Emraclidine for Schizophrenia

Recruiting at 74 trial locations

Overseen By Cerevel Clinical Trial Support

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Cerevel Therapeutics, LLC

Must be taking: Antipsychotics

Must not be taking: Antidepressants, Mood stabilizers

Disqualifiers: Substance use disorder, Cardiovascular, Diabetes, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

850 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial aims to evaluate the safety and tolerability of a medication called emraclidine, taken by mouth, in adults with schizophrenia.

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications before and during the study, as there is a washout period (time without taking certain medications) specified. You should discuss with the trial team which of your current medications are considered prohibited.

Is Emraclidine safe for humans?

In a study, Emraclidine was tested for safety in people with schizophrenia, and it was generally well-tolerated, meaning most people did not experience serious side effects. ^{1 2 3 4 5}

How is the drug Emraclidine different from other schizophrenia treatments?

Emraclidine is unique because it works by selectively modulating M4 receptors in the brain, which is different from most other schizophrenia drugs that target dopamine receptors. This novel mechanism may offer a new approach to treating schizophrenia with potentially fewer side effects. ^{1 6 7 8 9}

Research Team

Erica Koenig, PhD

Principal Investigator

Cerevel Therapeutics, LLC

Eligibility Criteria

This trial is for adults aged 18-65 with schizophrenia who can understand the study and follow its procedures. It's not for those whose only response to treatment has been clozapine, or have progressive brain diseases, severe head trauma history, seizures (except childhood febrile seizures), or a high risk of suicide.

Inclusion Criteria

You have been diagnosed with Schizophrenia

Do you have a Body Mass Index (BMI) between 18 - 40 kg/m

Are you currently taking Antipsychotic medication?

Exclusion Criteria

Have you been diagnosed with Major Depressive Disorder or PTSD or Obsessive-Compulsive Disorder?

Have you been diagnosed with Bipolar Disorder?

Have you been diagnosed with Schizoaffective Disorder?

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CVL-231 30 mg tablet once daily

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• CVL-231

Trial Overview The study is testing the long-term safety and how well people can tolerate CVL-231 (Emraclidine) at a dose of 30 mg. Emraclidine is taken orally by participants with schizophrenia to evaluate its effects over an extended period.

Participant Groups

Group I: CVL-231 30 mg Experimental Treatment 1 Intervention

Participants will receive CVL-231 30 milligrams (mg) tablet, once daily for 52 weeks.

Who Is Running the Clinical Trial?

Cerevel Therapeutics, LLC

Lead Sponsor

Trials

37

Recruited

5,500+

Findings from Research

Emraclidine, a selective M4 receptor modulator, was found to be safe and well-tolerated in a phase 1b trial involving 81 participants with schizophrenia, with no significant differences in adverse events compared to placebo.

The most common side effect was headache, and any increases in blood pressure and heart rate were modest and resolved over time, suggesting a favorable side-effect profile for further investigation as a treatment for schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emraclidine, a novel positive allosteric modulator of cholinergic M4 receptors, for the treatment of schizophrenia: a two-part, randomised, double-blind, placebo-controlled, phase 1b trial. Krystal, JH., Kane, JM., Correll, CU., et al.[2023]

Typical antipsychotic drugs primarily target D2 receptors but can cause significant side effects like extrapyramidal symptoms and increased prolactin levels, leading to poor patient compliance and higher relapse rates.

Atypical antipsychotics, such as olanzapine and sertindole, offer a better safety profile with fewer extrapyramidal effects and improved efficacy, making them a promising alternative for treating schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug treatments for schizophrenia - past, present and future. Rasmussen, JG.[2014]

Atypical antipsychotics are significantly associated with major adverse cardio- and cerebrovascular events (MACCE), with a reporting odds ratio of 2.46, indicating a higher risk compared to typical antipsychotics.

Antipsychotics that have a high affinity for certain receptors, such as Adrenergic alfa-1 and Serotoninergic 5-HT2A, as well as those with a higher risk of metabolic side effects, are linked to an increased risk of MACCE, suggesting that these receptor interactions may contribute to cardiovascular risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The association between receptor binding affinity and metabolic side effect profile of antipsychotics and major cardio- and cerebrovascular events: A case/non-case study using VigiBase. Aguiar, JP., Alves da Costa, F., Egberts, T., et al.[2021]

Novel antipsychotic medications like cariprazine, brexpiprazole, and brilaroxazine have shown effectiveness in treating acute relapse of schizophrenia, while lumateperone also helps with asocial and depressive symptoms.

