Pitolisant for Idiopathic Hypersomnia

Not currently recruiting at 69 trial locations

Overseen By Daniel Norman, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Harmony Biosciences Management, Inc.

Must not be taking: QT prolonging drugs

Disqualifiers: Breastfeeding, ESRD, Severe hepatic impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 21

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pitolisant, a medication for individuals with idiopathic hypersomnia (IH), a condition causing excessive daytime sleepiness. The trial aims to assess the long-term safety and effectiveness of pitolisant. Participants must have completed a previous phase of the study and have IH. Those experiencing constant sleepiness that disrupts daily life may be suitable candidates. As a Phase 3 trial, this is the final step before FDA approval, providing an opportunity to contribute to a treatment nearing availability.

Will I have to stop taking my current medications?

The trial requires participants to stop taking any medications that are specifically prohibited in the study protocol. If you are taking a medication known to prolong the QT interval, you must discontinue it to participate.

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

Research has shown that pitolisant is generally safe for people with idiopathic hypersomnia. Studies have found that the body's handling of the drug and its side effects are consistent with previous findings.

In one study, researchers tested pitolisant for eight weeks in adults with idiopathic hypersomnia. The results showed improvements in symptoms like excessive daytime sleepiness. Importantly, most participants did not experience severe side effects, indicating the treatment was well-tolerated.

Some participants reported side effects, but these were usually mild and manageable. Overall, the evidence suggests that pitolisant is a safe option for treating idiopathic hypersomnia and offers a promising way to manage this condition. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for idiopathic hypersomnia?

Unlike the standard treatments for idiopathic hypersomnia, which often include medications like modafinil or sodium oxybate, pitolisant offers a unique mechanism of action. It works as a histamine H3 receptor antagonist/inverse agonist, which helps to increase wakefulness by enhancing the activity of histamine in the brain. This approach is different from the typical dopamine or GABA-related pathways used by other treatments. Researchers are excited because pitolisant could provide an alternative for patients who do not respond well to existing options, potentially offering improved alertness with a novel, non-stimulant method.

What evidence suggests that pitolisant might be an effective treatment for idiopathic hypersomnia?

Research shows that the FDA has approved pitolisant for treating excessive daytime sleepiness and sudden muscle weakness (cataplexy) in people with narcolepsy. This approval indicates its effectiveness in addressing sleep-related issues. Studies have found that pitolisant may also reduce symptoms of idiopathic hypersomnia (IH), such as severe daytime fatigue. Participants in this trial will receive pitolisant, and some patients who completed an open-label phase reported significant benefits. This suggests that pitolisant could improve alertness and reduce IH symptoms. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with idiopathic hypersomnia who finished the prior study phase (HBS-101-CL-010) and can follow the study plan. Participants must not use certain drugs, have severe kidney or liver issues, or be at significant suicide risk. Women of childbearing age must test negative for pregnancy and agree to avoid pregnancy during the study.

Inclusion Criteria

Completed the Double-Blind Randomized Withdrawal Phase (EOT/Visit 5) from the HBS-101-CL-010 study

Is able to provide voluntary, informed consent

I understand and can follow the study's requirements.

Exclusion Criteria

Based on the judgment of the Investigator, is unsuitable for the study for any reason, including but not limited to an unstable or uncontrolled medical condition or one that might interfere with the conduct of the study, confound interpretation of study results, pose a health risk to the patient, or compromise the integrity of the study

Does not agree to discontinue any prohibited medication or substances listed in the protocol

Participation in an interventional research study with an investigational medication or device, other than pitolisant, for the duration of the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Titration

Participants are titrated up to a maximum dose of 35.6 mg of pitolisant over a 3-week period

3 weeks

Weekly visits for dose titration

Long-Term Dosing

Participants receive long-term dosing of pitolisant with dose adjustments based on safety and effectiveness

Up to approximately 3 years

On-site visits every 6 months, monthly telephone contacts

Follow-up

Participants receive safety follow-up telephone contacts to assess for adverse events and concomitant medication use

1 month

Telephone contacts at 15 and 30 days post-final dose

What Are the Treatments Tested in This Trial?

Interventions

• Pitolisant

Trial Overview The trial is evaluating the long-term safety and effectiveness of a medication called pitolisant in patients with excessive daytime sleepiness due to idiopathic hypersomnia, following their participation in an earlier phase of research.

How Is the Trial Designed?

Group I: Pitolisant Experimental Treatment 1 Intervention

Week 1: 8.9 mg pitolisant administered once daily in the morning upon wakening; Week 2: 17.8 mg pitolisant administered once daily in the morning upon wakening; Weeks 3 through end of treatment: 17.8 mg to 35.6 mg pitolisant administered 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 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 (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]

Citations

1. academic.oup.com academic.oup.com/sleep/article/48/Supplement_1/A375/8135756

0866 Effect of Pitolisant on Idiopathic Hypersomnia Symptoms ... Pitolisant is FDA approved for the treatment of excessive daytime sleepiness (EDS) or cataplexy in adult patients with narcolepsy and for the ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05156047

NCT05156047 | A Phase 3 Study to Assess the Safety and ... The primary objective of this study is to evaluate the safety and efficacy of pitolisant compared with placebo in treating excessive daytime sleepiness (EDS)

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05458128?term=AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(PITOLISANT))))&rank=2

A Long-Term Safety and Effectiveness Study to Evaluate ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

4. ir.harmonybiosciences.com ir.harmonybiosciences.com/news-releases/news-release-details/harmony-biosciences-announces-topline-data-phase-3-intune-study

Release Details - Harmony Biosciences Pitolisant demonstrated clinically meaningful benefit in patients completing the initial open label phase.

5. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK601765/

Clinical Review - Pitolisant Hydrochloride (Wakix) - NCBI - NIH Primary outcomes in clinical practice will likely be a reduction in EDS, a reduction in this report, treatment goals are primarily to improve quality ...

6. academic.oup.com academic.oup.com/sleep/article/48/Supplement_1/A376/8134741

0867 Effect of Pitolisant on Symptoms of Idiopathic ... In an 8-week OLP of a phase 3 clinical trial in adult patients with IH, pitolisant demonstrated robust improvements in EDS, sleep inertia, and a multitude of ...

7. neurologylive.com neurologylive.com/view/despite-missing-primary-end-point-pitolisant-shows-positive-outcomes-phase-3-intune-trial-idiopathic-hypersomnia

Despite Missing Primary End Point, Pitolisant Shows ... 83% of patients with idiopathic hypersomnia who completed treatment saw a significant reduction in sleepiness, with an average Epworth Sleepiness Scale change ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05458128

A Long-Term Safety and Effectiveness Study to Evaluate ... The primary objective of this study is to assess the long-term safety and effectiveness of pitolisant in patients with idiopathic hypersomnia (IH) who completed ...