Lumateperone for Bipolar Mania

Recruiting at 33 trial locations

Overseen By ITI Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Intra-Cellular Therapies, Inc.

Disqualifiers: Schizophrenia, Dementia, Substance use, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

350 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 to determine its effectiveness for people with bipolar mania, a condition involving intense mood swings with episodes of excitement or irritability. Researchers aim to assess whether lumateperone is effective and safe compared to a placebo (a pill with no active medicine). Individuals diagnosed with bipolar I disorder who are currently experiencing mania may be suitable for this study. Participants should have been recently hospitalized due to their manic episode. 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 option.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that lumateperone is generally well-tolerated by patients. The FDA has approved it for treating other conditions, such as major depressive disorder, indicating its safety. In one study, 80% of patients responded positively during a 26-week treatment period. Long-term safety data shows that many patients continue using the medication, with 85% maintaining its use over time. Studies have also examined possible side effects, such as discontinuation or adverse events, but these have been manageable overall. This evidence supports the safety of lumateperone for treating conditions like bipolar mania. ^{1 2 3 4 5}

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

Lumateperone is unique because it offers a novel approach to treating bipolar mania by targeting serotonin, dopamine, and glutamate systems in the brain, which are crucial for mood regulation. Unlike traditional treatments such as lithium or valproate, which primarily focus on mood stabilization, lumateperone's multi-receptor action may provide a more comprehensive effect on mood symptoms. Researchers are excited about lumateperone because it has the potential to offer fewer side effects and improved safety compared to current options, making it a promising alternative for individuals with bipolar mania.

What evidence suggests that Lumateperone might be an effective treatment for bipolar mania?

Studies have shown that a 42-mg dose of lumateperone, which participants in this trial may receive, significantly helps people with bipolar disorder. In trials involving 1,454 patients, this dose led to noticeable symptom improvements. This medication has proven effective in treating major depressive disorder, showing strong results on a scale measuring depression severity. Although mainly approved for bipolar depression, research suggests it can also help those experiencing manic episodes. Overall, lumateperone has a solid track record for improving mood disorders. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with bipolar I disorder experiencing manic or mixed episodes, which may include psychotic symptoms. Participants must meet the criteria outlined in the DSM 5.

Inclusion Criteria

Able to provide written informed consent before the initiation of any study specific procedures

Meets the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM 5) criteria for bipolar I disorder with a current episode of mania or mania with mixed features with or without psychotic symptoms, as confirmed by a trained and Sponsor-approved rater using the modified Structured Clinical Interview for DSM-5, Clinical Trials Version (SCID-5-CT)

YMRS total score ≥ 20 and a score of at least 4 on two of the following YMRS items: irritability, speech, content, and disruptive/aggressive behavior at Screening and Baseline

Exclusion Criteria

Has a current primary DSM 5 psychiatric diagnosis other than bipolar disorder. These include: schizophrenia, schizoaffective disorder, or other psychotic disorders; dementia or other cognitive disorders; intellectual disability; moderate or severe substance use disorder (excluding for nicotine); experiencing first manic episode

In the opinion of the Investigator, the patient has a significant risk for suicidal behavior during the course of his/her participation in the study or: at Screening, the patient scores 'yes' on Items 4 or 5 in the Suicidal Ideation section of the Columbia-Suicide Severity Rating Scale (C-SSRS) within 6 months prior to Screening; at Screening, the patient has had 1 or more suicidal attempts within 2 years prior to Screening; at Baseline, the patient scores 'yes' on Items 4 or 5 in the Suicidal Ideation section of the C-SSRS since the Screening Visit; at Screening or Baseline, scores ≥ 4 on Item 10 (suicidal thoughts) on the rater administered Montgomery-Åsberg Depression Rating Scale (MADRS); considered to be an imminent danger to himself/herself or others.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

Treatment

Participants receive lumateperone 42 mg or placebo for 3 weeks in a double-blind manner

3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Lumateperone

Trial Overview The study tests Lumateperone against a placebo to see its effectiveness in treating acute bipolar mania. It's a multicenter trial where participants are randomly assigned to either the drug or placebo group without knowing which one they receive (double-blind).

