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

NCT ID: NCT04820309

Last Updated: 2025-09-17

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

566 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-06-02

Study Completion Date

2024-05-24

Brief Summary

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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.

Detailed Description

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Conditions

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Schizophrenia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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KarXT

Group Type EXPERIMENTAL

Xanomeline and Trospium Chloride Capsules

Intervention Type 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.

Interventions

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Xanomeline and Trospium Chloride Capsules

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.

Intervention Type DRUG

Other Intervention Names

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KarXT

Eligibility Criteria

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Inclusion Criteria

1. Subject is aged 18 to 65 years at screening.
2. Subject is capable of providing informed consent.

1. A signed informed consent form (ICF) must be provided before any study assessments are performed.
2. Subject must be fluent in (oral and written) the language of the ICGF to consent.
3. 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.
4. 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.
5. PANSS total score ≤ 80 at screening and Baseline Visit B (Day 0).
6. Clinical Global Impression - Severity (CGI-S) score of ≤ 4 at screening and Baseline Visit B (Day 0).
7. 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.
8. In the opinion of the investigator, it is clinically appropriate for the subject to discontinue current antipsychotic therapy and initiate experimental treatment with KarXT.
9. Subject is willing and able, in the opinion of the investigator, to discontinue all antipsychotic medications prior to baseline visit.
10. 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.
11. At Day 0, subject will have been off lithium therapy for at least 2 weeks and must have discontinued all oral antipsychotic medications.
12. 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.
13. Body mass index must be ≥ 18 and ≤ 40 kg/m2.
14. Subject resides in a stable living situation and is anticipated to remain in a stable living situation for the duration of study enrollment, in the opinion of the investigator.
15. Women of childbearing potential or men with sexual partners of childbearing potential must be willing and able to use at least 1 highly effective method of contraception during the study and for at least 30 days after the last dose of KarXT. Sperm donation is not allowed for 30 days after the final dose of KarXT.

Exclusion Criteria

1. Any primary DSM-5 disorder other than schizophrenia within 12 months before screening (confirmed using MINI version 7.0.2 at screening).
2. 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.
3. 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
4. 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.
5. History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma
6. History of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months
7. Risk for suicidal behavior during the study as determined by the investigator's clinical assessment and Columbia-Suicide Severity Rating Scale (C-SSRS).
8. Clinically significant abnormal finding from the physical examination, medical history, ECG, or clinical laboratory results at screening.
9. 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.
10. 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
11. Pregnant, lactating, or less than 3 months postpartum.
12. 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.
13. Subjects has tested positive for coronavirus disease 2019 (COVID-19) within 2 weeks of screening.
14. Subject has extreme concerns relating to global pandemics, such as COVID-19, that preclude study participation.
15. Subject has had psychiatric hospitalization(s) for more than 30 days (cumulative) within the 6 months before screening.
16. Subject has prior exposure to KarXT.
17. Risk of violent or destructive behavior.
18. Current involuntary hospitalization or incarceration.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Karuna Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Inder Kaul, MD

Role: STUDY_DIRECTOR

Karuna Therapeutics

Locations

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Local Institution - 011-238

Little Rock, Arkansas, United States

Site Status

Woodland International Research Group

Little Rock, Arkansas, United States

Site Status

Local Institution - 011-201

Rogers, Arkansas, United States

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Woodland Research Northwest

Rogers, Arkansas, United States

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Local Institution - 011-240

Anaheim, California, United States

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Advanced Research Center, Inc.

Anaheim, California, United States

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Clinical Innovations, Inc

Bellflower, California, United States

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Local Institution - 011-222

Bellflower, California, United States

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Local Institution - 011-263

Bellflower, California, United States

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Local Institution - 011-257

Cerritos, California, United States

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ATP Clinical Research Inc

Costa Mesa, California, United States

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ATP Clinical Research, Inc.

Costa Mesa, California, United States

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Local Institution - 011-206

Culver City, California, United States

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ProScience Research Group

Culver City, California, United States

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Local Institution - 011-253

Garden Grove, California, United States

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Local Institution - 011-202

Glendale, California, United States

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Behavioral Clinical Research, Inc.

Glendale, California, United States

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Omega Clinical Trials

La Habra, California, United States

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Omega Clinical Trials

La Habra, California, United States

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Alliance for Wellness dba Alliance for Research

Long Beach, California, United States

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Alliance for Wellness

Long Beach, California, United States

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North County Clinical Research (NCCR)

Oceanside, California, United States

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Excell Research Inc

Oceanside, California, United States

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Local Institution - 011-229

Oceanside, California, United States

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Local Institution - 011-242

Orange, California, United States

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NRC Research Institute

Orange, California, United States

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CNRI-Los Angeles, LLC

Pico Rivera, California, United States

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Local Institution - 011-244

Pico Rivera, California, United States

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CITrials

Riverside, California, United States

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Local Institution - 011-233

Riverside, California, United States

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CITrials

Santa Ana, California, United States

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Local Institution - 011-251

Santa Rosa, California, United States

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Siyan Clinical Research

Santa Rosa, California, United States

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Local Institution - 011-246

Sherman Oaks, California, United States

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Schuster Medical Research Institute

Sherman Oaks, California, United States

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Collaborative Neuroscience Research

Torrance, California, United States

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Local Institution - 011-252

Torrance, California, United States

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Local Institution - 011-224

Hallandale, Florida, United States

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Velocity Clinical Research, Hallandale Beach

Hallandale, Florida, United States

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Local Institution - 011-261

Hollywood, Florida, United States

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Homestead Research Institute, Inc.

