Schizophrenia; PsychosisPhase 3SHINENCT07084831
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 Phase 3 study testing Xanomeline/trospium in people with Schizophrenia; Psychosis and Cognitive Impairment, run by European Group for Research In Schizophrenia at 16 sites in 10 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Schizophrenia; Psychosis, Cognitive Impairment
- What is being tested?
- Xanomeline/trospium
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 16 sitesin 10 countries
- Study dates
- 1 Jan 2027to 1 Jul 2029
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 18Show fewer
- 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:
- 12a. 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]).
- 12c. 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.
- 12d. 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.
- 12f. Participants with a history of bladder stones . 12g. Participants with a history of recurrent urinary tract infections. 12h. For all male participants, serum prostate-specific antigen >10 ng/mL at screening.
- 12i. 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.
- 12j. An eGFR of < 60 mL/min (which indicates renal dysfunction). 12k. 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.
Trial locations and contacts
16 sites in 10 countries.
16 sites in 10 countries
Germany4 sites
University of Augsburg
Augsburg, 86156
University Hospital Cologne
Cologne, 50937
Central Institute of Mental Health
Mannheim, 68159
Ludwig Maximilian University
München, 80336
Spain3 sites
Hospital Clínic de Barcelona
Barcelona, 08036
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitario Virgen del Rocío
Seville, 41013
Italy2 sites
University of Campania Luigi Vanvitelli
Naples, 80138
AOU Città della Salute e della Scienza di Torino
Torino, 10126
About this study
Official title: 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.
Read the 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
- Being tested
- Xanomeline/trospium
- Keywords
- functioning, quality of life, speech analyses
- Medical subject headings
- Schizophrenia, Psychotic Disorders, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Xanomeline/trospiumDrug
Also called KarXT/Cobenfy
Participants will receive oral xanomeline/trospium during the trial (target dose 125/30 BID).
| Study group | Role | What they receive |
|---|---|---|
| Xanomeline/trospium | Experimental | Xanomeline/trospium that is provided to all participants Receives: Drug: Xanomeline/trospium |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 24 weeks
Secondary outcomes (1)
Change in negative symptoms after 24 weeks of treatment, relative to baseline.
The within-participant change in the Positive And Negative Syndrome Scale (PANSS) negative subscale from baseline to follow-up after 24 weeks. A higher score means more schizophrenia-related symptoms. The maximum score is 49.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2025
- Study start1 Jan 2027 (estimated)
- Primary completion1 Jan 2029 (estimated)
- Study completion1 Jul 2029 (estimated)
Why it stopped: Ethical committee in Europe did not provide approval
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Schizophrenia; PsychosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Drug: Xanomeline/trospium
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- European Group for Research In Schizophrenia
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb, University Medical Center Groningen
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07084831
- Sponsor's protocol ID
- 2025-523060-20-00
- Other IDs
- 2025
- Acronym
- SHINE
- Status last verified
- Oct 2026
- First submitted
- 23 Jul 2025
- Last updated
- 30 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Our Publication Policy is as follows: researchers can submit a request to receive the data. The Study Management Team will review and approve when appropriate. After having put into place the Data Transfer Agreement (plus Standard Contractual Clauses if receiving party is based outside the EU), the data can be shared through a secure, encrypted data sharing platform.
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07084831
- Acronym / sponsor ID
- SHINE / 2025-523060-20-00
- Conditions
- Schizophrenia; Psychosis, Cognitive Impairment
- Keywords
- functioning, quality of life, speech analyses
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Ethical committee in Europe did not provide approval
- Enrolment
- 0 participants (actual)
- Lead sponsor
- European Group for Research In SchizophreniaUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb, University Medical Center Groningen
- Study start
- 1 Jan 2027 (estimated)
- Primary completion
- 1 Jan 2029 (estimated)
- Study completion
- 1 Jul 2029 (estimated)
- First posted
- 25 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Drug: Xanomeline/trospium
| Arm | Type | Receives |
|---|---|---|
| Xanomeline/trospium | Experimental | Drug: Xanomeline/trospiumXanomeline/trospium that is provided to all participants |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Xanomeline/trospiumAlso: KarXT/CobenfyParticipants will receive oral xanomeline/trospium during the trial (target dose 125/30 BID). | Drug | Xanomeline/trospium |
Primary outcome
Change in cognitive performance after 24 weeks of treatment, relative to baseline.
Time frame: 24 weeks
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).
1 secondary outcome
Change in negative symptoms after 24 weeks of treatment, relative to baseline.
Time frame: 24 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2026.
- Individual participant dataSharing planned: Yes. Our Publication Policy is as follows: researchers can submit a request to receive the data. The Study Management Team will review and approve when appropriate. After having put into place the Data Transfer Agreement (plus Standard Contractual Clauses if receiving party is based outside the EU), the data can be shared through a secure, encrypted data sharing platform.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
16 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Xanomeline/trospium in people with Schizophrenia; Psychosis and Cognitive Impairment, run by European Group for Research In Schizophrenia at 16 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 30 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Germany, Spain, Italy, Austria, Belgium and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in cognitive performance after 24 weeks of treatment, relative to baseline. (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2026.