Emraclidine for Schizophrenia
Recruiting in Palo Alto (17 mi)
+76 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
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
Prior Safety Data
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.
12345How 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.
16789Eligibility 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
Are you currently taking Antipsychotic medication?
Exclusion Criteria
I am on three or more medications for my blood pressure.
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?
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: CVL-231 30 mgExperimental Treatment1 Intervention
Participants will receive CVL-231 30 milligrams (mg) tablet, once daily for 52 weeks.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Ascension Illinois Clinical ResearchHoffman Estates, IL
Keralty Hospital MiamiMiami, FL
Cedarhurst, New YorkCedarhurst, NY
Phoenix, ArizonaPhoenix, AZ
More Trial Locations
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Who is running the clinical trial?
Cerevel Therapeutics, LLCLead Sponsor
References
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]Emraclidine is a novel, brain-penetrant, highly selective M4 receptor positive allosteric modulator in development for the treatment of schizophrenia. We aimed to evaluate the safety and tolerability of multiple ascending doses of emraclidine in patients with schizophrenia.
Drug treatments for schizophrenia - past, present and future. [2014]The typical antipsychotic drugs, which have been the mainstay of treatment for schizophrenia for many years, are potent antagonists of D2 receptors. However, their lack of selectivity for D2 receptors in the mesolimbic areas compared with the nigrostriatal areas of the brain has resulted in an association at therapeutic doses with extrapyramidal side-effects, an increased risk for tardive dyskinesia and increased prolactin levels. Together with other significant side-effects, this profile has limited their acceptability for antipsychotic treatment, resulting in poor compliance, increased risk of relapse and increased severity of disease. A new generation of antipsychotics, the 'atypicals', which show greater selectivity for mesolimbic D2 receptors combined with effects on 5-HT2 receptors, have demonstrated antipsychotic efficacy, with a significantly lower incidence of extrapyramidal effects than seen with haloperidol, and often at placebo level. The first atypical antipsychotic, clozapine, has been restricted to use in treatment-resistant schizophrenia because of an association with agranwlocytosis. Two other drugs are now available, olanzapine and sertindole, and two others, quetiapine and ziprasidone, are in late-stage development. The profile of these drugs is reviewed, together with future treatment possibilities.
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]Antipsychotics (APs) have been associated with major adverse cardio- and cerebrovascular events (MACCE), but the underlying mechanisms are unclear. Our aim was to elucidate the association between APs, stratified for receptor affinity and metabolic side effects (MSE), in the reporting of MACCE. A case/non-case study was conducted using data from the WHO global Individual Case Safety Report (ICSR) database, VigiBase, among all reports associated with an AP. Cases were ICSRs of MACCE, while non-cases were all other adverse drug reactions (ADRs). APs were classified by AP group, the degree of receptor affinity for adrenergic, dopaminergic, muscarinic, histaminic, and serotoninergic receptors and by MSE profile. The strength of the association was estimated with logistic regression and expressed as crude and adjusted reporting odds ratios (RORadj.) with corresponding 95% confidence intervals (95%CIs). We identified 4987 reports of MACCE and 328,907 reports of other ADRs. Atypical APs (RORadj. 2.46; 95%CI 2.20-2.74) were significantly associated with the reporting of MACCE compared to typical ones. APs with high affinity for Adrenergic alfa-1 (RORadj. 2.98; 95%CI 1.93-4.59), Histaminic H1 (RORadj. 2.31; 95%CI 1.98-2.68), Muscarinic M1 (RORadj. 1.87; 95%CI 1.74-2.01), and Serotoninergic 5-HT2A (RORadj. 3.19; 95%CI 2.07-4.92) were associated with a higher risk of reporting of MACCE compared to low affinity. APs with higher-risk of MSE were associated with higher risk of reporting of MACCE (RORadj. 1.88; 95%CI 1.73-2.05) compared to the lower-risk. APs with high affinity for Adrenergic alfa-1, Histaminic H1, Muscarinic M1, and Serotoninergic 5-HT2A receptors and with high-risk of MSE may explain the occurrence of those events.
