Clinical trial NCT06951711: A Study to Evaluate the Efficacy and Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder (BALSAM-2)
Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder (BALSAM-2)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Bipolar Disorder Type I With Mania or Mania With Mixed Features
Keywords: Bipolar-I disorder
Mania
Bipolar-I disorder with Mania
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2025-04-30
Enrollment: 274
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 3, randomized, double-blind, placebo-controlled, multicenter, inpatient study in participants with bipolar disorder experiencing an acute episode of mania or mania with mixed features.

The primary objective of the study is to evaluate the efficacy of KarXT compared to placebo in treating symptoms of mania during a 3-week inpatient period. The duration of the study including screening, the double-blind inpatient treatment period and safety-follow-up is no more than seven weeks.


Eligibility criteria: Inclusion Criteria:

* Participants must have a primary diagnosis of Bipolar-I disorder established by a comprehensive psychiatric evaluation.
* Participants must be experiencing an acute episode or relapse of mania or mania with mixed features (≤ 3 weeks).
* Participants must require hospitalization for the acute exacerbation or relapse of mania.
* Participants must have all psychotropic medications washed out in no more than 14 days prior to the first dose of the study drug.
* Participants must have a Young Mania Rating Scale (YMRS) score of ≥ 20 at Screening and at Baseline.
* Participants must have a Clinical Global Impressions-Bipolar (CGI-BP) ≥ 4 at Screening and at Baseline.

Exclusion Criteria:

* Participants must not have any primary Diagnostic and Statistical Manual of Mental Disorders (5th Edition, Text Revision) (DSM-5-TR) disorder, other than BP-I with mania or mania with mixed features within 12 months before 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.
* Participants must not have a primary diagnosis of BP-I with rapid cycling (≥ 4 distinct mood episodes in one year).
* Participants must not have a DSM-5-TR diagnosis of moderate to severe substance use disorder (except tobacco use disorder) within the 12 months before screening, or current use as determined by urine toxicology screen or alcohol test.
* Participants must not be at risk for suicidal behavior at screening or the baseline visit as determined by the Investigator's clinical assessment and the Columbia-Suicide Severity Rating Scale (C-SSRS).
* Participants must not have cirrhosis, liver cancer, clinically significant liver disease based on the liver function test results.
* Other protocol-defined Inclusion/Exclusion criteria apply.

