Xanomeline-trospium was found to significantly improve symptom severity of patients with schizophrenia, according to results from a phase 3 clinical trial presented at Psych Congress 2022 held from September 17 to 20, 2022.
This first-in-class therapy combines xanomeline, a dual M1/M4 muscarinic receptor agonist, with trospium, a restricted muscarinic receptor antagonist. The EMERGENT-2 study (ClinicalTrials.gov Identifier: NCT04659161) is a phase 3, randomized, double-blind, placebo-controlled, 5-week trial studying the efficacy of xanomeline-trospium in patients with schizophrenia. Patients (N=252) with schizophrenia experiencing symptoms of psychosis were randomly assigned 1:1 to receive either xanomeline-trospium 50 mg/20 mg twice daily, titrating to a maximum of 125 mg/30 mg, or placebo (n=126). The primary endpoint was change in Positive and Negative Syndrome Scale (PANSS) score from baseline, and key secondary endpoints included change from baseline to week 5 in PANSS positive score, PANSS negative score, PANSS negative Marder factor score, and Clinical Global Impression-Severity (CGI-S) scores.
The investigational and control cohorts were primarily men (75.4% vs 75.4%, respectively) and Black (77.0% vs 73.0%, respectively). At baseline, participants were a mean age of 45.6 and 46.2 years with PANSS total scores of 98.3 and 97.9, respectively.
At week 5, a clinically meaningful reduction in PANSS total score was observed among participants who received xanomeline-trospium compared with placebo (mean difference [MD], -21.2 vs -11.6 points; P <.0001). A significant group difference in PANSS total scores were observed as early as week 2 of treatment.
Participants who were xanomeline-trospium also experienced a 2.9-point greater reduction in PANSS positive subscale score (-6.8 vs -3.9, respectively; P <.0001), 1.8-point greater reduction in PANSS negative subscale score (-3.4 vs -1.6, respectively; P =.0055), and 2.2-point greater reduction in PANSS negative Marder factor subscale score (-4.2 vs -3.0, respectively; P =.0022) compared with participants who received placebo.
Treatment-emergent adverse events (TEAEs) occurred among 75% of xanomeline-trospium recipients and 58% of placebo recipients; discontinuation due to TEAEs occurred among 7% and 6% of recipients, respectively. The most frequently-reported TEAEs included constipation, dyspepsia, nausea, vomiting, headache, increased blood pressure, dizziness, acid reflux, abdominal discomfort, and diarrhea. Xanomeline-trospium was not associated with common problematic side effects seen in other therapies for patients with schizophrenia (somnolence, weight gain, extrapyramidal symptoms).
The major limitation of this study was a short treatment duration. Additional trials are needed to address the long-term treatment outcomes.
Study authors concluded, “[Xanomeline-trospium] has the potential to be the first in a new class of treatments for patients with schizophrenia.”
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
This article originally appeared on Psychiatry Advisor.
Correll CU, Miller AC, Sawchak S, Kaul I, Paul SM, Brannan SK. Safety and efficacy of KARxt (xanomeline–trospium) in patients with schizophrenia: results from a phase 3, randomized, double-blind, placebo-controlled trial (EMERGENT-2). Poster abstract presented at: Psych Congress 2022; September 17-20, 2022; New Orleans, LA. Poster 28.