Evidence map›Paper›PMID 36883238›Full record

Trial reportSleep2023

Safety and pharmacodynamics of a single infusion of danavorexton in adults with idiopathic hypersomnia.

Emmanuel Mignot, Richard K Bogan, Helene Emsellem, Nancy Foldvary-Schaefer, Melissa Naylor, Rachel Neuwirth, Hélène Faessel, Todd Swick, Tina Olsson

Registry-linked trialOpen access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Sleep, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04091438 (A Phase 1b Randomized, Double-Blind, Placebo-Controlled, Crossover Study of a Single Intravenous Infusion Dose of TAK-925 in Patients With Idiopathic Hypersomnia), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
2.5field-weighted citation impact, top 11% of its field
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.

NCT04091438 phase1completednot on this map

A Phase 1b Randomized, Double-Blind, Placebo-Controlled, Crossover Study of a Single Intravenous Infusion Dose of TAK-925 in Patients With Idiopathic Hypersomnia

TypeinterventionalSponsorMillennium Pharmaceuticals, Inc.Ran2020 to 2020Enrolled28ConditionsIdiopathic HypersomniaArmsTAK-925, TAK-925 Placebo
3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. A scoping review of the evidence on pharmacological and nonpharmacological interventions for idiopathic hypersomnia.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2024
    Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 1 country.

Emmanuel MignotStanford Department of Psychiatry and Behavioral Medicine, Center for Sleep Sciences and Medicine, Stanford University Medical School, Palo Alto, CA, USA.ORCID 0000-0002-6928-5310
Richard K BoganBogan Sleep Consultants, LLC, Columbia, SC, USA.ORCID 0000-0001-7043-2974
Helene EmsellemThe Center of Sleep & Wake Disorders, Chevy Chase, MD, USA.
Nancy Foldvary-SchaeferDepartment of Neurology, Sleep Disorders Center, Cleveland Clinic, Cleveland, OH, USA.
Melissa NaylorTakeda Development Center Americas, Inc., Lexington, MA, USA.
Rachel NeuwirthTakeda Development Center Americas, Inc., Lexington, MA, USA.
Hélène FaesselTakeda Development Center Americas, Inc., Lexington, MA, USA.
Todd SwickTakeda Development Center Americas, Inc., Lexington, MA, USA.
Tina OlssonTakeda Development Center Americas, Inc., Lexington, MA, USA.
Takeda (United States) · USCalifornia Center for Sleep Disorders · USCleveland Clinic · USStanford University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

STUDY

objectivesIdiopathic hypersomnia (IH) is a chronic disorder characterized by excessive daytime sleepiness unexplained by another disorder or drug/medication use. Although the orexin system plays a role in sleep-wake regulation, orexin A levels in the cerebrospinal fluid are normal in people with IH. This phase 1b, randomized, placebo-controlled, crossover study aimed to investigate the safety, pharmacokinetics, and pharmacodynamics of danavorexton, a small-molecule orexin-2 receptor agonist, in adults with IH.

methodsAdults with IH aged 18-75 years were randomized to one of two treatment sequences of single intravenous infusions of danavorexton 112 mg and placebo. Pharmacodynamic endpoints included the maintenance of wakefulness test (MWT), the Karolinska Sleepiness Scale (KSS), and the psychomotor vigilance task (PVT). Adverse events were monitored throughout the study period.

resultsOf 28 randomized participants, 12 (44.4%) had a treatment-emergent adverse event (TEAE) and 10 (37.0%) had a TEAE considered related to study drug, most of which were mild or moderate. Four participants (18.2%) had urinary TEAEs while receiving danavorexton, all of which were mild in severity. There were no deaths or TEAEs leading to discontinuation. Improvements in MWT, KSS, and PVT scores were observed with danavorexton compared to placebo. Following drug administration, a mean sleep latency of 40 min (maximum value) was observed during the MWT within 2 h of danavorexton infusion in most participants.

conclusionsA single infusion of danavorexton improves subjective and objective excessive daytime sleepiness in people with IH with no serious TEAEs, indicating orexin-2 receptor agonists are promising treatments for IH. Clinical Trial: Clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/NCT04091438.

Indexed as

Disorders of Excessive SomnolenceIdiopathic HypersomniaAdultBenzhydryl CompoundsCross-Over StudiesHumansModafinilOrexinsWakefulnessBenzhydryl CompoundsModafinilOrexinsdanavorextonexcessive daytime sleepinessidiopathic hypersomniaorexin type 2 receptor agonist

Identifiers

PMID36883238
PMCPMC10485568
OpenAlexW4323535498

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.