A Phase 3 Open-label Extension Study to Assess the Long-term Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder

Start 25 Sep 2025 · Status Authorised, recruiting · 9 EU/EEA countries · 42 sites · Protocol CN012-0038

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)

Status Authorised, recruiting

Participants planned 438

Countries 9

Sites 42

Mania or Mania with Mixed Features in Bipolar-I Disorder

To determine the long-term safety and tolerability of KarXT as monotherapy or as an add-on treatment for mania or mania with mixed features in bipolar-I disorder.

Key facts

Sponsor: Bristol-Myers Squibb Services Unlimited Company
Participant type: Patients
Age range: 18-64 years, 65+ years
Gender: Male and Female
Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]
Trial duration: 25 Sep 2025 → ongoing
Decision date (initial): 2025-09-01
Transition trial: No
Low-intervention: No
Rare-disease indication: No
Vulnerable population: No

External identifiers

EU CT number: 2024-520259-26-00
WHO UTN: U1111-1316-9287
ClinicalTrials.gov: NCT06929273

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

To determine the long-term safety and tolerability of KarXT as monotherapy or as an add-on treatment for mania or mania with mixed features in bipolar-I disorder.

Secondary objectives 1

To assess serious adverse events (SAEs), adverse events of special interest (AESIs), and discontinuations due to side effects. To monitor changes in suicidal ideation and behavior, movement disorders, and urinary symptoms.

Conditions and MedDRA coding

Mania or Mania with Mixed Features in Bipolar-I Disorder

Version	Level	Code	Term	System organ class
22.1	LLT	10026751	Mania aggravated	10037175
21.1	LLT	10004927	Bipolar affective disorder mixed	10037175
20.0	LLT	10004924	Bipolar affective disorder manic severe degree specified as with psychotic behavior	10037175
20.0	PT	10026749	Mania	100000004873
20.0	LLT	10004932	Bipolar affective disorder mixed severe degree specified as with psychotic behavior	10037175
20.0	LLT	10004925	Bipolar affective disorder manic severe degree without mention of psychotic behavior	10037175
20.0	LLT	10026750	Mania acute	10037175
21.1	LLT	10004919	Bipolar affective disorder manic	10037175
20.0	LLT	10004933	Bipolar affective disorder mixed severe degree without mention of psychotic behavior	10037175

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 4

Participants must be between 18-65 years old.
Participant must have a diagnosis of Bipolar-I disorder.
If participants are taking lithium, valproate, or lamotrigine, their dose should be stable.
Participants must be able to understand the study and agree to take part.

Exclusion criteria 3

Participants cannot join if they have a high risk of suicide or violent behavior, serious heart, liver, or kidney problems, are pregnant or breastfeeding, or have recently used medicines that cannot be safely stopped
The study excludes people with certain conditions that could be made worse by the study drug (due to its cholinergic activities), such as trouble urinating (urinary retention), stomach problems that slow digestion (gastric retention), untreated eye problems (narrow-angle glaucoma), irritable bowel syndrome, or serious constipation
Participants will be excluded from the study if they fail a urine drug screen or alcohol test when they come in for screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

To track any side effects that participants experience while receiving the treatment.

Secondary endpoints 3

To monitor for: serious side effects, specific side effects of concern, side effects that cause participants to stop treatment.
To observe any changes in how participants respond to questions about suicidal thoughts or behaviors.
To measure changes from the beginning of the study in: Movement and coordination (using tests like BARS, SAS, and AIMS); Urinary symptoms (for male participants aged 45 and older, using the IPSS questionnaire).

Investigational products

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

Test 4

KarXT

PRD12327546 · Product

Active substance: Trospium Chloride
Pharmaceutical form: CAPSULE
Route of administration: ORAL
Max daily dose: 10099940 mg milligram(s)
Max total dose: 700999280 mg milligram(s)
Max treatment duration: 1 Week(s)
Authorisation status: Not Authorised
MA holder: BRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATION
Paediatric formulation: No
Orphan designation: No

KarXT

PRD12327584 · Product

Active substance: Trospium Chloride
Pharmaceutical form: CAPSULE
Route of administration: ORAL
Max daily dose: 25099960 mg milligram(s)
Max total dose: 127509993060 mg milligram(s)
Max treatment duration: 51 Week(s)
Authorisation status: Not Authorised
MA holder: BRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATION
Paediatric formulation: No
Orphan designation: No

KarXT

PRD12327577 · Product

Active substance: Trospium Chloride
Pharmaceutical form: CAPSULE
Route of administration: ORAL
Max daily dose: 20099940 mg milligram(s)
Max total dose: 102009992040 mg milligram(s)
Max treatment duration: 51 Week(s)
Authorisation status: Not Authorised
MA holder: BRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATION
Paediatric formulation: No
Orphan designation: No

KarXT

PRD12327569 · Product

Active substance: Trospium Chloride
Pharmaceutical form: CAPSULE
Route of administration: ORAL
Max daily dose: 15099940 mg milligram(s)
Max total dose: 76509992040 mg milligram(s)
Max treatment duration: 51 Week(s)
Authorisation status: Not Authorised
MA holder: BRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATION
Paediatric formulation: No
Orphan designation: No

