NCT07084831

A Study Evaluating the Efficacy of Xanomeline/Trospium (XT) on Cognitive Impairment After 24 and 52 Weeks of Treatment in Adult Participants With Schizophrenia

A Prospective, Open-label, Single-arm, Multicenter Study Evaluating the Efficacy of Xanomeline/Trospium (XT) on Cognitive Impairment After 24 and 52 Weeks of Treatment in Adult Participants With Schizophrenia

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 171 (estimated)
• Sponsor: European Group for Research In Schizophrenia · Academic / Other
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Not accepted

Summary

Schizophrenia is a long-lasting and serious mental health disorder that affects about 1% of people worldwide. It can cause symptoms such as hallucinations and delusions (called positive symptoms), confused or disorganized thinking, reduced motivation and emotional expression (negative symptoms), difficulties with memory and concentration (cognitive symptoms), and movement problems like restlessness or slowed activity. Current treatments, called antipsychotics, mainly work by blocking dopamine in the brain. These medicines are helpful for hallucinations and delusions, but they do little to improve negative or cognitive symptoms. A new medicine, Xanomeline/Trospium (XT), works differently. It targets a brain system called the muscarinic acetylcholine receptors while limiting side effects elsewhere in the body. Clinical trials have shown that XT reduces psychotic symptoms effectively and is generally well tolerated. The FDA approved XT in 2024 for adults with schizophrenia. Importantly, early results also suggest that XT may help improve thinking and memory (cognition domains), though this has not yet been studied in depth. Most schizophrenia drug studies pay little attention to long-term changes in cognition, often using only short screening tests. This study will be the first to take a deep look at cognitive function over a full year of XT treatment. It will also examine how changes in thinking skills connect with other aspects of life, such as symptom control, daily functioning, and quality of life. By making cognition a central outcome, the study responds to an urgent need in schizophrenia research: moving beyond just controlling hallucinations and delusions toward improving real-world recovery. The results could help shape future treatment strategies and support the idea that cognition should be a core treatment target in schizophrenia.

Detailed description

This is a phase III, prospective, open-label, single-arm, international, multicenter study. At visit 1, the informed consent is signed and screening is performed to confirm eligibility. At visit 2, baseline measures are performed, and the new treatment is initiated. Max. 14 days after the baseline visit, the pre-study antipsychotic treatment is withdrawn via tapering. At visit 3, 4, 5, 7 and 9 participants' general wellbeing and safety is assessed. At visit 6, 8 and 10, baseline measures are repeated. Between visit 6-7, visit 7-8, visit 8-9 and visit 9-10, a phone call is planned to assess general psychopathology, adverse events and concomitant medication. The treatment duration is one year for each participant; with a safety follow up 4 weeks after the end of the trial. All participants are treated with XT open label.

Conditions

• Schizophrenia; Psychosis
• Cognitive Impairment

Interventions

Type	Name	Description
DRUG	Xanomeline/trospium	Participants will receive oral xanomeline/trospium during the trial (target dose 125/30 BID).

Timeline

• Start date: 2026-01-14
• Primary completion: 2028-01-01
• Completion: 2028-07-01
• First posted: 2025-07-25
• Last updated: 2026-03-03

Locations

16 sites across 10 countries: Austria, Belgium, Czechia, Denmark, Germany, Hungary, Israel, Italy, Netherlands, Spain