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Phase 3 Randomized Double‑Blind Study of Pitolisant versus Placebo for Safety and Efficacy in Adults with Idiopathic Hypersomnia

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What is this trial about?

A plain-language summary of the goals, design and what participants do

The condition under investigation is Idiopathic hypersomnia, a rare sleep disorder that causes ongoing sleepiness during the day and makes it hard to wake up after sleep. The investigational drug, identified by the code name HBS-301, is taken as an oral tablet, and a matching placebo tablet is used for comparison.

The purpose of the study is to evaluate whether HBS-301 reduces excessive daytime sleepiness compared with placebo. Participants are assigned by chance (randomized) to receive either HBS-301 or placebo, and neither the participants nor the study staff know which treatment is given (double‑blind). After an initial screening, a short titration phase adjusts the dose, followed by a double‑blind treatment period lasting several weeks, and then follow‑up visits to monitor safety and changes in symptoms; an open‑label extension may follow where all participants receive HBS-301.

The research process

The trial runs in 6 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Randomization and start of treatment

    After joining the study you will be assigned by chance to receive either pitolisant tablets or placebo tablets. this process is called randomized and ensures that the groups are comparable.

    The study is double-blind, meaning that neither you nor the study staff will know which type of tablet you are taking during this phase.

  2. Step 2

    Baseline assessments

    Before taking any tablets you will complete questionnaires that measure daytime sleepiness and other symptoms. the main tools are the Epworth Sleepiness Scale (ESS), the Idiopathic Hypersomnia Symptom Scale (IHSS), and the Sleep Inertia Questionnaire (SIQ).

    These results will be used as the reference point for later comparisons.

  3. Step 3

    Titration period (first two weeks)

    During the first two weeks you will take the assigned tablet each day. the dose may be adjusted by the study team based on how you respond, a process called titration.

    You will repeat the ESS questionnaire at the end of week 1 and again at the end of week 2 to track changes in sleepiness.

  4. Step 4

    Double‑blind treatment period

    After the titration period you will continue taking the same type of tablet (either pitolisant or placebo) for the remainder of the double‑blind phase. the tablets are taken by mouth and are in tablet form.

    The exact duration of this phase is not specified in the provided information, but you will continue the same daily routine until the end of the double‑blind period.

    Regular assessments using the ESS, IHSS, and SIQ will be performed at scheduled visits to evaluate the effect of the medication.

  5. Step 5

    End of double‑blind period assessments

    At the conclusion of the double‑blind phase you will again complete the ESS, IHSS, and SIQ questionnaires.

    The change in scores from the baseline visit will be compared to determine the effectiveness of the treatment.

  6. Step 6

    Open‑label extension

    If you choose to continue in the study after the double‑blind phase, you will enter an open‑label extension where all participants receive the active medication, pitolisant.

    During this extension you will keep taking the tablets daily and may have additional assessments, although specific timing is not detailed in the source data.

Who can join the trial?

7 criteria

  • You must be able to give voluntary, written informed consent, meaning you understand the study and agree to take part.
  • You need a confirmed diagnosis of idiopathic hypersomnia (IH) based on recognized criteria, with a sleep study called polysomnography (PSG) and a daytime sleepiness test called the multiple sleep latency test (MSLT) (or a 24‑hour PSG or an actigraphy report with a sleep log) that was completed within the past 10 years.
  • You must be at least 18 years old at the time of screening.
  • If you are taking any allowed long‑term medicines or supplements (such as certain antidepressants or wake‑promoting agents), the dose must have been stable for at least 3 months before screening and you must keep that same dose throughout the study. You cannot use “as needed” (PRN) stimulants like modafinil or armodafinil.
  • If you are being treated for obstructive sleep apnea (OSA) or other breathing‑related sleep problems, you must use your prescribed medical device (such as a CPAP machine) or oral appliance as directed and stay compliant for the whole study.
  • Women who could become pregnant (female participants of child‑bearing potential) must have a negative pregnancy test at screening and at baseline, and must either remain abstinent or use a non‑hormonal method of birth control during the study and for at least 30 days after the last dose. Women using hormonal birth control must also add a non‑hormonal method. Men who are not sterile (not azoospermic) must also remain abstinent or use an effective method of contraception during the study and for 30 days after the last dose.
  • The investigator (your doctor) must believe you are capable of understanding the study procedures and can follow the requirements for taking the oral study medication.

Who cannot join the trial?