Primary outcomes:
measure: Change from baseline in Young Mania Rating Scale (YMRS) score
timeFrame: At week 3
Secondary outcomes:
measure: Change from baseline in Clinical Global Impressions-Bipolar (CGI-BP)
timeFrame: At week 3
measure: Occurrence of response based on ≥ 50% decrease from baseline in YMRS score or total score
timeFrame: At week 3
measure: Occurrence of response based on change from baseline ≥ 1 in CGI-BP
timeFrame: At week 3
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Local Institution - 0014
state: Arkansas
city: Rogers
country: United States
facility: Local Institution - 0025
state: Arkansas
city: Culver City
country: United States
facility: Local Institution - 0021
state: California
city: Riverside
country: United States
facility: Local Institution - 0018
state: California
city: Torrance
country: United States
facility: Local Institution - 0074
state: California
city: Hialeah Gardens
country: United States
facility: Local Institution - 0036
state: Florida
city: Hollywood
country: United States
facility: Local Institution - 0032
state: Florida
city: Miami Springs
country: United States
facility: Local Institution - 0015
state: Florida
city: Miami
country: United States
facility: Local Institution - 0026
state: Florida
city: Saint Petersburg
country: United States
facility: Local Institution - 0019
state: Florida
city: Atlanta
country: United States
facility: Local Institution - 0022
state: Georgia
city: Decatur
country: United States
facility: Local Institution - 0016
state: Georgia
city: Chicago
country: United States
facility: Local Institution - 0020
state: Illinois
city: Gaithersburg
country: United States
facility: Local Institution - 0024
state: Maryland
city: Flowood
country: United States
facility: Local Institution - 0017
state: Mississippi
city: Saint Louis
country: United States
facility: Local Institution - 0023
state: Missouri
city: North Las Vegas
country: United States
facility: Local Institution - 0076
state: Nevada
city: Marlton
country: United States
facility: Local Institution - 0031
state: New Jersey
city: Charlotte
country: United States
facility: Local Institution - 0075
state: North Carolina
city: Cincinnati
country: United States
facility: Local Institution - 0029
state: Ohio
city: North Canton
country: United States
facility: Local Institution - 0038
state: Ohio
city: DeSoto
country: United States
facility: Local Institution - 0012
state: Texas
city: Houston
country: United States
facility: Local Institution - 0028
state: Texas
city: Richardson
country: United States
facility: Local Institution - 0037
state: Texas
city: Zagreb
country: Croatia
facility: Local Institution - 0009
state: Grad Zagreb
city: Zagreb
country: Croatia
facility: Local Institution - 0008
city: Zagreb
country: Croatia
facility: Local Institution - 0010
city: Zagreb
country: Croatia
facility: Local Institution - 0063
city: Vadodara
country: India
facility: Local Institution - 0065
state: Gujarat
city: Kozhikode
country: India
facility: Local Institution - 0053
state: Kerala
city: Hyderabad
country: India
facility: Local Institution - 0052
state: Telangana
city: Hyderabad
country: India
facility: Local Institution - 0055
state: Telangana
city: Kolkata
country: India
facility: Local Institution - 0054
state: West Bengal
city: Ludhiana
country: India
facility: Local Institution - 0051
city: Be'er Sheva
country: Israel
facility: Local Institution - 0066
state: HaDarom
city: Hod HaSharon
country: Israel
facility: Local Institution - 0042
state: HaMerkaz
city: Ness Ziona
country: Israel
facility: Local Institution - 0046
state: HaMerkaz
city: Petah Tikva
country: Israel
facility: Local Institution - 0058
state: HaMerkaz
city: Ramat Gan
country: Israel
facility: Local Institution - 0011
state: HaMerkaz
city: Jerusalem
country: Israel
facility: Local Institution - 0045
city: Milano
country: Italy
facility: Local Institution - 0001
state: Lombardia
city: Pisa
country: Italy
facility: Local Institution - 0056
state: Toscana
city: Siena
country: Italy
facility: Local Institution - 0007
state: Toscana
city: Ancona
country: Italy
facility: Local Institution - 0041
city: Genova
country: Italy
facility: Local Institution - 0040
city: Bucharest
country: Romania
facility: Local Institution - 0048
state: București
city: Bucharest
country: Romania
facility: Local Institution - 0049
state: București
city: Bucharest
country: Romania
facility: Local Institution - 0050
state: București
city: Bucharest
country: Romania
facility: Local Institution - 0059
state: București
city: Bucharest
country: Romania
facility: Local Institution - 0060
state: București
city: Bucharest
country: Romania
facility: Local Institution - 0062
state: București
city: Bucharest
country: Romania
facility: Local Institution - 0064
state: București
city: București
country: Romania
facility: Local Institution - 0057
city: Iași
country: Romania
facility: Local Institution - 0047
city: Sanpetru /Brasov
country: Romania
facility: Local Institution - 0061
city: Kosice
country: Slovakia
facility: Local Institution - 0071
state: Košický Kraj
city: Košice
country: Slovakia
facility: Local Institution - 0073
state: Košický Kraj
city: Vranov nad Topľou
country: Slovakia
facility: Local Institution - 0072
state: Prešovský Kraj
city: Barcelona
country: Spain
facility: Local Institution - 0069
state: Barcelona [Barcelona]
city: Barcelona
country: Spain
facility: Local Institution - 0044
state: Catalunya [Cataluña]
city: Bilbo
country: Spain
facility: Local Institution - 0039
state: País Vasco
city: Nacka
country: Sweden
facility: Local Institution - 0077
state: Stockholms Län [se-01]
city: Uppsala
country: Sweden
facility: Local Institution - 0067
state: Uppsala Län [se-03]
city: Gothenburg
country: Sweden
facility: Local Institution - 0070
state: Västra Götalands Län [se-14]
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: