Evidence mapPaperPMID 40605372Full record

Trial reportJournal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine2025

A proof-of-concept study of pitolisant for excessive daytime sleepiness in patients with Prader-Willi syndrome.

Amee Revana, Rakesh Bhattacharjee, Jennifer L Miller, Aaron Chidekel, Priya Khanna, Sarayu Ratnam, Grant Runyan, Eric Bauer, Krystle Davis Rapchak, David Seiden and 2 more

Registry-linked trialAbstract readRandomized Controlled TrialClinical Trial, Phase II
In one paragraph

Trial report in Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04257929 (A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate the Safety and Efficacy of Pitolisant in Patients With Prader-Willi Syndrome, Followed by an Open Label Extension), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04257929 phase2completednot on this map

A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate the Safety and Efficacy of Pitolisant in Patients With Prader-Willi Syndrome, Followed by an Open Label Extension

TypeinterventionalSponsorHarmony Biosciences Management, Inc.Ran2020 to 2026Enrolled65ConditionsPrader-Willi SyndromeArmsPitolisant oral tablets, Placebo oral tablet
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Amee RevanaBaylor College of Medicine, Texas Children's Hospital, Houston, Texas.
Rakesh BhattacharjeeRady Children's Hospital, University of California San Diego, San Diego, California.
Jennifer L MillerUniversity of Florida Health Shands Hospital, Gainesville, Florida.
Aaron ChidekelNemours Children's Health, Wilmington, Delaware.
Priya KhannaAnn & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.
Sarayu RatnamAnn & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.
Grant RunyanHarmony Biosciences, Plymouth Meeting, Pennsylvania.
Eric BauerHarmony Biosciences, Plymouth Meeting, Pennsylvania.
Krystle Davis RapchakHarmony Biosciences, Plymouth Meeting, Pennsylvania.
David SeidenHarmony Biosciences, Plymouth Meeting, Pennsylvania.
Kumar BudurHarmony Biosciences, Plymouth Meeting, Pennsylvania.
Jeffrey M DaynoHarmony Biosciences, Plymouth Meeting, Pennsylvania.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

STUDY

objectivesThe majority of patients with Prader-Willi syndrome experience excessive daytime sleepiness (EDS). This study evaluated the effects of pitolisant, a histamine 3 (H

methodsIn this phase 2, randomized, double-blind, placebo-controlled, proof-of-concept study, patients ages 6-65 years with a confirmed diagnosis of Prader-Willi syndrome with EDS were randomized 1:1:1 to receive lower-dose pitolisant (children/adolescents/adults, 8.9/13.35/17.8 mg), higher-dose pitolisant (children/adolescents/adults, 17.8/26.7/35.6 mg), or matching placebo for 11 weeks (3-week titration/8-week maintenance). The primary endpoint was change from baseline to week 11 in Epworth Sleepiness Scale for Children and Adolescents (parent/caregiver version) score. Other measures included the Caregiver Global Impression of Severity for EDS, Aberrant Behavior Checklist-Community, second edition, and Hyperphagia Questionnaire for Clinical Trials.

resultsOf 65 patients randomized and treated, 59 (90.8%) completed the double-blind phase. Least-squares (LS) mean improvement from baseline to week 11 in Epworth Sleepiness Scale for Children and Adolescents score was greater for higher-dose pitolisant (-5.0) vs placebo (-3.9; LS mean [standard error] difference, -1.1 [1.52]), but not for lower-dose pitolisant (-3.5) vs placebo (LS mean [standard error] difference, 0.5 [1.6]). The largest effect of pitolisant was seen in children (ages 6 to < 12 years; LS mean [standard error] difference for higher-dose pitolisant vs placebo, -3.5 [1.90]). Improvements were observed across other measures, especially in the higher-dose pitolisant group, including LS mean (standard error) change of -5.5 (1.2) on the irritability domain of the Aberrant Behavior Checklist-Community, second edition, and -3.1 (1.0) on the Hyperphagia Questionnaire for Clinical Trials. The most common adverse events in pitolisant-treated patients (doses pooled) were anxiety, irritability, and headache (11.9% each), consistent with the known safety profile of pitolisant.

conclusionsResults of this proof-of-concept study support further evaluation of pitolisant in patients with Prader-Willi syndrome and EDS. CLINICAL

trial registrationRegistry: ClinicalTrials.gov; Name: A Phase 2 Study to Evaluate the Safety and Efficacy of Pitolisant in Patients With Prader-Willi Syndrome, Followed by an Open Label Extension; URL: https://clinicaltrials.gov/study/NCT04257929; Identifier: NCT04257929. CITATION: Revana A, Bhattacharjee R, Miller JL, et al. A proof-of-concept study of pitolisant for excessive daytime sleepiness in patients with Prader-Willi syndrome.

Indexed as

Disorders of Excessive SomnolencePiperidinesPrader-Willi SyndromeAdolescentAdultAgedChildDose-Response Relationship, DrugDouble-Blind MethodFemaleHumansMaleMiddle AgedProof of Concept StudyTreatment OutcomeYoung AdultPiperidinespitolisantbehavioral symptomsexcessive daytime sleepinessHhistamine Hproof-of-concept study

Identifiers

PMID40605372
PMCPMC12582198

What Socratic holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.