A Phase 3 Study to Evaluate the Efficacy and Safety of Adjunctive KarXT for the Treatment of Mania, With or Without Mixed Features, in Bipolar-I Disorder Taking Lithium, Valproate, or Lamotrigine

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bristol-Myers Squibb Services Unlimited Company

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

2 Mar 2026 → ongoing

Decision date (initial)

2026-01-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2025-521845-26-00

WHO UTN

U1111-1321-1513

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

- To determine the superiority of KarXT plus lithium, valproate, or lamotrigine compared with placebo (pill with no medicine) plus lithium, valproate, or lamotrigine in reducing the severity of acute mania, with or without mixed features, in participants with BP-I.
- To determine if KarXT plus lithium, valproate or lamotrigine is better than placebo (“a dummy drug” with no medicine) plus lithium, valproate or lamotrigine in reducing the severity and symptoms of mania in participants with BP-I.

Secondary objectives 1

1. To determine whether people with mania associated with BP-I feel better overall when taking KarXT plus lithium, valproate or lamotrigine compared with placebo plus lithium, valproate or lamotrigine.

Conditions and MedDRA coding

BP-I mania or mania with mixed features

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myers Squibb's data sharing policy and process can be found at: https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosure-commitment.html.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Participant must be 18 to 65 years of age, inclusive, at the time of signing the ICF.
2. 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 Standard with Borderline Personality Disorder version.
3. Individual is experiencing an acute exacerbation or relapse of manic episode, with or without mixed features (≤ 3 weeks).
4. The individual requires hospitalization for the acute exacerbation or relapse of mania.
5. Body mass index ≥ 18 and ≤ 40 kg/m2
6. 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.
7. YMRS Total Score of ≥ 18 at Screening and at Baseline, and < 20% reduction in YMRS from screening to baseline.
8. Clinical Global Impression Severity scale (CGI-BP) ≥ 4

Exclusion criteria 8

1. Any primary DSM-5-TR disorder other than BP-I within 12 months before screening (confirmed using MINI version 7.0.2 Standard with Borderline Personality Disorder version at screening) including BP-I depression, BP-I with rapid cycling, first manic episode, BP-II, borderline personality disorder, and major depressive disorder.
2. 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 Standard with Borderline Personality Disorder version at screening), or current use as determined by urine toxicology screen or alcohol test.
3. 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 suicide attempt within 12 months before screening, or between screening and baseline
4. History of irritable bowel syndrome (with or without constipation) or any serious constipation requiring treatment within the last 6 months.
5. History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma.
6. Participants with HIV, cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections based on either medical history or the LFT results.
7. Elevations in hepatic transaminases at screening ≥ 2 × ULN for ALT and AST and/or bilirubin > 1.5× ULN, unless in the context of Gilbert’s syndrome.
8. All grades of hepatic impairment (mild [Child-Pugh Class A], moderate [Child-Pugh Class B], and severe [Child-Pugh Class C]).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in Young Mania Rating Scale (YMRS, used to evaluate manic symptoms) score at Week 5.

Secondary endpoints 1

1. Change from baseline in CGI-BP (used to evaluate daily functioning) at Week 5.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bristol-Myers Squibb Services Unlimited Company

Sponsor organisation

Bristol-Myers Squibb Services Unlimited Company

Address

Plaza 254, Blanchardstown Corporate Park 2 Blanchardstown Corporate Park 2

City

Dublin 15

Postcode

D15 T867

Country

Ireland

Scientific contact point

Organisation

Bristol-Myers Squibb Services Unlimited Company

Contact name

GSM-CT

Public contact point

Organisation

Bristol-Myers Squibb Services Unlimited Company

Contact name

GSM-CT

Third parties 10

Locations

6 EU/EEA countries · 27 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 55 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications