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

NCT07084831 | Recruiting Phase 3 DMC

• 1 other identifier: 2025-523060-20-00
• Study Type: interventional
• Target: 171
• Locations: 10 countries
• Sites: 16

Brief 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.

Conditions

Schizophrenia; Psychosis; Cognitive Impairment

Keywords

functioning; quality of life; speech analyses

Outcome Measures

Primary Outcomes (1)

• Change in cognitive performance after 24 weeks of treatment, relative to baseline.

  The within-participant change in the Brief Assessment of Cognition in Schizophrenia composite cognitive score from baseline to follow-up after 24 weeks. Higher score means better cognition. There is no max score, as the tests have different scoring methods (number correct, reaction time).

  24 weeks

Secondary Outcomes (1)

• Change in negative symptoms after 24 weeks of treatment, relative to baseline.

  24 weeks

Other Outcomes (23)

• Change in Functional Skills assessment and training (FUNSAT) scores for ATM banking, ticket kiosk, and medication management after 12, 24 and 52 weeks of treatment, relative to baseline.

  12, 24 and 52 weeks

• Change in Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS) between baseline and week 24

  24 weeks

• Change in Subjective Scale to Investigate Social Cognition Scale scores (MRMET) between baseline and week 24

  24 weeks

Study Arms (1)

Xanomeline/trospium

EXPERIMENTAL

Xanomeline/trospium that is provided to all participants

Drug: Xanomeline/trospium

Interventions

Xanomeline/trospium DRUG

Participants will receive oral xanomeline/trospium during the trial (target dose 125/30 BID).

Also known as: KarXT/Cobenfy

Xanomeline/trospium

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• Be pregnant, lactating, or less than 3 months postpartum.
• Be at significant risk of committing suicide. This is defined as: participants with active suicidal ideation with some intent to act, without specific plan ("Yes" to question 4 of the Columbia-Suicide Severity Rating Scale (C-SSRS) or active suicidal ideation with specific plan and intent ("Yes" to question 5 of the C-SSRS), followed by an assessment by the treating clinician who determines it is not safe for the participant to participate in the study.
• Currently meet DSM-5 criteria for a manic episode or major depressive disorder as confirmed by the MINI.
• Currently meeting DSM-5 criteria for severe substance and/or alcohol use disorder as confirmed by the MINI (≥6 on module K for alcohol use disorder and/or ≥6 on module J for substance use disorder, unless being in early or sustained remission).
• Have a positive urine toxicology for phencyclidine, amphetamines, opiates (unless participant has a valid prescription for short-term use), cocaine, or alcohol (clinically significant alcohol use in the opinion of the Investigator). Nicotine and caffeine use is allowed. Stimulants and cannabis is allowed when used sporadically and recreationally as per the judgement of the clinician.
• Present with an intellectual disability, drug-induced psychosis, or history of clinically significant brain trauma as per the judgement of the clinician.
• Have current or past use of clozapine (used for at least 6 weeks in an effective dose range) and/or current use of a long-acting injectable antipsychotic, or anticholinergic treatment that cannot be discontinued before the baseline visit.
• Be expected to require more than the allowed psychotropic concomitant medication during the study (from baseline on). This is defined as: needing benzodiazepines of more than 2 mg lorazepam equivalent (daily), quetiapine, antidepressants, mood stabilizers or benzodiazepines at a dose exceeding the allowed threshold. If these treatments are used at the screening visit, they must be tapered down before the baseline visit.
• Have clinically significant abnormal finding on the physical examination, medical history, ECG (at screening), or clinically significant laboratory results at screening.
• Participated in any cognitive remediation/training program or completed the BACS within 4 weeks of Screening.
• Having a known allergy to xanomeline, trospium chloride or any of the ingredients of XT.
• Have current presence of clinically significant cardiovascular, pulmonary, renal, hematologic, gastrointestinal (e.g., obstructive disorders \[including conditions that may decrease GI motility, such as ulcerative colitis, intestinal atony, and myasthenia gravis\], endocrine, immunologic, dermatologic, neurologic, or oncologic disease or any other condition that, in the opinion of the investigator, would jeopardize the safety of the participant or the validity of the study results. This includes:
• a. Have history or high risk of urinary retention. 12b. All grades of hepatic impairment (mild \[Child-Pugh Class A\], moderate \[Child-Pugh Class B\], and severe \[Child-Pugh Class C\]).
• c. Elevations in hepatic transaminases at screening ≥ 2× ULN for ALT and AST and/or bilirubin \> 2 × ULN, unless in the context of Gilbert's syndrome.
• d. Have a history or high risk for narrow-angle glaucoma. 12e. Active biliary disease (e.g., symptomatic gallstones). Participants with other biliary histories are eligible and should be discussed with the sponsor.

Sponsors & Collaborators

• European Group for Research In Schizophrenia: lead
• Bristol-Myers Squibb: collaborator
• University Medical Center Groningen: collaborator

Study Sites (16)

Medical University Innsbruck

Innsbruck, 6020, Austria

NOT YET RECRUITING

UPC KU Leuven

Leuven, 3070, Belgium

NOT YET RECRUITING

National Institute of Mental Health

Klecany, 250 67, Czechia

NOT YET RECRUITING

Psykiatrisk Center Glostrup

Glostrup Municipality, 2600, Denmark

NOT YET RECRUITING

University of Augsburg

Augsburg, 86156, Germany

NOT YET RECRUITING

University Hospital Cologne

Cologne, 50937, Germany

NOT YET RECRUITING

Central Institute of Mental Health

Mannheim, 68159, Germany

NOT YET RECRUITING

Ludwig Maximilian University

München, 80336, Germany

NOT YET RECRUITING

Semmelweis University

Budapest, 1083, Hungary

NOT YET RECRUITING

Sheba Medical Center

Ramat Gan, Israel

RECRUITING

University of Campania Luigi Vanvitelli

Naples, 80138, Italy

NOT YET RECRUITING

AOU Città della Salute e della Scienza di Torino

Torino, 10126, Italy

NOT YET RECRUITING

University Medical Center Groningen

Groningen, Netherlands

NOT YET RECRUITING

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

NOT YET RECRUITING

Hospital Universitario La Paz

Madrid, 28046, Spain

NOT YET RECRUITING

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

NOT YET RECRUITING

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; Cognitive Dysfunction

Interventions

xanomeline; trospium chloride

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Cognition Disorders; Neurocognitive Disorders

Central Study Contacts

Inge Winter, Dr.

CONTACT

+31614674276; i.winter-vanrossum@umcg.nl

Cynthia C Okhuijsen, Dr.

CONTACT

+31652385871; c.okhuijsen-pfeifer@umcg.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Drug: Xanomeline/trospium

Study Record Dates

• First Submitted: July 23, 2025
• First Posted: July 25, 2025
• Study Start: January 14, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: March 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: To be determined
• Access Criteria: See publication policy described above.

Locations

IL (1); DK (1); IT (2); ES (3); AU (1); CZ (1); DE (4); NL (1); BE (1); HU (1)