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

NCT05145413 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: CN012-0008KAR-012
• Study Type: interventional
• Target: 396
• Locations: 8 countries
• Sites: 166

Brief Summary

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.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6

  PANSS Total Score is a clinician administered measure of schizophrenia symptom severity used widely in antipsychotic research. It includes 30 items across 3 subscales: * Positive Symptoms (7 items) assessing excesses or distortions such as hallucinations, delusions, or grandiosity * Negative Symptoms (7 items) assessing diminished function such as social withdrawal or reduced motivation and * General Psychopathology (16 items) capturing broader symptoms like anxiety, depression, guilt, or cognitive impairment Each item is scored from 1 (absent) to 7 (extreme), producing a PANSS Total Score ranging from 30 to 210, with higher scores indicating more severe symptoms. Baseline is defined as the last non missing PANSS Total Score before first dose. This endpoint evaluates change from Baseline to Week 6, with negative values indicating improvement.

  Baseline to Week 6

Secondary Outcomes (6)

• Change From Baseline in Personal and Social Performance Scale (PSP) at Week 6

  Baseline to Week 6

• Change From Baseline in Clinical Global Impression-Severity Scale (CGI-S) at Week 6

  Baseline to Week 6

• Change From Baseline in Positive and Negative Syndrome Scale Marder Positive (PANSS M-Pos) Symptom Factor Score at Week 6

  Baseline to Week 6

• Change From Baseline in Positive and Negative Syndrome Scale Marder Negative (PANSS M-Neg) Symptom Factor Score at Week 6

  Baseline to Week 6

• Percentage of Participants Achieving a ≥ 30% Improvement in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6

  At Week 6

Study Arms (2)

Drug: KarXT

EXPERIMENTAL

Drug: Xanomeline and Trospium Chloride Capsules

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Xanomeline and Trospium Chloride Capsules DRUG

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

Drug: KarXT

Placebo DRUG

Placebo Capsules

Placebo

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 the time of randomization
• Subject is capable of providing signed Informed Consent Form before any study assessments will be performed
• 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
• 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)
• 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
• 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
• To be eligible for randomization, subjects need to have detectable levels of background antipsychotic medication (measured at Visit 1)
• Positive and Negative Syndrome Scale (PANSS) total score ≥ 70 at Screening and randomization
• Clinical Global Impression-Severity (CGI-S) scale with a score ≥ 4 (moderate) at Screening and randomization
• 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
• Subjects with ≤ 20-point decrease in PANSS Total score between Visit 1 and Visit 3
• 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
• Body Mass Index (BMI) must be within 18 to 40 kg/m2 (inclusive of both values)
• Subject resides in a stable living situation in the opinion of the Investigator
• 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.

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)
• The subject has a history of moderate to severe substance use disorder (other than nicotine) within the past 12 months
• 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
• 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
• 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.
• History of symptom instability
• a. \> 3 psychiatric hospitalizations over the last 12 months or 2 over the last 6 months
• Current APD is other than aripiprazole, risperidone, paliperidone, or their LAI versions, ziprasidone, lurasidone, or cariprazine
• Subjects who are diagnosed with schizophreniform disorder or are experiencing their first treated episode of schizophrenia
• 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
• eGFR \< 60 mL/min
• Alanine transaminase or aspartate transaminase (AST) \> 1.5 x upper limit of normal (ULN)
• Total bilirubin \> 1.5 x ULN (Subjects with Gilbert's syndrome can be included as long as direct bilirubin is ≤ 1.5 x ULN)
• 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

Sponsors & Collaborators

• Karuna Therapeutics, Inc., a Bristol Myers Squibb company: lead

Study Sites (166)

IMA Clinical Research

Phoenix, Arizona, 85012, United States

Location

Local Institution - 147

Phoenix, Arizona, 85012, United States

Location

Pillar Clinical Research, LLC

Little Rock, Arkansas, 72204, United States

Location

Woodland International Research Group, LLC

Little Rock, Arkansas, 72211, United States

Location

Advanced Research Center, Inc.

Anaheim, California, 92805, United States

Location

CITrials - Bellflower

Bellflower, California, 90706-7079, United States

Location

Synexus Clinical Research US, Inc.

Cerritos, California, 90703, United States

Location

Clinical Innovations Inc.

