EMERGENT-3
Trial question
What is the effect of xanomeline/trospium chloride in patients with schizophrenia experiencing acute psychosis?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
25.0% female
75.0% male
N = 256
256 patients (65 female, 191 male).
Inclusion criteria: adult patients with schizophrenia experiencing acute psychosis.
Key exclusion criteria: primary disorder other than schizophrenia within 12 months preceding screening; history of treatment resistance to antipsychotic medication; ≥ 20% improvement in Positive and Negative Syndrome Scale total score between screening and baseline.
Interventions
N=125 xanomeline/trospium chloride (maximum dose xanomeline/trospium 125 mg/30 mg for 5 weeks).
N=131 placebo (matching placebo for 5 weeks).
Primary outcome
Reduction in Positive and Negative Syndrome Scale total score at week 5
20.6 points
12.2 points
20.6 points
15.5 points
10.3 points
5.2 points
0.0 points
Xanomeline/trospium
chloride
Placebo
Significant
increase ▲
Significantly greater reduction in Positive and Negative Syndrome Scale total score at week 5 (20.6 points vs. 12.2 points; MD 8.4, 95% CI 4.3 to 12.4).
Secondary outcomes
Significantly greater reduction in Positive and Negative Syndrome Scale positive subscale score at week 5 (7.1 points vs. 3.6 points; MD 3.5, 95% CI 2.2 to 4.7).
Significantly greater reduction in Clinical Global Improvement-Severity at week 5 (1.1 points vs. 0.6 points; MD 0.5, 95% CI 0.3 to 0.8).
Significant increase in the percentage of patients achieving ≥ 30% improvement in Positive and Negative Syndrome Scale total scores at week 5 (50.6% vs. 25.3%; AD 35.4%, 95% CI 10.8 to 38.5).
Safety outcomes
No significant difference in discontinuation of treatment due to treatment-emergent adverse event.
Conclusion
In adult patients with schizophrenia experiencing acute psychosis, xanomeline/trospium chloride was superior to placebo with respect to reduction in Positive and Negative Syndrome Scale total score at week 5.
Reference
Inder Kaul, Sharon Sawchak, David P Walling et al. Efficacy and Safety of Xanomeline-Trospium Chloride in Schizophrenia: A Randomized Clinical Trial. JAMA Psychiatry. 2024 Aug 1;81(8):749-756.
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