New and emerging treatments for schizophrenia: a narrative review of their pharmacology, efficacy and side effect profile relative to established antipsychotics. [2023]Schizophrenia is associated with substantial unmet needs, highlighting the necessity for new treatments. This narrative review compares the pharmacology, clinical trial data and tolerability of novel medications to representative antipsychotics. Cariprazine, brexpiprazole and brilaroxazine are partial dopamine agonists effective in acute relapse. Lumateperone (serotonin and dopamine receptor antagonist) additionally benefits asocial and depressive symptoms. F17464 (D3 antagonist and 5-HT1A partial agonist) has one positive phase II study. Lu AF35700 (dopamine and serotonin receptor antagonist) was tested in treatment-resistance with no positive results. Pimavanserin, roluperidone, ulotaront and xanomeline do not act directly on the D2 receptor at clinical doses. Initial studies indicate pimavanserin and roluperidone improve negative symptoms. Ulotaront and xanomeline showed efficacy for positive and negative symptoms of schizophrenia in phase II trials. BI 409306, BI 425809 and MK-8189 target glutamatergic dysfunction in schizophrenia, though of these only BI 425809 showed efficacy. These medications largely have favourable cardiometabolic side-effect profiles. Overall, the novel pharmacology, clinical trial and tolerability data indicate these compounds are promising new additions to the therapeutic arsenal.
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]To describe the efficacy, tolerability and safety of brexpiprazole for the treatment of schizophrenia and as adjunct for major depressive disorder (MDD).
Pimavanserin (Nuplazid): A Treatment for Hallucinations and Delusions Associated With Parkinson's Disease. [2022]Pimavanserin (Nuplazid) for the treatment of hallucinations and delusions associated with Parkinson's disease.
Efficacy and safety of the sigma receptor ligand EMD 57445 (panamesine) in patients with schizophrenia: an open clinical trial. [2012]EMD 57455 (panamesine) is a new sigma receptor ligand alleged to have antipsychotic effects. Animal studies have demonstrated that EMD 57445 has a functional antidopaminergic activity without extrapyramidal side effects and a c-fos expression pattern similar to that obtained with atypical neuroleptics. Therefore, the substance might be of interest for the treatment of schizophrenia. The present article describes the results of an exploratory open clinical trial that was aimed at determining the appropriate dose range for clinical efficacy and safety of EMD 57455 in patients with an acute episode of schizophrenia. In a treatment period of 4 weeks, 12 patients received EMD 57445 up to 60 mg/day for 4 weeks. Seven patients completed the study: four were classified as responders (as defined by at least a 50% decrease in the BPRS total score), two improved slightly and one patient remained unimproved. The intent-to-treat analysis showed significant improvement in the psychometric variables assessed by the Brief Psychiatric Rating Scale, Clinical Global Impression and Positive and Negative Symptoms Scale. Major side effects were extrapyramidal symptoms in two patients and restlessness in one patient. With respect to efficacy and safety, our data agree with a previous study, except that in our study EMD 57455 was not totally free of extrapyramidal side effects.
Assessment of antipsychotic activity of an unique agent: SU-23397. [2007]SU-23397 is a unique new hybrid molecule, the animal profile being characteristic of neuroleptic activity. Although the trial was uncontrolled, there appears to be no doubt that SU-23397 exerts antipsychotic activity between 20 mg and 250 mg daily in severely ill schizophrenic patients. Seven of the ten subjects required at least transient antiparkinson medication. Two patients demonstrated premature ventricular contractions. One patient had infrequent PVCs at baseline which increased in frequency with rising dosage. The other patient developed frequent premature ventricular contractions only after active and medication was initiated and was subsequently withdrawn from the study.
Occupancy of striatal D(2)-like dopamine receptors after treatment with the sigma ligand EMD 57445, a putative atypical antipsychotic. [2019]EMD 57445 (panamesine) is a high affinity sigma ligand with the profile of an atypical antipsychotic in animal studies. It has been reported recently to have antipsychotic activity in schizophrenia. However, its metabolite, EMD 59983, binds also to D(2) and D(3) dopamine (DA) receptors.