KarXT for Mania

(BALSAM-1 Trial)

Recruiting at 96 trial locations

Overseen By BMS Study Connect www.BMSStudyConnect.com

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bristol-Myers Squibb

Must not be taking: Psychotropics

Disqualifiers: Substance use disorder, Suicidal risk, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

274 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called KarXT to determine its effectiveness for people with Bipolar-I Disorder experiencing manic episodes. Researchers aim to assess whether KarXT is safe and effective compared to a placebo, a non-active substance resembling the treatment. Suitable participants have been diagnosed with Bipolar-I Disorder and are currently experiencing a severe manic episode that may require hospitalization. Participants will receive either KarXT with flexible dosing or a placebo to evaluate the treatment's impact on their condition. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Do I need to stop my current medications to join the trial?

Yes, you will need to stop taking all psychotropic medications (drugs that affect mood, perception, or behavior) at least 14 days before starting the trial medication.

Is there any evidence suggesting that KarXT is likely to be safe for humans?

Research has shown that KarXT is generally well tolerated. One study found that the side effects of KarXT align with the action of its active ingredients in the body, meaning the side effects were expected and typical. Although the study did not list specific side effects, it suggests that most people can handle the treatment.

Additionally, advanced clinical trials are testing KarXT, indicating some confidence in its safety for humans. For those considering joining a trial, this information might be reassuring. Always consult a healthcare provider to discuss any concerns. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

KarXT is unique because it combines xanomeline, a muscarinic receptor agonist, with trospium, a peripheral muscarinic antagonist. This combination offers a novel way to address mania by targeting the muscarinic acetylcholine system, which is different from the usual dopamine-focused approach of current treatments like mood stabilizers and atypical antipsychotics. Researchers are excited because this mechanism could offer a new pathway to manage symptoms with potentially fewer side effects related to dopamine pathways, which are common in existing therapies.

What evidence suggests that KarXT might be an effective treatment for manic episodes in Bipolar-I Disorder?

Research has shown that KarXT, which participants in this trial may receive, may help treat symptoms of mania. In earlier studies, KarXT significantly improved symptoms compared to a placebo, as measured by a specific scale used to assess these symptoms. This indicates that the treatment can effectively reduce the severity of manic symptoms. KarXT has also demonstrated long-term benefits in treating schizophrenia, suggesting it might be effective for mania in Bipolar-I Disorder. These findings support the idea that KarXT could be a helpful option for managing manic episodes. ^{2 6 7 8 9}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for individuals with Bipolar-I Disorder experiencing a manic or mixed episode requiring hospitalization. They must score ≥20 on the YMRS, have a CGI-BP of ≥4, and be off psychotropic meds for up to 14 days before starting the study drug. Exclusions include substance use disorders within the last year (except tobacco), other primary DSM-5-TR diagnoses, high suicide risk, urinary or gastric retention risks, rapid cycling bipolar disorder, and recent serious constipation issues.

Inclusion Criteria

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

I am hospitalized due to a severe manic episode.

Exclusion Criteria

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 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 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)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive KarXT or placebo during a 3-week inpatient period to evaluate efficacy in treating manic episodes

3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• KarXT

Trial Overview The trial is testing KarXT against a placebo to see how well it works and how safe it is in treating manic episodes in Bipolar-I Disorder patients. Participants will either receive KarXT or an inactive pill without knowing which one they are taking.

How Is the Trial Designed?

Group I: KarXT Experimental Treatment 1 Intervention

Flexible dosing

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06951711

NCT06951711 | A Study to Evaluate the Efficacy and ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9681874/

Effectiveness of KarXT (xanomeline-trospium) for cognitive ... KarXT met the primary endpoint of change in Positive and Negative Syndrome Scale (PANSS) total score at week 5 (–17.4 points with KarXT vs. –5.9 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06951698

NCT06951698 | A Study to Evaluate the Efficacy and ... 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 ...

4. bmsclinicaltrials.com bmsclinicaltrials.com/us/en/clinical-trials/NCT07140913

Trial ID CN012-0046 | NCT07140913 - BMS Clinical Trials The purpose of this study is to evaluate the efficacy and safety of adjunctive KarXT for the treatment of mania in participants with Bipolar-I Disorder.

5. psychiatrist.com psychiatrist.com/news/evaluating-pooled-data-from-the-emergent-study-programs/

Evaluating Pooled Data from the EMERGENT Study ... In the open-label extension EMERGENT-4 trial, KarXT significantly improved symptoms of schizophrenia across all efficacy measures at 52 weeks.

6. nature.com nature.com/articles/s41537-022-00320-1

Safety and tolerability of KarXT (xanomeline–trospium) in a ... KarXT was generally well tolerated with an AE profile consistent with the activity of xanomeline–trospium at muscarinic receptors.

7. bmsclinicaltrials.com bmsclinicaltrials.com/us/en/clinical-trials/NCT06951698

Trial ID CN012-0036 | NCT06951698 - BMS Clinical Trials The purpose of this study is to evaluate the efficacy and safety of KarXT for the treatment of manic episodes in Bipolar-I Disorder.

8. bmsstudyconnect.com bmsstudyconnect.com/cz/en/clinical-trials/NCT06929273.html

A Study to Assess the Long-term Safety of KarXT for the ... 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 ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT06951711

A Study to Evaluate the Efficacy and Safety of KarXT ... 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 ...