Demographic Disparities in Clinical Trials of Xanomeline–Trospium for Schizophrenia: A Cross-Sectional Analysis of Data from ClinicalTrials.gov
A. Kwaśny, D. Świeczkowski, A. Włodarczyk, A. Wilkowska, J. Słupski, W. J. CubałaIntroduction
Xanomeline, a muscarinic receptor agonist with preferential affinity for the M₁ and M₄ subtypes, has demonstrated antipsychotic efficacy, thereby revitalizing interest in muscarinic receptor–targeted pharmacotherapy for schizophrenia. To mitigate xanomeline-associated peripheral cholinergic adverse effects, it has been co-formulated with trospium chloride, a peripherally restricted muscarinic receptor antagonist. On 26 September 2024, the United States Food and Drug Administration (FDA) approved the oral co-formulation of xanomeline and trospium chloride for the treatment of schizophrenia in adults (Fabiano et al. ECNP 2025; 92, 62-73). Despite substantial advances in neuropsychopharmacology, the persistent underrepresentation of diverse demographic groups in clinical trials remains a widely acknowledged barrier to both scientific understanding and the equitable translation of research findings into clinical practice.
Objectives
The present cross-sectional analysis seeks to characterize the demographic composition of participants enrolled in clinical trials evaluating xanomeline–trospium, drawing upon publicly accessible data from ClinicalTrials.gov.
Methods
A comprehensive search of ClinicalTrials.gov was performed on the 26 April 2025 (see Figure 1). Trials were included if they met the following eligibility criteria: (1) interventional study design; (2) availability of published results on ClinicalTrials.gov; (3) a primary investigational focus on schizophrenia; and (4) classification as a phase 2, phase 3, or phase 4 clinical trial. For each eligible trial, data were extracted on the National Clinical Trial (NCT) identifier, total sample size, study site location, and participant demographic characteristics, including age, sex, race, and ethnicity.
Results
Five clinical trials conducted in the United States and Ukraine (n = 842) met the inclusion criteria. Black participants comprised 68.76% of the pooled sample, White participants 29.45%, and Asian participants 1.07%. Representation from other racial groups, including American Indian or Alaska Native, and Native Hawaiian or Other Pacific Islander, was negligible. At least 8.3% of participants identified as Hispanic or Latino, whereas no fewer than 70.43% were classified as Not Hispanic or Latino; ethnicity data were not reported for trial NCT03697252. Women accounted for 24.7% of participants, and the mean age across trials ranged from 42.5 to 45.9 years (see Table 1). Some trials did not provide complete demographic information.
Image 1: Long description.