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
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.
• Be between 18 and 55 years of age.
• Be willing and able to provide informed consent, after the nature of the study has been fully explained. This includes being able to understand the locally approved informed consent (and information letter) in the local language.
• Have a current DSM-5 diagnosis of schizophrenia, which needs to be confirmed by MINI.
• Have all PANSS positive items + G8 and G10 ≤4 at screening.
• Be on a stable dose of oral antipsychotic medication(s) for at least 4 weeks prior to Screening. Participants should be on monotherapy oral AP for baseline visit.
• Have a SCIP total below 70.
• Test negative for pregnancy at the screening visit and must be using a highly effective contraceptive method during the study and 30 days after the study, if being a female of childbearing potential.