ManiaPhase 3NCT07140913
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
A Phase 3 study testing Xanomeline/Trospium Chloride in people with Mania and Bipolar Disorder, run by Bristol-Myers Squibb at 104 sites in 13 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Mania, Bipolar Disorder
- What is being tested?
- Xanomeline/Trospium Chloride
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 424 participants
- Where
- 104 sitesin 13 countries
- Study dates
- 8 Oct 2025to 28 Jun 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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]).
- Other protocol-defined Inclusion/Exclusion criteria apply.
Trial locations and contacts
104 sites in 13 countries. Contact the study team or a site near you to ask about taking part.
BMS Clinical Trials Contact Center www.BMSClinicalTrials.com contact
First line of the email MUST contain NCT # and Site #. contact
104 sites in 13 countries
United States20 sites, 20 recruiting
- Recruiting
Community Clinical Research
Austin, Texas, 78754
David Brown, Site 0026, 512-323-2622
- Recruiting
Clinical Innovations, Inc. dba CITrials
Bellflower, California, 90706
Gerald Maguire, Site 0110, 562-249-6956
- Recruiting
Pillar Clinical Research - Bentonville
Bentonville, Arkansas, 72712
Fayz Hudefi, Site 0029, 479-367-2688
- Recruiting
Pillar Clinical Research -Chicago
Chicago, Illinois, 60641
Roueen Rafeyan, Site 0017, 312-865-6336
- Recruiting
Inland Psychiatric Medical Group.
Chino, California, 91710
Nandita Puchakayala, Site 0049, 909-488-9116
- Recruiting
Proscience Research Group
Culver City, California, 90230
Marina Bussel, Site 0014, 424-227-8127
- Recruiting
Velocity Clinical Research, Hallandale Beach
Hallandale, Florida, 33009
Beth Safirstein, Site 0015
- Recruiting
Elevate Clinical Research-Houston
Houston, Texas, 77058
Matthew Brams, Site 0160
- Recruiting
Omega Clinical Trials - La Habra
La Habra, California, 90631
Wakelin McNeel, Site 0151, 562-690-2200
- Recruiting
Pillar Clinical Research- Little Rock
Little Rock, Arkansas, 72204
Leslie Smith, Site 0018, 501-350-3285
- Recruiting
Prime Clinical Research - Mansfield
Mansfield, Texas, 76063
Jamie Alexander, Site 0156, 817-907-7330
- Recruiting
South Florida Research Phase I-IV
Miami, Florida, 33166
Silvia Silva Duluc, Site 0021, 305-669-6166
- Recruiting
Catalina Research Institute, LLC
Montclair, California, 91763
Stephen Volk, Site 0037, 909-590-8409
- Recruiting
NRC Research Institute
Orange, California, 92868
Tony Ortiz, Site 0148, 714-289-1100
- Recruiting
Pillar Clinical Research - Richardson
Richardson, Texas, 75080
Scott Bartley, Site 0033, 214-396-4844
- Recruiting
Clinical Innovations, Inc. dba CITrials
Riverside, California, 92506
Evagelos Coskinas, Site 0106, 951-300-4924
- Recruiting
CenExel iResearch, LLC
Savannah, Georgia, 31405
Yael Elfassy, Site 0136, 912-744-0800
- Recruiting
Arch Clinical Trials
St Louis, Missouri, 63141
Junaid Syed, Site 0023, 314-771-6387
- Recruiting
Richmond Behavioral Associates
Staten Island, New York, 10314
Peter Weiden, Site 0032, 917-701-7484
- Recruiting
Health Synergy Clinical Research
West Palm Beach, Florida, 33407
Mohammad Nisar, Site 0016, 786-831-7303
Japan13 sites, 11 recruiting
- Recruiting
Juntendo University Hospital
Bunkyo-ku, Tokyo, 113-8431
Tadafumi Kato, Site 0180, +81-(0)3-3813-3111
- Recruiting
Nippon Medical School Hospital
Bunkyo-ku, Tokyo, 1138603
Amane Tateno, Site 0139, +81-3-3822-2131
- Recruiting
