A Study to Assess Efficacy and Safety of Adjunctive KarXT in Subjects With Inadequately Controlled Symptoms of Schizophrenia

NCT ID: NCT05145413

Last Updated: 2025-03-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

396 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-12

Study Completion Date

2025-03-19

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This is a Phase 3, 6-week, randomized, double-blind, placebo-controlled, multicenter, outpatient study in subjects with schizophrenia with an inadequate response to their current atypical antipsychotic treatment. The primary objective of the study is to assess the efficacy of adjunctive KarXT (a fixed dose combination of xanomeline and trospium chloride twice daily \[BID\]) versus placebo in the treatment of subjects with inadequately controlled symptoms of schizophrenia as measured by the Positive and Negative Syndrome Scale (PANSS) Total Score.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Schizophrenia

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Drug: KarXT

Group Type EXPERIMENTAL

Xanomeline and Trospium Chloride Capsules

Intervention Type DRUG

KarXT 50 mg/20 mg BID KarXT 75mg/20 mg BID KarXT 100mg/20 mg BID KarXT 125mg/30 mg BID

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo Capsules

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Xanomeline and Trospium Chloride Capsules

KarXT 50 mg/20 mg BID KarXT 75mg/20 mg BID KarXT 100mg/20 mg BID KarXT 125mg/30 mg BID

Intervention Type DRUG

Placebo

Placebo Capsules

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Subject is aged ≥18 to \<65 years at the time of randomization
2. Subject is capable of providing signed Informed Consent Form before any study assessments will be performed
3. Subject has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the DSM-5 criteria and confirmed by Mini International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorder Studies (MINI) version 7.0.2
4. Subject is currently being treated with stable dosing of monotherapy risperidone, paliperidone, aripiprazole, or their LAIs ziprasidone, lurasidone, or cariprazine and has been taking this treatment with the same dosing regimen for at least 8 weeks at the time of Day 1 (Visit 3)
5. The subject has had at least 1 previous inadequate response to above antipsychotics that was dosed appropriately (within the label) for at least 6 weeks
6. The subject has not required psychiatric hospitalization, incarceration in prison, acute crisis intervention, or other increase in the level of care due to symptom exacerbation within 8 weeks of Screening and is psychiatrically stable in the opinion of the Investigator
7. To be eligible for randomization, subjects need to have detectable levels of background antipsychotic medication (measured at Visit 1)
8. Positive and Negative Syndrome Scale (PANSS) total score ≥ 70 at Screening and randomization
9. Clinical Global Impression-Severity (CGI-S) scale with a score ≥ 4 (moderate) at Screening and randomization
10. PANSS Marder Positive symptom factor ≥ 4 on 2 (or more) items (PANSS items, delusions, hallucinations, grandiosity, suspiciousness and persecution, stereotyped thinking, somatic concern, unusual thought content or lack of judgment and insight), at Screening and randomization
11. Subjects with ≤ 20-point decrease in PANSS Total score between Visit 1 and Visit 3
12. Subject is willing and able to visit the clinic in an outpatient setting for the study duration, follow instructions, and comply with the protocol requirements
13. Body Mass Index (BMI) must be within 18 to 40 kg/m2 (inclusive of both values)
14. Subject resides in a stable living situation in the opinion of the Investigator
15. Subject has identified a reliable informant/ caregiver willing and able to assist with study activities as needed throughout the subject's participation in the study. The informant needs to be physically present at the Baseline visit, but can complete the remaining study visits assessments via phone (as needed and as per local regulations). In Bulgaria, the informant needs to physically present at the Baseline visit and should be physically present at all study visits where the Investigator determines that his/her input would be beneficial.
16. Women of childbearing potential (WOCP), or men whose sexual partners are WOCP, must be able and willing to use at least 1 highly effective method of contraception during the study and for at least 1 menstrual cycle (e.g., 30 days) after the last dose of study drug. Sperm donation is not allowed for 30 days after the final dose of the study drug. A female subject is considered to be a WOCP after menarche and until she is in a postmenopausal state for 12 months or otherwise permanently sterile (for which acceptable methods include hysterectomy, bilateral salpingectomy, or bilateral oophorectomy)

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. The subject has a history of moderate to severe substance use disorder (other than nicotine) within the past 12 months

