Efficacy of Xanomeline and Trospium Chloride in Schizophrenia: Post Hoc Analyses of Data Pooled From Three 5-Week, Randomized, Double-Blind, Placebo-Controlled EMERGENT Trials
Background: In data pooled from the EMERGENT-1 (NCT03697252), EMERGENT-2 (NCT04659161), and EMERGENT-3 (NCT04738123) clinical trials of adults with schizophrenia, xanomeline and trospium chloride demonstrated significant improvements in Positive and Negative Syndrome Scale (PANSS) total and subscale scores compared with placebo.
Objective: Further assess efficacy of xanomeline/trospium in data pooled from EMERGENT trials.
Methods: The EMERGENT trials were randomized, double-blind, placebo-controlled, 5-week, inpatient trials of xanomeline/trospium in adults with acute exacerbations of schizophrenia. Inclusion criteria included recent worsening of positive symptoms warranting hospitalization, PANSS total score of 80-120, and a Clinical Global Impression–Severity (CGI-S) score of ≥4. Eligible participants were randomized 1:1 to receive xanomeline/trospium or placebo. Dosing of xanomeline/trospium started at 50 mg/20 mg BID and increased to a maximum of 125 mg/30 mg BID. Analyses of data pooled from the EMERGENT trials included change from baseline at week 5 in CGI-S and PANSS Marder 5-factor symptom domain scores.
Results: A total of 640 participants (xanomeline/trospium, n=314; placebo, n=326) comprised the pooled modified intention-to-treat population. Baseline demographics were similar between treatment groups. Xanomeline/trospium was associated with significant improvements from baseline at week 5 compared with placebo in CGI-S (least squares mean [LSM] difference: -0.6; P < 0.0001) and PANSS Marder 5-factor symptom domain (LSM difference: negative factor, -2.0; hostility, -1.5; positive factor, -2.9; disorganized thought, -2.0; depression, -1.6; P < 0.0001 for all) scores.
Conclusions: Results lend further support to the potential of xanomeline/trospium to be first in a new class of antipsychotics based on muscarinic agonism instead of D2 dopamine receptor antagonism.
