A Phase 3 Study to Evaluate the Efficacy and Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder

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

25 Sep 2025 → ongoing

Decision date (initial)

2025-08-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-520195-94-00

WHO UTN

U1111-1316-7466

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To determine if KarXT is better than placebo (“dummy drug” with no medicine) 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 compared with placebo (dummy drug).

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

No

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 7

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, v7.0.2).
3. Individual is experiencing an acute episode or relapse of mania or mania with mixed features (≤ 3 weeks).
4. The individual requires hospitalization for the acute exacerbation or relapse of mania.
5. All psychotropic medications are washed out in no more than 14 days prior to the first dose of the study drug
6. Young Mania Rating Scale (YMRS) score of ≥ 20 at Screening and at Baseline.
7. Clinical Global Impressions-Bipolar (CGI-BP) ≥ 4 at Screening and at Baseline.

Exclusion criteria 6

1. Any primary DSM-5-TR disorder, other than BP-I with mania or mania with mixed features within 12 months before screening (ie, primary focus of treatment, confirmed using MINI version 7.0.2 at screening), including BP-I with depression (for previous 3 months only), BP-II disorder, major depressive disorder, and primary psychotic disorder, with the exception of mild anxiety disorders.
2. Primary diagnosis of BP-I with rapid cycling (≥ 4 distinct mood episodes in one year)
3. 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
4. Risk for suicidal behavior at screening as determined by the investigator’s clinical assessment and the C-SSRS with an answer “Yes” on items 4 or 5 (C-SSRS – ideation) within 6 months of screening, or "Yes” to any of 5 items (C-SSRS – behavior) within 12 months of screening or between screening and baseline.
5. History of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months.
6. History or high risk of urinary retention, gastric retention, or untreated narrow-angle glaucoma.

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 3.

Secondary endpoints 3

1. Change from baseline in CGI-BP (used to evaluate daily functioning) at Week 3.
2. Occurrence of TEAEs, SAEs, and TEAEs leading to treatment discontinuation and change in C-SSRS responses during the treatment period.
3. Change from baseline in BARS, SAS, AIMS, and IPSS (males aged ≥ 45 years only) at Week 3.

Investigational products

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

Test 3

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 13

Locations

5 EU/EEA countries · 21 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 47 files

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

Application history

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