1. A Screening subject with mild substance use disorder within the 12 months before Screening must be discussed with the Medical Monitor before being allowed into the study
2. Subjects who test positive for cannabis at Screening may be permitted to enroll in consultation with the Medical Monitor if the subject's pattern of use is not indicative of a moderate to severe substance use disorder
3. Subject has a history of treatment-resistant schizophrenia defined as:

a. Failure to minimally respond to 2 adequate courses of antipsychotic drug (APD) pharmacotherapy Note: Failure to minimally respond is defined as persistence symptoms of moderate severity in 2 or more psychotic symptom domains or persistence of severe symptoms in 1 or more psychotic symptom domains despite adequate dose and duration (6 weeks or longer) of APD treatment.
4. History of symptom instability

a. \> 3 psychiatric hospitalizations over the last 12 months or 2 over the last 6 months
5. Current APD is other than aripiprazole, risperidone, paliperidone, or their LAI versions, ziprasidone, lurasidone, or cariprazine
6. Subjects who are diagnosed with schizophreniform disorder or are experiencing their first treated episode of schizophrenia
7. Significant or severe medical conditions including pulmonary, cardiovascular, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or oncologic disease or any other condition that, in the opinion of the Investigator, could jeopardize the safety of the subject or the validity of the study results

1. eGFR \< 60 mL/min
2. Alanine transaminase or aspartate transaminase (AST) \> 1.5 x upper limit of normal (ULN)
3. Total bilirubin \> 1.5 x ULN (Subjects with Gilbert's syndrome can be included as long as direct bilirubin is ≤ 1.5 x ULN)
8. Subjects with human immunodeficiency virus (HIV), cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections as indicated by medical history, serologies or LFT results
9. History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma as evaluated by the Investigator
10. History of irritable bowel syndrome (with or without constipation) or any serious constipation requiring treatment within the last 6 months
11. Risk for suicidal behavior during the study as determined by the Investigator's clinical assessment and/or C-SSRS as confirmed by the following:

1. Answers "Yes" on items 4 or 5 (C-SSRS - ideation) with the most recent episode occurring within the 2 months before Screening or,
2. Answers "Yes" to any of the 5 items (C-SSRS behavior) with an episode occurring within the 12 months before Screening
12. Clinically significant abnormal finding on the physical examination, medical history, ECG, or clinical laboratory results at Screening
13. Urine toxicology screen is positive for phencyclidine, amphetamines, opiates, cocaine, or alcohol (clinically significant alcohol use in the opinion of the Investigator)
14. Subject is currently taking, or plans to take while in the study, any prohibited concomitant medication.
15. Pregnant, lactating, or less than 3 months postpartum
16. If, in the opinion of the Investigator and/or Sponsor/Medical Monitor subject is unsuitable for enrollment in the study or subject has any finding that, in the view of the Investigator and/or Sponsor/Medical Monitor, may compromise the safety of the subject or affect his/her ability to adhere to the protocol visit schedule or fulfill visit requirements
17. Positive test for coronavirus (COVID-19) within 2 weeks or at Screening
18. Subjects with extreme concerns relating to global pandemics, such as COVID-19, that would obscure ratings or be expected to disrupt adherence to trial procedures
19. Unable to taper and discontinue a concomitant medication that would preclude participation in the double-blind adjunctive treatment (e.g., cannot stop anticholinergic)
20. Subjects with prior exposure to KarXT
21. Subjects who experienced any adverse effects due to xanomeline or trospium
22. Subjects who received investigational product as part of a clinical trial within 3 months of Screening
23. Risk of violent or destructive behavior as per Investigator's judgment that would interfere with subject's participation
24. Current involuntary hospitalization or incarcerationor on parole/probation
25. For all male subjects only, any one of the following:

1. History of bladder stones
2. History of recurrent urinary tract infections
3. Serum prostate specific antigen (PSA) \>10 ng/mL
4. An International Prostate Symptom Score (IPSS) of 5 (almost always) on either item 1, 3, 5, or 6
5. A sum of scores on IPSS items 1, 3, 5, and 6 of ≥9 Note: IPSS will be required only for male subjects ≥ 45 years of age. Subjects already enrolled in the study will have these assessments at their next clinic visit planned after re-consenting to determine current eligibility.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Karuna Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

IMA Clinical Research

Phoenix, Arizona, United States

Site Status

Local Institution - 147

Phoenix, Arizona, United States

Site Status

Pillar Clinical Research, LLC

Little Rock, Arkansas, United States

Site Status

Woodland International Research Group, LLC

Little Rock, Arkansas, United States

Site Status

Advanced Research Center, Inc.

Anaheim, California, United States

Site Status

CITrials - Bellflower

Bellflower, California, United States

Site Status

Synexus Clinical Research US, Inc.

Cerritos, California, United States

Site Status

Clinical Innovations Inc.

Costa Mesa, California, United States

Site Status

Proscience Research Group

Culver City, California, United States

Site Status

CenExel Collaborative Neuroscience Research

Garden Grove, California, United States

Site Status

Omega Clinical Trials

La Habra, California, United States

Site Status

Sunwise Clinical Research, LLC.

Lafayette, California, United States

Site Status

Synergy Clinical Research of Escondido

Lemon Grove, California, United States

Site Status

Encino Hospital Medical Center

Los Angeles, California, United States

Site Status

Excell Research, Inc.

Oceanside, California, United States

Site Status

Neuropsychiatric Research Center of Orange County

Orange, California, United States

Site Status

CNRI - Los Angeles, LLC

Pico Rivera, California, United States

Site Status

CenExel Clinical Innovations, Inc.

Riverside, California, United States

Site Status

Cnri-San Diego

San Diego, California, United States

Site Status

Stanford University School of Medicine

Stanford, California, United States

Site Status

CenExel Collaborative Neuroscience Research

Torrance, California, United States

Site Status

Local Institution - 186

Coral Gables, Florida, United States

Site Status

Reliable Clinical Research LLC

Hialeah, Florida, United States

Site Status

Galiz Research, LLC

Hialeah, Florida, United States

Site Status

Adaptive Clinical Research, Inc

Lauderhill, Florida, United States

Site Status

Behavioral Clinical Research , Inc

Miami, Florida, United States

Site Status

Premier Clinical Research Institute, Inc.

Miami, Florida, United States

Site Status

San Marcus Research Clinic, Inc.

Miami Lakes, Florida, United States

Site Status

Assertive Research Center

Miami Lakes, Florida, United States

Site Status

Envision Trials LLC

Miami Springs, Florida, United States

Site Status

Local Institution - 124

Orange City, Florida, United States

Site Status

Pines Care Research Center, Inc.

Pembroke Pines, Florida, United States

Site Status

Interventional Psychiatry of Tampa Bay

Tampa, Florida, United States

Site Status

Grady Memorial Hospital

Atlanta, Georgia, United States

Site Status

Synexus Clinical Research US, Inc.

Atlanta, Georgia, United States

Site Status

Local Institution - 192

Atlanta, Georgia, United States

Site Status

Local Institution - 135

Augusta, Georgia, United States

Site Status

CenExel iResearch Atlanta

Decatur, Georgia, United States

Site Status

Psych Atlanta, P.C.

Marietta, Georgia, United States

Site Status

CenExel iResearch, LLC

Savannah, Georgia, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

American Medical Research, Inc.

Chicago, Illinois, United States

Site Status

Uptown Research Institute, LLC

Chicago, Illinois, United States

Site Status

Phoenix Medical Research, Inc.

Prairie Village, Kansas, United States

Site Status

IMA Clinical Research

Monroe, Louisiana, United States

Site Status

CenExel Center for Behavioral Health

Gaithersburg, Maryland, United States

Site Status

Local Institution - 158

Boston, Massachusetts, United States

Site Status

Local Institution - 187

Boston, Massachusetts, United States

Site Status

Local Institution - 185

Worcester, Massachusetts, United States

Site Status

Michigan Clinical Research Institute PC

Ann Arbor, Michigan, United States

Site Status

Cherry Health

Grand Rapids, Michigan, United States

Site Status

Western Michigan University Homer Stryker M.D. School of Medicine

Kalamazoo, Michigan, United States

Site Status

Local Institution - 129

St Louis, Missouri, United States

Site Status

Arch Clinical Trials LLC

St Louis, Missouri, United States

Site Status

Omaha Insomnia and Psychiatric Services LLC

Omaha, Nebraska, United States

Site Status

Altea Research Institute, Las Vegas

Las Vegas, Nevada, United States

Site Status

CenExel Hassman Research Institute

Berlin, New Jersey, United States

Site Status

Synexus Clinical Research US, Inc.

