An Open-label Study to Assess the Long-term Safety, Tolerability, and Efficacy of KarXT in Adult Patients With Schizophrenia (EMERGENT-5)

NCT04820309 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: CN012-0007KAR-011
• Study Type: interventional
• Target: 566
• Locations: 2 countries
• Sites: 117

Brief Summary

This is a Phase 3, multicenter, 56-week, outpatient, open-label (OL) study to evaluate the long-term safety, tolerability, and efficacy of KarXT in de novo subjects with Diagnostic and Statistical Manual-Fifth Edition (DSM-5) schizophrenia. In this OL study, all subjects will receive KarXT (a fixed combination of xanomeline 125 mg and trospium chloride 30 mg twice daily \[BID\]) for up to 52 weeks. The primary objective of the study is to assess the long-term safety and tolerability of KarXT in subjects with a DSM-5 diagnosis of schizophrenia. The secondary objective of this study is to assess the long-term efficacy and characterize the pharmacokinetics of xanomeline and trospium after administration of KarXT.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  TEAEs are defined as events with an onset date on or after the first dose of KarXT. An Adverse Event is any symptom, physical sign, syndrome, or disease that either emerges during the study or, if present at baseline, worsens during the study, regardless of the suspected cause of the event using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.

  From time of consent to end of study (approximately 400 days)

Secondary Outcomes (21)

• Number of Participants With Serious Treatment Emergent Adverse Events (STEAEs)

  From time of consent to end of study (approximately 400 days)

• Number of Participants With TEAE Leading to Study Drug Discontinuation

  From time of consent to end of study (approximately 400 days)

• Change From Baseline in PANSS Total Score at Week 52

  At baseline and week 52

• Change From Baseline in PANSS Positive Score at Week 52

  At baseline and week 52

• Change From Baseline in PANSS Negative Score at Week 52

  At baseline and week 52

Study Arms (1)

KarXT

EXPERIMENTAL

Drug: Xanomeline and Trospium Chloride Capsules

Interventions

Xanomeline and Trospium Chloride Capsules DRUG

Oral xanomeline 50 mg/trospium 20 mg BID on days 1-2 followed by xanomeline 100 mg/trospium 20 mg BID on days 3-7. The dose is increased to xanomeline 125 mg/trospium 30 mg BID on days 8-364 unless the subject is experiencing adverse events from the xanomeline 100 mg/ trospium 20 mg dose. Subjects who were increased to xanomeline 125 mg/trospium 30 mg will have the option to return to xanomeline 100 mg/ trospium 20 mg depending on clinical response and tolerability. Re-escalation to 125/30 BID or re-titration in cases in which the subject has been off KarXT for a longer period of time (at least a week) is allowed and will require a discussion between the principal investigator and the medical monitor.

Also known as: KarXT

KarXT

Eligibility Criteria

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

You may qualify if:

• Subject is aged 18 to 65 years at screening.
• Subject is capable of providing informed consent.
• A signed informed consent form (ICF) must be provided before any study assessments are performed.
• Subject must be fluent in (oral and written) the language of the ICGF to consent.
• Subject 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.
• Subject has not required psychiatric hospitalization, acute crisis intervention, or other increase in level of care due to symptom exacerbation within 8 weeks of screening and is psychiatrically stable in the opinion of the investigator.
• PANSS total score ≤ 80 at screening and Baseline Visit B (Day 0).
• Clinical Global Impression - Severity (CGI-S) score of ≤ 4 at screening and Baseline Visit B (Day 0).
• At the time of screening, or at any time within the 30 days prior to screening, the subject must have received an oral antipsychotic medication daily at a dose and frequency consistent with the drug label.
• In the opinion of the investigator, it is clinically appropriate for the subject to discontinue current antipsychotic therapy and initiate experimental treatment with KarXT.
• Subject is willing and able, in the opinion of the investigator, to discontinue all antipsychotic medications prior to baseline visit.
• Subject has an identified reliable informant willing to be able to address some questions related to certain study visits, if needed. An informant may not be necessary if the subject has been the patient of the investigator for ≥1 year.
• At Day 0, subject will have been off lithium therapy for at least 2 weeks and must have discontinued all oral antipsychotic medications.
• Subjects taking a long-acting injectable antipsychotic could not have received a dose of medication for at least 12 weeks (24 weeks for paliperidone palmitate) before Day 0.
• Body mass index must be ≥ 18 and ≤ 40 kg/m2.

