my current medications for the trial?

You may need to stop taking certain medications before joining the trial. If you're on wake-promoting treatments or sedating medications, you must either be on a stable dose or agree to stop them for a period of time before starting the trial. Check with the trial team to see if your specific medications are affected.

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

Research shows that pitolisant is generally well-tolerated. In earlier studies, the most common side effects included anxiety, irritability, and headache, each affecting about 11.9% of participants. These side effects align with findings from other studies. While some may experience mild discomfort, the treatment is considered relatively safe. Additionally, the FDA has approved pitolisant for another condition, supporting its safety profile. However, individual experiences can vary, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

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

Unlike the standard treatments for Prader-Willi Syndrome, which often include hormone therapy and behavioral interventions, pitolisant offers a novel approach by targeting the brain's histamine H3 receptors. This mechanism may help manage symptoms such as excessive daytime sleepiness and behavioral issues by promoting wakefulness and improving cognitive function. Researchers are excited because pitolisant could provide a new option that directly addresses neurological aspects of the syndrome, potentially improving quality of life for patients in ways current treatments do not.

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

Studies have shown that pitolisant can help reduce excessive daytime sleepiness in people with Prader-Willi Syndrome. In this trial, participants will receive either a lower or higher dose of pitolisant, or a placebo. Research indicates that higher doses of pitolisant have especially positive effects. Specifically, children aged 6 to 12 who took pitolisant experienced less sleepiness and improved thinking skills. Additionally, pitolisant has helped with sleep problems in other conditions, supporting its reliability. Overall, these early findings suggest pitolisant may effectively manage sleepiness in Prader-Willi Syndrome. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals aged 6 to 65 with Prader-Willi Syndrome who experience excessive daytime sleepiness. Participants must have a confirmed diagnosis, get enough nightly sleep, and if on certain medications or treatments, they need to be on stable doses. Females of childbearing age must use nonhormonal contraception and not be pregnant.

Inclusion Criteria

Is able to provide voluntary, written informed consent (patient or parent[s]/legal guardian[s]) and, where applicable, voluntary, written assent (patient, as appropriate).

I understand and can follow the study's requirements and take oral medication as directed.

I have been on a stable dose of CBD/THC for 28 days and agree to keep it the same during the study.

Exclusion Criteria

I am not currently taking strong medication that affects my liver enzymes or certain allergy medications, or I can stop them for the required time before joining the study.

You have had problems with alcohol or drugs in the past year.

I have had seizures but have been stable for 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-Blind Treatment

Participants receive either pitolisant or placebo during an 11-week period, including a 3-week titration and 8-week stable dose period

11 weeks

Weekly visits for dose adjustment and monitoring

Open Label Extension

Eligible participants receive open-label pitolisant with a 3-week titration period followed by long-term treatment

Multi-year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pitolisant
• Placebo

Trial Overview The study tests the safety and effectiveness of pitolisant oral tablets against placebo in reducing excessive daytime sleepiness in Prader-Willi Syndrome patients. It includes an initial phase where participants are randomly given either the medication or a placebo, followed by an open label extension where all receive pitolisant.

How Is the Trial Designed?

Group I: Open-Label Pitolisant Experimental Treatment 1 Intervention

Age-based dosing (prior to implementation of amendment 6) with maximum once daily doses of 17.8 mg for pediatric patients (6 to \<12 years), 26.7 mg for adolescent patients (12 to \<18 years), or 35.6 mg for adult patients (18 to 65 years). Weight-based dosing (after implementation of amendment 6) with maximum once daily doses of 17.8 mg for patients ≤40 kg, 35.6 mg for patients \>40 to ≤80 kg, and 44.5 mg for patients \>80 kg.

Group II: Double-Blind Treatment Phase Lower Dose Pitolisant Active Control 1 Intervention

Pediatric patients (6 to less than 12 years of age): Week 1: 4.45 mg pitolisant administered once daily in the morning; Week 2: 8.9 mg pitolisant administered once daily in the morning; Weeks 3 through 11: 8.9 mg pitolisant administered once daily in the morning. Adolescent patients (12 to less than 18 years of age): Week 1: 4.45 mg pitolisant administered once daily in the morning; Week 2: 8.9 mg pitolisant administered once daily in the morning; Weeks 3 through 11: 13.35 mg pitolisant administered once daily in the morning. Adult patients (18 to 65 years of age): Week 1: 4.45 mg pitolisant administered once daily in the morning; Week 2: 8.9 mg pitolisant administered once daily in the morning; Weeks 3 through 11: 17.8 mg pitolisant administered once daily in the morning.

Group III: Double-Blind Treatment Phase Higher Dose Pitolisant Active Control 1 Intervention

Pediatric patients (6 to less than 12 years of age): Week 1: 4.45 mg pitolisant administered once daily in the morning; Week 2: 8.9 mg pitolisant administered once daily in the morning; Weeks 3 through 11: 17.8 mg pitolisant administered once daily in the morning. Adolescent patients (12 to less than 18 years of age): Week 1: 8.9 mg pitolisant administered once daily in the morning; Week 2: 17.8 mg pitolisant administered once daily in the morning; Weeks 3 through 11: 26.7 mg pitolisant administered once daily in the morning. Adult patients (18 to 65 years of age): Week 1: 8.9 mg pitolisant administered once daily in the morning; Week 2: 17.8 mg pitolisant administered once daily in the morning; Weeks 3 through 11: 35.6 mg pitolisant administered once daily in the morning.

Group IV: Double-Blind Treatment Phase Placebo Placebo Group 1 Intervention

Pediatric patients (6 to less than 12 years of age): Week 1: Matching placebo tablets; Week 2: Matching placebo tablets; Weeks 3 through 11: Matching placebo tablets Adolescent patients (12 to less than 18 years of age): Week 1: Matching placebo tablets; Week 2: Matching placebo tablets; Weeks 3 through 11: Matching placebo tablets Adult patients (18 to 65 years of age): Week 1: Matching placebo tablets; Week 2: Matching placebo tablets; Weeks 3 through 11: Matching placebo tablets

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 Management, Inc.

Lead Sponsor

Trials

9

Recruited

2,000+

Harmony Biosciences, LLC

Lead Sponsor

Trials

9

Recruited

2,000+

Published Research Related to This Trial

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]

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]

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 (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]

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, 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]

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. 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.

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6478354/

Cognitive Improvements in Children with Prader-Willi ... We have observed that pediatric patients with PWS prescribed pitolisant demonstrate decreased daytime sleepiness and improved cognition.

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 AEs in pitolisant-treated patients (doses pooled) were anxiety, irritability, and headache (11.9% each), consistent with the ...

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)