SCHIZOPHRENIA 1 (Disorder)Phase 1/2NCT07423546
A PET/MRI Study of Cobenfy on Dopamine Transmission in Schizophrenia
A Phase 1/2 study testing Xanomeline and trospium chloride (KarXT) in people with SCHIZOPHRENIA 1 (Disorder) and Schizoaffecitve Disorder, run by New York State Psychiatric Institute at 1 site in United States.
Trial summary
This is a single site clinical trial in which 12 participants with schizophrenia will be randomized to one of three doses of treatment with Cobenfy for 5 weeks. [18F]DOPA PET scans will be obtained before and after treatment to examine the effects of Cobenfy on dopamine transmission. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- SCHIZOPHRENIA 1 (Disorder), Schizoaffecitve Disorder
- What is being tested?
- Xanomeline and trospium chloride (KarXT)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2026to 31 Dec 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Individuals aged 18 to 50, inclusive at screen
- Capable of understanding the study procedures and able to provide informed consent
- Diagnosed with schizophrenia, schizoaffective, or schizophreniform disorder
- Antipsychotic free at Visit 1 (by choice and for reasons unrelated to the study), and for at least 3 weeks (4 for aripiprazole, Cobenfy or LAIs) at the time of the baseline PET scan, inclusive of any antipsychotic-free time prior to consent
- PANSS total score > 80 and < 120
- Willing to use qualified methods of contraception (listed in section 5.3) for the study duration (for women of childbearing potential only)
- Stable dosing of herbal/dietary supplements for at least 6 weeks at the time of the first dose of Cobenfy and willingness to avoid products with known hepatotoxic ingredients (e.g., green tea extract, kratom, ashwagandha).
Who cannot join
- Diagnosis of moderate or severe substance use disorder within the previous month (from first PET scan)
- A history of poor or inadequate response to Cobenfy for any reason, hypersensitivity to Cobenfy or trospium or no justifiable reason to expect improvement on Cobenfy, or treatment with Cobenfy within 4 weeks of the first PET Scan
- EKG abnormality that is clinically significant including a QT interval > 450 msec for men and > 470 msec for women, as corrected by the Fridericia formula (QTcF)
- Pregnant or breast-feeding women. Women of child-bearing potential must have a negative serum β-hCG pregnancy test at Visit 1, must have been using an acceptable method of contraception (section 5.3) for 30 days before the study, and must agree to do so for the whole study and 30 days after (unless post-menopausal or surgically sterile)
- Any clinically significant or unstable medical illness, condition, or disorder that is anticipated to potentially compromise participant safety on study medication, including (but not necessarily limited to) the following: urinary retention, moderate or severe hepatic impairment, gastric retention, untreated narrow-angle glaucoma, hypernasality, resting heart rate >100 bpm or systolic Blood Pressure >150 mmHg, a history of orthostatic hypotension or abnormal orthostatic blood pressure (change in mean arterial pressure [1/3 systolic + 2/3 diastolic] of > 20% between supine and standing blood pressures), known human immunodeficiency virus (i.e., by history), cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, symptomatic gallstone disease, active hepatic infections, history of bladder stones, recurrent urinary tract infections, or International Prostate Symptom Score > 7 or any one item > 2 (not including the nocturia item).
- Any material in the body that is a contraindication for MRI procedures or participated in prior nuclear medicine procedures in the past year that exceed FDA-defined limits when combined with radiation dosimetry from PET scanning in this protocol to avoid exceeding annual dosimetry limits (metal screener repeated before MRI scan during visit 2)
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- Participants with suicidal ideation with intent or plan (indicated by affirmative answers to items 4 or 5 of the Suicidal Ideation section of the baseline C-SSRS) in the past 1 month or suicidal behavior in the past 3 months
- Laboratory abnormality that would compromise the well-being of the participant, including Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value > 2 times the upper limit of the laboratory normal reference range, elevated bilirubin (i.e., >2 x upper limit of normal (ULN)), or serum prostate specific antigen (PSA) >10 ng/ml (for men only).
