Efficacy of Xanomeline/Trospium in Adults with Schizophrenia for the Treatment of Cognitive Impairment: A Prospective Multicenter Study
- Trial ID
- 2025-523060-20-00
- Protocol
- SHINE
Trial statistics
Objectives
The primary objective of this study is to evaluate the efficacy of xanomeline/trospium in addressing cognitive impairment associated with schizophrenia. The secondary objectives include:
- Assessment of efficacy in the management of negative symptoms.
Participants
This study involves a total of 11 patients diagnosed with schizophrenia. The study population includes both males and females between the ages of 18 and 55. Participants must have a current diagnosis confirmed by the Mini-International Neuropsychiatric Interview. Eligible individuals are required to maintain a stable dose of oral antipsychotic medication monotherapy for a minimum of four weeks prior to screening. Key requirements include a Scale for the Assessment of Negative Symptoms total score consistent with specific clinical parameters and a Scale for Cognitive Impairment in Psychosis score below 70. Females of childbearing potential must demonstrate a negative pregnancy test and utilize highly effective contraception. The primary objective is to evaluate the efficacy of the investigational product on cognitive impairment.
Plans and Procedures
This prospective, open-label, single-arm, multicenter study is designed to evaluate the efficacy of xanomeline/trospium in addressing cognitive impairment in adults diagnosed with schizophrenia. The research methodology involves a phase 5 clinical trial design. Following a screening visit to confirm the diagnosis using the Mini International Neuropsychiatric Interview and to assess baseline positive and negative syndrome scale scores, participants will receive oral capsules of the investigational product. The primary endpoint is the change from baseline to week 24 in the Brief Assessment of Continuous Performance composite cognitive score. Secondary endpoints include changes in the negative subscale of the syndrome scale. The total duration of participant involvement is expected to extend up to 52 weeks, with assessments conducted at 24 and 52 weeks. Participants must maintain a stable dose of antipsychotic medication and adhere to specific contraceptive requirements to remain in the study.
Treatment
The experimental medication, KarXT, is an oral capsule containing two active substances: xanomeline tartrate and trospium chloride. This investigational product is administered in doses of 100 mg, 200 mg, or 250 mg.
Efficacy
The efficacy of xanomeline/trospium is evaluated in participants with schizophrenia. The primary endpoint is the change from baseline to week 24 in the Brief Assessment of Cognition in Schizophrenia (BACS) composite cognitive score.
Secondary efficacy assessment includes the change from baseline to week 24 in the Positive and Negative Syndrome Scale (PANSS) negative subscale.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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.
- 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.
Exclusion Criteria
- Be pregnant, lactating, or less than 3 months postpartum.
- 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. 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.
- Having a known allergy to xanomeline, trospium chloride or any of the ingredients of XT.
- 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.
- 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.
- 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Not Yet Recruiting | 01 Jan 2026 | 11 |
 Belgium | Not Yet Recruiting | 01 Jan 2026 | 15 |
 Czechia | Not Yet Recruiting | 01 Jan 2026 | 11 |
 Denmark | Not Yet Recruiting | 01 Jan 2026 | 11 |
 Germany | Not Yet Recruiting | 01 Jan 2026 | 36 |
 Hungary | Not Yet Recruiting | 01 Jan 2026 | 11 |
 Italy | Not Yet Recruiting | 01 Jan 2026 | 23 |
 The Netherlands | Not Yet Recruiting | 01 Jan 2026 | — |
 Spain | Not Yet Recruiting | 01 Jan 2026 | 30 |
| Netherlands | — | — | 12 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
KarXT | Test | CAPSULE | ORAL | 200 | 52 | PRD12327577 |
KarXT | Test | CAPSULE | ORAL | 100 | 52 | PRD12327546 |
KarXT | Test | CAPSULE | ORAL | 250 | 52 | PRD12327584 |