What is the mechanism of action of this treatment?

Common treatments for schizophrenia primarily include typical and atypical antipsychotics, which work by blocking dopamine D2 receptors to reduce psychotic symptoms such as hallucinations and delusions. However, these medications can have significant side effects, including movement disorders and metabolic issues. Newer treatments, like muscarinic M4 receptor positive allosteric modulators (e.g., CVL-231 or Emraclidine), target muscarinic receptors to modulate neurotransmitter systems more selectively. This approach aims to alleviate symptoms with potentially fewer side effects, improving overall treatment tolerability and patient outcomes.

What side effects are associated with this type of intervention?

Common treatments for schizophrenia include second-generation antipsychotics such as aripiprazole, risperidone, and olanzapine. These medications are generally preferred over first-generation antipsychotics due to a lower risk of extrapyramidal symptoms (EPS) like akathisia, dystonia, and parkinsonism. However, they can still cause side effects such as weight gain, metabolic syndrome, sedation, and increased prolactin levels. Specific to muscarinic receptor modulators like CVL-231 (Emraclidine), while detailed side effect profiles are still under investigation, potential side effects may include gastrointestinal disturbances, dry mouth, and cognitive effects, given the role of muscarinic receptors in various bodily functions.

What prior FDA approvals exist?

The FDA has approved several antipsychotic medications for the treatment of schizophrenia, primarily focusing on dopamine and serotonin receptor antagonists. These include first-generation antipsychotics like haloperidol and chlorpromazine, and second-generation antipsychotics such as risperidone, olanzapine, quetiapine, and aripiprazole. While CVL-231 (Emraclidine) is a Muscarinic M4 receptor positive allosteric modulator, which represents a novel mechanism of action, there are no specific FDA-approved drugs in this exact category yet. The current treatments mainly target dopamine D2 and serotonin 5-HT2A receptors to manage symptoms of schizophrenia.

What other types of research exist?

Promising novel alternatives to CVL-231 for schizophrenia treatment in 2024 include: 1) SEP-363856, a novel trace amine-associated receptor 1 (TAAR1) agonist, which has shown efficacy in clinical trials without the common side effects associated with dopamine antagonists. 2) KarXT, a combination of xanomeline (a muscarinic receptor agonist) and trospium (a peripheral muscarinic receptor antagonist), which has demonstrated significant improvements in schizophrenia symptoms. 3) Ulotaront (SEP-363856), which targets TAAR1 and 5-HT1A receptors, offering a new mechanism of action distinct from traditional antipsychotics.

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NMDA receptor antagonist

Emraclidine for Schizophrenia

Phase 2

Waitlist Available

Research Sponsored by Cerevel Therapeutics, LLC

Eligibility Criteria Checklist

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

Must have

Body mass index of 18.0 to 40.0 kg/m2 and a total body weight ≥50 kg (110 lbs).

Primary diagnosis of schizophrenia per DSM-5, as confirmed by the MINI for Psychotic Disorders

Must not have

Use of prohibited medications prior to randomization within the required wash-out period or likely to require prohibited concomitant therapy during the trial

Active central nervous system infection, demyelinating disease, degenerative neurological disease, brain tumor, prior hospitalization for severe head trauma, seizures (excluding febrile seizures in childhood), or any central nervous system disease deemed to be progressive during the course of the trial that may confound the interpretation of the trial results

Timeline

Screening 3 weeks

Treatment Varies

Follow Up time frame: week 3 and week 6

Summary

This trial is testing a new medication called Emraclidine, given in two different doses daily. It aims to help people with schizophrenia who are having severe symptom flare-ups. The medication works by targeting specific parts of the brain to reduce symptoms like hallucinations and delusions.

Who is the study for?

This trial is for adults with schizophrenia who are moderately to severely ill, have had a recent worsening of symptoms, and meet specific health criteria. They must not be resistant to antipsychotic treatments or have certain other mental health conditions.

What is being tested?

The trial tests two doses (15 mg and 30 mg) of a drug called CVL-231 against a placebo in people with schizophrenia over six weeks to see if it's effective and safe for treating acute psychosis.

What are the potential side effects?

While the side effects aren't listed here, common ones for antipsychotics include drowsiness, weight gain, dry mouth, restlessness, and sometimes more serious effects 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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My BMI is between 18 and 40, and I weigh at least 50 kg (110 lbs).

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I have been diagnosed with schizophrenia.

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My BMI is between 18 and 40, and I weigh at least 50 kg (110 lbs).

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I have been diagnosed with schizophrenia.

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My psychotic symptoms worsened less than 60 days ago.

Exclusion Criteria

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

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I have not taken, nor will I need to take, any forbidden medications during the trial.

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I do not have any active brain infections, diseases, or severe head injuries that could affect the study.

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I have been diagnosed with schizophrenia for the first time.

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

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I am not pregnant, breastfeeding, nor planning to become pregnant soon.

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I am experiencing my first episode of severe mental disturbance.

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I have either responded well to clozapine or not responded at all.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ time frame: week 3 and week 6

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~time frame: week 3 and week 6

This trial's timeline: 3 weeks for screening, Varies for treatment, and time frame: week 3 and week 6 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 at Week 6 in the Positive and Negative Syndrome Scale (PANSS) total score

Secondary study objectives

Change from Baseline at Week 6 in the Clinical Global Impression - Severity (CGI-S score)

Change from Baseline at all time points in Positive and Negative Syndrome Scale (PANSS) total score

Change from Baseline at all time points in the Clinical Global Impression - Severity (CGI-S) score

+8 more

Other study objectives

Change from Baseline at all time points in PANSS Marder Factor scores Change from Baseline at all time points in PANSS Marder Factor scores Change from Baseline at all time points in PANSS Marder Factor scores

Change from Baseline at all time points in Positive and Negative Syndrome Scale (PANSS) positive, negative, and general psychopathology subscale scores

Clinical Global Impression - Improvement (CGI-I) score at Weeks 3 and 6

Trial Design

3Treatment groups

Experimental Treatment

Placebo Group

Group I: CVL-231 30 mg, once daily (QD)Experimental Treatment1 Intervention

Oral Dose

Group II: CVL-231 15 mg, once daily (QD)Experimental Treatment1 Intervention

Oral Dose

Group III: Placebo, once daily (QD)Placebo Group1 Intervention

Oral Dose

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 include typical and atypical antipsychotics, which work by blocking dopamine D2 receptors to reduce psychotic symptoms such as hallucinations and delusions. However, these medications can have significant side effects, including movement disorders and metabolic issues. Newer treatments, like muscarinic M4 receptor positive allosteric modulators (e.g., CVL-231 or Emraclidine), target muscarinic receptors to modulate neurotransmitter systems more selectively. This approach aims to alleviate symptoms with potentially fewer side effects, improving overall treatment tolerability and patient outcomes.

Clinical Effectiveness of Muscarinic Receptor-Targeted Interventions in Neuropsychiatric Disorders: A Systematic Review.