Costa Mesa, California, 92626, United States

Location

Proscience Research Group

Culver City, California, 90230, United States

Location

CenExel Collaborative Neuroscience Research

Garden Grove, California, 92845, United States

Location

Omega Clinical Trials

La Habra, California, 90631, United States

Location

Sunwise Clinical Research, LLC.

Lafayette, California, 94549, United States

Location

Synergy Clinical Research of Escondido

Lemon Grove, California, 91945, United States

Location

Encino Hospital Medical Center

Los Angeles, California, 91403, United States

Location

Excell Research, Inc.

Oceanside, California, 92056, United States

Location

Neuropsychiatric Research Center of Orange County

Orange, California, 92868, United States

Location

CNRI - Los Angeles, LLC

Pico Rivera, California, 90660, United States

Location

CenExel Clinical Innovations, Inc.

Riverside, California, 92506, United States

Location

Cnri-San Diego

San Diego, California, 92123, United States

Location

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

CenExel Collaborative Neuroscience Research

Torrance, California, 90504, United States

Location

Local Institution - 186

Coral Gables, Florida, 33134, United States

Location

Reliable Clinical Research LLC

Hialeah, Florida, 33012, United States

Location

Galiz Research, LLC

Hialeah, Florida, 33016-1814, United States

Location

Adaptive Clinical Research, Inc

Lauderhill, Florida, 33319-4985, United States

Location

Behavioral Clinical Research , Inc

Miami, Florida, 33016, United States

Location

Premier Clinical Research Institute, Inc.

Miami, Florida, 33122, United States

Location

San Marcus Research Clinic, Inc.

Miami Lakes, Florida, 33014, United States

Location

Assertive Research Center

Miami Lakes, Florida, 33016, United States

Location

Envision Trials LLC

Miami Springs, Florida, 33166, United States

Location

Local Institution - 124

Orange City, Florida, 32763, United States

Location

Pines Care Research Center, Inc.

Pembroke Pines, Florida, 33024, United States

Location

Interventional Psychiatry of Tampa Bay

Tampa, Florida, 33629, United States

Location

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

Synexus Clinical Research US, Inc.

Atlanta, Georgia, 30328, United States

Location

Local Institution - 192

Atlanta, Georgia, 30331, United States

Location

Local Institution - 135

Augusta, Georgia, 30912, United States

Location

CenExel iResearch Atlanta

Decatur, Georgia, 30030, United States

Location

Psych Atlanta, P.C.

Marietta, Georgia, 30060, United States

Location

CenExel iResearch, LLC

Savannah, Georgia, 31405, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

American Medical Research, Inc.

Chicago, Illinois, 60612-2307, United States

Location

Uptown Research Institute, LLC

Chicago, Illinois, 60640, United States

Location

Phoenix Medical Research, Inc.

Prairie Village, Kansas, 66208, United States

Location

IMA Clinical Research

Monroe, Louisiana, 71201-2986, United States

Location

CenExel Center for Behavioral Health

Gaithersburg, Maryland, 20877, United States

Location

Local Institution - 158

Boston, Massachusetts, 02114, United States

Location

Local Institution - 187

Boston, Massachusetts, 02118, United States

Location

Local Institution - 185

Worcester, Massachusetts, 01655, United States

Location

Michigan Clinical Research Institute PC

Ann Arbor, Michigan, 48105, United States

Location

Cherry Health

Grand Rapids, Michigan, 49548-6927, United States

Location

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

Kalamazoo, Michigan, 49001, United States

Location

Local Institution - 129

St Louis, Missouri, 63128, United States

Location

Arch Clinical Trials LLC

St Louis, Missouri, 63141, United States

Location

Omaha Insomnia and Psychiatric Services LLC

Omaha, Nebraska, 68144, United States

Location

Altea Research Institute, Las Vegas

Las Vegas, Nevada, 89102, United States

Location

CenExel Hassman Research Institute

Berlin, New Jersey, 08009, United States

Location

Synexus Clinical Research US, Inc.

New York, New York, 10017, United States

Location

Manhattan Psychiatric Center

New York, New York, 10027, United States

Location

Manhattan Behavioral Medicine, PLLC

New York, New York, 10036, United States

Location

Psychiatry and Alzheimer's Care of Rochester. PLLC

Rochester, New York, 14623, United States

Location

Richmond Behavioral Associates ERG Clinical Research - New York PLLC

Staten Island, New York, 10314, United States

Location

Clinical Trials of America - Psychiatry

Hickory, North Carolina, 28601, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

Local Institution - 168

Garfield Heights, Ohio, 44125, United States

Location

Insight Clinical Trials LLC

Independence, Ohio, 44131, United States

Location

The Rivus Wellness & Research Institute

Oklahoma City, Oklahoma, 73112, United States

Location

Prevention Science Institute

Eugene, Oregon, 97403, United States

Location

Community Clinical Research, Inc.

