A Study to Evaluate the Efficacy and Safety of Adjunctive KarXT for the Treatment of Mania, With or Without Mixed Features, in Participants With Bipolar-I Disorder Taking Lithium, Valproate, or Lamotrigine

NCT07140913 | Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: CN012-00462025-521845-26U1111-1321-1513
• Study Type: interventional
• Target: 424
• Locations: 13 countries
• Sites: 103

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of adjunctive KarXT for the treatment of mania in participants with Bipolar-I Disorder.

Conditions

Mania; Bipolar Disorder

Keywords

Bipolar-I Disorder; Mania; KarXT; adjunctive treatment; mood stabilizer

Outcome Measures

Primary Outcomes (1)

• Change from baseline in Young Mania Rating Scale (YMRS) at Week 5

  At Week 5

Secondary Outcomes (11)

• Change from baseline in Clinical Global Impressions Bipolar (CGI-BP) at Week 5

  At Week 5

• Occurrence of response at Week 5 assessed as the number of participants with a ≥ 50% decrease from baseline in Young Mania Rating Scale (YMRS) score

  At Week 5

• Occurrence of response at Week 5 assessed as the number of participants with a ≥ 1 change from baseline in CGI-BP

  At Week 5

• Number of participants with Treatment-emergent Adverse Events (TEAEs)

  Up to Week 7

• Number of participants with Serious Adverse Events (SAEs)

  Up to Week 7

Study Arms (2)

KarXT + Lithium, Valproate, or Lamotrigine

EXPERIMENTAL

Drug: Xanomeline/Trospium Chloride

Placebo + Lithium, Valproate, or Lamotrigine

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Xanomeline/Trospium Chloride DRUG

Specified dose on specified days

Also known as: KarXT, BMS-986510

KarXT + Lithium, Valproate, or Lamotrigine

Placebo DRUG

Specified dose on specified days

Placebo + Lithium, Valproate, or Lamotrigine

Eligibility Criteria

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

You may qualify if:

• Individuals have a primary diagnosis of Bipolar-I disorder established by a comprehensive psychiatric evaluation based on the DSM-5-TR criteria and confirmed by the Mini International Neuropsychiatric Interview (MINI) version 7.0.2.
• Individual is experiencing an acute exacerbation or relapse of manic episode, with or without mixed features (≤ 3 weeks).
• The individual requires hospitalization for the acute exacerbation or relapse of mania.
• Body mass index ≥ 18 and ≤ 40 kg/m2.
• Currently experiencing an acute episode of mania or mania with mixed features with a therapeutic dose of lithium, valproate, or lamotrigine. The dose of the mood stabilizer must have remained stable for at least two weeks prior to screening. Additionally, participants on valproate must have been receiving treatment with valproate for a minimum of seven months.
• YMRS Total Score of ≥ 18 at Screening and at Baseline, and \< 20% reduction in YMRS from screening to baseline.

You may not qualify if:

• Any primary DSM-5-TR disorder other than BP-I within 12 months before screening (confirmed using MINI version 7.0.2 at screening) including BP-I depression (for previous 3 months only), BP-I with rapid cycling, first manic episode, BP-II, primary psychotic disorder, borderline personality disorder, and major depressive disorder, with the exception of mild anxiety disorders.
• Individual has a DSM-5-TR diagnosis of moderate to severe substance use disorder (except tobacco use disorder) within the 12 months before screening (confirmed using MINI version 7.0.2 at screening), or current use as determined by urine toxicology screen or alcohol test.
• Risk for suicidal behavior at screening as determined by the investigator's clinical assessment and the C-SSRS with an answer "Yes" to item 4 or 5 within 6 months before screening or between screening and baseline, or "Yes" to any of the 5 items (C-SSRS behavior) with an event occurring within the 12 months before screening, or between screening and baseline.
• History of irritable bowel syndrome (with or without constipation) or any serious constipation requiring treatment within the last 6 months.
• History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma.
• Participants with HIV, cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections based on either medical history or the LFT results.
• Elevations in hepatic transaminases at screening ≥ 2 × ULN for ALT or AST and/or bilirubin \> 1.5× ULN, unless in the context of Gilbert's syndrome.
• All grades of hepatic impairment (mild \[Child-Pugh Class A\], moderate \[Child-Pugh Class B\], and severe \[Child-Pugh Class C\]).

