Evidence map›Paper›PMID 36414626›Full record

Trial reportTranslational psychiatry2022

Effectiveness of KarXT (xanomeline-trospium) for cognitive impairment in schizophrenia: post hoc analyses from a randomised, double-blind, placebo-controlled phase 2 study.

Colin Sauder, Luke A Allen, Elizabeth Baker, Andrew C Miller, Steven M Paul, Stephen K Brannan

Registry-linked trialOpen access · goldAbstract readRandomized Controlled TrialClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Translational psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03697252 (A Phase 2, Randomized, Double-blinded Study to Assess the Safety, Tolerability, and Efficacy of KarXT in Hospitalized Adults With DSM-5 Schizophrenia), which is not on this map. Cited by 55 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 6 pooled it
7.9field-weighted citation impact, top 1% 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.

NCT03697252 phase2completednot on this map

A Phase 2, Randomized, Double-blinded Study to Assess the Safety, Tolerability, and Efficacy of KarXT in Hospitalized Adults With DSM-5 Schizophrenia

TypeinterventionalSponsorKaruna Therapeutics, Inc., a Bristol Myers Squibb companyRan2018 to 2019Enrolled182ConditionsSchizophreniaArmsXanomeline and Trospium Chloride Capsules, Placebo Capsules
3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 6 syntheses or guidelines pooled it, 95 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  5. Pooled it
  6. Pooled it
  7. Trial
  8. Article
  9. Review
  10. Lower Muscarinic MBiological psychiatry · 2026
    Article
  11. Phosphatase Signaling as a Therapeutic Strategy in Schizophrenia.International journal of molecular sciences · 2026
    Review
  12. Neuropsychiatric symptoms in Alzheimer's disease: Past, present, and future.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  13. Targeting muscarinic receptors for treating schizophrenia.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. Xanomeline-Trospium for the Treatment of Schizophrenia.Focus (American Psychiatric Publishing) · 2025
    Review
  19. Article
  20. Review
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

6 authors at 2 institutions in 2 countries.

Colin SauderKaruna Therapeutics, Boston, MA, USA. csauder@karunatx.com.ORCID 0000-0002-0151-5191
Luke A AllenCambridge Cognition, Cambridge, UK.
Elizabeth BakerCambridge Cognition, Cambridge, UK.
Andrew C MillerKaruna Therapeutics, Boston, MA, USA.
Steven M PaulKaruna Therapeutics, Boston, MA, USA.
Stephen K BrannanKaruna Therapeutics, Boston, MA, USA.
Cambridge Cognition (United Kingdom) · GBKaryopharm Therapeutics (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The muscarinic receptor agonist xanomeline improved cognition in phase 2 trials in Alzheimer's disease and schizophrenia. We present data on the effect of KarXT (xanomeline-trospium) on cognition in schizophrenia from the 5-week, randomised, double-blind, placebo-controlled EMERGENT-1 trial (NCT03697252). Analyses included 125 patients with computerised Cogstate Brief Battery (CBB) subtest scores at baseline and endpoint. A post hoc subgroup analysis evaluated the effects of KarXT on cognitive performance in patients with or without clinically meaningful cognitive impairment at baseline, and a separate outlier analysis excluded patients with excessive intraindividual variability (IIV) across cognitive subdomains. ANCOVA models assessed treatment effects for completers and impairment subgroups, with or without removal of outliers. Sample-wide, cognitive improvement was numerically but not statistically greater with KarXT (n = 60) than placebo (n = 65), p = 0.16. However, post hoc analyses showed 65 patients did not exhibit clinically meaningful cognitive impairment at baseline, while eight patients had implausibly high IIV at one or both timepoints. Significant treatment effects were observed after removing outliers (KarXT n = 54, placebo n = 63; p = 0.04). Despite the small sample size, a robust (d = 0.50) and significant effect was observed among patients with cognitive impairment (KarXT n = 23, placebo n = 37; p = 0.03). These effects did not appear to be related to improvement in PANSS total scores (linear regression, R

Indexed as

Cognitive DysfunctionSchizophreniaThiadiazolesHumansPyridinesQuaternary Ammonium CompoundsPyridinesQuaternary Ammonium CompoundsThiadiazolesxanomeline

Identifiers

PMID36414626
PMCPMC9681874
OpenAlexW4309651428

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.