KarXT for Bipolar Disorder

Recruiting at 104 trial locations

Overseen By BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bristol-Myers Squibb

Must be taking: Lithium, Valproate, Lamotrigine

Disqualifiers: Substance use disorder, Suicidal risk, others

Stay on Your Current Meds You can continue your current medications while participating

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: 8 weeks

424 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of a new treatment, KarXT, for managing mania in people with Bipolar-I Disorder. Participants will receive either KarXT or a placebo (a substance with no therapeutic effect) alongside their regular medication, such as lithium, valproate, or lamotrigine. It targets individuals currently experiencing a severe manic episode that requires hospitalization and are on a stable dose of specific mood stabilizers. As a Phase 3 trial, this is the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Do I have to stop taking my current medications for the trial?

The trial requires that you stay on a stable dose of lithium, valproate, or lamotrigine for at least two weeks before screening. If you're on valproate, you must have been taking it for at least seven months.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that KarXT was tested for safety in earlier studies. Most side effects were mild and occurred in the first one to two weeks of treatment, resolving quickly. Overall, participants generally tolerated the treatment well. This suggests that KarXT is likely safe for people, though individual experiences may vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bipolar disorder?

Unlike standard treatments for bipolar disorder, which often rely on mood stabilizers like lithium, valproate, or lamotrigine, KarXT offers a new approach. Researchers are excited about KarXT because it combines xanomeline, a muscarinic receptor agonist, with trospium chloride, which reduces unwanted side effects. This unique mechanism targets both the M1 and M4 muscarinic receptors in the brain, potentially improving cognition and mood symptoms more effectively than current options. By offering a novel pathway for managing bipolar disorder, KarXT could provide a significant advancement in treatment.

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

Research has shown that KarXT yields promising results for mental health conditions. In one study involving individuals with schizophrenia, KarXT significantly improved symptoms over a year. Another study found that a patient using KarXT for just five weeks experienced a 39.53% reduction in symptom severity. These findings suggest that KarXT might also help reduce symptoms in bipolar disorder. In this trial, participants will receive either KarXT combined with Lithium, Valproate, or Lamotrigine, or a placebo combined with these medications. While specific data for bipolar disorder is still being gathered, the positive results in related conditions are encouraging. ^{6 7 8 9 10}

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 adults with Bipolar-I disorder experiencing a manic episode, who are hospitalized and have been on a stable dose of lithium, valproate, or lamotrigine for at least two weeks. They must have a BMI between 18-40 kg/m2 and meet specific severity criteria. Excluded are those with certain liver diseases, other primary psychiatric disorders within the last year, recent substance abuse issues, suicidal risk behaviors, or conditions like irritable bowel syndrome.

Inclusion Criteria

I have been diagnosed with Bipolar-I disorder according to DSM-5-TR and MINI 7.0.2.

Clinical Global Impression Severity scale (CGI-BP) ≥ 4

I am currently hospitalized due to a severe manic episode.

Exclusion Criteria

I do not have HIV, cirrhosis, liver-related issues, or active liver infections.

Presence of any primary DSM-5-TR disorder other than BP-I within 12 months before screening

Elevations in hepatic transaminases at screening ≥ 2 × ULN for ALT and AST and/or bilirubin > 1.5× ULN

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive adjunctive KarXT or placebo alongside Lithium, Valproate, or Lamotrigine for the treatment of mania

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• KarXT

Trial Overview

The study tests KarXT's effectiveness and safety as an additional treatment for mania in people already taking lithium, valproate, or lamotrigine. Participants will be randomly assigned to receive either KarXT or placebo alongside their current medication to compare outcomes.

How Is the Trial Designed?

Group I: KarXT + Lithium, Valproate, or Lamotrigine Experimental Treatment 4 Interventions

Group II: Placebo + Lithium, Valproate, or Lamotrigine Placebo Group 4 Interventions

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

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

The CGI-BP is designed to assess the severity, improvement, and efficacy of treatment in individuals with bipolar disorder. Only section I, illness severity, ...

2.

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.

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11124398/

The New Horizon of Antipsychotics beyond the Classic ...

The NNH values for KarXT, derived from the results of this trial, were 9 for nausea, 23 for vomiting, 8 for constipation, and 13 for dry mouth [71]. According ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S2773021225000379

Positive response to adjunctive KarXT (xanomeline ...

Overall, our patient saw a 39.53 % decrease in total PANSS score from 86 just prior to the first dose of KarXT to 52 at five weeks on the medication. This ...

5.

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 ...

6.

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 ...

7.

bmsstudyconnect.com

bmsstudyconnect.com/es/en/clinical-trials/NCT06951711.html

study connect - BMS Clinical Trials

A Study to Evaluate the Efficacy and Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder (BALSAM-2) - CN012-0037.

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9719488/

Safety and tolerability of KarXT (xanomeline–trospium) in a ...

The majority of procholinergic and anticholinergic AEs with KarXT were mild, occurred in the first 1−2 weeks of treatment, and were transient ...

9.

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.

10.

trialx.com

trialx.com/clinical-trials/listings/310277/a-study-to-evaluate-the-efficacy-and-safety-of-karxt-for-the-treatment-of-manic-episodes-in-bipolar-i-disorder/

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 ...