Lumateperone for Schizophrenia and Bipolar Disorder

Recruiting at 41 trial locations

Overseen By Deepa V

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Intra-Cellular Therapies, Inc.

Must be taking: Psychostimulants

Disqualifiers: Suicidal risk, Catatonia, Psychotic features, others

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

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

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

Compensation: Varies

Number of Visits: Unknown

500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the safety and tolerance of lumateperone, a potential medication for young people with schizophrenia, bipolar disorder, or autism spectrum disorder. Researchers will assess how well patients handle this treatment over a 26-week period. The study is suitable for children and teens diagnosed with one of these conditions who are currently receiving outpatient treatment. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking medication for ADHD, you must have been on a stable treatment for 30 days before the study and continue it throughout the study.

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

Research has shown that lumateperone has been tested in over 2,600 adults with conditions like bipolar depression and schizophrenia. These studies found lumateperone to be generally safe for these patients. Importantly, no major safety issues emerged, and it did not significantly cause extra movements, known as extrapyramidal symptoms (EPS).

For those concerned about side effects, the results are reassuring. Lumateperone usually has a better safety profile compared to many other treatments for similar conditions, meaning patients generally tolerate it well.

Although this new study focuses on younger patients with schizophrenia, bipolar disorder, or autism spectrum disorder, previous research in adults provides a strong foundation. Lumateperone is already approved by the FDA for certain conditions, adding another layer of confidence in its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for schizophrenia?

Unlike the standard antipsychotic treatments for schizophrenia and bipolar disorder, such as risperidone or olanzapine, lumateperone stands out due to its novel mechanism of action. Most treatments work primarily by blocking dopamine receptors, but lumateperone uniquely targets serotonin, dopamine, and glutamate pathways, offering a more balanced approach. This multi-target action not only promises to be effective but also may reduce the risk of common side effects like weight gain and movement disorders. Researchers are excited about lumateperone because it could offer a safer, more comprehensive treatment option for individuals with these conditions.

What evidence suggests that lumateperone might be an effective treatment for schizophrenia and bipolar disorder?

Research shows that lumateperone, which participants in this trial will receive, helps treat bipolar depression by significantly improving depressive symptoms in people with bipolar I and II disorder. However, it is less effective in easing symptoms of schizophrenia. Studies have found that lumateperone can lift mood and lessen depression in those with bipolar disorder. There is less evidence of its effectiveness for schizophrenia, suggesting it may work better for mood-related symptoms in bipolar disorder. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for children and teenagers with schizophrenia or bipolar disorder. Specific details about who can join are not provided, but typically participants must meet certain health standards and have a diagnosis of the conditions being studied.

Inclusion Criteria

I am a minor with schizophrenia or bipolar disorder and can give my consent.

Rollover Patients entering from the lead-in study must have safely completed the lead-in study, in the opinion of the Investigator and be able to provide consent as follows: The patient's LAR must provide written, informed consent; The patient must provide written assent to study enrollment

Exclusion Criteria

In the opinion of the Investigator, the patient has a significant risk for suicidal behavior during their participation in the study or At Screening, the patient scores 'yes' on Suicidal Ideation Items 3, 4, or 5 of the Columbia-Suicide Severity Rating Scale (C SSRS) within 6 months prior to Screening or, at Baseline, the patient scores 'yes' on Suicidal Ideation Items 3, 4, or 5 since the Screening Visit; At Screening, the patient has had 1 or more suicidal attempts within the 2 years prior to Screening; or At Screening or Baseline, scores > 3 on Item 13 (suicidal ideation) of the CDRS-R (for bipolar disorder patients only); or The patient is considered to be an imminent danger to him/herself or others. Because all Rollover Patients were required to not meet any exclusion criteria for participation in the lead-in study, the Investigator should assess if there has been any change in patient health status. Any newly-emergent medical condition reported during the lead-in study must be evaluated by the Investigator and should be discussed with the Sponsor or designee before enrolling the patient in this study.