You may not qualify if:

• Any primary DSM-5 disorder other than schizophrenia within 12 months before screening (confirmed using MINI version 7.0.2 at screening).
• Subject has a history of moderate to severe alcohol use disorder or a substance (other than nicotine or caffeine) use disorder within the past 12 months or a positive urine drug screen (UDS) for a substance other than cannabis at screening or baseline.
• History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or oncologic disease or any other condition that, in the opinion of the investigator, would jeopardize the safety of the subject or the validity of the study results
• Subject has human immunodeficiency virus (HIV), cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections based on either medical history or liver function test results.
• History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma
• History of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months
• Risk for suicidal behavior during the study as determined by the investigator's clinical assessment and Columbia-Suicide Severity Rating Scale (C-SSRS).
• Clinically significant abnormal finding from the physical examination, medical history, ECG, or clinical laboratory results at screening.
• Subjects cannot currently (within 5 half-lives before Day 0) be receiving monoamine oxidase inhibitors, anticonvulsants, tricyclic antidepressants, centrally active anticholinergics, or any other psychoactive medications other than daily antipsychotic maintenance therapy. As-needed anxiolytics and/or sleep aids are permitted. Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors taken at stable dose may be permitted.
• Subject has a history of treatment resistance to schizophrenia medications defined as failure to respond to 2 adequate courses of pharmacotherapy (a minimum of 4 weeks at an adequate dose per the label) within the past 12 months or having received clozapine within the past 3 years
• Pregnant, lactating, or less than 3 months postpartum.
• If, in the opinion of the investigator (and/or Sponsor), subject is unsuitable for enrollment in the study or subject has any finding that, in the view of the investigator (and/or Sponsor), may compromise the safety of the subject or affect his/her ability to adhere to the protocol visit schedule or fulfill visit requirements.
• Subjects has tested positive for coronavirus disease 2019 (COVID-19) within 2 weeks of screening.
• Subject has extreme concerns relating to global pandemics, such as COVID-19, that preclude study participation.
• Subject has had psychiatric hospitalization(s) for more than 30 days (cumulative) within the 6 months before screening.

Sponsors & Collaborators

• Karuna Therapeutics: lead

Study Sites (117)

Local Institution - 011-238

Little Rock, Arkansas, 72211-3702, United States

Location

Woodland International Research Group

Little Rock, Arkansas, 72211, United States

Location

Local Institution - 011-201

Rogers, Arkansas, 72758, United States

Location

Woodland Research Northwest

Rogers, Arkansas, 72758, United States

Location

Local Institution - 011-240

Anaheim, California, 92805-5854, United States

Location

Advanced Research Center, Inc.

Anaheim, California, 92805, United States

Location

Clinical Innovations, Inc

Bellflower, California, 90706, United States

Location

Local Institution - 011-222

Bellflower, California, 90706, United States

Location

Local Institution - 011-263

Bellflower, California, 90706, United States

Location

Local Institution - 011-257

Cerritos, California, 90703, United States

Location

ATP Clinical Research Inc

Costa Mesa, California, 92626, United States

Location

ATP Clinical Research, Inc.

Costa Mesa, California, 92626, United States

Location

Local Institution - 011-206

Culver City, California, 90230, United States

Location

ProScience Research Group

Culver City, California, 90230, United States

Location

Local Institution - 011-253

Garden Grove, California, 92845, United States

Location

Local Institution - 011-202

Glendale, California, 91206-4282, United States

Location

Behavioral Clinical Research, Inc.