Kuramitsu Hospital
Fukuoka, 819-0037
Noriko Tamaru, Site 0174, +81-92-811-1821
- Not yet recruiting
Local Institution - 0205
Ichikawa, Chiba, 272-8516
Site 0205
- Withdrawn
Local Institution - 0172
Iizuka, Fukuoka, 820-8505
- Recruiting
Rainbow and Sea Hospital
Karatsu, Saga-ken, 847-0031
Taro Shindo, Site 0175, 0955770711
- Withdrawn
Local Institution - 0141
Kitakyushu-shi, Fukuoka, 8078555
- Recruiting
Kochi Health Sciences Center
Kochi, 781-8555
Ken Sawada, Site 0142, +81-88-837-3000
- Not yet recruiting
Local Institution - 0201
Kodaira, Tokyo, 187-8551
Site 0201
- Recruiting
Goryokai Medical Corporation - Goryokai Hospital
Sapporo, Hokkaido, 002-8029
Kimihiro Nakajima, Site 0108, +81-11-771-5660
- Recruiting
Narimasu Kosei Hospital
tabashi City, Tokyo, 175-0091
Yuya Tenjin, Site 0176, 0339391191
- Recruiting
Okehazama Hospital
Toyoake, Aichi-ken, 470-1168
kiyoshi Fujita, Site 0173, 0562971361
- Not yet recruiting
Local Institution - 0107
Yokohama, Kanagawa, 234-0051
Site 0107
Ukraine12 sites, 12 recruiting
- Not yet recruiting
Local Institution - 0165
Dnipro, Dnipropetrovsk Oblast, 49005
Site 0165
- Not yet recruiting
Local Institution - 0169
Hlevakha, Kyivska Oblast, 08631
Site 0169
- Not yet recruiting
Local Institution - 0162
Kyiv, Kyivska Oblast, 04080
Site 0162
- Not yet recruiting
Local Institution - 0164
Lviv, Lviv Oblast, 79021
Site 0164
- Not yet recruiting
Local Institution - 0163
Nove, Kirovohrad Oblast, 25491
Site 0163
- Not yet recruiting
Local Institution - 0170
Odesa, Odesa Oblast, 67513
Site 0170
- Not yet recruiting
Local Institution - 0171
Odesa, 65006
Site 0171
- Not yet recruiting
Local Institution - 0177
Poltava, 36000
Site 0177
- Not yet recruiting
Local Institution - 0178
Skarzhyntsi, Khmelnytskyi Oblast, 32120
Site 0178
- Not yet recruiting
Local Institution - 0167
Smila, Cherkasy Oblast, 20708
Site 0167
- Not yet recruiting
Local Institution - 0206
Ternopil, 46027
Site 0206
- Not yet recruiting
Local Institution - 0168
Vinnytsia, Vinnytsia Oblast, 21037
Site 0168
China11 sites, 11 recruiting
- Not yet recruiting
Local Institution - 0193
Baoding, Hebei, 071000
Site 0193
- Not yet recruiting
Local Institution - 0185
Beijing, Beijing Municipality, 100088
Site 0185
- Not yet recruiting
Local Institution - 0190
Beijing, Beijing Municipality, 100096
Site 0190
- Not yet recruiting
Local Institution - 0195
Changsha, 450052
Site 0195
- Not yet recruiting
Local Institution - 0192
Chengdu, Sichuan, 610036
Site 0192
- Not yet recruiting
Local Institution - 0191
Guangzhou, Guangdong, 510370
Site 0191
- Not yet recruiting
Local Institution - 0196
Nanjing, Jiangsu, 210029
Site 0196
- Not yet recruiting
Local Institution - 0197
Ningbo, Zhejiang, 315201
Site 0197
- Not yet recruiting
Local Institution - 0187
Shijiazhuang, Hebei, 050031
Site 0187
- Not yet recruiting
Local Institution - 0188
Tianjin, Tianjin Municipality, 300022
Site 0188
- Not yet recruiting
Local Institution - 0186
Xi'an, Shaanxi, 710061
Site 0186
Romania11 sites, 11 recruiting
- Not yet recruiting
Local Institution - 0093
Bucharest, Bucharest, 041914
Site 0093
- Recruiting
Prof. Dr. Alexandru Obregia Psychiatry Hospital
Bucharest, Bucharest, 041914
Valentin Matei, Site 0092, +40721243869
- Recruiting
Prof. Dr. Alexandru Obregia Psychiatry Hospital
Bucharest, Bucharest, 041914
ADELA CIOBANU, Site 0098, 0040723671301
- Recruiting
Prof. Dr. Alexandru Obregia Psychiatry Hospital
Bucharest, Bucharest, 041914
Laura Cristina Dolis, Site 0094, 0040757243543
