Clinical trial NCT06929273: A Study to Assess the Long-term Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder (BALSAM-3)
Official title: A Phase 3, Open-label Extension Study to Assess the Long-term Safety of KarXT for the Treatment of Mania or Mania With Mixed Features in Bipolar-I Disorder (BALSAM-3)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Bipolar Disorder Type I With Mania
Keywords: Bipolar-I disorder
Mania
Bipolar-I disorder with Mania
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2025-04-16
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase 3, open-label extension study to assess the long-term safety of KarXT for the treatment of mania or mania with mixed features in Bipolar-I disorder (BP-I)

The primary objective of the study is to evaluate the long-term safety and tolerability of KarXT in the treatment of participants with mania or mania with mixed features associated with BP-I.


Eligibility criteria: Inclusion Criteria:

* Participants who participated in double-blind placebo-controlled study (CN0120036 or CN0120037):

  a. Participants must have completed treatment period of parent study.
* De novo participants who did not participate in double-blind placebo-controlled studies:

  1. Participants must have primary diagnosis of Bipolar-I disorder established by a comprehensive psychiatric evaluation based on DSM-5-TR criteria and confirmed by the Mini International Neuropsychiatric Interview (MINI, v7.0.2), with symptoms of mania or mixed mania.
  2. Participants must have Young Mania Rating Scale (YMRS) score of ≥ 14 at Screening and at baseline.
  3. Participants must have CGI-BP score of ≥ 3 at Screening and at baseline.
  4. Participants does not require hospitalization for acute mania.

Exclusion Criteria:

* Participants who participated in double-blind placebo-controlled study (CN0120036 or CN0120037):

  a. Discontinuation from any KarXT parent studies.
* De novo participants who did not participate in double-blind placebo-controlled studies:

  1. All participants with a risk for suicidal behavior at baseline as determined by Investigator's clinical assessment or history of suicidal behavior as assessed on C-SSRS.
  2. Participants must not have primary diagnosis of BP-I with rapid cycling (ie, ≥ 4 distinct mood episodes in one year).
  3. Participants must not have any primary DSM-5-TR disorder other than BP-I with mania or mania with mixed features within 12 months before Screening (confirmed using MINI version 7.0.2 at Screening), including BP-I with depression, (previous 3 months only), Bipolar-II disorder, major depressive disorder, and primary psychotic disorder, with the exception of mild anxiety disorders.
  4. 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.
  5. Participants must not have history of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months.
  6. Participants must not have history or high risk of urinary retention, gastric retention, or untreated narrow-angle glaucoma.
  7. Other protocol-defined Inclusion/Exclusion criteria apply.

