Lumateperone for Major Depressive Disorder

Recruiting at 54 trial locations

Overseen By ITI Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Intra-Cellular Therapies, Inc.

Must be taking: Antidepressants

Disqualifiers: Schizophrenia, Bipolar, Anxiety, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 1

Duration: 6 weeks

470 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called lumateperone for individuals with major depressive disorder (MDD) who haven't improved enough with their current medications. Researchers are comparing lumateperone to a placebo (a harmless pill with no active drug) to determine if it provides better relief from depression symptoms. The study seeks individuals who have had MDD for at least 12 weeks, experience significant distress, and haven't responded well to at least two different antidepressants. As a Phase 3 trial, this is the final step before potential FDA approval, offering participants a chance to contribute to the development of a promising new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it requires that you have an inadequate response to at least two antidepressants and continue taking one of them at the minimum effective dose for at least six weeks.

Is there any evidence suggesting that lumateperone is likely to be safe for humans?

Research has shown that lumateperone, at a dose of 42 mg, is generally safe and well-tolerated for people with major depressive disorder (MDD). Studies have found that lumateperone can significantly improve depression symptoms without causing serious side effects. In these studies, most patients did not experience harmful effects, suggesting that lumateperone is reasonably safe for treating depression, based on data from previous trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for major depressive disorder?

Lumateperone is unique because it offers a novel approach to treating Major Depressive Disorder (MDD). Unlike most antidepressants, which typically target serotonin or norepinephrine pathways, lumateperone works differently by modulating serotonin, dopamine, and glutamate receptors. This broader mechanism of action could potentially lead to more effective and faster relief of depressive symptoms. Researchers are particularly excited about its potential to improve outcomes without some of the common side effects associated with existing antidepressants.

What evidence suggests that lumateperone might be an effective treatment for major depressive disorder?

Research has shown that lumateperone, when combined with other antidepressants, can significantly alleviate symptoms of major depressive disorder (MDD). In this trial, participants will receive either 42 mg of lumateperone or a placebo. One study found that taking 42 mg of lumateperone led to greater improvement in depression symptoms and overall condition compared to a placebo. This treatment may benefit individuals who haven't found success with other antidepressants. In summary, lumateperone could be an effective option for easing depression symptoms in those with MDD. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with Major Depressive Disorder (MDD) who haven't had enough improvement from their current antidepressant treatment. They must have been on a stable dose of certain antidepressants for at least 6 weeks and meet specific criteria indicating moderate to severe depression.

Inclusion Criteria

My depression hasn't improved much with current medication, despite taking it as prescribed for over 6 weeks.

I have been diagnosed with major depression, including with psychotic features.

Exclusion Criteria

Within the patient's lifetime, has a confirmed DSM-5 psychiatric diagnosis other than MDD, including specified disorders

In the opinion of the Investigator, the patient has a significant risk for suicidal behavior during participation in the study or meets specified criteria

The patient experiences a ≥ 25% decrease in the QIDS-SR-16 total score between Screening and Baseline

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 2 weeks

Treatment

Participants receive either placebo or lumateperone 42 mg/day in a double-blind manner

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Lumateperone
• Placebo

Trial Overview The study tests Lumateperone as an additional treatment alongside existing antidepressant therapy (ADT) compared to a placebo, in patients with MDD who are not responding well to their current ADT. It's a multicenter, randomized, double-blind trial ensuring neither participants nor researchers know who receives the actual drug or placebo.

How Is the Trial Designed?

Group I: Lumateperone 42 mg Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Intra-Cellular Therapies, Inc.

Lead Sponsor

Trials

42

Recruited

10,700+

Published Research Related to This Trial

In a study of 376 adults with bipolar I or II disorder experiencing a major depressive episode, lumateperone 42 mg significantly improved depression symptoms and overall disease severity compared to placebo, regardless of the presence of mixed features.

The treatment was well-tolerated, with rare occurrences of treatment-emergent adverse events related to mania or hypomania, indicating a favorable safety profile for lumateperone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy of Lumateperone in Patients With Bipolar Depression With Mixed Features. McIntyre, RS., Durgam, S., Huo, J., et al.[2023]

Lumateperone tosylate is a first-in-class investigational drug that works through multiple neurotransmitter systems, including serotonergic, dopaminergic, and glutamatergic pathways, which may lead to rapid antidepressant effects.

In clinical trials, lumateperone demonstrated a safety profile similar to placebo, with significant improvements in both depressive and psychotic symptoms in patients with schizophrenia, indicating its potential for treating various mood disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lumateperone: a new treatment approach for neuropsychiatric disorders. Kumar, B., Kuhad, A., Kuhad, A.[2019]

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]

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 an FDA-approved antipsychotic for treating major depressive episodes in type I and II bipolar disorder, showing superior efficacy compared to placebo when used alone or with mood stabilizers.