- Recruiting
Prof. Dr. Alexandru Obregia Psychiatry Hospital
Bucharest, Bucharest, 041914
Mihnea Manea, Site 0100, 0040745974029
- Recruiting
Institutul Național de Gerontologie și Geriatrie "Ana Aslan"
Bucharest, 011241
Traian Purnichi, Site 0102, +40749156565
- Not yet recruiting
Local Institution - 0099
Bucharest, 0
Site 0099
- Not yet recruiting
Local Institution - 0203
Bucharest, 41914
Site 0203
- Not yet recruiting
Local Institution - 0097
Iași, 700282
Site 0097
- Recruiting
Spitalul de Psihiatrie și Neurologie Brașov
Sanpetru /Brasov, 507190
Petru Ifteni, Site 0095, 0040724993329
- Not yet recruiting
Local Institution - 0101
Sibiu, 550082
Site 0101
Argentina6 sites, 6 recruiting
- Not yet recruiting
Local Institution - 0011
ABB, Buenos Aires F.D., C1199ABB
Site 0011
- Not yet recruiting
Local Institution - 0010
Córdoba, 5000
Site 0010
- Not yet recruiting
Local Institution - 0012
Córdoba, 5000
Site 0012
- Not yet recruiting
Local Institution - 0008
Córdoba, X5003DCE
Site 0008
- Not yet recruiting
Local Institution - 0009
Mendoza, 5502
Site 0009
- Not yet recruiting
Local Institution - 0114
Santiago del Estero, 4200
Site 0114
Bulgaria5 sites, 5 recruiting
- Not yet recruiting
Local Institution - 0184
Kazanlak, Stara Zagora, 6100
Site 0184
- Recruiting
State Psychiatric Hospital Sv. Ivan Rilski Novi Iskar
Novi Iskar, 1282
Tsveteslava Galabova, Site 0124, 359892444643
- Recruiting
"University Multiprofile Hospital for Active Treatment - Dr. Georgi Stranski" EAD
Pleven, 5800
Maya Stoimenova - Popova, Site 0125, +359888227165
- Not yet recruiting
Local Institution - 0181
Sliven, 8800
Site 0181
- Not yet recruiting
Local Institution - 0086
Targovishte, 7700
Site 0086
France5 sites, 3 recruiting
- Not yet recruiting
Local Institution - 0085
Clermont-Ferrand, Puy-de-Dôme, 63000
Site 0085
- Withdrawn
Local Institution - 0087
Marseille, 13274
- Not yet recruiting
Local Institution - 0129
Montpellier, 34295
Site 0129
- Not yet recruiting
Local Institution - 0126
Nice, Alpes-Maritimes, 06000
Site 0126
- Withdrawn
Local Institution - 0089
Paris, 75014
Israel5 sites, 5 recruiting
- Not yet recruiting
Local Institution - 0053
Ashkelon, Southern District, 7830604
Site 0053
- Recruiting
Be'er Sheva Mental Health Center
Beersheba, Southern District, 8461144
Yuli Bersudsky, Site 0199
- Not yet recruiting
Local Institution - 0052
Hod HaSharon, Central District, 4534708
Site 0052
- Not yet recruiting
Local Institution - 0083
Jerusalem, 9112001
Site 0083
- Recruiting
Sheba Medical Center
Ramat Gan, Central District, 5265601
Linda Levi-Haramati, Site 0050, 0585950299
Italy5 sites, 5 recruiting
- Not yet recruiting
Local Institution - 0004
Ancona, 60126
Site 0004
- Not yet recruiting
Local Institution - 0002
Genova, 16132
Site 0002
- Recruiting
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
Milan, Lombardy, 20122
Paolo Brambilla, Site 0003, 0255035982
- Not yet recruiting
Local Institution - 0005
Pisa, Tuscany, 56126
Site 0005
- Recruiting
Azienda Ospedaliero Universitaria Senese
Siena, Tuscany, 53100
Andrea Fagiolini, Site 0001, +390577585409
India4 sites, 4 recruiting
- Not yet recruiting
Local Institution - 0118
Kolkata, West Bengal, 700025
Site 0118
- Not yet recruiting
Local Institution - 0116
Kolkata, 700014
Site 0116
- Not yet recruiting
Local Institution - 0123
Madurai, Tamil Nadu, 625020
Site 0123
- Not yet recruiting
Local Institution - 0121
Mangalore, Karnataka, 575003
Site 0121
Poland4 sites, 4 recruiting
