An 8-week Open-label Study of an Accelerated and Slower Switching to Xanomeline/Trospium Following Atypical Antipsychotic Treatment in Participants With Schizophrenia

NCT06924255 | Not Yet Recruiting Phase 4 FDA Drug

• 1 other identifier: CN012-0079
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 7

Brief Summary

The study design is a de-escalation of current atypical AP treatment to X/T at a maintenance dose of X/T established either at 100 mg xanomeline/20 mg trospium chloride BID (total daily dose 200 mg xanomeline/40 mg trospium chloride) or 125 mg xanomeline/30 mg trospium chloride BID (total daily dose 250 mg xanomeline/60 mg trospium chloride) based on participants' clinical response and/or tolerability. While the package insert for X/T provides guidance for clinicians on dosing, this study is designed to assess how transitioning will occur in the "real world" situation.

Conditions

Schizophrenia Disorders

Keywords

Schizophrenia

Outcome Measures

Primary Outcomes (1)

• discontinuation rate of accelerated and slower switching of atypical antipsychotic (AP) treatment to xanomeline and trospium chloride (X/T)

  To evaluate all-cause X/T discontinuation rate of accelerated and slower switching of atypical antipsychotic (AP) treatment to xanomeline and trospium chloride (X/T) over a period of 8 weeks

  8 weeks

Secondary Outcomes (2)

• evaluate the effectiveness of switching outpatients from standard atypical AP treatment to X/T

  8 weeks

• evaluate the safety and tolerability of X/T following switch from atypical AP

  8 weeks

Study Arms (2)

accelerated transition

OTHER

accelerated transition arm will reduce the atypical AP treatment at a rate of 50% of the initial treatment over a 2-week period,

Drug: Xanomeline and Trospium Chloride

slower transition

OTHER

slower transition arm will reduce the atypical AP treatment at a rate of 25% of the initial treatment over a 4-week period

Drug: Xanomeline and Trospium Chloride

Interventions

Xanomeline and Trospium Chloride DRUG

accelerated titration of Xanomeline and Trospium Chloride

accelerated transition; slower transition

Eligibility Criteria

• Age: 18 Years - 65 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is aged 18 to 65 years, inclusive, at Screening.
• Participant is capable of providing informed consent.
• A signed informed consent form (ICF) must be provided before any study assessments are performed.
• Participant must be fluent in English (oral and written) as the language of the ICF to consent. No translations will be permitted.
• Participant has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (American Psychiatric Association 2013) criteria and confirmed by MINI for Schizophrenia and Psychotic Disorder Studies version 7.0.2.
• Participant has not required psychiatric hospitalization, acute crisis intervention, or other increase in level of care due to symptom exacerbation within 12 weeks of Screening and is psychiatrically stable in the opinion of the Investigator.
• PANSS Total Score of ≤80 at Screening and Baseline Visits.
• a. Score of ≤4 for the following core Positive Subscale items on PANSS: i. Item 2 (P2): Conceptual disorganization ii. Item 7 (P7): Hostility
• CGI-S score of ≤4 at Screening and Baseline Visits.
• Participant must be judged by the Investigator to be an appropriate candidate for transitioning from current oral AP medication due to safety or tolerability concerns and/or insufficient efficacy.
• Participant must be currently treated with one of the following selected atypical oral AP at the same dosing regimen at package insert specified dose range for schizophrenia for ≥6 weeks:
• Risperidone
• Paliperidone
• Aripiprazole
• Ziprasidone

You may not qualify if:

• Participant has a history of moderate to severe alcohol use disorder or a substance (other than nicotine or caffeine) use disorder within the past 6 months or a positive urine drug screen (UDS) for a substance other than cannabis at Screening or Baseline.
• Participants with mild substance use disorder within the 6 months before Screening must be discussed and agreed upon with the Principal Investigator (PI) before they can be allowed into the study.
• Participants with positive UDS for cannabis are permitted to enroll in the study provided that the participants' pattern of use is not indicative of a substance use disorder.
• Urine toxicology screen positive for phencyclidine, amphetamines, opiates, cocaine, or alcohol (clinically significant alcohol use in the opinion of the Investigator).
• History or presence of clinically significant cardiovascular (e.g., 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.
• Participant with cirrhosis, biliary duct abnormalities, and/or hepatobiliary carcinoma based on either medical history or liver function test results.
• All grades of hepatic impairment (mild \[Child-Pugh Class A\], moderate \[Child-Pugh Class B\], and severe \[Child-Pugh Class C\]).
• History or high risk of urinary retention or gastric retention.
• History of narrow-angle glaucoma.
• History of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months.
• Clinically significant abnormal finding on the physical examination, medical history, or clinical laboratory results at Screening.
• An eGFR of \< 60 mL/min
• Elevations in hepatic transaminases at screening ≥3× ULN for ALT and AST and/or bilirubin \> 2× ULN, unless in the context of Gilbert's syndrome
• History of unstable hypertension or tachycardia as evidenced by:
• Blood pressure of ≥160/100 mmHg (single seated measure) at screening

Sponsors & Collaborators

• Collaborative Neuroscience Research, LLC: lead
• Bristol-Myers Squibb: collaborator

Study Sites (7)

CenExel CIT LA

Bellflower, California, 90706, United States

Location

CenExel CNS - Garden Grove

Garden Grove, California, 92845, United States

Location

CenExel CIT IE

Riverside, California, 92506, United States

Location

CenExel CNS - Torrance

Torrance, California, 90504, United States

Location

CenExel RCA

Hollywood, Florida, 33024, United States

Location

CenExel CBH

Gaithersburg, Maryland, 20877, United States

Location

CenExel HRI Marlton

Marlton, New Jersey, 08053, United States

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

xanomeline; trospium chloride

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: Open label

Study Record Dates

• First Submitted: March 31, 2025
• First Posted: April 11, 2025
• Study Start: April 1, 2025
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: April 11, 2025

Record last verified: 2025-04

Locations

US (7)