Primary outcomes:
measure: Number of participants with treatment emergent adverse events (TEAEs)
timeFrame: Up to week 54
Secondary outcomes:
measure: Number of participants with AEs of special interest (AESIs)
timeFrame: Up to week 54
measure: Number of participants with serious AEs (SAEs)
timeFrame: Up to week 54
measure: Number of participants with TEAEs leading to treatment discontinuation
timeFrame: Up to week 54
measure: Number of participants with change in suicidal ideation as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Up to week 54
measure: Change from baseline in Barnes Akathisia Rating Scale (BARS) score
timeFrame: Up to week 54
measure: Change from baseline in Simpson Angus Scale (SAS) score
timeFrame: Up to week 54
measure: Chnage from baseline in Abnormal Involuntary Movement Scale (AIMS) score
timeFrame: Up to week 54
measure: Change from baseline in International Prostate Symptom Score (IPSS)
timeFrame: Up to week 54
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Local Institution - 0120
state: Arizona
city: Bentonville
country: United States
facility: Local Institution - 0022
state: Arkansas
city: Little Rock
country: United States
facility: Local Institution - 0021
state: Arkansas
city: Little Rock
country: United States
facility: Local Institution - 0038
state: Arkansas
city: Rogers
country: United States
facility: Local Institution - 0057
state: Arkansas
city: Anaheim
country: United States
facility: Local Institution - 0027
state: California
city: Cerritos
country: United States
facility: Local Institution - 0044
state: California
city: Culver City
country: United States
facility: Local Institution - 0037
state: California
city: Garden Grove
country: United States
facility: Local Institution - 0085
state: California
city: Montclair
country: United States
facility: Local Institution - 0056
state: California
city: Orange
country: United States
facility: Local Institution - 0039
state: California
city: Riverside
country: United States
facility: Local Institution - 0043
state: California
city: Santa Ana
country: United States
facility: Local Institution - 0050
state: California
city: Torrance
country: United States
facility: Local Institution - 0123
state: California
city: Hialeah Gardens
country: United States
facility: Local Institution - 0026
state: Florida
city: Hollywood
country: United States
facility: Local Institution - 0059
state: Florida
city: Hollywood
country: United States
facility: Local Institution - 0053
state: Florida
city: Miami Lakes
country: United States
facility: Local Institution - 0047
state: Florida
city: Miami Springs
country: United States
facility: Local Institution - 0025
state: Florida
city: Miami
country: United States
facility: Local Institution - 0030
state: Florida
city: Miami
country: United States
facility: Local Institution - 0028
state: Florida
city: Saint Petersburg
country: United States
facility: Local Institution - 0045
state: Florida
city: Stuart
country: United States
facility: Local Institution - 0032
state: Florida
city: Atlanta
country: United States
facility: Local Institution - 0052
state: Georgia
city: Atlanta
country: United States
facility: Local Institution - 0054
state: Georgia
city: Decatur
country: United States
facility: Local Institution - 0023
state: Georgia
city: Savannah
country: United States
facility: Local Institution - 0024
state: Georgia
city: Chicago
country: United States
facility: Local Institution - 0031
state: Illinois
city: Chicago
country: United States
facility: Local Institution - 0020
state: Illinois
city: Gaithersburg
country: United States
facility: Local Institution - 0049
state: Maryland
city: Flowood
country: United States
facility: Local Institution - 0029
state: Mississippi
city: Saint Louis
country: United States
facility: Local Institution - 0042
state: Missouri
city: North Las Vegas
country: United States
facility: Local Institution - 0121
state: Nevada
city: North Las Vegas
country: United States
facility: Local Institution - 0122
state: Nevada
city: Marlton
country: United States
facility: Local Institution - 0058
state: New Jersey
city: Staten Island
country: United States
facility: Local Institution - 0033
state: New York
city: Charlotte
country: United States
facility: Local Institution - 0124
state: North Carolina
city: Cincinnati
country: United States
facility: Local Institution - 0055
state: Ohio
city: North Canton
country: United States
facility: Local Institution - 0040
state: Ohio
city: DeSoto
country: United States
facility: Local Institution - 0048
state: Texas
city: Houston
country: United States
facility: Local Institution - 0046
state: Texas
city: Irving
country: United States
facility: Local Institution - 0036
state: Texas
city: Richardson
country: United States
facility: Local Institution - 0034
state: Texas
city: ABB
country: Argentina
facility: Local Institution - 0128
state: Ciudad Autónoma De Buenos Aires
city: Córdoba
country: Argentina
facility: Local Institution - 0127
city: Mendoza
country: Argentina
facility: Local Institution - 0126
city: St Leonards
country: Australia
facility: Local Institution - 0105
state: New South Wales
city: Brisbane
country: Australia
facility: Local Institution - 0087
state: Queensland
city: Burgas
country: Bulgaria
facility: Local Institution - 0082
city: Novi Iskar
country: Bulgaria
facility: Local Institution - 0107
city: Pleven
country: Bulgaria
facility: Local Institution - 0081
city: Sliven
country: Bulgaria
facility: Local Institution - 0113