- Recruiting
Uniwersyteckie Centrum Kliniczne
Gdansk, Pomeranian Voivodeship, 80-214
Wieslaw Cubala, Site 0113, +48503642588
- Not yet recruiting
Local Institution - 0103
Rybnik, Silesian Voivodeship, 44-200
Site 0103
- Recruiting
Clinica Inventiva
Tuszyn, 95-080
Jaroslaw Strzelec, Site 0082, 602305132
- Recruiting
Instytut Psychiatrii i Neurologii
Warsaw, Masovian Voivodeship, 02-957
Adam Wichniak, Site 0104, +48600-107-410
Denmark3 sites, 3 recruiting
- Not yet recruiting
Local Institution - 0054
Aalborg, North Denmark, 9000
Site 0054
- Not yet recruiting
Local Institution - 0091
Glostrup Municipality, 2600
Site 0091
- Not yet recruiting
Local Institution - 0088
Hillerød, Capital Region, 3400
Site 0088
About this study
Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled, Study to Evaluate the Efficacy and Safety of Adjunctive KarXT for the Treatment of Mania, With or Without Mixed Features, in Individuals With Bipolar-I Disorder Taking Lithium, Valproate, or Lamotrigine
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
- Being tested
- Xanomeline/Trospium Chloride, Placebo
- Keywords
- Bipolar-I Disorder, Mania, KarXT, adjunctive treatment, mood stabilizer
- Medical subject headings
- Mania, Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Xanomeline/Trospium ChlorideDrug
Also called KarXT, BMS-986510
Specified dose on specified days
PlaceboDrug
Specified dose on specified days
| Study group | Role | What they receive |
|---|---|---|
| KarXT + Lithium, Valproate, or Lamotrigine | Experimental | Not described Receives: Drug: Xanomeline/Trospium Chloride |
| Placebo + Lithium, Valproate, or Lamotrigine | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in Young Mania Rating Scale (YMRS) at Week 5
Measured: At Week 5
Secondary outcomes (11)
Change from baseline in Clinical Global Impressions Bipolar (CGI-BP) at Week 5
Measured: 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
Measured: At Week 5
Occurrence of response at Week 5 assessed as the number of participants with a ≥ 1 change from baseline in CGI-BP
Measured: At Week 5
Number of participants with Treatment-emergent Adverse Events (TEAEs)
Measured: Up to Week 7
Number of participants with Serious Adverse Events (SAEs)
Measured: Up to Week 7
Number of participants with TEAEs leading to treatment discontinuation
Measured: Up to Week 5
Change from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS)
Measured: Up to Week 7
Change from baseline in Barnes Akathisia Rating Scale (BARS) at Week 5
Measured: At Week 5
Change from baseline in Simpson Angus Scale (SAS) at Week 5
Measured: At Week 5
Change from baseline in Abnormal Involuntary Movement Scale (AIMS) at Week 5
Measured: At Week 5
Change from baseline in International Prostate Symptom Score (IPSS) at Week 5
Measured: At Week 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2025
- Study start8 Oct 2025
- Primary completion28 Jun 2027 (estimated)
- Study completion28 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ManiaStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 424 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07140913
- Sponsor's protocol ID
- CN012-0046
- Other IDs
- 2025-521845-26, U1111-1321-1513, 2025
- Status last verified
- Jun 2026
- First submitted
- 21 Aug 2025
- Last updated
- 23 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myer Squibb's data sharing policy and process can be found at https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html