- A history of treatment resistance to antipsychotics
- Use of nicotine products within the previous month (prior to first PET scan)
- History of significant violent behavior when antipsychotic-free or currently homicidal
- Positive toxicology screen for any substances of abuse
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
New York State Psychiatric Institute
New York, New York, 10032
About this study
Official title: A Multimodal PET/MRI Study of Cobenfy on Dopamine Transmission in Schizophrenia
This is a single site clinical trial in which 12 participants with schizophrenia will be randomized to one of three doses of treatment with Cobenfy for 5 weeks. [18F]DOPA PET scans will be obtained before and after treatment to examine the effects of Cobenfy on dopamine transmission.
The overall objective of the current study is to measure Cobenfy's ability to engage its putative target (DA transmission/synthesis capacity in the striatum and midbrain as measured by [18F]DOPA Kicer ([18F]DOPA relative uptake rate)).
- Being tested
- Xanomeline and trospium chloride (KarXT)
- Keywords
- Cobenfy, PET, MRI
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Xanomeline and trospium chloride (KarXT)Drug
Also called Cobenfy
Subjects will be randomized to 5 weeks of low, middle, or high dose of Xanomeline and trospium chloride, and will complete a PET scan with [18]F DOPA at the beginning and end of the treatment period.
| Study group | Role | What they receive |
|---|---|---|
| Xanomeline 50 mg and trospium chloride 20mg (KarXT) | Experimental | 5 weeks of xanomeline 50mg/trospium 20mg bid (low dose arm). Receives: Drug: Xanomeline and trospium chloride (KarXT) |
| Xanomeline 100 mg and trospium chloride 20mg (KarXT) | Experimental | 5 weeks of xanomeline 100mg/trospium 20mg bid (middle dose arm). Receives: Drug: Xanomeline and trospium chloride (KarXT) |
| Xanomeline 125 mg and trospium chloride 30mg (KarXT) | Experimental | 5 weeks of xanomeline 125mg/trospium 30mg bid (high dose arm). Receives: Drug: Xanomeline and trospium chloride (KarXT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
[18F]DOPA Kicer ([18F]DOPA relative uptake rate)
Measured: Pre/post 5 weeks of Xanomeline and trospium chloride (KarXT)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2026
- Study start1 Jul 2026
- Primary completion30 Apr 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SCHIZOPHRENIA 1 (Disorder)Studies 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 1/2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Principal investigator, Joshua Kantrowitz, New York State Psychiatric Institute
- Investigators
- Joshua T Kantrowitz, MD, Principal investigator, New York State Psychiatric InstituteRagy Girgis, MD, Principal investigator, New York State Psychiatric Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07423546
- Sponsor's protocol ID
- NYSPI2025-158
- Status last verified
- Jul 2026
- First submitted
- 13 Feb 2026
- Last updated
- 14 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Data may be shared with direct and valid request.
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multimodal PET/MRI Study of Cobenfy on Dopamine Transmission in Schizophrenia
- ClinicalTrials.gov ID
- NCT07423546
- Acronym / sponsor ID
- NYSPI2025-158
- Keywords
- Cobenfy, PET, MRI
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 1 Jul 2026 (actual)
- Primary completion
- 30 Apr 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 20 Feb 2026 (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.
This is a single site clinical trial in which 12 participants with schizophrenia will be randomized to one of three doses of treatment with Cobenfy for 5 weeks. [18F]DOPA PET scans will be obtained before and after treatment to examine the effects of Cobenfy on dopamine transmission.
The overall objective of the current study is to measure Cobenfy's ability to engage its putative target (DA transmission/synthesis capacity in the striatum and midbrain as measured by [18F]DOPA Kicer ([18F]DOPA relative uptake rate)).
