KarXT for Schizophrenia

Recruiting at 147 trial locations

Overseen By Karuna Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Karuna Therapeutics

Must be taking: Oral antipsychotics

Must not be taking: MAO inhibitors, Anticonvulsants

Disqualifiers: Substance use disorder, Cardiovascular disease, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

568 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests KarXT, a combination of two drugs, on people with schizophrenia. It aims to see if the medication is safe and effective over time. KarXT works by improving symptoms and reducing side effects. KarXT, a combination of xanomeline and trospium, has shown positive results in reducing schizophrenia symptoms.

Will I have to stop taking my current medications?

Yes, you will need to stop taking your current antipsychotic medications before starting the trial. You must be off oral antipsychotic medications by the baseline visit and off long-acting injectable antipsychotics for at least 12 weeks (24 weeks for paliperidone palmitate) before the trial begins.

What data supports the effectiveness of the drug KarXT for treating schizophrenia?

Research shows that KarXT, which combines xanomeline and trospium, has been effective in reducing symptoms of schizophrenia and improving cognitive function. In clinical trials, it was well tolerated and showed significant improvements in patients with cognitive impairment. ^{1 2 3 4 5}

Is KarXT safe for humans?

In a study with adults hospitalized for schizophrenia, KarXT (a combination of xanomeline and trospium chloride) was assessed for safety and tolerability. However, the specific safety outcomes or adverse effects from this study are not detailed in the available information. ^{6 7 8 9 10}

What makes the drug KarXT unique for treating schizophrenia?

KarXT is unique because it targets muscarinic receptors (M1 and M4) instead of the usual dopamine D2 receptors, potentially offering a new way to treat schizophrenia with fewer side effects. It combines xanomeline, which has antipsychotic effects, with trospium to reduce side effects, making it more tolerable for patients. ^{1 2 4 5 9}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

Adults aged 18-65 with schizophrenia, stable and not hospitalized for psychiatric reasons in the last 8 weeks. They must have a BMI of 18-40, be on oral antipsychotic medication, and can consent to the study. Women of childbearing age and men with partners of childbearing potential must use contraception.

Inclusion Criteria

Subject must be fluent in (oral and written) the language of the ICGF to consent.

Women of childbearing potential or men with sexual partners of childbearing potential must be willing and able to use at least 1 highly effective method of contraception during the study and for at least 30 days after the last dose of KarXT. Sperm donation is not allowed for 30 days after the final dose of KarXT.

I have been taking an oral antipsychotic medication as prescribed for the last 30 days.

Exclusion Criteria

You have a history or likelihood of behaving in a violent or destructive manner.

Pregnant, lactating, or less than 3 months postpartum.

If, in the opinion of the investigator (and/or Sponsor), subject is unsuitable for enrollment in the study or subject has any finding that, in the view of the investigator (and/or Sponsor), may compromise the safety of the subject or affect his/her ability to adhere to the protocol visit schedule or fulfill visit requirements.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive KarXT (a fixed combination of xanomeline 125 mg and trospium chloride 30 mg twice daily) for up to 52 weeks

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

Treatment Details

Interventions

• KarXT

Trial Overview The trial is testing KarXT (xanomeline-trospium) capsules over a period of one year to see how safe and effective they are for long-term treatment of schizophrenia in adults who meet specific health criteria.

Participant Groups

Group I: KarXT Experimental Treatment 1 Intervention

KarXT is already approved in United States for the following indications:

Approved in United States as Cobenfy for:

• Schizophrenia

Who Is Running the Clinical Trial?

Karuna Therapeutics

Lead Sponsor

Trials

17

Recruited

4,100+

Findings from Research

In a 5-week study involving 170 patients with schizophrenia, the combination treatment KarXT (xanomeline-trospium) showed significantly higher response rates compared to placebo, with 59% of patients achieving at least a 20% reduction in symptoms by week 2.

KarXT demonstrated early and sustained improvements across all symptom domains of schizophrenia, including positive and negative symptoms, with significant effects observed as early as 2 weeks into treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antipsychotic Efficacy of KarXT (Xanomeline-Trospium): Post Hoc Analysis of Positive and Negative Syndrome Scale Categorical Response Rates, Time Course of Response, and Symptom Domains of Response in a Phase 2 Study. Weiden, PJ., Breier, A., Kavanagh, S., et al.[2022]

In a phase 1 clinical trial with 68 healthy volunteers, the combination of xanomeline and trospium (KarXT) significantly reduced cholinergic adverse events by 46% compared to xanomeline alone, improving tolerability.

KarXT also showed a better safety profile, with no cases of syncope and lower rates of postural dizziness compared to xanomeline alone, while maintaining xanomeline's pharmacokinetic profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence of trospium's ability to mitigate cholinergic adverse events related to xanomeline: phase 1 study results. Breier, A., Brannan, SK., Paul, SM., et al.[2023]

In a 5-week trial involving 125 patients with schizophrenia, KarXT (xanomeline-trospium) showed a significant improvement in cognitive performance among those with clinically meaningful cognitive impairment, with a robust effect size of 0.50.