Glendale, California, 91206, United States

Location

Omega Clinical Trials

La Habra, California, 90631-3842, United States

Location

Omega Clinical Trials

La Habra, California, 90631, United States

Location

Alliance for Wellness dba Alliance for Research

Long Beach, California, 90807, United States

Location

Alliance for Wellness

Long Beach, California, 90807, United States

Location

North County Clinical Research (NCCR)

Oceanside, California, 92054, United States

Location

Excell Research Inc

Oceanside, California, 92056, United States

Location

Local Institution - 011-229

Oceanside, California, 92056, United States

Location

Local Institution - 011-242

Orange, California, 92868, United States

Location

NRC Research Institute

Orange, California, 92868, United States

Location

CNRI-Los Angeles, LLC

Pico Rivera, California, 90660, United States

Location

Local Institution - 011-244

Pico Rivera, California, 90660, United States

Location

CITrials

Riverside, California, 92506, United States

Location

Local Institution - 011-233

Riverside, California, 92506, United States

Location

CITrials

Santa Ana, California, 92705, United States

Location

Local Institution - 011-251

Santa Rosa, California, 95401-4691, United States

Location

Siyan Clinical Research

Santa Rosa, California, 95401, United States

Location

Local Institution - 011-246

Sherman Oaks, California, 91403-1747, United States

Location

Schuster Medical Research Institute

Sherman Oaks, California, 91403, United States

Location

Collaborative Neuroscience Research

Torrance, California, 90502, United States

Location

Local Institution - 011-252

Torrance, California, 90504, United States

Location

Local Institution - 011-224

Hallandale, Florida, 33009, United States

Location

Velocity Clinical Research, Hallandale Beach

Hallandale, Florida, 33009, United States

Location

Local Institution - 011-261

Hollywood, Florida, 33024, United States

Location

Homestead Research Institute, Inc.

Homestead, Florida, 33030, United States

Location

Local Institution - 011-231

Homestead, Florida, 33030, United States

Location

Local Institution - 011-203

Miami, Florida, 33122-1335, United States

Location

Premier Clinical Research Institute

Miami, Florida, 33122, United States

Location

Central Miami Medical Institute

Miami, Florida, 33125, United States

Location

Local Institution - 011-215

Miami, Florida, 33125, United States

Location

Local Institution - 011-220

Miami, Florida, 33165, United States

Location

Phoenix Medical Research

Miami, Florida, 33165, United States

Location

Innovative Clinical Research

Miami Lakes, Florida, 33016, United States

Location

Local Institution - 011-234

Miami Lakes, Florida, 33016, United States

Location

Research Centers of America at Fort Lauderdale Behavioral Health Center

Oakland Park, Florida, 33334, United States

Location

Health Synergy Clinical Research

Okeechobee, Florida, 34972, United States

Location

Local Institution - 011-216

Okeechobee, Florida, 34972, United States

Location

Local Institution - 011-219

Pembroke Pines, Florida, 33024, United States

Location

Pines Care Research Center

Pembroke Pines, Florida, 33024, United States

Location

Local Institution - 011-262

West Palm Beach, Florida, 33407, United States

Location

Neuroscience Research Institute

West Palm Beach, Florida, 33407, United States

Location

Local Institution - 011-259

Atlanta, Georgia, 30328, United States

Location

Synexus Clinical Research US, Inc.

