Safety and tolerability of KarXT (xanomeline–trospium) in a phase 2, randomized, double-blind, placebo-controlled study in patients with schizophrenia

• DOI: 10.1038/s41537-022-00320-1
• Publication Date: 2022-12-03T10:02:50Z
• Authors: Christoph U. Correll; Angel S. Angelov; Andrew C. Miller; Peter J. Weiden; Stephen K. Brannan
• Keywords: Tolerability; Extrapyramidal symptoms

KarXT combines xanomeline, an M1/M4 preferring muscarinic agonist with no direct D2 receptor antagonism, the peripherally restricted anticholinergic trospium. In EMERGENT-1 (NCT03697252), a 5-week, randomized, double-blind, placebo-controlled, phase 2 study in inpatients schizophrenia, met primary efficacy endpoint, numerous secondary endpoints, and was generally well tolerated. Here, we conducted additional post hoc analyses of safety tolerability data from particular focus on adverse events (AEs) that may be associated agonism (nausea or vomiting) antagonism (dry mouth constipation). A total 179 patients received at least one dose either (n = 89) placebo 90) were included analyses. low overall AE burden. The majority procholinergic AEs mild, occurred first 1-2 weeks treatment, transient median duration ranging 1 day for vomiting to 13 days dry mouth. No treatment group discontinued due any AEs. Incidence somnolence/sedation similar those group. significant clinically relevant changes body weight, metabolic parameters, vital signs. tolerated profile consistent activity xanomeline-trospium receptors.