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Randomized Controlled Trial
. 2025 Feb 26;86(1):24m15497.
doi: 10.4088/JCP.24m15497.

Safety and Tolerability of Xanomeline and Trospium Chloride in Schizophrenia: Pooled Results From the 5-Week, Randomized, Double-Blind, Placebo-Controlled EMERGENT Trials

Inder Kaul  1 , Amy Claxton  1 , Sharon Sawchak  1 , Colin Sauder  1 , Stephen K Brannan  2 , Edwin Raj  3 , Shiling Ruan  4 , George Konis  5 , David Brown  6 , Andrew J Cutler  7 , Ronald Marcus  2   8
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Free article
Randomized Controlled Trial

Safety and Tolerability of Xanomeline and Trospium Chloride in Schizophrenia: Pooled Results From the 5-Week, Randomized, Double-Blind, Placebo-Controlled EMERGENT Trials

Inder Kaul et al. J Clin Psychiatry. .
Free article

Abstract

Objective: To further characterize the safety and tolerability of oral xanomeline and trospium chloride in the treatment of people with schizophrenia experiencing acute psychosis.

Methods: Pooled analyses were performed on safety data from the 5-week, randomized, double-blind, placebo-controlled, inpatient EMERGENT-1, EMERGENT-2, and EMERGENT-3 trials of xanomeline/ trospium in adults with schizophrenia with a recent worsening of psychosis requiring hospitalization. Adverse events (AEs) including extrapyramidal motor symptoms (EPS), vital signs, and clinical laboratory values were monitored. Additional analyses of AEs were conducted on subgroups based on age (<45 years or ≥45 years), sex, race (Black or White), ethnicity (Hispanic/Latino or not Hispanic/ Latino), country (United States or Ukraine), and baseline body mass index (<30 kg/m2 or ≥30 kg/m2).

Results: The pooled safety population comprised 683 participants from the acute trials. Discontinuation rates were similar between groups (xanomeline/ trospium, 27.6%; placebo, 22.7%). Treatment-emergent AEs were reported by 67.9% (xanomeline/trospium) and 51.3% (placebo) of participants, and 51.8% (xanomeline/trospium) and 29.4% (placebo) experienced AEs deemed related to treatment. The most common AEs with xanomeline/trospium were mild or moderate in intensity, transient, and generally gastrointestinal in nature. Subgroups demonstrated clinically nonsignificant differences in incidences of the most common AEs. Rates of EPS, somnolence, and weight gain were low in both groups.

Conclusions: In pooled analyses, xanomeline/trospium was generally well tolerated in people with schizophrenia. The most common AEs were mild or moderate in intensity, transient, and consistent with the activity of xanomeline and trospium at muscarinic receptors. Rates of EPS, somnolence, and weight gain were low.

Trial Registration: ClinicalTrials.gov identifiers: NCT03697252, NCT04659161, NCT04738123.

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