Austin, Texas, 78754, United States

Location

InSite Clinical Research; LLC

DeSoto, Texas, 75115, United States

Location

JPS Health Network

Fort Worth, Texas, 76104, United States

Location

Ben Taub Hospital

Houston, Texas, 77030, United States

Location

Clinical Trial Network LLC

Houston, Texas, 77074, United States

Location

University Hills Clinical Research - Irving

Irving, Texas, 75062, United States

Location

Pillar Clinical Research, LLC

Richardson, Texas, 75080, United States

Location

At Health Texas

Richmond, Texas, 77407, United States

Location

Perceptive Pharma Research

Richmond, Texas, 77407, United States

Location

Green Mountain Research Institute

Rutland, Vermont, 05701, United States

Location

Northwest Clinical Research Center

Bellevue, Washington, 98007, United States

Location

MHAT Dr. Hristo Stambolski, EOOD

Kazanlak, Stara Zagora, 6100, Bulgaria

Location

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

Cherven Bryag, 5980, Bulgaria

Location

Medical Centre 'Asklepii', OOD

Dupnitsa, 2600, Bulgaria

Location

Medical Center Lifemed

Kardzhali, 6600, Bulgaria

Location

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

Novi Iskar, 1282, Bulgaria

Location

Medical Center Medconsult Pleven OOD

Pleven, 5800, Bulgaria

Location

UMHAT 'Dr. Georgi Stranski', EAD

Pleven, 5800, Bulgaria

Location

UMHAT Sv. Georgi, EAD

Plovdiv, 4002, Bulgaria

Location

Local Institution - 321

Plovdiv, 4004, Bulgaria

Location

Local Institution - 313

Razgrad, 7200, Bulgaria

Location

MHAT Dr Ivan Seliminski AD

Sliven, 8800, Bulgaria

Location

Medical Center 'Sv.Naum'