city: Vratsa
country: Bulgaria
facility: Local Institution - 0114
city: Zagreb
country: Croatia
facility: Local Institution - 0018
state: Grad Zagreb
city: Zagreb
country: Croatia
facility: Local Institution - 0017
city: Zagreb
country: Croatia
facility: Local Institution - 0019
city: Zagreb
country: Croatia
facility: Local Institution - 0103
city: Győr
country: Hungary
facility: Local Institution - 0109
state: Győr-Moson-Sopron
city: Budapest
country: Hungary
facility: Local Institution - 0110
city: Budapest
country: Hungary
facility: Local Institution - 0108
city: Vadodara
country: India
facility: Local Institution - 0111
state: Gujarat
city: Kozhikode
country: India
facility: Local Institution - 0079
state: Kerala
city: Hyderabad
country: India
facility: Local Institution - 0078
state: Telangana
city: Hyderabad
country: India
facility: Local Institution - 0080
state: Telangana
city: Kolkata
country: India
facility: Local Institution - 0076
state: West Bengal
city: Ludhiana
country: India
facility: Local Institution - 0077
city: Be'er Sheva
country: Israel
facility: Local Institution - 0106
state: HaDarom
city: Hod HaSharon
country: Israel
facility: Local Institution - 0068
state: HaMerkaz
city: Ness Ziona
country: Israel
facility: Local Institution - 0075
state: HaMerkaz
city: Petah Tikva
country: Israel
facility: Local Institution - 0084
state: HaMerkaz
city: Ramat Gan
country: Israel
facility: Local Institution - 0067
state: HaMerkaz
city: Jerusalem
country: Israel
facility: Local Institution - 0074
city: Milano
country: Italy
facility: Local Institution - 0066
state: Lombardia
city: Pisa
country: Italy
facility: Local Institution - 0083
state: Toscana
city: Siena
country: Italy
facility: Local Institution - 0065
state: Toscana
city: Ancona
country: Italy
facility: Local Institution - 0070
city: Genova
country: Italy
facility: Local Institution - 0069
city: Konan
country: Japan
facility: Local Institution - 0008
state: Aichi
city: Toyoake
country: Japan
facility: Local Institution - 0003
state: Aichi
city: Ichikawa
country: Japan
facility: Local Institution - 0001
state: Chiba
city: Kitakyushu
country: Japan
facility: Local Institution - 0063
state: Fukuoka
city: Obihiro
country: Japan
facility: Local Institution - 0015
state: Hokkaido
city: Sapporo
country: Japan
facility: Local Institution - 0005
state: Hokkaido
city: Sakai-shi
country: Japan
facility: Local Institution - 0007
state: Osaka
city: Karatsu-shi
country: Japan
facility: Local Institution - 0011
state: Saga-Ken
city: Iruma
country: Japan
facility: Local Institution - 0016
state: Saitama
city: Kumagaya
country: Japan
facility: Local Institution - 0012
state: Saitama
city: Itabashi City
country: Japan
facility: Local Institution - 0009
state: Tokyo
city: Kodaira
country: Japan
facility: Local Institution - 0072
state: Tokyo
city: Fukuoka
country: Japan
facility: Local Institution - 0006
city: Miyazaki
country: Japan
facility: Local Institution - 0004
city: Osaka
country: Japan
facility: Local Institution - 0010
city: Osaka
country: Japan
facility: Local Institution - 0013
city: Tokyo
country: Japan
facility: Local Institution - 0073
city: Wakayama
country: Japan
facility: Local Institution - 0002
city: Yamagata
country: Japan
facility: Local Institution - 0014
city: Auckland
country: New Zealand
facility: Local Institution - 0086
city: Warsaw
country: Poland
facility: Local Institution - 0092
state: Mazowieckie
city: Bialystok
country: Poland
facility: Local Institution - 0090
state: Podlaskie
city: Gdańsk
country: Poland
facility: Local Institution - 0093
state: Pomorskie
city: Poznań
country: Poland
facility: Local Institution - 0088
state: Wielkopolskie
city: Tuszyn
country: Poland
facility: Local Institution - 0091
state: Łódzkie
city: Chorzów
country: Poland
facility: Local Institution - 0089
state: Śląskie
city: Bucharest
country: Romania
facility: Local Institution - 0095
state: București
city: Bucharest
country: Romania
facility: Local Institution - 0096
state: București
city: Bucharest
country: Romania
facility: Local Institution - 0098
state: București
city: Bucharest
country: Romania
facility: Local Institution - 0099
state: București
city: Bucharest
country: Romania
facility: Local Institution - 0101
state: București
city: Bucharest
country: Romania
facility: Local Institution - 0102
state: București
city: Bucharest
country: Romania
facility: Local Institution - 0104
state: București
city: București
country: Romania
facility: Local Institution - 0094
city: Iași
country: Romania
facility: Local Institution - 0097
city: Sanpetru /Brasov
country: Romania
facility: Local Institution - 0100
city: Kosice
country: Slovakia
facility: Local Institution - 0118
state: Košický Kraj
city: Košice
country: Slovakia
facility: Local Institution - 0119
state: Košický Kraj
city: Vranov nad Topľou
country: Slovakia
facility: Local Institution - 0117
state: Prešovský Kraj
city: Barcelona
country: Spain
facility: Local Institution - 0115
state: Barcelona [Barcelona]
city: Barcelona
country: Spain
facility: Local Institution - 0071
state: Catalunya [Cataluña]
city: Bilbo
country: Spain
facility: Local Institution - 0064
state: País Vasco
city: Nacka
country: Sweden
facility: Local Institution - 0125
state: Stockholms Län [se-01]
city: Uppsala
country: Sweden
facility: Local Institution - 0112
state: Uppsala Län [se-03]
city: Gothenburg
country: Sweden
facility: Local Institution - 0116
state: Västra Götalands Län [se-14]
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: