An Open-Label Study to Evaluate the Efficacy and Tolerability of Xanomeline/Trospium In First Episode/Early Phase Schizophrenia Patients

NCT06923891 | Not Yet Recruiting Phase 4 FDA Drug

• 1 other identifier: FEP Cobenfy
• Study Type: interventional
• Target: 172
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label study of the treatment satisfaction, efficacy and tolerability of xanomeline/ trospium in a population of 172 participants diagnosed with schizophrenia in the early phase of illness. Participants will be followed for 24 weeks with scheduled assessments conducted by centralized raters, local mental health professionals and self-assessments completed by patients. Recruitment will be based on insufficient efficacy of previous antipsychotic or due to dissatisfaction with treatment as a result of unacceptable side effects on previous antipsychotic/patient choice, with approximately 50% for each enrollment criteria. Participants who present with both insufficient efficacy and unacceptable side effects will be considered as belonging to the insufficient efficacy subgroup. Treatment and assessments will be identical for the 2 groups. Primary outcome for participants enrolled will be improvement in overall treatment satisfaction as measured by the MSQ.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Medication Satisfaction Questionnaire (MSQ)

  Change in total MSQ from baseline to week 12

  12 weeks

Secondary Outcomes (8)

• Positive and Negative Syndrome Scale (PANSS)

  12 weeks

• Clinical Global Impression - Severity Scale (CGI-S)

  12 weeks

• Treatment Satisfaction Questionnaire for Medication (TSQM)

  12 weeks

• Personal and social performance scale (PSP)

  12 weeks

• All cause discontinuation

  12 weeks

Study Arms (1)

Xanomeline/Trospium

ACTIVE COMPARATOR

Cobenfy

Drug: Xanomeline/Trospium

Interventions

Xanomeline/Trospium DRUG

Xanomeline/Trospium (titrated dose)

Also known as: Cobenfy

Xanomeline/Trospium

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participant is aged 18-40 years, inclusive, at time of signing the ICF
• Participant has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the DSM-5 (American Psychiatric Association 2013) criteria and confirmed by Mini International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorder Studies (MINI) version 7.0.2.
• Participant Scores MSQ ≤3 for the Medication Satisfaction Questionnaire (MSQ)
• Within 5 years of first antipsychotic treatment for psychosis at time of signing ICF
• Clinical reason to seek a change in antipsychotic treatment due to psychosis symptom severity, it is clinically appropriate for the participant to seek a change in antipsychotic treatment due to psychosis symptom severity, adverse effects, both, or overall patient judgement/choice.
• Symptom Severity Criteria:
• Clinical reasons include Positive and Negative Syndrome Scale (PANSS) total score of ≤ 120 at screening if participant is experiencing inefficacy from current antipsychotic treatment and
• A score of ≥ 4 (moderate or greater) for ≥ 1 of the following PANSS Positive Subscale (P) items: i. Item 1 (P1; delusions), ii. Item 2 (P2; conceptual disorganization), iii. Item 3 (P3; hallucinatory behavior), iv. Item 6 (P6; suspiciousness/persecution) and
• A Clinical Global Impressions-Severity scale (CGI-S) score of ≥ 4 at screening and baseline visits.
• Adverse Event or Overall Patient Choice Criteria:
• A score of \<4 for all the following PANSS Positive Subscale (P) items: i. Item 1 (P1; delusions), ii. Item 2 (P2; conceptual disorganization), iii. Item 3 (P3; hallucinatory behavior), iv. Item 6 (P6; suspiciousness/persecution)
• Participant Scores MSQ ≤3 for the Medication Satisfaction Questionnaire (MSQ)Clinical reason to seek a change in antipsychotic treatment due to adverse effects or overall patient judgement/choice.
• Upon screening, the treatment plan is for outpatient level of care. Transition to inpatient level of care after enrollment does not exclude the patient from participating in the study
• a. Anticholinergic drugs (e.g., benztropine) are allowed at baseline but need to be washed out during cross titration within 1 week after initiating xanomeline/trospium.
• Subject can provide informed consent. A signed informed consent form must be provided before any study assessments are performed. Subject must be fluent (oral and written) in English to consent. Female participants must be willing and capable to use birth control throughout the time of the trial as defined in Section 3.1.3

You may not qualify if:

• Any DSM-5 disorder other than schizophrenia within 6 months before screening (confirmed using MINI version 7.0.2 at screening) requiring clinical attention.
• Active substance or alcohol abuse or dependence in the past 6 months (cannabis use is allowed if not fulfilling abuse criteria)
• Urine toxicology screen is positive for phencyclidine, amphetamines, opiates, cocaine, or alcohol (clinically significant alcohol use in the opinion of the Investigator)
• Developmental disorder or intellectual disability
• History of serious suicide attempt within the past 6 months
• Risk of suicidal behavior as determined by the Investigator's clinical assessment. Lifetime history of clinically significant head trauma, or current history of other acute or serious medical condition or
• History or presence of clinically significant cardiovascular (eg, untreated or unstable hypertension, clinically significant tachycardia), pulmonary, renal, hematologic, gastrointestinal (\[GI\] 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.
• Active biliary disease (eg, symptomatic gallstones). Participants with other biliary histories are eligible and should be discussed with the medical monitor
• History or high risk of urinary retention, gastric retention,
• Untreated narrow-angle glaucoma
• An estimated glomerular filtration rate (eGFR) of \< 60 mL/min at the screening visit.
• Elevations in hepatic transaminases at screening ≥ 3× ULN for ALT and AST and/or ≥ 2× ULN for total bilirubin
• History of hypersensitivity or prior exposure to xanomeline/trospium or trospium chloride
• History of any significant drug allergy (such as anaphylaxis or hepatotoxicity).
• Intellectual disability or autism spectrum disorder (by history)

Sponsors & Collaborators

• Vanguard Research Group: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Clinical Site

Richmond, Texas, 77407, United States

Location

Related Publications (1)

• Howes OD, McCutcheon R, Agid O, de Bartolomeis A, van Beveren NJ, Birnbaum ML, Bloomfield MA, Bressan RA, Buchanan RW, Carpenter WT, Castle DJ, Citrome L, Daskalakis ZJ, Davidson M, Drake RJ, Dursun S, Ebdrup BH, Elkis H, Falkai P, Fleischacker WW, Gadelha A, Gaughran F, Glenthoj BY, Graff-Guerrero A, Hallak JE, Honer WG, Kennedy J, Kinon BJ, Lawrie SM, Lee J, Leweke FM, MacCabe JH, McNabb CB, Meltzer H, Moller HJ, Nakajima S, Pantelis C, Reis Marques T, Remington G, Rossell SL, Russell BR, Siu CO, Suzuki T, Sommer IE, Taylor D, Thomas N, Ucok A, Umbricht D, Walters JT, Kane J, Correll CU. Treatment-Resistant Schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology. Am J Psychiatry. 2017 Mar 1;174(3):216-229. doi: 10.1176/appi.ajp.2016.16050503. Epub 2016 Dec 6.

  PMID: 27919182 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Schizophrenia

Interventions

xanomeline; trospium chloride

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Central Study Contacts

Patricia Marcy

CONTACT

9043020811; pmarcy@northwell.edu

Cristina Gonzalez

CONTACT

3478043605; cgomes@northwell.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2025
• First Posted: April 11, 2025
• Study Start: April 16, 2025
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: April 11, 2025

Record last verified: 2025-04

Locations

US (1)