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 14

Organisation	City, country	Duties
Labcorp Central Laboratory Services LP ORG-100032236	Indianapolis, United States	Other
WCG Clinical Inc. ORG-100040730	Princeton, United States	Other
Labcorp Central Laboratory Services SARL ORG-100011524	Meyrin, Switzerland	Other
Accenture Solutions Private Limited ORG-100032592	Bangaluru, India	Other
Medidata Solutions Inc. ORG-100016256	New York, United States	Data management
Syneos Health Clinique Inc. ORG-100028348	Quebec, Canada	Other
Accenture Solutions Private Limited ORG-100032592	Bangaluru, India	Other
Greenphire LLC ORG-100041621	King Of Prussia, United States	Other
Accenture Solutions Private Limited ORG-100032592	Bangaluru, India	Other
Iqvia Inc. ORG-100010622	Durham, United States	Other
Signant Health Global LLC ORG-100040604	Blue Bell, United States	Other
EndPoint Clinical Inc. ORL-000012578	Wakefield, United States	Other
Accenture Solutions Private Limited ORG-100032592	Chennai, India	Other
Azenta US Inc. ORG-100012907	Indianapolis, United States	Other

Locations

9 EU/EEA countries · 42 investigational sites

By country

Country	MS status	Planned subjects	Sites
Bulgaria	Authorised, recruitment pending	23	6
Croatia	Authorised, recruiting	7	4
Hungary	Authorised, recruiting	8	3
Italy	Authorised, recruitment pending	12	5
Poland	Authorised, recruiting	34	6
Romania	Authorised, recruitment pending	60	11
Slovakia	Authorised, recruitment pending	5	3
Spain	Authorised, recruiting	6	3
Sweden	Authorised, recruiting	5	1
Rest of world India, Japan, United States, New Zealand, Argentina, Australia, Israel	—	278	—

Investigational sites

Bulgaria

6 sites · Authorised, recruitment pending

"Multiprofile Hospital for Active Treatment Dr. Hristo Stambolski" EOOD, Kazanlak

Psychiatry Level II, 16 "Starozagorska" Str., 6100, Kazanlak

Center For Mental Health Prof. Dr. Ivan Temkov Burgas EOOD

Department for Treatment of Emergency Psychiatric Conditions - Psychiatry Level III, Complex Lazur, Lake Park, Burgas

MBAL Dr. Ivan Seliminski - Sliven AD

Department-Psychiatry Level II, Bulevard Hristo Botev 1, 8801, Sliven

Center For Mental Health Vratsa EOOD

Department of General Psychiatry Psychiatry-Level III, Belasita Str 1, 3000, Vratsa

University Multiprofile Hospital For Active Treatment Dr. Georgi Stranski EAD

First Psychiatric Clinic-Psychiatry Level III, Ulitsa Storgoziya 113, 5802, Pleven

State Psychiatric Saint Ivan Rilski Hospital

Department of General Psyhiatry-closed type for adult-men Department of General Psyhiatry-closed ty, Ulitsa Hristo Botev 140, 1282, Novi Iskir

Croatia

4 sites · Authorised, recruiting

Klinika za psihijatriju Vrapce

Zavod za psihotične poremećaje ženski, Bolnicka Cesta 32, Zagreb, Grad Zagreb

Clinic for psychiatry Sveti Ivan

Psychiatry, Jankomir 11, Zagreb, Grad Zagreb

Klinika za psihijatriju Vrapce

Zavod za biologijsku psihijatriju i psihogerijatriju, Bolnicka Cesta 32, Zagreb, Grad Zagreb

Klinika za psihijatriju Vrapce

Zavod za oporavak i podršku zajednici, Bolnicka Cesta 32, Zagreb, Grad Zagreb

Hungary

3 sites · Authorised, recruiting

Nyiro Gyula Orszagos Pszichiatriai Es Addiktologiai Intezet

Gyula Nyírő National Institute of Psychiatry and Addiction, Lehel Utca 59/XIII, XIII Kerulet, Budapest

Gyor-Moson-Sopron Varmegyei Petz Aladar Egyetemi Oktato Korhaz

Department of Psychiatry, Mental Health and Addiction, Vasvari Pal Utca 2-4, 9024, Gyor

Semmelweis University

Department of Psychiatry and Psychotherapy, Balassa J Utca 6, 1083, Budapest

Italy

5 sites · Authorised, recruitment pending

Azienda Ospedaliero Universitaria Pisana

UO Psichiatria 2, Via Roma 67, 56126, Pisa

IRCCS Azienda Ospedaliera Metropolitana

Clinica Psichiatrica, Largo Rosanna Benzi 10, 16132, Genoa

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

SC Psichiatria, Via Francesco Sforza 35, 20122, Milan

Azienda Ospedaliero-Universitaria Senese

U.O.C. Psichiatria, Strada Delle Scotte 14, 53100, Siena

Azienda Ospedaliero Universitaria Delle Marche

Clinica Psichiatrica, Via Conca 71, 60126, Ancona

Poland

6 sites · Authorised, recruiting

Instytut Psychiatrii I Neurologii

III Klinika Psychiatryczna, Ul. Jana III Sobieskiego 9, 02-957, Warsaw

Centrum Medyczne Hcp Sp. z o.o.

Oddzial Dzienny Psychiatryczny, Ul. 28 Czerwca 1956 R. 194, 61-485, Poznan

Uniwersytecki Szpital Kliniczny W Bialymstoku

Klinika Psychiatrii, Ul. Wolodyjowskiego 2, 15-272, Bialystok

NZOZ Prywatna Klinika Psychiatryczna INVENTIVA

N/A, Polna 16, 95-080, Tuszyn

M2M Med. Sp. z o.o. Sp. j.

Oddział w Rybniku, Ul. Gliwicka 33, 44-200, Rybnik

Uniwersyteckie Centrum Kliniczne

Klinika Psychiatrii Dorosłych, Ul. Mariana Smoluchowskiego 17, 80-214, Gdansk

Romania

11 sites · Authorised, recruitment pending