Sofia, 1113, Bulgaria

Location

MHC - Sofia, EOOD

Sofia, 1202, Bulgaria

Location

Local Institution - 320

Sofia, 1407, Bulgaria

Location

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

Sofia, 1408, Bulgaria

Location

Medical Center Akademika EOOD

Sofia, 1431, Bulgaria

Location

Medical Center Hera EOOD

Sofia, 1510, Bulgaria

Location

Medical Center Intermedica, OOD

Sofia, 1680, Bulgaria

Location

Medical Center VAS OOD

Targovishte, 7700, Bulgaria

Location

DCC Mladost M - Varna, OOD

Varna, 9020, Bulgaria

Location

Mental Health Center-Vratsa EOOD

Vratsa, 3000, Bulgaria

Location

Local Institution - 616

Guwahati, Assam, 781032, India

Location

Local Institution - 607

Ahmedabad, Gujarat, 380008, India

Location

Local Institution - 604

Ahmedabad, Gujarat, 380013, India

Location

Local Institution - 609

Surat, Gujarat, 395001, India

Location

Local Institution - 613

Vadodara, Gujarat, 390021, India

Location

Local Institution - 617

Belgavi, Karnataka, 590001, India

Location

Local Institution - 614

Mangalore, Karnataka, 575003, India

Location

Local Institution - 602

Mangalore, Karnataka, 575018, India

Location

Local Institution - 601

Mysore, Karnataka, 570001, India

Location

Local Institution - 611

Kozhikode, Kerala, 673009, India

Location

Local Institution - 610

Aurangabad, Maharashtra, 431005, India

Location

Local Institution - 619

Mumbai, Maharashtra, 400008, India

Location

Local Institution - 603

Nagpur, Maharashtra, 440010, India

Location

Local Institution - 608

Nashik, Maharashtra, 422001, India

Location

Local Institution - 605

Nashik, Maharashtra, 422005, India

Location

Local Institution - 615

Ajmer, Rajasthan, 305001, India

Location

Local Institution - 618

Bikaner, Rajasthan, 334003, India

Location

Local Institution - 606

Rajkot, Rajasthan, 360001, India

Location

Local Institution - 612

Lucknow, Uttar Pradesh, 226003, India

Location

Local Institution - 258

Kōnan, Aichi-ken, 483-8248, Japan

Location

Local Institution - 250

Toyoake-shi, Aichi-ken, 470-1168, Japan

Location

Local Institution - 257

Shirakawa, Fukushima, 961-0021, Japan

Location

Local Institution - 254

Karatsu-shi, Saga-ken, 847-0031, Japan

Location

Local Institution - 255

Fukuoka, 819-0037, Japan

Location

Local Institution - 256

Tokyo, 162-0843, Japan

Location

Local Institution - 506

Bialystok, 15-404, Poland

Location

Local Institution - 507

Gdansk, 80-546, Poland

Location

Local Institution - 509

Grudziądz, 86-300, Poland

Location

Local Institution - 501

Kielce, 25-411, Poland

Location

Local Institution - 503

Lodz, 90-227, Poland

Location

Local Institution - 505

Lublin, 20-109, Poland

Location

Local Institution - 502

Siemianowice Śląskie, 41-100, Poland

Location

Local Institution - 508

Suchy Las, 62-002, Poland

Location

Local Institution - 504

Tuszyn, 95-080, Poland

Location

Local Institution - 803

Brasov, 500123, Romania

Location

Local Institution - 809

Bucharest, 041914, Romania

Location

Local Institution - 804

Bucharest, 10825, Romania

Location

Local Institution - 810

Bucharest, 40874, Romania

Location

Local Institution - 802

Bucharest, 41914, Romania

Location

Local Institution - 807

Bucharest, 60222, Romania

Location

Local Institution - 808

Craiova, 200157, Romania

Location

Local Institution - 801

Galati, 800179, Romania

Location

Local Institution - 806

Iași, 700282, Romania

Location

Local Institution - 805

Sibiu, 550281, Romania

Location

Clinical Center ' Dr Dragisa Misovic Dedinje'

Belgrade, 11000, Serbia

Location

Institute of Mental Health

Belgrade, 11000, Serbia

Location

Local Institution - 413

Belgrade, 11000, Serbia

Location

Local Institution - 417

Belgrade, 11000, Serbia

Location

University Clinical Center of Serbia

Belgrade, 11000, Serbia

Location

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

Kovin, 26220, Serbia

Location

Special Hospital for Psychiatric Diseases 'Kovin'

Kovin, 26220, Serbia

Location

University Clinical Center Kragujevac

Kragujevac, 34000, Serbia

Location

University Clinical Center Nis

Niš, 18000, Serbia

Location

Special Hospital for Psychiatric Diseases 'Gornja Toponica'

Niš, 18202, Serbia

Location

Special Hospital for Psychiatric Diseases 'Sveti Vracevi'

Novi Kneževac, 23330, Serbia

Location

Special Hospital for Psychiatric Disease 'Dr Slavoljub Bakalovic'

Vršac, 26300, Serbia

Location

Local Institution - 707

Pool, Reruth, Cornwall, TR15 3QE, United Kingdom

Location

Local Institution - 705

Brighton, East Sussex, BN1 9RY, United Kingdom

Location

Local Institution - 701

London, Greater London, SE5 8AF, United Kingdom

Location

Local Institution - 706

Ashton-under-Lyne, Greater Manchester, OL6 7SR, United Kingdom

Location

Local Institution - 710

Manchester, Greater Manchester, M8 5RB, United Kingdom

Location

Local Institution - 709

Maidstone, Kent, ME16 9PH, United Kingdom

Location

Local Institution - 708

Oxford, Oxfordshire, OX3 7JX, United Kingdom

Location

Local Institution - 704

Glasgow, Strathclyde, G51 4TF, United Kingdom

Location

Local Institution - 702

Chertsey, Surrey, KT16 9AU, United Kingdom

Location

Local Institution - 703

Birmingham, West Midlands, B4 6NH, United Kingdom

Location

Related Links

• BMS Clinical Trial Information
• 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

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2021
• First Posted: December 6, 2021
• Study Start: November 12, 2021
• Primary Completion: March 19, 2025
• Study Completion: March 19, 2025
• Last Updated: May 5, 2026
• Results First Posted: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

RO (10); BU (21); US (79); JP (6); PL (9); SE (12); IN (19); GB (10)