Lumateperone for Schizophrenia

Overseen By Abaigeal Grant, BA

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Xiaoduo Fan

Must be taking: Clozapine

Must not be taking: Lumateperone, Dopamine partial agonists

Disqualifiers: Substance use disorder, Seizure history, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether lumateperone can reduce side effects like weight gain and high sugar and cholesterol levels in people taking clozapine, a medication for schizophrenia. Participants will receive either lumateperone or a placebo while continuing their clozapine treatment for 12 weeks. Ideal candidates have schizophrenia or schizoaffective disorder, have been on clozapine for at least six months, and have been stable on their medication for at least one month. As a Phase 4 trial, lumateperone is already FDA-approved and proven effective, and this research aims to understand how it benefits more patients.

Will I have to stop taking my current medications?

No, you will not have to stop taking your current medications. Participants will continue their regularly prescribed clozapine while taking either lumateperone or a placebo during the trial.

What is the safety track record for lumateperone?

Research shows that lumateperone is usually well-tolerated and safe. Studies have found no serious side effects directly linked to the drug. In past research, participants taking lumateperone did not experience severe or harmful reactions. Additionally, the FDA has approved the drug for treating schizophrenia, further supporting its safety. Overall, lumateperone appears to be a safe choice for those considering participation in a clinical trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Lumateperone is unique because it offers a novel approach to treating schizophrenia by targeting serotonin, dopamine, and glutamate pathways, all at once. Most existing treatments, like antipsychotics, primarily focus on dopamine receptors, which can lead to side effects like weight gain and movement disorders. Researchers are excited about lumateperone because it has shown promise in reducing these side effects while still effectively managing symptoms of schizophrenia. This could mean a more balanced and tolerable treatment option for patients.

What evidence suggests that lumateperone might be an effective treatment for reducing side effects of clozapine in schizophrenia?

Research has shown that lumateperone effectively treats schizophrenia. It significantly reduces both positive symptoms, like hallucinations, and negative symptoms, such as a lack of emotion, compared to a placebo. Some studies found that it helps prevent relapse in people with schizophrenia, reducing the risk by 63% compared to those taking a placebo. In this trial, participants will receive either lumateperone or a placebo to further explore its effects. Although lumateperone is already approved for treating schizophrenia, this study explores whether it can also help with side effects from clozapine, such as weight gain and high cholesterol. ^{2 5 6 7 8}

Who Is on the Research Team?

Xiaoduo Fan, MD

Principal Investigator

UMass Chan Medical School

Are You a Good Fit for This Trial?

This trial is for individuals with schizophrenia or schizoaffective disorder who have been on clozapine treatment for at least six months and are stable on their current antipsychotic medication. They must be compliant with outpatient medications and use birth control if applicable. People can't join if they're psychiatrically unstable, have severe medical conditions, a history of seizures, are pregnant/breastfeeding, or have used lumateperone or certain other antipsychotics recently.

Inclusion Criteria

I have been on a steady dose of my antipsychotic medication for at least 1 month.

I have been on clozapine treatment for at least 6 months.

Meets the DSM-5 criteria for diagnoses of schizophrenia or schizoaffective disorder based on the MINI International Neuropsychiatric Interview (MINI 7.0)

Exclusion Criteria

I have been treated with lumateperone in the last 3 months.

I have been on a specific antipsychotic medication in the last 3 months.

I am not on a stable dose of antipsychotic medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomly assigned to take lumateperone or placebo for 12 weeks, in addition to clozapine. They will answer questions about psychiatric and daily functioning, have blood drawn, and have body composition analyzed.

12 weeks

3 visits (in-person) at Week 0, Week 6, and Week 12

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lumateperone

Trial Overview

The study tests whether lumateperone can reduce side effects like weight gain and high sugar/cholesterol levels in patients taking clozapine. Participants will either receive lumateperone (Caplyta) or a placebo alongside their regular clozapine dose for 12 weeks while monitoring psychiatric health, blood parameters, and body composition.

How Is the Trial Designed?

Group I: Lumateperone Experimental Treatment 1 Intervention

42mg (two 21mg capsules) lumateperone (Caplyta) taken orally per day for 12 weeks

Group II: Placebo Placebo Group 1 Intervention

2 Placebo capsules taken orally per day for 12 weeks

Who Is Running the Clinical Trial?

Xiaoduo Fan

Lead Sponsor

Trials

2

Recruited

60+

University of Massachusetts, Worcester

Lead Sponsor

Trials

372

Recruited

998,000+

Intra-Cellular Therapies, Inc.

Industry Sponsor

Trials

42

Recruited

10,700+

Published Research Related to This Trial

Lumateperone (CaptylaR) is a new atypical antipsychotic approved by the FDA for treating schizophrenia, offering a potential option for patients with treatment-resistant cases or those at risk for metabolic issues and movement disorders.

However, lumateperone is not recommended for certain populations, including pregnant or breastfeeding women, children, adolescents, elderly patients with dementia-related psychosis, and those with specific health risks, highlighting the need for careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of lumateperone in the treatment of schizophrenia. Syed, AB., Brašić, JR.[2021]

Lumateperone 42 mg has a favorable safety and tolerability profile in treating schizophrenia, with treatment-emergent adverse events (TEAEs) being predominantly mild and similar to placebo (0.5% discontinuation rate) compared to risperidone (4.7%).