New York, New York, United States

Site Status

Manhattan Psychiatric Center

New York, New York, United States

Site Status

Manhattan Behavioral Medicine, PLLC

New York, New York, United States

Site Status

Psychiatry and Alzheimer's Care of Rochester. PLLC

Rochester, New York, United States

Site Status

Richmond Behavioral Associates ERG Clinical Research - New York PLLC

Staten Island, New York, United States

Site Status

Clinical Trials of America - Psychiatry

Hickory, North Carolina, United States

Site Status

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Site Status

Local Institution - 168

Garfield Heights, Ohio, United States

Site Status

Insight Clinical Trials LLC

Independence, Ohio, United States

Site Status

The Rivus Wellness & Research Institute

Oklahoma City, Oklahoma, United States

Site Status

Prevention Science Institute

Eugene, Oregon, United States

Site Status

Community Clinical Research, Inc.

Austin, Texas, United States

Site Status

InSite Clinical Research; LLC

DeSoto, Texas, United States

Site Status

JPS Health Network

Fort Worth, Texas, United States

Site Status

Ben Taub Hospital

Houston, Texas, United States

Site Status

Clinical Trial Network LLC

Houston, Texas, United States

Site Status

University Hills Clinical Research - Irving

Irving, Texas, United States

Site Status

Pillar Clinical Research, LLC

Richardson, Texas, United States

Site Status

At Health Texas

Richmond, Texas, United States

Site Status

Perceptive Pharma Research

Richmond, Texas, United States

Site Status

Green Mountain Research Institute

Rutland, Vermont, United States

Site Status

Northwest Clinical Research Center

Bellevue, Washington, United States

Site Status

MHAT Dr. Hristo Stambolski, EOOD

Kazanlak, Stara Zagora, Bulgaria

Site Status

Ambulatory for Individual Practice for Specialized Medical Care in Psychiatry - Dr Ivo Natsov

Cherven Bryag, , Bulgaria

Site Status

Medical Centre 'Asklepii', OOD

Dupnitsa, , Bulgaria

Site Status

Medical Center Lifemed

Kardzhali, , Bulgaria

Site Status

State Psychiatric Hospital 'Sv. Ivan Rilski', Novi Iskar

Novi Iskar, , Bulgaria

Site Status

Medical Center Medconsult Pleven OOD

Pleven, , Bulgaria

Site Status

UMHAT 'Dr. Georgi Stranski', EAD

Pleven, , Bulgaria

Site Status

UMHAT Sv. Georgi, EAD

Plovdiv, , Bulgaria

Site Status

Local Institution - 321

Plovdiv, , Bulgaria

Site Status

Local Institution - 313

Razgrad, , Bulgaria

Site Status

MHAT Dr Ivan Seliminski AD

Sliven, , Bulgaria

Site Status

Medical Center 'Sv.Naum'