It has a unique mechanism of action with minimal dopamine-related side effects due to less than 50% D2 receptor occupancy, making it well tolerated compared to other similar medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating lumateperone for its use in treating depressive episodes associated with bipolar I or II disorder in adults. Abuelazm, H., Elsayed, OH., El-Mallakh, RS.[2023]

Lumateperone (ITI-007) has a unique mechanism of action that targets multiple neurotransmitter systems, including serotonin, dopamine, and glutamate, making it a promising treatment for schizophrenia and potentially other psychiatric conditions.

It has shown a favorable safety profile, with no significant side effects like extrapyramidal symptoms or hyperprolactinemia, suggesting it could be a safer alternative to traditional antipsychotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence on the New Drug Lumateperone (ITI-007) for Psychiatric and Neurological Disorders. Mazza, M., Marano, G., Traversi, G., et al.[2021]

In a Phase 3 study involving patients with bipolar I and II disorders, lumateperone 42 mg significantly improved depression symptoms compared to placebo over 6 weeks, showing effectiveness across all 10 items of the Montgomery-Åsberg Depression Rating Scale (MADRS).

The treatment also notably enhanced the anhedonia factor of the MADRS, indicating improvements in symptoms like sadness and inability to feel pleasure, with effect sizes suggesting meaningful clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of lumateperone on symptoms of depression in bipolar I and bipolar II disorder: Secondary and post hoc analyses. McIntyre, RS., Durgam, S., Kozauer, SG., et al.[2023]

In a phase 3 study involving 377 patients with bipolar I or II disorder, lumateperone at 42 mg/day significantly improved depression symptoms compared to placebo, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) and Clinical Global Impressions Scale-Bipolar Version (CGI-BP-S).

Lumateperone was generally well tolerated, with only somnolence and nausea occurring at a higher rate than placebo, and a low incidence of extrapyramidal symptoms, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Lumateperone for Major Depressive Episodes Associated With Bipolar I or Bipolar II Disorder: A Phase 3 Randomized Placebo-Controlled Trial. Calabrese, JR., Durgam, S., Satlin, A., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40875502/

Results From a Randomized, Double-Blind, Phase 3 Trial Conclusions: Lumateperone 42 mg adjunctive to ADT significantly improved depression symptoms and disease severity vs adjunctive placebo and was ...

2. jnj.com jnj.com/media-center/press-releases/johnson-johnson-to-highlight-breadth-of-its-major-depressive-disorder-portfolio-at-2025-ecnp-congress

Johnson & Johnson to highlight breadth of its major ... New post-hoc analysis of CAPLYTA® (lumateperone) Phase 3 data evaluates the impact on sexual function in MDD, reinforcing potential to reset ...

3. psychiatrist.com psychiatrist.com/jcp/lumateperone-adjunctive-therapy-major-depressive-disorder-randomized-double-blind-phase-3-trial/

Results From a Randomized, Double-Blind, Phase 3 Trial Conclusions: Lumateperone 42 mg adjunctive to ADT significantly improved depression symptoms and disease severity vs adjunctive placebo and was ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04985942

NCT04985942 | Clinical Trial of Lumateperone as ... Each item is rated on a 7-point scale from 0-6. The total score ranges from 0 to 60 with a higher score indicating increased severity of depressive symptoms.

5. psychiatrictimes.com psychiatrictimes.com/view/new-ecnp-poster-data-on-adjunctive-lumateperone-for-major-depressive-disorder

New ECNP Poster Data on Adjunctive Lumateperone for ... In Study 502, lumateperone 42 mg/day adjunctive to antidepressants significantly improved depressive symptoms compared with placebo adjunctive ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11882193/

Lumateperone for the Treatment of Major Depressive ... Lumateperone 42 mg significantly improved depression symptoms and disease severity and was generally safe and well-tolerated in patients with MDD or bipolar ...

7. prnewswire.com prnewswire.com/news-releases/johnson--johnson-to-highlight-breadth-of-its-major-depressive-disorder-portfolio-at-2025-ecnp-congress-302580374.html

Johnson & Johnson to highlight breadth of its major ... 17 abstracts from across the Company's portfolio and pipeline highlight new clinical and real-world data on major depressive disorder and ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05061719

NCT05061719 | An Open-label Study of Lumateperone as ... A Safety Follow-up visit will occur on Visit 17/Day 197, approximately 2 weeks after the last dose of open-label lumateperone 42 mg.

9. jnjmedicalconnect.com jnjmedicalconnect.com/media/attestation/congresses/itci/2025/apa/longterm-adjunctive-lumateperone-treatment-in-major-depressive-disorder-results-from-a-sixmonth-open.pdf

Long-Term Adjunctive Lumateperone Treatment in Major ... Conclusions: Lumateperone 42mg adjunctive to ADT was safe and effective during 26-week treatment in patients with MDD and inadequate ADT ...