Rollover Patients will directly enroll from the lead-in efficacy study at Day 1 of this long-term safety study. Rollover Patients who are unable to comply with study procedures or judged to be inappropriate for the study, in the opinion of the Investigator; have a significant risk for suicidal behavior during the course of her/his participation in the study or is considered to be an imminent danger to her/himself or others, in the opinion of the Investigator, and/or: At the Baseline Visit the patient scores 'yes' on Suicidal Ideation Items 3, 4, or 5 of the C-SSRS using the 'Since the Last Visit' version (used at Visit 8/Week 6 of the lead in study); At the Baseline Visit, scores > 3 on Item 13 (suicidal ideation) of the CDRS-R (based on the Visit 8/Week 6 assessment from the lead in study); or The patient is considered to be an imminent danger to him/herself or others. The patient had any abnormal clinical laboratory tests results during the lead-in study that were considered clinically significant and preclude safe participation in this study, based on the Investigator's clinical judgement.

I have a mental health condition, but it's not severe schizophrenia, bipolar I or II, or severe intellectual disability.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 2 weeks

Open-label Treatment

Participants receive open-label lumateperone once daily

26 weeks

Safety Follow-up

Participants are monitored for safety approximately 2 weeks after the last dose of open-label lumateperone

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lumateperone

Trial Overview The study is testing Lumateperone, a medication intended to treat psychiatric conditions like schizophrenia and bipolar disorder in young people over a period of 26 weeks. It's an open-label trial, meaning both the researchers and participants know what treatment is being given.

How Is the Trial Designed?

Group I: Lumateperone Experimental Treatment 1 Intervention

Lumateperone is already approved in United States for the following indications:

Approved in United States as Caplyta for:

• Schizophrenia
• Bipolar I or II disorder (bipolar depression)

Who Is Running the Clinical Trial?

Intra-Cellular Therapies, Inc.

Lead Sponsor

Trials

42

Recruited

10,700+

Published Research Related to This Trial

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 (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]

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 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, 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 (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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39487717/

Efficacy and safety of lumateperone for bipolar depression ... Lumateperone is effective in treating bipolar depression but does not significantly reduce symptom severity in schizophrenia.

2. caplytahcp.com caplytahcp.com/efficacy-summary

Efficacy Summary | CAPLYTA® (lumateperone) CAPLYTA has proven efficacy in adults across bipolar I depression, bipolar II depression, and schizophrenia.

3. academic.oup.com academic.oup.com/ijnp/article/27/11/pyae052/7863712

Efficacy and safety of lumateperone for bipolar depression ... The results revealed that lumateperone effectively improved MADRS scores in bipolar depression but did not significantly reduce total PANSS scores in ...

4. journals.sagepub.com journals.sagepub.com/doi/10.1177/02698811251364389

Dose-response efficacy and safety of lumateperone in ... In terms of efficacy, our results showed that lumateperone at a dose of 42 mg significantly improved depressive symptoms, global illness ...

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

Lumateperone as Adjunctive Therapy in Patients With ... Conclusions: Lumateperone 42 mg adjunctive to ADT significantly improved depression symptoms and disease severity vs adjunctive placebo and was ...

6. caplytahcp.com caplytahcp.com/safety-summary

Safety Summary | CAPLYTA® (lumateperone) CAPLYTA demonstrated safety in 2,664 adult patients with bipolar depression and schizophrenia. In clinical studies, there was no single adverse reaction ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11580221/

Efficacy and safety of lumateperone for bipolar depression ... Notably, no significant serious safety concerns were reported, and administration of lumateperone did not lead to a significant increase in EPS. Moreover, ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/209500s009lbl.pdf

Caplyta - accessdata.fda.gov The safety of CAPLYTA has been evaluated in placebo-controlled clinical trials in 2664 adult patients with schizophrenia and bipolar depression exposed to one ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT06229210

Study Details | NCT06229210 | Safety and Tolerability Trial ... This is a multicenter, global, 26-week, open-label study to assess the safety and tolerability of lumateperone in pediatric patients with schizophrenia, bipolar ...

10. cureus.com cureus.com/articles/415017-lumateperone-safety-and-tolerability-in-schizophrenia-a-narrative-review

Lumateperone Safety and Tolerability in Schizophrenia Current findings suggest that lumateperone reduces core symptoms of schizophrenia while demonstrating a more favorable safety profile than many ...