Poster
78
(#78) Efficacy and Safety of Strategies for Switching to Xanomeline and Trospium Chloride From Standard of Care Atypical Antipsychotics: Design of an Open-Label Trial in People With Schizophrenia
Psych Congress 2025
Abstract: Background: The dual M1/M4 muscarinic receptor agonist xanomeline combined with the pan-muscarinic receptor antagonist trospium chloride is approved by the U.S. Food and Drug Administration for treatment of schizophrenia in adults. Evidence-based guidance on safely and effectively switching from standard-of-care atypical antipsychotics (AAs) to xanomeline/trospium (X/T) is needed. This is the first study to evaluate switching from AAs to an approved muscarinic compound.
Methods: The 8-week, open-label, multicenter, outpatient trial (NCT06924255) will assess the efficacy, safety, and tolerability of X/T in adults with schizophrenia switching from AAs. Approximately 100 adults aged 18-65 years with a primary diagnosis of schizophrenia, stable symptoms, stable oral AA regimen for ≥6 weeks, and baseline scores of ≤80 on the Positive and Negative Syndrome Scale (PANSS) and ≤4 on the Clinical Global Impression-Severity (CGI-S) scale will be enrolled. Exclusion criteria include history of antipsychotic therapy resistance, psychiatric hospitalization >30 days within 12 months of screening, and prior xanomeline or trospium exposure. The design employs oral AA therapy de-escalation and X/T titration to a therapeutic dose. Following a ≤2-week screening period, participants will be randomized to either an accelerated (by week 2) or slower (by week 4) cross-titration switch with X/T treatment for up to 8 weeks. Safety follow-up will occur 1 week post treatment.
Results: The primary endpoint is all-cause discontinuation. Secondary endpoints include adverse events incidence and change from baseline in PANSS total, CGI-S, and Personal and Social Performance scale scores.
Conclusion: Results will inform clinical decision-making when switching from oral AAs to X/T.
Short Description: Xanomeline combined with trospium chloride is approved by the U.S. Food and Drug Administration for schizophrenia treatment in adults, representing a new class of medications for this population. Evidence-based guidance on safely and effectively switching from standard-of-care atypical antipsychotics to X/T are needed to inform clinical decision-making. This planned 8-week, open-label, multicenter, outpatient trial will assess the efficacy, safety, and tolerability of X/T in adults with schizophrenia switching from atypical
Name of Sponsoring Organization(s): Bristol Myers Squibb
Methods: The 8-week, open-label, multicenter, outpatient trial (NCT06924255) will assess the efficacy, safety, and tolerability of X/T in adults with schizophrenia switching from AAs. Approximately 100 adults aged 18-65 years with a primary diagnosis of schizophrenia, stable symptoms, stable oral AA regimen for ≥6 weeks, and baseline scores of ≤80 on the Positive and Negative Syndrome Scale (PANSS) and ≤4 on the Clinical Global Impression-Severity (CGI-S) scale will be enrolled. Exclusion criteria include history of antipsychotic therapy resistance, psychiatric hospitalization >30 days within 12 months of screening, and prior xanomeline or trospium exposure. The design employs oral AA therapy de-escalation and X/T titration to a therapeutic dose. Following a ≤2-week screening period, participants will be randomized to either an accelerated (by week 2) or slower (by week 4) cross-titration switch with X/T treatment for up to 8 weeks. Safety follow-up will occur 1 week post treatment.
Results: The primary endpoint is all-cause discontinuation. Secondary endpoints include adverse events incidence and change from baseline in PANSS total, CGI-S, and Personal and Social Performance scale scores.
Conclusion: Results will inform clinical decision-making when switching from oral AAs to X/T.
Short Description: Xanomeline combined with trospium chloride is approved by the U.S. Food and Drug Administration for schizophrenia treatment in adults, representing a new class of medications for this population. Evidence-based guidance on safely and effectively switching from standard-of-care atypical antipsychotics to X/T are needed to inform clinical decision-making. This planned 8-week, open-label, multicenter, outpatient trial will assess the efficacy, safety, and tolerability of X/T in adults with schizophrenia switching from atypical
Name of Sponsoring Organization(s): Bristol Myers Squibb