Sofia, , Bulgaria

Site Status

MHC - Sofia, EOOD

Sofia, , Bulgaria

Site Status

Local Institution - 320

Sofia, , Bulgaria

Site Status

DCC 'Sv. Vrach and Sv. Sv. Kuzma and Damyan', OOD

Sofia, , Bulgaria

Site Status

Medical Center Akademika EOOD

Sofia, , Bulgaria

Site Status

Medical Center Hera EOOD

Sofia, , Bulgaria

Site Status

Medical Center Intermedica, OOD

Sofia, , Bulgaria

Site Status

Medical Center VAS OOD

Targovishte, , Bulgaria

Site Status

DCC Mladost M - Varna, OOD

Varna, , Bulgaria

Site Status

Mental Health Center-Vratsa EOOD

Vratsa, , Bulgaria

Site Status

Local Institution - 616

Guwahati, Assam, India

Site Status

Local Institution - 607

Ahmedabad, Gujarat, India

Site Status

Local Institution - 604

Ahmedabad, Gujarat, India

Site Status

Local Institution - 609

Surat, Gujarat, India

Site Status

Local Institution - 613

Vadodara, Gujarat, India

Site Status

Local Institution - 617

Belgavi, Karnataka, India

Site Status

Local Institution - 614

Mangalore, Karnataka, India

Site Status

Local Institution - 602

Mangalore, Karnataka, India

Site Status

Local Institution - 601

Mysore, Karnataka, India

Site Status

Local Institution - 611

Kozhikode, Kerala, India

Site Status

Local Institution - 610

Aurangabad, Maharashtra, India

Site Status

Local Institution - 619

Mumbai, Maharashtra, India

Site Status

Local Institution - 603

Nagpur, Maharashtra, India

Site Status

Local Institution - 608

Nashik, Maharashtra, India

Site Status

Local Institution - 605

Nashik, Maharashtra, India

Site Status

Local Institution - 615

Ajmer, Rajasthan, India

Site Status

Local Institution - 618

Bikaner, Rajasthan, India

Site Status

Local Institution - 606

Rajkot, Rajasthan, India

Site Status

Local Institution - 612

Lucknow, Uttar Pradesh, India

Site Status

Local Institution - 258

Kōnan, Aichi-ken, Japan

Site Status

Local Institution - 250

Toyoake-shi, Aichi-ken, Japan

Site Status

Local Institution - 257

Shirakawa, Fukushima, Japan

Site Status

Local Institution - 254

Karatsu-shi, Saga-ken, Japan

Site Status

Local Institution - 255

Fukuoka, , Japan

Site Status

Local Institution - 256

Tokyo, , Japan

Site Status

Local Institution - 506

Bialystok, , Poland

Site Status

Local Institution - 507

Gdansk, , Poland

Site Status

Local Institution - 509

Grudziądz, , Poland

Site Status

Local Institution - 501

Kielce, , Poland

Site Status

Local Institution - 503

Lodz, , Poland

Site Status

Local Institution - 505

Lublin, , Poland

Site Status

Local Institution - 502

Siemianowice Śląskie, , Poland

Site Status

Local Institution - 508

Suchy Las, , Poland

Site Status

Local Institution - 504

Tuszyn, , Poland

Site Status

Local Institution - 803

Brasov, , Romania

Site Status

Local Institution - 809

Bucharest, , Romania

Site Status

Local Institution - 804

Bucharest, , Romania

Site Status

Local Institution - 810

Bucharest, , Romania

Site Status

Local Institution - 802

Bucharest, , Romania

Site Status

Local Institution - 807

Bucharest, , Romania

Site Status

Local Institution - 808

Craiova, , Romania

Site Status

Local Institution - 801

Galati, , Romania

Site Status

Local Institution - 806

Iași, , Romania

Site Status

Local Institution - 805

Sibiu, , Romania

Site Status

Clinical Center ' Dr Dragisa Misovic Dedinje'

Belgrade, , Serbia

Site Status

Institute of Mental Health

Belgrade, , Serbia

Site Status

Local Institution - 413

Belgrade, , Serbia

Site Status

Local Institution - 417

Belgrade, , Serbia

Site Status

University Clinical Center of Serbia

Belgrade, , Serbia

Site Status

"Special Hospital for Psychiatric Diseases ""Kovin"""

Kovin, , Serbia

Site Status

Special Hospital for Psychiatric Diseases 'Kovin'

Kovin, , Serbia

Site Status

University Clinical Center Kragujevac

Kragujevac, , Serbia

Site Status

University Clinical Center Nis

Niš, , Serbia

Site Status

Special Hospital for Psychiatric Diseases 'Gornja Toponica'

Niš, , Serbia

Site Status

Special Hospital for Psychiatric Diseases 'Sveti Vracevi'

Novi Kneževac, , Serbia

Site Status

Special Hospital for Psychiatric Disease 'Dr Slavoljub Bakalovic'

Vršac, , Serbia

Site Status

Local Institution - 707

Pool, Reruth, Cornwall, United Kingdom

Site Status

Local Institution - 705

Brighton, East Sussex, United Kingdom

Site Status

Local Institution - 701

London, Greater London, United Kingdom

Site Status

Local Institution - 706

Ashton-under-Lyne, Greater Manchester, United Kingdom

Site Status

Local Institution - 710

Manchester, Greater Manchester, United Kingdom

Site Status

Local Institution - 709

Maidstone, Kent, United Kingdom

Site Status

Local Institution - 708

Oxford, Oxfordshire, United Kingdom

Site Status

Local Institution - 704

Glasgow, Strathclyde, United Kingdom

Site Status

Local Institution - 702

Chertsey, Surrey, United Kingdom

Site Status

Local Institution - 703

Birmingham, West Midlands, United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Bulgaria India Japan Poland Romania Serbia United Kingdom

Related Links

Access external resources that provide additional context or updates about the study.

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

CN012-0008

Identifier Type: OTHER

Identifier Source: secondary_id

KAR-012

Identifier Type: OTHER

Identifier Source: secondary_id

CN012-0008

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

A Study in Schizophrenia Patients
NCT01086748 COMPLETED PHASE2