Atlanta, Georgia, 30328, United States

Location

Atlanta Center for Medical Research

Atlanta, Georgia, 30331, United States

Location

Local Institution - 011-237

Atlanta, Georgia, 30331, United States

Location

Local Institution - 011-235

Decatur, Georgia, 30030-2549, United States

Location

Local Institution - 011-204

Chicago, Illinois, 60640-5017, United States

Location

Uptown Research Institute

Chicago, Illinois, 60640, United States

Location

Local Institution - 011-223

Wichita, Kansas, 67214-2878, United States

Location

Ascension Via Christi Research

Wichita, Kansas, 67214, United States

Location

Local Institution - 011-205

Shreveport, Louisiana, 71101, United States

Location

Louisiana Clinical Research

Shreveport, Louisiana, 71101, United States

Location

CBH Health, LLC

Gaithersburg, Maryland, 20877, United States

Location

Local Institution - 011-211

Gaithersburg, Maryland, 20877, United States

Location

Local Institution - 011-232

Ann Arbor, Michigan, 48105-3205, United States

Location

Michigan Clinical Research Institute PC

Ann Arbor, Michigan, 48105, United States

Location

Local Institution - 011-226

Flowood, Mississippi, 39170, United States

Location

Precise Research Centers

Flowood, Mississippi, 39170, United States

Location

Local Institution - 011-227

Saint Charles, Missouri, 63304, United States

Location

Midwest Research Group - St. Charles Psychiatric Associates

Saint Charles, Missouri, 63304, United States

Location

St. Charles Psychiatric Associates/Midwest Research Group

Saint Charles, Missouri, 63304, United States

Location

Arch Clinical Trials

St Louis, Missouri, 63118, United States

Location

Local Institution - 011-241

St Louis, Missouri, 63141, United States

Location

Altea Research Institute

Las Vegas, Nevada, 89102, United States

Location

Local Institution - 011-239

Las Vegas, Nevada, 89102, United States

Location

Hassman Research Institute

Berlin, New Jersey, 08009, United States

Location

Local Institution - 011-230

Berlin, New Jersey, 08009, United States

Location

Hassman Research Institute

Marlton, New Jersey, 08053, United States

Location

Local Institution - 011-249

Marlton, New Jersey, 08053, United States

Location

Local Institution - 011-256

New York, New York, 10036, United States

Location

Manhattan Behavioral Medicine, PLLC

New York, New York, 10036, United States

Location

Local Institution - 011-210

New York, New York, 10128, United States

Location

The Medical Research Network, LLC

New York, New York, 10128, United States

Location

Finger Lakes Clinical Research

Rochester, New York, 14618, United States

Location

Local Institution - 011-250

Rochester, New York, 14618, United States

Location

Clinical Trials of America

Hickory, North Carolina, 28601, United States

Location

Local Institution - 011-218

Dayton, Ohio, 45417, United States

Location

Midwest Clinical Research Center

Dayton, Ohio, 45417, United States

Location

Local Institution - 011-248

North Canton, Ohio, 44720, United States

Location

Neuro-Behavioral Clinical Research, Inc

North Canton, Ohio, 44720, United States

Location

Cincy Science

West Chester, Ohio, 45069, United States

Location

Local Institution - 011-221

West Chester, Ohio, 45069, United States

Location

SP Research PLLC

Oklahoma City, Oklahoma, 73112, United States

Location

Suburban Research Associates

Media, Pennsylvania, 19063, United States

Location

Global Medical Institutes LLC Scranton Medical Institute

Moosic, Pennsylvania, 18507, United States

Location

Local Institution - 011-207

West Chester, Pennsylvania, 19380, United States

Location

Psychiatric Consultants

Franklin, Tennessee, 37067, United States

Location

Community Clinical Research

Austin, Texas, 78754, United States

Location

Local Institution - 011-243

Austin, Texas, 78754, United States

Location

BioBehavioral Research of Austin P.C.

Austin, Texas, 78759, United States

Location

BioBehavioral Research of Austin

Austin, Texas, 78759, United States

Location

InSite Clinical Research, LLC

DeSoto, Texas, 75115, United States

Location

Local Institution - 011-236

DeSoto, Texas, 75115, United States

Location

Local Institution - 011-258

Fort Worth, Texas, 76104, United States

Location

Core Clinical Research

Richmond, Texas, 77407, United States

Location

healthTx

Richmond, Texas, 77407, United States

Location

Cedar Clinical Research

Draper, Utah, 84020, United States

Location

Local Institution - 011-209

Bellevue, Washington, 98007-4879, United States

Location

Northwest Clinical Research Center

Bellevue, Washington, 98007, United States

Location

Local Institution - 011-260

Everett, Washington, 98201, United States

Location

INSPIRA Clinical Research

San Juan, PR, 918, Puerto Rico

Location

Related Links

• BMS Clinical Trial Information
• FDA Safety Alerts and Recalls
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Schizophrenia

Interventions

xanomeline; trospium chloride

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

1-855-907-3286

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

• Inder Kaul, MD

  Karuna Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2021
• First Posted: March 29, 2021
• Study Start: June 2, 2021
• Primary Completion: May 24, 2024
• Study Completion: May 24, 2024
• Last Updated: September 17, 2025
• Results First Posted: September 17, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

PR (1); US (116)