A one-year study to assess if Xanomeline/Trospium (XT) can improve cognitive function in adults living with schizophrenia.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

European Group for Research in Schizophrenia Stichting

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Decision date (initial)

2026-03-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Bristol Myers-Squibb

External identifiers

EU CT number

2025-523060-20-00

ClinicalTrials.gov

NCT07084831

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess efficacy of XT on cognitive impairment.

Secondary objectives 1

1. To assess efficacy of XT in management of negative symptoms.

Conditions and MedDRA coding

Schizophrenia

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Be between 18 and 55 years of age.
2. 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.
3. Have a current DSM-5 diagnosis of schizophrenia, , which needs to be confirmed by MINI.
4. Have all PANSS positive items + G8 and G10 ≤4 at screening.
5. 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.
6. Have a SCIP total below 70.
7. 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.

Exclusion criteria 12

1. Be pregnant, lactating, or less than 3 months postpartum.
2. Present with an intellectual disability, drug-induced psychosis, or history of clinically significant brain trauma as per the judgement of the clinician.
3. 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.
4. 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. If these treatments are used at the screening visit, they must be tapered down before the baseline visit. NB. Stable use of mood stabilizers is allowed during the study. This is defined as being on the stable dosage for at least 4 weeks prior to baseline.
5. Having a known allergy to xanomeline, trospium chloride or any of the ingredients of XT.
6. Have clinically significant abnormal finding on the physical examination, medical history, ECG (at screening), or clinically significant laboratory results at screening.
7. Participated in any cognitive remediation/training program or completed the BACS within 4 weeks of Screening.
8. 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. b. 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. e. Active biliary disease (e.g., symptomatic gallstones). Participants with other biliary histories are eligible and should be discussed with the sponsor. f. Participants with a history of bladder stones. g. Participants with a history of recurrent urinary tract infections. h. For all male participants, serum prostate-specific antigen >10 ng/mL at screening. i. For male participants ≥ 45 years of age, an IPSS score of 5 (i.e, “almost always”) on items 1, 3, 5, or 6, and/or for male participants ≥ 45 years of age, an IPSS score ≥ 9 for the sum of items 1, 3, 5, and 6. j. An eGFR of < 60 mL/min (which indicates renal dysfunction). k. History of unstable hypertension or tachycardia as evidenced by a blood pressure of ≥ 160/100 mmHg at screening and/or a heart rate of ≥ 110 bpm at screening.
9. 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.
10. Currently meet DSM-5 criteria for a manic episode or major depressive disorder as confirmed by the MINI.
11. 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).
12. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline to week 24 in the BACS composite cognitive score.

Secondary endpoints 1

1. Change from baseline to week 24 in the PANSS negative subscale.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

European Group for Research in Schizophrenia Stichting

Sponsor organisation

European Group for Research in Schizophrenia Stichting

Address

Retstraat 13

City

Beneden-Leeuwen

Postcode

6658 DB

Country

Netherlands

Scientific contact point

Organisation

European Group for Research in Schizophrenia Stichting

Contact name

Dr. Inge Winter

Public contact point

Organisation

European Group for Research in Schizophrenia Stichting

Contact name

Dr. Inge Winter

Third parties 2

Locations

8 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 89 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications