What is the mechanism of action of this treatment?

The most common treatments for schizophrenia are antipsychotic medications, which primarily target dopamine and serotonin receptors in the brain. These medications work by blocking dopamine D2 receptors, which helps reduce the positive symptoms of schizophrenia such as hallucinations and delusions. Additionally, many second-generation antipsychotics also target serotonin 5-HT2A receptors, which can help alleviate negative symptoms and cognitive deficits. This dual action is crucial for improving overall patient outcomes, as it addresses a broader range of symptoms and can lead to better adherence and quality of life for schizophrenia patients.

What side effects are associated with this type of intervention?

Second-generation antipsychotics, commonly used to treat schizophrenia, include medications like olanzapine, risperidone, and quetiapine. These drugs often target dopamine and serotonin receptors. Known side effects include extrapyramidal symptoms (such as tremors and rigidity), weight gain, and metabolic syndrome, which encompasses conditions like diabetes and dyslipidemia. Other potential adverse effects include sedation, cardiovascular issues, and increased mortality risk in elderly patients with dementia. Monitoring and managing these side effects are crucial for optimizing treatment outcomes.

What prior FDA approvals exist?

The FDA has approved several antipsychotic agents for the treatment of schizophrenia, focusing on those that target dopamine and serotonin receptors. First-generation antipsychotics like haloperidol and chlorpromazine primarily target dopamine D2 receptors. Second-generation antipsychotics, which include risperidone, olanzapine, quetiapine, and aripiprazole, target both dopamine and serotonin receptors, offering a broader mechanism of action and often fewer side effects. These medications have been shown to be effective in managing both positive and negative symptoms of schizophrenia.

What other types of research exist?

Promising novel alternatives to MK-8189 for schizophrenia treatment include LY2140023, an mGlu2/3 receptor agonist, which has shown significant reduction in positive and negative symptoms with good safety and tolerability. Additionally, olanzapine, sertindole, and clozapine have demonstrated potential in improving cognition and reversing MK-801-induced effects in preclinical studies.

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MK-8189 for Schizophrenia

Verified Trial

Phase 2

Recruiting

Research Sponsored by Merck Sharp & Dohme Corp.

Eligibility Criteria Checklist

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

Must have

Meet the diagnostic criteria for schizophrenia according to the DSM-5

Have an illness duration for schizophrenia of at least 1 year

Must not have

Has a known history of (a) borderline personality disorder, anti-social personality disorder, or bipolar disorder (b) traumatic brain injury causing ongoing cognitive difficulties, Alzheimer's Disease, or another form of dementia, or any chronic organic disease of the central nervous system (c) intellectual disability of a severity that would impact ability to participate in the study

Has a current diagnosis of a psychotic disorder other than schizophrenia or a behavioral disturbance thought to be due to substance abuse

Timeline

Screening 3 weeks

Treatment Varies

Follow Up ~up to week 14

Summary

This trial tests the effectiveness and safety of a medication called MK-8189 in adults with acute schizophrenia. The study compares different doses of the medication to see if it can better reduce symptoms. The goal is to find out if MK-8189 can help improve the condition of these patients.

Who is the study for?

This trial is for adults with an acute episode of schizophrenia, diagnosed per DSM-5 criteria. Participants must be moderately ill or worse and have had schizophrenia for at least a year. It excludes those with other psychotic disorders, certain personality disorders, brain injuries affecting cognition, Alzheimer's, other dementias, severe central nervous system diseases, or intellectual disabilities.

What is being tested?

The study tests the effectiveness and safety of MK-8189 in doses of 8 mg (limited to early enrollees), 16 mg, and 24 mg against placebos. The goal is to see if MK-8189 can better reduce symptoms measured by the PANSS score after six weeks compared to placebo.

What are the potential side effects?

While specific side effects are not listed here, typical antipsychotic medication side effects may include drowsiness, weight gain, dry mouth, restlessness and sometimes more serious conditions like movement disorders or metabolic changes.

Eligibility Criteria

Inclusion Criteria

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

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I have been diagnosed with schizophrenia.

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I have been diagnosed with schizophrenia for at least one year.

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You have a score of 4 or higher on the CGI-S scale, which means you are moderately ill.

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I am between 18 and 51 years old.

Exclusion Criteria

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

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I do not have a mental health condition or brain disorder that would affect my study participation.

