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

Trial Summary

What is the purpose of this trial?

The main question this study is trying to answer is whether lumateperone, an FDA-approved antipsychotic drug, can help reduce possible side effects of clozapine, such as weight gain and elevated levels of sugar and bad cholesterol. Participants will be randomly assigned to either take lumateperone (Caplyta) or a placebo for 12 weeks, in addition to their regularly prescribed clozapine. During their participation, patients will answer questions about their psychiatric and daily functioning, have blood drawn, and have their body composition analyzed (similar to stepping on a scale).

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 data supports the effectiveness of the drug Lumateperone for treating schizophrenia?

Lumateperone has been shown to be effective in treating schizophrenia through its unique action on brain chemicals like serotonin, dopamine, and glutamate, which help manage symptoms. Clinical trials have demonstrated its efficacy and good tolerability in patients with schizophrenia. ^{1 2 3 4 5}

Is lumateperone safe for humans?

Lumateperone, also known as Caplyta, has been shown to be generally safe in humans, with most side effects being mild, such as sleepiness and dry mouth. Studies found that it has a favorable safety profile compared to other antipsychotics, with fewer issues like weight gain and movement problems. ^{1 2 3 4 6}

How is the drug lumateperone different from other schizophrenia treatments?

Lumateperone is unique because it modulates serotonin, dopamine, and glutamate pathways simultaneously, which may help with a broad range of schizophrenia symptoms. It also has a favorable metabolic profile, potentially leading to less weight gain compared to other antipsychotics. ^{1 3 4 7 8}

Research Team

Xiaoduo Fan, MD

Principal Investigator

UMass Chan Medical School

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Lumateperone Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

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+

Findings from Research

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 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 (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 (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]

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]

References

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

Lumateperone: New Drug or Same Old Drug With a New Dress? [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and tolerability of lumateperone 42 mg: An open-label antipsychotic switch study in outpatients with stable schizophrenia. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Lumateperone: First Approval. [2021]

4. England pubmed.ncbi.nlm.nih.gov

An evaluation of lumateperone tosylate for the treatment of schizophrenia. [2020]

5. England pubmed.ncbi.nlm.nih.gov

The role of lumateperone in the treatment of schizophrenia. [2021]

6. England 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. [2023]

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

Lumateperone for the Treatment of Adults With Schizophrenia: a Systematic Review. [2022]

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

Illuminating Hope for Mental Health: A Drug Review on Lumateperone. [2023]