What side effects are associated with this type of intervention?

Common treatments for schizophrenia include second-generation antipsychotics like olanzapine, quetiapine, risperidone, and ziprasidone. These medications can cause side effects such as weight gain, metabolic syndrome, sedation, and extrapyramidal symptoms (e.g., tremors, rigidity). Treatments similar to KarXT, which involve muscarinic receptor modulation, may have side effects related to cholinergic activity, such as dry mouth, constipation, blurred vision, and cognitive disturbances. It is important to monitor these side effects and adjust treatment as necessary in consultation with a healthcare provider.

What prior FDA approvals exist?

The FDA has approved several antipsychotic medications for the treatment of schizophrenia, including clozapine, olanzapine, quetiapine, and risperidone. These drugs primarily target dopamine and serotonin receptors to alleviate symptoms. Clozapine, approved in 1989, is notable for its effectiveness in treatment-resistant cases. While KarXT, which combines xanomeline (a muscarinic receptor agonist) and trospium chloride (a muscarinic receptor antagonist), represents a novel approach targeting muscarinic receptors, there is limited information on prior FDA approvals specifically for drugs with similar mechanisms.

What other types of research exist?

Promising novel alternatives to KarXT for schizophrenia patients in 2024 include: 1) Clozapine augmentation with Electroconvulsive Therapy (ECT) for treatment-resistant cases, 2) Lamotrigine, topiramate, and minocycline as adjunctive treatments, 3) Repetitive Transcranial Magnetic Stimulation (rTMS) for non-responders to pharmacotherapy, and 4) Pimavanserin, a serotonin receptor modulator, particularly for psychosis in dementia-related conditions but potentially applicable to schizophrenia.

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Cholinergic Agonist

KarXT for Schizophrenia

Phase 3

Waitlist Available

Research Sponsored by Karuna Therapeutics

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

At the time of screening, or at any time within the 30 days prior to screening, the subject must have received an oral antipsychotic medication daily at a dose and frequency consistent with the drug label.

At Day 0, subject will have been off lithium therapy for at least 2 weeks and must have discontinued all oral antipsychotic medications.

Must not have

Subject has a history of treatment resistance to schizophrenia medications defined as failure to respond to 2 adequate courses of pharmacotherapy (a minimum of 4 weeks at an adequate dose per the label) within the past 12 months or having received clozapine within the past 3 years

Subject has had psychiatric hospitalization(s) for more than 30 days (cumulative) within the 6 months before screening.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from initial dose through 7 days after the final dose (up to 53 weeks)

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include digestive issues like constipation or irritable bowel syndrome, urinary retention problems, dry mouth due to reduced saliva production, blurred vision or eye discomfort if prone to narrow-angle glaucoma.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I stopped taking lithium and all antipsychotic medications 2 weeks ago.

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I have been diagnosed with schizophrenia by a psychiatrist.

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I am between 18 and 65 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have schizophrenia and haven't responded to 2 different treatments in the last year, or I've been on clozapine in the past 3 years.

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I have been hospitalized for psychiatric reasons for over 30 days in the last 6 months.

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I have HIV, liver issues, or a liver infection.

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I have not been diagnosed with a mental health disorder other than schizophrenia in the last year.

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I have previously been treated with KarXT.

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I have a history or high risk of problems with bladder, stomach emptying, or a specific eye condition.

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I have no significant abnormal findings in my recent medical exams.

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I have had serious constipation or irritable bowel syndrome in the last 6 months.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from initial dose through 7 days after the final dose (up to 53 weeks)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from initial dose through 7 days after the final dose (up to 53 weeks)

This trial's timeline: 3 weeks for screening, Varies for treatment, and from initial dose through 7 days after the final dose (up to 53 weeks) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of treatment-emergent adverse events (TEAEs)

Secondary study objectives

Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 52

Change From Baseline in PANSS Negative Marder Factor Score

Change From Baseline in PANSS Negative Score at Week 52

+5 more

Side effects data

From 2022 Phase 3 trial • 252 Patients • NCT04659161

21%

Constipation

19%

Dyspepsia

19%

Nausea

14%

Vomiting

13%

Headache

10%

Hypertension

Dizziness

Abdominal discomfort

Gastrooesophageal reflux disease

Diarrhoea

Anxiety

Dry mouth

Somnolence

Vision blurred

Abdominal pain

Heart rate increased

Orthostatic hypotension

Insomnia

Suicidal ideation

Agitation

Salivary hypersecretion

Back pain

Psychotic disorder

Toothache

100%

80%

60%

40%

20%

Study treatment Arm

KarXT

Placebo

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

1Treatment groups

Experimental Treatment

Group I: KarXTExperimental Treatment1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Xanomeline and Trospium Chloride Capsules

2021

Completed Phase 3

~1410

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for schizophrenia primarily target dopamine and serotonin receptors to manage symptoms. Traditional antipsychotics block dopamine D2 receptors to reduce positive symptoms, while second-generation antipsychotics also target serotonin receptors to help with negative symptoms and cognitive deficits. KarXT, combining xanomeline (a muscarinic receptor agonist) and trospium chloride (a muscarinic receptor antagonist), modulates the cholinergic system, potentially improving cognitive function, which is a significant unmet need in schizophrenia treatment.

Adverse effects of antipsychotic agents. Do newer agents offer advantages?Clozapine's multiple cellular mechanisms: What do we know after more than fifty years? A systematic review and critical assessment of translational mechanisms relevant for innovative strategies in treatment-resistant schizophrenia.Discovery of Procognitive Antipsychotics by Combining Muscarinic M1 Receptor Structure-Activity Relationship with Systems Response Profiles in Zebrafish Larvae.