When outliers were removed, KarXT demonstrated a statistically significant cognitive benefit compared to placebo (p=0.04), suggesting that it may effectively enhance cognition independently of overall symptom improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of KarXT (xanomeline-trospium) for cognitive impairment in schizophrenia: post hoc analyses from a randomised, double-blind, placebo-controlled phase 2 study. Sauder, C., Allen, LA., Baker, E., et al.[2023]

KarXT, which contains xanomeline, targets muscarinic M1 and M4 receptors instead of the traditional dopamine D2 receptor, showing promise in treating schizophrenia based on successful phase 3 trials.

The effectiveness of muscarinic receptor activation may vary among individuals with schizophrenia, suggesting the need for personalized treatment approaches to identify those who would benefit most from this type of therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Muscarinic M1 and M4 receptor agonists for schizophrenia: promising candidates for the therapeutic arsenal. Dean, B.[2023]

In a 5-week phase 2 study involving 179 patients with schizophrenia, KarXT demonstrated significant efficacy and was generally well tolerated, with a low overall burden of adverse events (AEs).

Most AEs related to muscarinic receptor activity were mild and transient, with no patients discontinuing treatment due to these side effects, indicating a favorable safety profile for KarXT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of KarXT (xanomeline-trospium) in a phase 2, randomized, double-blind, placebo-controlled study in patients with schizophrenia. Correll, CU., Angelov, AS., Miller, AC., et al.[2022]

Brexpiprazole, a newly approved medication for schizophrenia, was found to be well-tolerated with statistically insignificant adverse reactions, making it a promising option for patients.

Unlike some other antipsychotics, brexpiprazole has a favorable metabolic profile, which is important given the metabolic side effects associated with many atypical antipsychotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexpiprazole: A New Treatment Option for Schizophrenia. Scarff, JR.[2020]

Brexpiprazole has been shown to significantly improve symptoms of schizophrenia in short-term studies, with a clinically meaningful reduction in the Positive and Negative Syndrome Scale (PANSS) total score, indicating its efficacy as a treatment option.

The medication also demonstrated a favorable safety profile, with minimal side effects and no significant safety concerns, making it a viable long-term maintenance therapy for adults with schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexpiprazole in patients with schizophrenia: overview of short- and long-term phase 3 controlled studies. Marder, SR., Hakala, MJ., Josiassen, MK., et al.[2018]

Cariprazine is an effective treatment for adults with schizophrenia and manic or mixed episodes of bipolar disorder, showing a favorable tolerability profile with common side effects like akathisia and nausea.

It is taken once daily and requires dose adjustments for patients on certain medications, making it a convenient option, but it should be avoided in those with severe liver or kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cariprazine for Schizophrenia and Bipolar Disorder. Scarff, JR.[2020]

In a 5-week randomized, double-blind study involving 148 hospitalized adults with schizophrenia, KarXT (a combination of xanomeline and trospium chloride) showed significantly greater improvement in symptoms compared to placebo, as measured by the Positive and Negative Syndrome Scale (PANSS).

The study utilized blinded, site-independent ratings from audio recordings of PANSS interviews, which confirmed the efficacy of KarXT and demonstrated a high correlation with site-based ratings, suggesting this method could enhance the reliability of clinical assessments in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Site-independent confirmation of primary site-based PANSS ratings in a schizophrenia trial. Targum, SD., Murphy, C., Breier, A., et al.[2022]

Brexpiprazole at doses of 2 mg and 4 mg significantly reduced symptoms of acute schizophrenia compared to placebo, as measured by the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impressions Scale (CGI) after 6 weeks.

The treatment was generally well-tolerated, with akathisia being the most common side effect, and only moderate weight gain observed, indicating that brexpiprazole is a viable option for managing acute schizophrenia exacerbations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Brexpiprazole for the Treatment of Acute Schizophrenia: A 6-Week Randomized, Double-Blind, Placebo-Controlled Trial. Correll, CU., Skuban, A., Ouyang, J., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Antipsychotic Efficacy of KarXT (Xanomeline-Trospium): Post Hoc Analysis of Positive and Negative Syndrome Scale Categorical Response Rates, Time Course of Response, and Symptom Domains of Response in a Phase 2 Study. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Evidence of trospium's ability to mitigate cholinergic adverse events related to xanomeline: phase 1 study results. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Effectiveness of KarXT (xanomeline-trospium) for cognitive impairment in schizophrenia: post hoc analyses from a randomised, double-blind, placebo-controlled phase 2 study. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Muscarinic M1 and M4 receptor agonists for schizophrenia: promising candidates for the therapeutic arsenal. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Safety and tolerability of KarXT (xanomeline-trospium) in a phase 2, randomized, double-blind, placebo-controlled study in patients with schizophrenia. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Brexpiprazole: A New Treatment Option for Schizophrenia. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Brexpiprazole in patients with schizophrenia: overview of short- and long-term phase 3 controlled studies. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Cariprazine for Schizophrenia and Bipolar Disorder. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Site-independent confirmation of primary site-based PANSS ratings in a schizophrenia trial. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Brexpiprazole for the Treatment of Acute Schizophrenia: A 6-Week Randomized, Double-Blind, Placebo-Controlled Trial. [2022]