PMID- 36463237
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221206
IS  - 2754-6993 (Electronic)
IS  - 2754-6993 (Linking)
VI  - 8
IP  - 1
DP  - 2022 Dec 3
TI  - Safety and tolerability of KarXT (xanomeline-trospium) in a phase 2, randomized, 
      double-blind, placebo-controlled study in patients with schizophrenia.
PG  - 109
LID - 10.1038/s41537-022-00320-1 [doi]
LID - 109
AB  - KarXT combines xanomeline, an M(1)/M(4) preferring muscarinic agonist with no 
      direct D(2) receptor antagonism, with the peripherally restricted anticholinergic 
      trospium. In EMERGENT-1 (NCT03697252), a 5-week, randomized, double-blind, 
      placebo-controlled, phase 2 study in inpatients with schizophrenia, KarXT met the 
      primary efficacy endpoint, numerous secondary endpoints, and was generally well 
      tolerated. Here, we conducted additional post hoc analyses of safety and 
      tolerability data of KarXT from EMERGENT-1 with a particular focus on adverse 
      events (AEs) that may be associated with muscarinic receptor agonism (nausea or 
      vomiting) or antagonism (dry mouth or constipation). A total of 179 patients 
      received at least one dose of either KarXT (n = 89) or placebo (n = 90) and were 
      included in the analyses. KarXT was associated with a low overall AE burden. The 
      majority of procholinergic and anticholinergic AEs with KarXT were mild, occurred 
      in the first 1-2 weeks of treatment, and were transient with a median duration 
      ranging from 1 day for vomiting to 13 days for dry mouth. No patients in either 
      treatment group discontinued the study due to any procholinergic or 
      anticholinergic AEs. Incidence of somnolence/sedation AEs with KarXT were low and 
      similar to those in the placebo group. KarXT was associated with no significant 
      or clinically relevant changes in body weight, metabolic parameters, or vital 
      signs. KarXT was generally well tolerated with an AE profile consistent with the 
      activity of xanomeline-trospium at muscarinic receptors.
CI  - (c) 2022. The Author(s).
FAU - Correll, Christoph U
AU  - Correll CU
AD  - Department of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY, 
      USA. CCorrell@northwell.edu.
AD  - Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School 
      of Medicine at Hofstra/Northwell, Hempstead, NY, USA. CCorrell@northwell.edu.
AD  - Department of Child and Adolescent Psychiatry, Charite Universitatsmedizin 
      Berlin, Berlin, Germany. CCorrell@northwell.edu.
FAU - Angelov, Angel S
AU  - Angelov AS
AD  - Karuna Therapeutics, Boston, MA, USA.
FAU - Miller, Andrew C
AU  - Miller AC
AD  - Karuna Therapeutics, Boston, MA, USA.
FAU - Weiden, Peter J
AU  - Weiden PJ
AUID- ORCID: 0000-0001-5583-5871
AD  - Karuna Therapeutics, Boston, MA, USA.
FAU - Brannan, Stephen K
AU  - Brannan SK
AD  - Karuna Therapeutics, Boston, MA, USA.
LA  - eng
PT  - Journal Article
DEP - 20221203
PL  - Germany
TA  - Schizophrenia (Heidelb)
JT  - Schizophrenia (Heidelberg, Germany)
JID - 9918367987006676
PMC - PMC9719488
COIS- The sponsor was involved in the design and conduct of the study; collection, 
      analysis, and interpretation of data; preparation, review, and approval of the 
      manuscript; and the decision to submit the manuscript for publication. Dr. 
      Correll has been a consultant and/or advisor to or has received honoraria from 
      AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Boehringer-Ingelheim, 
      Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Gedeon 
      Richter, Hikma, Holmusk, IntraCellular Therapies, Janssen/Johnson & Johnson, 
      Karuna Therapeutics, LB Pharma, Lundbeck, MedAvante-ProPhase, MedinCell, Merck, 
      Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Newron, Noven, Otsuka, 
      Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Seqirus, SK Life 
      Science, Sunovion, Sun Pharma, Supernus, Takeda, Teva, and Viatris; provided 
      expert testimony for Janssen and Otsuka; served on a Data Safety Monitoring Board 
      for Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva; has received grant 
      support from Janssen and Takeda; received royalties from UpToDate; and is a stock 
      option holder of Cardio Diagnostics, Mindpax, and LB Pharma. Drs. Angelov, 
      Miller, Weiden, and Brannan are employees of and hold equity in Karuna 
      Therapeutics.
EDAT- 2022/12/04 06:00
MHDA- 2022/12/04 06:01
PMCR- 2022/12/03
CRDT- 2022/12/03 23:26
PHST- 2022/09/08 00:00 [received]
PHST- 2022/11/21 00:00 [accepted]
PHST- 2022/12/03 23:26 [entrez]
PHST- 2022/12/04 06:00 [pubmed]
PHST- 2022/12/04 06:01 [medline]
PHST- 2022/12/03 00:00 [pmc-release]
AID - 10.1038/s41537-022-00320-1 [pii]
AID - 320 [pii]
AID - 10.1038/s41537-022-00320-1 [doi]
PST - epublish
SO  - Schizophrenia (Heidelb). 2022 Dec 3;8(1):109. doi: 10.1038/s41537-022-00320-1.