Many of these new treatments, such as pimavanserin and ulotaront, demonstrate promise in improving both positive and negative symptoms of schizophrenia, and they generally have favorable side-effect profiles compared to traditional antipsychotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New and emerging treatments for schizophrenia: a narrative review of their pharmacology, efficacy and side effect profile relative to established antipsychotics. Lobo, MC., Whitehurst, TS., Kaar, SJ., et al.[2023]

Brexpiprazole is effective for treating schizophrenia, with a response rate of 45.5% compared to 31.0% for placebo, and a number needed to treat (NNT) of 7, indicating it is a beneficial option for patients.

It is also well tolerated, with lower discontinuation rates due to adverse events compared to placebo, and while akathisia was the most common side effect, its occurrence was not significantly higher than in the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexpiprazole for schizophrenia and as adjunct for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antipsychotic - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed? Citrome, L.[2022]

Pimavanserin (Nuplazid) is specifically designed to treat hallucinations and delusions in patients with Parkinson's disease, showing promise in improving their quality of life.

Clinical studies have demonstrated that pimavanserin effectively reduces these symptoms without significantly impacting motor function, making it a safer alternative to traditional antipsychotics for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pimavanserin (Nuplazid): A Treatment for Hallucinations and Delusions Associated With Parkinson's Disease. Cruz, MP.[2022]

In a 4-week exploratory trial involving 12 patients with acute schizophrenia, EMD 57455 (panamesine) showed significant improvement in psychiatric symptoms, with 4 out of 7 completers classified as responders based on a 50% reduction in their BPRS scores.

While EMD 57455 demonstrated potential antipsychotic effects similar to atypical neuroleptics, it was not completely free of side effects, as two patients experienced extrapyramidal symptoms and one had restlessness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of the sigma receptor ligand EMD 57445 (panamesine) in patients with schizophrenia: an open clinical trial. Huber, MT., Gotthardt, U., Schreiber, W., et al.[2012]

SU-23397, a new hybrid molecule, shows promising antipsychotic activity in severely ill schizophrenic patients at doses ranging from 20 mg to 250 mg daily, despite the trial being uncontrolled.

However, the treatment was associated with some safety concerns, as seven out of ten subjects required antiparkinson medication, and two patients experienced premature ventricular contractions, indicating potential cardiac risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of antipsychotic activity of an unique agent: SU-23397. Mielke, EH., Gallant, DM., Bishop, G., et al.[2007]

In a study involving five neuroleptic-free schizophrenic patients, treatment with EMD 57445 (panamesine) showed a high occupancy of D(2)-like dopamine receptors, similar to typical antipsychotic medications.

The findings suggest that the antipsychotic effects of EMD 57445 may be primarily due to its metabolite EMD 59983's strong binding to dopamine receptors rather than its sigma receptor affinity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Occupancy of striatal D(2)-like dopamine receptors after treatment with the sigma ligand EMD 57445, a putative atypical antipsychotic. Gründer, G., Müller, MJ., Andreas, J., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Emraclidine, a novel positive allosteric modulator of cholinergic M4 receptors, for the treatment of schizophrenia: a two-part, randomised, double-blind, placebo-controlled, phase 1b trial. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Drug treatments for schizophrenia - past, present and future. [2014]

3. Netherlands pubmed.ncbi.nlm.nih.gov

The association between receptor binding affinity and metabolic side effect profile of antipsychotics and major cardio- and cerebrovascular events: A case/non-case study using VigiBase. [2021]

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

New and emerging treatments for schizophrenia: a narrative review of their pharmacology, efficacy and side effect profile relative to established antipsychotics. [2023]

5. India pubmed.ncbi.nlm.nih.gov

Brexpiprazole for schizophrenia and as adjunct for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antipsychotic - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed? [2022]

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

Pimavanserin (Nuplazid): A Treatment for Hallucinations and Delusions Associated With Parkinson's Disease. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of the sigma receptor ligand EMD 57445 (panamesine) in patients with schizophrenia: an open clinical trial. [2012]

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

Assessment of antipsychotic activity of an unique agent: SU-23397. [2007]

9. Germany pubmed.ncbi.nlm.nih.gov

Occupancy of striatal D(2)-like dopamine receptors after treatment with the sigma ligand EMD 57445, a putative atypical antipsychotic. [2019]