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (103)

Pillar Clinical Research - Bentonville

Bentonville, Arkansas, 72712, United States

RECRUITING

Pillar Clinical Research- Little Rock

Little Rock, Arkansas, 72204, United States

RECRUITING

Clinical Innovations, Inc. dba CITrials

Bellflower, California, 90706, United States

RECRUITING

Inland Psychiatric Medical Group.

Chino, California, 91710, United States

RECRUITING

Proscience Research Group

Culver City, California, 90230, United States

RECRUITING

Omega Clinical Trials - La Habra

La Habra, California, 90631, United States

RECRUITING

Catalina Research Institute, LLC

Montclair, California, 91763, United States

RECRUITING

NRC Research Institute

Orange, California, 92868, United States

RECRUITING

Clinical Innovations, Inc. dba CITrials

Riverside, California, 92506, United States

RECRUITING

Velocity Clinical Research, Hallandale Beach

Hallandale, Florida, 33009, United States

RECRUITING

South Florida Research Phase I-IV

Miami, Florida, 33166, United States

RECRUITING

Health Synergy Clinical Research

West Palm Beach, Florida, 33407, United States

RECRUITING

CenExel iResearch, LLC

Savannah, Georgia, 31405, United States

RECRUITING

Pillar Clinical Research -Chicago

Chicago, Illinois, 60641, United States

RECRUITING

Arch Clinical Trials

St Louis, Missouri, 63141, United States

RECRUITING

Richmond Behavioral Associates

Staten Island, New York, 10314, United States

RECRUITING

Community Clinical Research

Austin, Texas, 78754, United States

RECRUITING

Local Institution - 0160

Houston, Texas, 77058, United States

NOT YET RECRUITING

Prime Clinical Research - Mansfield

Mansfield, Texas, 76063, United States

RECRUITING

Pillar Clinical Research - Richardson

Richardson, Texas, 75080, United States

RECRUITING

Local Institution - 0011

ABB, Buenos Aires F.D., C1199ABB, Argentina

NOT YET RECRUITING

Local Institution - 0010

Córdoba, 5000, Argentina

NOT YET RECRUITING

Local Institution - 0012

Córdoba, 5000, Argentina

NOT YET RECRUITING

Local Institution - 0008

Córdoba, X5003DCE, Argentina

NOT YET RECRUITING

Local Institution - 0009

Mendoza, 5502, Argentina

NOT YET RECRUITING

Local Institution - 0114

Santiago del Estero, 4200, Argentina

NOT YET RECRUITING

Local Institution - 0184

Kazanlak, Stara Zagora, 6100, Bulgaria

NOT YET RECRUITING

Local Institution - 0124

Novi Iskar, 1282, Bulgaria

NOT YET RECRUITING

"University Multiprofile Hospital for Active Treatment - Dr. Georgi Stranski" EAD