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You have a mental illness other than schizophrenia or behavioral problems caused by substance abuse.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ ~up to week 14

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~~up to week 14

This trial's timeline: 3 weeks for screening, Varies for treatment, and ~up to week 14 for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Change from baseline in Positive and Negative Syndrome Scale (PANSS) total score at Week 6: MK-8189 24 mg, MK-8189 16 mg, or placebo

Number of participants who discontinue study treatment due to an AE

Number of participants who experience one or more adverse events (AEs)

Secondary study objectives

Change from baseline in Clinical Global Impression-Severity of Illness (CGI-S) score at Week 6: MK-8189 24 mg, MK-8189 16 mg, or placebo

Change from baseline in PANSS positive subscale (PSS) score at Week 6: MK-8189 24 mg, MK-8189 16 mg, or placebo

Change from baseline in weight at Week 12: MK-8189 24 mg, MK-8189 16 mg, or risperidone

+1 more

Side effects data

From 2018 Phase 2 trial • 224 Patients • NCT03055338

18%

Weight increased

13%

Sedation

11%

Headache

Dizziness

Akathisia

Nausea

Fatigue

Dyspepsia

Lethargy

Agitation

Schizophrenia

Somnolence

Decreased appetite

Vomiting

Anxiety

Alcohol poisoning

100%

80%

60%

40%

20%

Study treatment Arm

Risperidone

MK-8189

Placebo

Trial Design

5Treatment groups

Experimental Treatment

Active Control

Group I: Placebo to MK-8189 (Acute) - MK-8189 24 mg (Extension)Experimental Treatment3 Interventions

Participants will be treated for a total of 12 weeks. Participants will receive MK-8189-matching placebo QD in the acute treatment period from Week 1-6 followed by MK-8189 24 mg QD in the extension treatment period from Week 7-12 and participants will simultaneously receive risperidone-matching placebo QD from Week 1-12.

Group II: MK-8189 8 mg (Acute) - MK-8189 8 mg (Extension)Experimental Treatment2 Interventions

Participants will be treated for a total of 12 weeks. Participants will receive MK-8189 8 mg once daily (QD) in the acute treatment period from Week 1-6 followed by MK-8189 8 mg QD in the extension treatment period from Week 7-12 and participants will simultaneously receive risperidone-matching placebo QD from Week 1-12. Enrollment of participants in the MK-8189 8 mg arm was closed with Amendment 4. Participants enrolled before Amendment 4 that have been assigned to 8 mg MK-8189 will remain on 8 mg MK-8189 per protocol.

Group III: MK-8189 24 mg (Acute) - MK-8189 24 mg (Extension)Experimental Treatment2 Interventions

Participants will be treated for a total of 12 weeks. Participants will receive MK-8189 24 mg QD in the acute treatment period from Week 1-6 followed by MK-8189 24 mg QD in the extension treatment period from Week 7-12 and participants will simultaneously receive risperidone-matching placebo QD from Week 1-12.

Group IV: MK-8189 16 mg (Acute) - MK-8189 16 mg (Extension)Experimental Treatment2 Interventions

Participants will be treated for a total of 12 weeks. Participants will receive MK-8189 16 mg QD in the acute treatment period from Week 1-6 followed by MK-8189 16 mg QD in the extension treatment period from Week 7-12 and participants will simultaneously receive risperidone-matching placebo QD from Week 1-12.

Group V: Risperidone 6 mg (Acute) - Risperidone 6 mg (Extension)Active Control2 Interventions

Participants will be treated for a total of 12 weeks. Participants will receive risperidone 6 mg QD in the acute treatment period from Week 1-6 followed by risperidone 6 mg QD in the extension treatment period from Week 7-12 and participants will simultaneously receive MK-8189-matching placebo QD from Week 1-12.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

MK-8189

2020

Completed Phase 2

~680

Placebo to MK-8189

2023

Completed Phase 1

~20

0 / 6Eligibility 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

The most common treatments for schizophrenia are antipsychotic medications, which primarily target dopamine and serotonin receptors in the brain. These medications work by blocking dopamine D2 receptors, which helps reduce the positive symptoms of schizophrenia such as hallucinations and delusions. Additionally, many second-generation antipsychotics also target serotonin 5-HT2A receptors, which can help alleviate negative symptoms and cognitive deficits. This dual action is crucial for improving overall patient outcomes, as it addresses a broader range of symptoms and can lead to better adherence and quality of life for schizophrenia patients.

Treatment of early onset schizophrenia: recent trends, challenges and future considerations.