Long-term xanomeline-trospium chloride combo safe, effective in adults with schizophrenia

Treatment with xanomeline and trospium chloride (X/T) over 52 weeks appears safe and well tolerated, demonstrating durable symptom improvements in individuals with schizophrenia, reports a study. 

A total of 366 participants completed the EMERGENT-2 or EMERGENT-3 trials were enrolled in this open-label extension trial (EMERGENT-4). Between February 2021 and October 2023, 152 participants initiated twice-daily oral doses of xanomeline 50 mg/trospium 20 mg, which were titrated to a maximum dose of twice-daily oral xanomeline 125 mg/trospium 30 mg. 

The primary endpoint was the proportion of participants reporting a treatment-emergent adverse event (TEAE), while efficacy measured included Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impressions severity scale (CGI-S). 

Of the treated participants, 81 (53.3 percent) had at least one TEAE. The most frequent treatment-related adverse events were gastrointestinal disorders (eg, nausea, vomiting, dyspepsia, dry mouth), which were mild or moderate in severity and resolved with continued treatment. New safety or tolerability issues were not reported. 

X/T showed no significant association with motor symptoms, hyperprolactinemia, weight gain, or adverse effects on metabolic parameters, but it correlated with continued symptom improvement over 52 weeks. 

In the acute trials, mean changes in PANSS total score from baseline to week 52 were ‒33.8 in the X/T group and ‒31.3 in the placebo group. Similar patterns of continued improvement were also seen for scores on the CGI-S, PANSS positive subscale, and PANSS negative subscale. 

“X/T reduced symptoms and was generally well tolerated in two phase III, 5-week, randomized, double-blind, placebo-controlled trials in adults with schizophrenia,” the authors said.