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Xanomeline 50 mg and trospium chloride 20mg (KarXT) | Experimental | Drug: Xanomeline and trospium chloride (KarXT)5 weeks of xanomeline 50mg/trospium 20mg bid (low dose arm). |
| Xanomeline 100 mg and trospium chloride 20mg (KarXT) | Experimental | Drug: Xanomeline and trospium chloride (KarXT)5 weeks of xanomeline 100mg/trospium 20mg bid (middle dose arm). |
| Xanomeline 125 mg and trospium chloride 30mg (KarXT) | Experimental | Drug: Xanomeline and trospium chloride (KarXT)5 weeks of xanomeline 125mg/trospium 30mg bid (high dose arm). |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Individuals aged 18 to 50, inclusive at screen
- Capable of understanding the study procedures and able to provide informed consent
- Diagnosed with schizophrenia, schizoaffective, or schizophreniform disorder
- Antipsychotic free at Visit 1 (by choice and for reasons unrelated to the study), and for at least 3 weeks (4 for aripiprazole, Cobenfy or LAIs) at the time of the baseline PET scan, inclusive of any antipsychotic-free time prior to consent
- PANSS total score > 80 and < 120
Key exclusion criteria (12 listed)
- Diagnosis of moderate or severe substance use disorder within the previous month (from first PET scan)
- A history of poor or inadequate response to Cobenfy for any reason, hypersensitivity to Cobenfy or trospium or no justifiable reason to expect improvement on Cobenfy, or treatment with Cobenfy within 4 weeks of the first PET Scan
- EKG abnormality that is clinically significant including a QT interval > 450 msec for men and > 470 msec for women, as corrected by the Fridericia formula (QTcF)
- Pregnant or breast-feeding women. Women of child-bearing potential must have a negative serum β-hCG pregnancy test at Visit 1, must have been using an acceptable method of contraception (section 5.3) for 30 days before the study, and must agree to do so for the whole study and 30 days after (unless post-menopausal or surgically sterile)
- Any clinically significant or unstable medical illness, condition, or disorder that is anticipated to potentially compromise participant safety on study medication, including (but not necessarily limited to) the following: urinary retention, moderate or severe hepatic impairment, gastric retention, untreated narrow-angle glaucoma, hypernasality, resting heart rate >100 bpm or systolic Blood Pressure >150 mmHg, a history of orthostatic hypotension or abnormal orthostatic blood pressure (change in mean arterial pressure [1/3 systolic + 2/3 diastolic] of > 20% between supine and standing blood pressures), known human immunodeficiency virus (i.e., by history), cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, symptomatic gallstone disease, active hepatic infections, history of bladder stones, recurrent urinary tract infections, or International Prostate Symptom Score > 7 or any one item > 2 (not including the nocturia item).
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 and trospium chloride (KarXT)Also: CobenfySubjects will be randomized to 5 weeks of low, middle, or high dose of Xanomeline and trospium chloride, and will complete a PET scan with [18]F DOPA at the beginning and end of the treatment period. | Drug | Xanomeline 100 mg and trospium chloride 20mg (KarXT), Xanomeline 125 mg and trospium chloride 30mg (KarXT), Xanomeline 50 mg and trospium chloride 20mg (KarXT) |
Primary outcome
[18F]DOPA Kicer ([18F]DOPA relative uptake rate)
Time frame: Pre/post 5 weeks of Xanomeline and trospium chloride (KarXT)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2026.
- Individual participant dataSharing planned: Undecided. Data may be shared with direct and valid request.
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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.
Joshua T Kantrowitz, MD principal investigator
New York State Psychiatric Institute
Ragy Girgis, MD principal investigator
New York State Psychiatric Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Xanomeline and trospium chloride (KarXT) in people with SCHIZOPHRENIA 1 (Disorder) and Schizoaffecitve Disorder, run by New York State Psychiatric Institute at 1 site in United States.
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 12 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: looking for participants now, as of the sponsor's last update on 14 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Shannon Peleg (646-774-8477, shannon.peleg@nyspi.columbia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
[18F]DOPA Kicer ([18F]DOPA relative uptake rate) (time frame: Pre/post 5 weeks of Xanomeline and trospium chloride (KarXT)). 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 14 Jul 2026.