22 criteria

  • Having excessive daytime sleepiness (called hypersomnia) that is caused by another medical problem, not by idiopathic hypersomnia.
  • Having used the medication pitolisant within about five drug half‑lives (the time it takes for half of the drug to leave your body) before the screening visit.
  • Taking part in another clinical trial with an experimental drug, device, or treatment within 30 days (or within five drug half‑lives, whichever is longer) before screening.
  • Having a primary psychiatric illness, such as depression, that is not well‑controlled (symptoms or medicines have not been stable for at least three months).
  • Having a history of bipolar disorder or psychosis (a condition that can cause loss of contact with reality).
  • Having acute or chronic liver disease, or moderate to severe liver problems as classified by the Child‑Pugh scoring system (Class B or C).
  • Having a kidney function measurement called BSA‑corrected eGFR that is below 60 mL/min, indicating reduced kidney filtration.
  • Having one or more abnormal screening lab results that the doctor considers clinically important.
  • Having a medical history that raises the risk for dangerous heart rhythm problems (called proarrhythmia), such as a heart attack within the past year, heart failure, very slow or fast heart rhythms, ventricular arrhythmias, torsade de pointes, unstable chest pain, or high‑grade heart block.
  • Having a known history of long QT syndrome or any serious abnormality on an electrocardiogram (ECG), such as a heart attack within the past year or a clinically significant arrhythmia.
  • Having a family history of sudden cardiac death, unexplained death, or death from a primary heart rhythm problem that can be linked to a prolonged QT interval.
  • Having a corrected QT interval (QTcF) greater than 450 milliseconds on a screening or baseline ECG, which suggests a higher risk for abnormal heart rhythms.
  • Having a current or recent (within the past year) substance use disorder or dependence, including alcohol or caffeine use problems, as defined by the DSM‑V (the standard manual for diagnosing mental health conditions).
  • Having any surgery planned during the screening, baseline, or double‑blind treatment periods of the study.
  • Having taken any prohibited medication within about five drug half‑lives before screening. Prohibited medicines include strong CYP3A4 enzyme inducers, centrally acting H1‑receptor antagonists (certain antihistamines), non‑benzodiazepine sleep aids, and drugs that can lengthen the QT interval.
  • Having taken any medication on an as‑needed (PRN) basis that could affect daytime sleepiness—such as oxybates, stimulants, modafinil, or armodafinil—within about five drug half‑lives before screening.
  • Having a positive urine drug screen for substances that are not prescribed by a health‑care professional or are otherwise prohibited in the study.
  • Having a significant risk of suicide, based on personal history, a routine psychiatric exam, the investigator’s judgment, or answering “yes” to certain questions on the C‑SSRS (a suicide risk questionnaire) at screening or baseline, or any suicidal behavior in the past 12 months.
  • Being currently breastfeeding or planning to breastfeed during the study; lactating women must agree not to breastfeed for the entire study and for seven days after the last dose.
  • Having a history of seizures (episodes of uncontrolled electrical activity in the brain).
  • Being judged by the investigator as unsuitable for the study for any reason, such as having unstable or uncontrolled medical conditions (including psychiatric, neurological, or gastrointestinal problems or surgeries like bariatric or weight‑loss surgery that could affect how the study drug is absorbed), or any condition that could interfere with the study, pose a health risk, or compromise the study’s integrity.
  • If required by local rules, not being covered by the appropriate national health‑insurance system.
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Investigated drugs

Pitolisant is an oral tablet taken by mouth. It is being tested as the active treatment in this study to see if it can help reduce excessive daytime sleepiness in people with idiopathic hypersomnia. Participants will take the medication each day, and researchers will monitor how well it works and whether it is safe to use.

What is already known about the treatment

Pitolisant - Pitolisant is taken as an oral tablet that is swallowed whole. It is an approved medicine for treating excessive daytime sleepiness in narcolepsy and is being studied for idiopathic hypersomnia, so it appears in medical literature as a wake‑promoting drug. It works by blocking the histamine H3 receptor in the brain, which leads to higher levels of histamine and helps keep a person alert. Pharmacologically, it is classified as a histamine H3‑receptor antagonist (inverse agonist) and a central nervous system stimulant.

Investigated diseases

Idiopathic hypersomnia (IH) - Idiopathic hypersomnia is a sleep disorder characterized by excessive daytime sleepiness despite adequate or prolonged nighttime sleep. People with the condition often sleep more than nine hours and still feel unrefreshed. They may experience difficulty waking up, known as sleep inertia, and a persistent feeling of fatigue throughout the day. The severity of symptoms can remain stable for years or gradually increase, leading to greater impairment in daily activities. Over time, the need for longer or more frequent naps may develop as the condition persists.
Trial detailsLast updated 8 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2025-523822-42-00Protocol codeHBS-301-CL-302Estimated enrolment184 patientsSponsorHarmony Biosciences Management Inc.

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