Health Condition 1: F312- Bipolar disorder, current episodemanic severe with psychotic features
Conditions
Interventions
Intervention1: KarXT Arm:
Intervention: KarXT (xanomeline/trospium chloride)
Dosage Levels: Flexible dosing with the following possible strengths, administered orally, twice daily (BID):
50 mg/20 mg
Sponsors
BRISTOL MYERS SQUIBB INDIA PRIVATE LIMITED
Eligibility
Inclusion criteria
Inclusion criteria: 1) Participants must be able and willing to sign and date an IRB/IEC-approved written ICF in accordance with regulatory, local, and institutional guidelines. This ICF must be obtained before performing any protocol-related procedures that are not part of normal participant care. Participant must be fluent in the language of the ICF to consent. Type of Participant and Target Disease Characteristics 2) Primary diagnosis of Bipolar-I disorder established by a comprehensive psychiatric evaluation based on the DSM-5-TR criteria18 and confirmed by the Mini International Neuropsychiatric Interview (MINI, v7.0.2). 3) Experiencing an acute episode or relapse of mania or mania with mixed features (less than or equal to 3 weeks) based on DSM-5-TR criteria.18 4) Young Mania Rating Scale (YMRS) score of greater than or equal to 20 at Screening and at Baseline. 5) CGI-BP score of greater than or equal to 4 at screening and at baseline. 6) Requires hospitalization for acute exacerbation or relapse of mania. 7) Hospitalized voluntarily before or during Screening with a mania diagnosis not greater than 21 days before Screening. Hospital admission must be a result of the current manic episode. (See Appendix 4 for country-specific requirements). 8) Body mass index greater than or equal to 18 and less than or equal to 40 kg/m2. 9) All psychotropic medications are washed out in no more than 14 days prior to the first dose of the study drug. 10) Able to comprehend and satisfactorily comply with protocol requirements per investigator judgment. Age of Participant 11) Aged 18 (or the legal age of consent in the jurisdiction in which the study is taking place, if higher) to 65 years of age, inclusive, at the time of signing the ICF. Reproductive Status Note: The investigator or designee shall counsel individuals of childbearing potential (IOCBP) (as defined in APPENDIX 3) and male (as assigned at birth) participants who are sexually active with IOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Note: The investigator or designee shall evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. Note: Local laws and regulations may require the use of alternative and/or additional contraceptive methods (see APPENDIX 4). 12) Female (as assigned at birth) participants: Note: Female (as assigned at birth) participants who are individuals not of childbearing potential (INOCBP) (as defined in APPENDIX 3) must have documented proof. Note: Documentation can be obtained from the site personnel s review of the participant s medical records, medical examination, or medical history interview. Note: Participants who are INOCBP are exempt from contraceptive requirements. a) IOCBP must have a negative highly sensitive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of study intervention. Note: A positive serum pregnancy test or an ambiguous urine pregnancy test must be repeated and sent to the central laboratory (serum sample). If either pregnancy test cannot be confirmed as negative (eg, an ambiguous result), the participant must be excluded from participation. Note: The investigator is responsible for rev
Exclusion criteria
Exclusion criteria: Psychiatric Conditions 1) Primary diagnosis of BP-I where present mania is first manic episode. 2) Primary diagnosis of BP-I with rapid cycling (ie, greater than or equal to 4 distinct mood episodes in one year). 3) 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. 4) A DSM-5-TR diagnosis of moderate to severe substance use disorder (except tobacco use disorder) within 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. a) Participants who test positive for cannabis at screening may be permitted to enroll in consultation with the medical monitor if the participant s pattern of use is not indicative of a substance use disorder. 5) Risk for suicidal behavior at screening as determined by the Investigator s clinical assessment, and/or C-SSRS as confirmed by the following: a) Answer Yes on items 4 or 5 (C-SSRS - ideation) within 6 months of screening, or between screening and baseline b) Answer Yes to any of the 5 items (C-SSRS - behavior) within 12 months of screening or between screening and baseline. 6) Currently receiving oral psychoactive drugs that cannot be safely discontinued in the 14 days of screening prior to first dose, or whose half-life is greater than 14 days. For participants receiving monthly long-acting injectables (LAIs), the last injection cannot be less than five weeks before the first dose. Participants on LAIs with a two-month frequency cannot have had their last injection less than 10 weeks before the first dose of study treatment. Participants on LAIs with longer frequency periods will be excluded. 7) Lifetime history of any clozapine use. 8) Had a separate psychiatric hospitalization(s), unrelated to the current manic episode, within 90 days before screening. 9) YMRS total score less than 20 at baseline or greater than or equal to 20% reduction in YMRS from screening to baseline. 10) If, in the opinion of the investigator (and/or Sponsor), participant is unsuitable for enrollment in the study, or the participant has any finding that in the view of the investigator (and/or Sponsor) may compromise the safety of the participant or affect their ability to adhere to the protocol visit schedule or fulfill visit requirements. General Medical Conditions 11) History or present illness suggestive of uncontrolled hyperthyroidism. 12) History of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months. 13) History or high risk of urinary retention, gastric retention, or untreated narrow-angle glaucoma. 14) History or presence of clinically significant cardiovascular (eg, untreated or unstable hypertension, clinically significant tachycardia), pulmonary, renal, hematologic, gastrointestinal (eg, obstructive disorders [including conditions that may decrease GI motility, such as ulcerative colitis, intestinal atony, and myasthenia gravis]), endocrine, immunologic, dermatologic, neurologic, or oncologic di
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in Young Mania Rating Scale (YMRS) total scoreTimepoint: 3 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Change in C-SSRS responses during treatmentTimepoint: Treatment Period;Change from baseline in Clinical Global Impression-Bipolar (CGI-BP) overall scoreTimepoint: Week 3;Occurrence of response based on greater than or equal to 50 present decrease from baseline in YMRS scoreTimepoint: Week 3;Occurrence of response based on CGI-BP change from baseline greater than or equal to 1Timepoint: Week 3;Occurrence of treatment-emergent adverse events (TEAEs), serious AEs (SAEs), and TEAEs leading to discontinuationTimepoint: Treatment Period;Change from baseline in movement disorder scales (BARS, SAS, AIMS, IPSS for males greater than or equal to 45)Timepoint: Week 3 | — |
Countries
Croatia, India, Israel, Romania, Slovakia, Spain, Sweden, United States of America
Contacts
Public ContactShilpi Sinha
Bristol-Myers Squibb India Pvt. Ltd.
Outcome results
None listed