Pleven, 5800, Bulgaria

RECRUITING

Local Institution - 0084

Pleven, 5800, Bulgaria

NOT YET RECRUITING

Local Institution - 0181

Sliven, 8800, Bulgaria

NOT YET RECRUITING

Local Institution - 0086

Targovishte, 7700, Bulgaria

NOT YET RECRUITING

Local Institution - 0185

Beijing, Beijing Municipality, 100088, China

NOT YET RECRUITING

Local Institution - 0190

Beijing, Beijing Municipality, 100096, China

NOT YET RECRUITING

Local Institution - 0191

Guangzhou, Guangdong, 510370, China

NOT YET RECRUITING

Local Institution - 0193

Baoding, Hebei, 71000, China

NOT YET RECRUITING

Local Institution - 0187

Shijiazhuang, Hebei, 050031, China

NOT YET RECRUITING

Local Institution - 0196

Nanjing, Jiangsu, 210029, China

NOT YET RECRUITING

Local Institution - 0186

Xi'an, Shaanxi, 710061, China

NOT YET RECRUITING

Local Institution - 0192

Chengdu, Sichuan, 610036, China

NOT YET RECRUITING

Local Institution - 0188

Tianjin, Tianjin Municipality, 300022, China

NOT YET RECRUITING

Local Institution - 0197

Ningbo, Zhejiang, 315201, China

NOT YET RECRUITING

Local Institution - 0195

Changsha, 450052, China

NOT YET RECRUITING

Local Institution - 0088

Hillerød, Capital Region, 3400, Denmark

NOT YET RECRUITING

Local Institution - 0054

Aalborg, North Denmark, 9000, Denmark

NOT YET RECRUITING

Local Institution - 0091

Glostrup Municipality, 2600, Denmark

NOT YET RECRUITING

Local Institution - 0126

Nice, Alpes-Maritimes, 06000, France

NOT YET RECRUITING

Local Institution - 0085

Clermont-Ferrand, Puy-de-Dôme, 63000, France

NOT YET RECRUITING

Local Institution - 0087

Marseille, 13274, France

WITHDRAWN

Local Institution - 0129

Montpellier, 34295, France

NOT YET RECRUITING

Local Institution - 0089

Paris, 75014, France

WITHDRAWN

Local Institution - 0121

Mangalore, Karnataka, 575003, India

NOT YET RECRUITING

Local Institution - 0123

Madurai, Tamil Nadu, 625020, India

NOT YET RECRUITING

Local Institution - 0118

Kolkata, West Bengal, 700025, India

NOT YET RECRUITING

Local Institution - 0116

Kolkata, 700014, India

NOT YET RECRUITING

Local Institution - 0052

Hod HaSharon, Central District, 4534708, Israel

NOT YET RECRUITING

Sheba Medical Center

Ramat Gan, Central District, 5265601, Israel

RECRUITING

Local Institution - 0053

Ashkelon, Southern District, 7830604, Israel

NOT YET RECRUITING

Local Institution - 0199

Beersheba, Southern District, 8461144, Israel

NOT YET RECRUITING

Local Institution - 0200

Bnei Brak, 5154475, Israel

NOT YET RECRUITING

Local Institution - 0083

Jerusalem, 9112001, Israel

NOT YET RECRUITING

Local Institution - 0003

Milan, Lombardy, 20122, Italy

NOT YET RECRUITING

Local Institution - 0005

Pisa, Tuscany, 56126, Italy

NOT YET RECRUITING

Local Institution - 0001

Siena, Tuscany, 53100, Italy

NOT YET RECRUITING

Local Institution - 0004

Ancona, 60126, Italy

NOT YET RECRUITING

Local Institution - 0002

Genova, 16132, Italy

NOT YET RECRUITING

Okehazama Hospital

Toyoake, Aichi-ken, 470-1168, Japan

RECRUITING

Local Institution - 0205

Ichikawa, Chiba, 272-8516, Japan

NOT YET RECRUITING

Local Institution - 0172

Iizuka, Fukuoka, 820-8505, Japan

WITHDRAWN

Local Institution - 0141

Kitakyushu-shi, Fukuoka, 8078555, Japan

WITHDRAWN

Goryokai Medical Corporation - Goryokai Hospital

Sapporo, Hokkaido, 002-8029, Japan

RECRUITING

Local Institution - 0107

Yokohama, Kanagawa, 234-0051, Japan

NOT YET RECRUITING

Rainbow and Sea Hospital

Karatsu, Saga-ken, 847-0031, Japan

RECRUITING

Local Institution - 0180

Bunkyo-ku, Tokyo, 113-8431, Japan

NOT YET RECRUITING

Local Institution - 0139

Bunkyo-ku, Tokyo, 1138603, Japan

NOT YET RECRUITING

Local Institution - 0201

Kodaira, Tokyo, 187-8551, Japan

NOT YET RECRUITING

Local Institution - 0176

tabashi City, Tokyo, 175-0091, Japan

NOT YET RECRUITING

Kuramitsu Hospital

Fukuoka, 819-0037, Japan

RECRUITING

Kochi Health Sciences Center

Kochi, 781-8555, Japan

RECRUITING

Local Institution - 0103

Rybnik, Silesian Voivodeship, 44-200, Poland

NOT YET RECRUITING

Clinica Inventiva

Tuszyn, 95-080, Poland

RECRUITING

Local Institution - 0093

Bucharest, Bucharest, 041914, Romania

NOT YET RECRUITING

Prof. Dr. Alexandru Obregia Psychiatry Hospital

Bucharest, Bucharest, 041914, Romania

RECRUITING

Prof. Dr. Alexandru Obregia Psychiatry Hospital

Bucharest, Bucharest, 041914, Romania

RECRUITING

Prof. Dr. Alexandru Obregia Psychiatry Hospital

Bucharest, Bucharest, 041914, Romania

RECRUITING

Local Institution - 0102

Bucharest, 011241, Romania

NOT YET RECRUITING

Local Institution - 0099

Bucharest, 0, Romania

NOT YET RECRUITING

Local Institution - 0203

Bucharest, 41914, Romania

NOT YET RECRUITING

Local Institution - 0097

Iași, 700282, Romania

NOT YET RECRUITING

Local Institution - 0095

Sanpetru /Brasov, 507190, Romania

NOT YET RECRUITING

Local Institution - 0101

Sibiu, 550082, Romania

NOT YET RECRUITING

Local Institution - 0167

Smila, Cherkasy Oblast, 20708, Ukraine

NOT YET RECRUITING

Local Institution - 0165

Dnipro, Dnipropetrovsk Oblast, 49005, Ukraine

NOT YET RECRUITING

Local Institution - 0178

Skarzhyntsi, Khmelnytskyi Oblast, 32120, Ukraine

NOT YET RECRUITING

Local Institution - 0163

Nove, Kirovohrad Oblast, 25491, Ukraine

NOT YET RECRUITING

Local Institution - 0169

Hlevakha, Kyivska Oblast, 08631, Ukraine

NOT YET RECRUITING

Local Institution - 0162

Kyiv, Kyivska Oblast, 04080, Ukraine

NOT YET RECRUITING

Local Institution - 0164

Lviv, Lviv Oblast, 79021, Ukraine

NOT YET RECRUITING

Local Institution - 0206

Ternopil, Ternopil Oblast, 460027, Ukraine

NOT YET RECRUITING

Local Institution - 0168

Vinnytsia, Vinnytsia Oblast, 21037, Ukraine

NOT YET RECRUITING

Local Institution - 0170

Odesa, 65006, Ukraine

NOT YET RECRUITING

Local Institution - 0171

Odesa, 65006, Ukraine

NOT YET RECRUITING

Local Institution - 0177

Poltava, 36000, Ukraine

NOT YET RECRUITING

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Mania; Bipolar Disorder

Interventions

xanomeline; trospium chloride

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Central Study Contacts

BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

CONTACT

855-907-3286; Clinical.Trials@bms.com

First line of the email MUST contain NCT # and Site #.

CONTACT

Study Design

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

Study Record Dates

• First Submitted: August 21, 2025
• First Posted: August 26, 2025
• Study Start: October 8, 2025
• Primary Completion (Estimated): June 28, 2027
• Study Completion (Estimated): June 28, 2027
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

BU (6); CN (11); IT (5); US (20); AR (6); IN (4); DK (3); UA (12); FR (5); PL (2); JP (13); IL (6); RO (10)