The treatment did not significantly affect metabolic parameters or cause weight gain, showing less impact on these factors than risperidone, making lumateperone a potentially better-tolerated option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of lumateperone for the treatment of schizophrenia: a pooled analysis of late-phase placebo- and active-controlled clinical trials. Kane, JM., Durgam, S., Satlin, A., et al.[2023]

Lumateperone is a first-in-class investigational drug for schizophrenia that works by targeting multiple neurotransmitter systems, including serotonergic, glutamatergic, and dopaminergic pathways, which may help alleviate a wide range of symptoms associated with the disorder.

Clinical trials suggest that lumateperone has unique pharmacological properties that could significantly improve schizophrenia symptoms, and future studies are expected to provide more insights into its long-term efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of lumateperone tosylate for the treatment of schizophrenia. Vyas, P., Hwang, BJ., Brašić, JR.[2020]

Lumateperone (Caplyta®) is a newly approved medication for schizophrenia that works by blocking serotonin 2A receptors and has a unique mechanism involving partial agonism at presynaptic dopamine receptors and modulation of glutamate receptors, which may help address symptoms of the disorder.

Clinical trials (Phase II and III) suggest that Lumateperone's novel mechanism could offer benefits in treating schizophrenia, although it shares similarities with existing second- and third-generation antipsychotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lumateperone: New Drug or Same Old Drug With a New Dress? Limandri, BJ.[2021]

In a study of 301 outpatients with stable schizophrenia, lumateperone was found to be well tolerated, with only 45.5% experiencing treatment-emergent adverse events, most of which were mild or moderate, and a very low incidence of extrapyramidal symptoms (1.0%).

Patients switching to lumateperone showed significant improvements in metabolic parameters, such as reduced cholesterol and body weight, while maintaining stable schizophrenia symptoms, indicating its safety and efficacy compared to previous antipsychotic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of lumateperone 42 mg: An open-label antipsychotic switch study in outpatients with stable schizophrenia. Correll, CU., Vanover, KE., Davis, RE., et al.[2021]

Lumateperone (Caplyta®) is a first-in-class medication that modulates serotonin, dopamine, and glutamate, making it a unique treatment option for schizophrenia and potentially other neuropsychiatric disorders.

Approved in December 2019 for schizophrenia in adults, lumateperone is also being studied for various conditions, including bipolar depression and Alzheimer's-related behavioral disorders, highlighting its broad therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lumateperone: First Approval. Blair, HA.[2021]

Lumateperone, approved by the FDA for schizophrenia and bipolar depression, works by partially activating dopamine D2 receptors and also affects the dopamine transporter, NMDA receptor, and serotonin transporter, which contributes to its therapeutic effects.

Clinical trials indicate that lumateperone has a favorable metabolic profile, showing less weight gain and better body measurements compared to other second-generation antipsychotics, while demonstrating efficacy and safety in treating schizophrenia and bipolar disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Illuminating Hope for Mental Health: A Drug Review on Lumateperone. Tarzian, M., Ndrio, M., Chique, B., et al.[2023]

Lumateperone (LUM) has been shown to significantly reduce the severity of schizophrenia symptoms compared to placebo, based on data from four clinical studies involving randomized controlled trials and an open-label trial.

LUM has a favorable safety and tolerability profile, exhibiting placebo-level rates of weight gain, metabolic changes, and extrapyramidal side effects, making it a strong candidate for first-line treatment in adults with schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lumateperone for the Treatment of Adults With Schizophrenia: a Systematic Review. Jawad, MY., Alnefeesi, Y., Ceban, F., et al.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7511146/

Lumateperone for the Treatment of Schizophrenia - PMC

Lumateperone has been shown to effectively reduce both the positive and negative symptoms of schizophrenia when compared with placebo.

2.

caplytahcp.com

caplytahcp.com/schizophrenia/primary-efficacy

Primary Efficacy - Schizophrenia | CAPLYTA® (lumateperone)

CAPLYTA demonstrated statistically superior improvement vs placebo in 2 clinical trials 1 For schizophrenia in adults Significant improvement in PANSS total ...

3.

jnj.com

jnj.com/media-center/press-releases/supplemental-new-drug-application-submitted-to-u-s-fda-for-caplyta-lumateperone-with-data-demonstrating-significant-schizophrenia-relapse-prevention-compared-to-placebo

Supplemental new drug application submitted to U.S. FDA ...

Submission is based on long-term Phase 3 data demonstrating 63 percent reduction in risk of relapse in adults with schizophrenia compared to placebo.

4.

jamanetwork.com

jamanetwork.com/journals/jamapsychiatry/fullarticle/2758022

Efficacy and Safety of Lumateperone for Treatment ...

Treatment with 42 mg of lumateperone compared with placebo significantly improved symptoms in patients with acute exacerbation of schizophrenia ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02282761

A Trial to Assess the Antipsychotic Efficacy of ITI-007

The study will be conducted as a randomized, double-blind, parallel-group, placebo-controlled, multi-center study in patients diagnosed with schizophrenia.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10741391/

The Novel Antipsychotic Lumateperone (Iti-007) in the ...

Lumateperone has demonstrated effectiveness in addressing positive, negative, and cognitive symptoms associated with schizophrenia. The evaluation of safety ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5888466/

F46. LUMATEPERONE (ITI-007): FAVORABLE SAFETY ...

Results. Lumateperone was generally well-tolerated with a favorable safety profile. There was no drug related serious adverse event. In comparison to treatment ...

8.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03817528?term=AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(ITI-007))&rank=2&tab=results

Study Results | ITI-007 (Lumateperone Tosylate) for Schizophrenia

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.