Homestead, Florida, United States

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Local Institution - 011-231

Homestead, Florida, United States

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Local Institution - 011-203

Miami, Florida, United States

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Premier Clinical Research Institute

Miami, Florida, United States

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Central Miami Medical Institute

Miami, Florida, United States

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Local Institution - 011-215

Miami, Florida, United States

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Local Institution - 011-220

Miami, Florida, United States

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Phoenix Medical Research

Miami, Florida, United States

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Innovative Clinical Research

Miami Lakes, Florida, United States

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Local Institution - 011-234

Miami Lakes, Florida, United States

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Research Centers of America at Fort Lauderdale Behavioral Health Center

Oakland Park, Florida, United States

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Health Synergy Clinical Research

Okeechobee, Florida, United States

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Local Institution - 011-216

Okeechobee, Florida, United States

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Local Institution - 011-219

Pembroke Pines, Florida, United States

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Pines Care Research Center

Pembroke Pines, Florida, United States

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Local Institution - 011-262

West Palm Beach, Florida, United States

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Neuroscience Research Institute

West Palm Beach, Florida, United States

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Local Institution - 011-259

Atlanta, Georgia, United States

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Synexus Clinical Research US, Inc.

Atlanta, Georgia, United States

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Atlanta Center for Medical Research

Atlanta, Georgia, United States

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Local Institution - 011-237

Atlanta, Georgia, United States

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Local Institution - 011-235

Decatur, Georgia, United States

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Local Institution - 011-204

Chicago, Illinois, United States

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Uptown Research Institute

Chicago, Illinois, United States

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Local Institution - 011-223

Wichita, Kansas, United States

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Ascension Via Christi Research

Wichita, Kansas, United States

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Local Institution - 011-205

Shreveport, Louisiana, United States

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Louisiana Clinical Research

Shreveport, Louisiana, United States

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CBH Health, LLC

Gaithersburg, Maryland, United States

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Local Institution - 011-211

Gaithersburg, Maryland, United States

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Local Institution - 011-232

Ann Arbor, Michigan, United States

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Michigan Clinical Research Institute PC

Ann Arbor, Michigan, United States

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Local Institution - 011-226

Flowood, Mississippi, United States

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Precise Research Centers

Flowood, Mississippi, United States

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Local Institution - 011-227

Saint Charles, Missouri, United States

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Midwest Research Group - St. Charles Psychiatric Associates

Saint Charles, Missouri, United States

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St. Charles Psychiatric Associates/Midwest Research Group

Saint Charles, Missouri, United States

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Arch Clinical Trials

St Louis, Missouri, United States

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Local Institution - 011-241

St Louis, Missouri, United States

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Altea Research Institute

Las Vegas, Nevada, United States

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Local Institution - 011-239

Las Vegas, Nevada, United States

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Hassman Research Institute

Berlin, New Jersey, United States

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Local Institution - 011-230

Berlin, New Jersey, United States

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Hassman Research Institute

Marlton, New Jersey, United States

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Local Institution - 011-249

Marlton, New Jersey, United States

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Local Institution - 011-256

New York, New York, United States

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Manhattan Behavioral Medicine, PLLC

New York, New York, United States

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Local Institution - 011-210

New York, New York, United States

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The Medical Research Network, LLC

New York, New York, United States

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Finger Lakes Clinical Research

Rochester, New York, United States

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Local Institution - 011-250

Rochester, New York, United States

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Clinical Trials of America

Hickory, North Carolina, United States

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Local Institution - 011-218

Dayton, Ohio, United States

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Midwest Clinical Research Center

Dayton, Ohio, United States

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Local Institution - 011-248

North Canton, Ohio, United States

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Neuro-Behavioral Clinical Research, Inc

North Canton, Ohio, United States

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Cincy Science

West Chester, Ohio, United States

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Local Institution - 011-221

West Chester, Ohio, United States

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SP Research PLLC

Oklahoma City, Oklahoma, United States

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Suburban Research Associates

Media, Pennsylvania, United States

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Global Medical Institutes LLC Scranton Medical Institute

Moosic, Pennsylvania, United States

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Local Institution - 011-207

West Chester, Pennsylvania, United States

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Psychiatric Consultants

Franklin, Tennessee, United States

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Community Clinical Research

Austin, Texas, United States

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Local Institution - 011-243

Austin, Texas, United States

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BioBehavioral Research of Austin P.C.

Austin, Texas, United States

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BioBehavioral Research of Austin

Austin, Texas, United States

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InSite Clinical Research, LLC

DeSoto, Texas, United States

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Local Institution - 011-236

DeSoto, Texas, United States

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Local Institution - 011-258

Fort Worth, Texas, United States

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Core Clinical Research

Richmond, Texas, United States

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healthTx

Richmond, Texas, United States

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Cedar Clinical Research

Draper, Utah, United States

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Local Institution - 011-209

Bellevue, Washington, United States

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Northwest Clinical Research Center

Bellevue, Washington, United States

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Local Institution - 011-260

Everett, Washington, United States

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INSPIRA Clinical Research

San Juan, PR, Puerto Rico

Site Status

Countries

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United States Puerto Rico

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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CN012-0007

Identifier Type: OTHER

Identifier Source: secondary_id

KAR-011

Identifier Type: OTHER

Identifier Source: secondary_id

CN012-0007

Identifier Type: -

Identifier Source: org_study_id

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