How Is the Trial Designed?

Group I: Lumateperone 42 mg Experimental Treatment 1 Intervention

Lumateperone 42 mg capsules

Group II: Placebo Placebo Group 1 Intervention

Matching placebo

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

In a study of nine cats with dermatophytosis caused by Microsporum canis, a treatment regimen of itraconazole was effective, with eight cats cured after 56 days of therapy.

The treatment involved an initial 28 days of daily itraconazole followed by a pulse therapy schedule, and the success was determined by achieving two consecutive negative fungal cultures, indicating the protocol's potential efficacy for treating this fungal infection in cats.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of itraconazole as a combined continuous/pulse therapy in feline dermatophytosis: preliminary results in nine cases. Colombo, S., Cornegliani, L., Vercelli, A.[2019]

Newer antifungal agents like itraconazole and terbinafine are more effective than older treatments such as griseofulvin and ketoconazole for dermatophyte pedal onychomycosis.

Itraconazole can be taken continuously for 3 months at 200 mg per day or in a pulse therapy regimen, while terbinafine is given continuously at 250 mg per day for the same duration, providing flexible treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Onychomycosis. New therapies for an old disease. Gupta, AK., Scher, RK., De Doncker, P., et al.[2018]

The study found that combining itraconazole (ITZ) with amiodarone (AMD) and nifedipine (NIF) showed significant synergistic effects against ITZ-resistant strains of Aspergillus fumigatus, suggesting a potential new treatment strategy for invasive infections.

The strongest synergy was observed with the ITZ-AMD combination, indicating that using nonantimicrobial membrane-active compounds could enhance the efficacy of antifungal treatments, particularly for resistant strains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potent synergistic in vitro interaction between nonantimicrobial membrane-active compounds and itraconazole against clinical isolates of Aspergillus fumigatus resistant to itraconazole. Afeltra, J., Vitale, RG., Mouton, JW., et al.[2021]

The study found that falcarindiol (FADOH) combined with itraconazole (ITC) showed synergistic antifungal effects against 86.7% of tested dermatophytes, particularly effective against Trichophyton rubrum and Trichophyton mentagrophytes.

This is the first report of the in vitro synergistic effect of FADOH and ITC against dermatophytes, suggesting that FADOH could be a promising addition to antifungal therapies for skin infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic activity of the combination of falcarindiol and itraconazole in vitro against dermatophytes. Kan, S., Tan, J., Cai, Q., et al.[2023]

Ravuconazole (RVZ) and luliconazole (LCZ) have been found to be more effective than traditional antifungals itraconazole (ITZ) and terbinafine (TRF) against Microsporum canis, a fungus causing skin infections in pets.

The study suggests that RVZ can be administered orally and LCZ can be applied topically, providing new treatment options for managing dermatophytosis in animals and preventing potential zoonotic infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antifungal Susceptibility Testing for Microsporum canis from Cats in Japan. Kano, R., Watanabe, M., Tsuchihashi, H., et al.[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]

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]

Valproate has been shown to be effective in both acute and preventive treatment of bipolar disorder, especially for patients who do not respond well to lithium, based on a review of studies since the 1960s.

The drug may be particularly beneficial for specific groups of bipolar patients, such as those with rapid cycling or mixed mania, indicating its potential as a targeted treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valproate in the treatment of bipolar disorder: literature review and clinical guidelines. McElroy, SL., Keck, PE., Pope, HG., et al.[2019]

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]

Valproate is an effective treatment for mania in bipolar disorder, showing particular efficacy in subgroups like those with mixed mania and prominent irritability, and is comparable to olanzapine in maintenance treatment while being better tolerated.

The drug has several mechanisms of action, including inhibition of glycogen synthase kinase and activation of extracellular signal-regulated kinase, and may lead to side effects such as weight gain and reduced platelet count, especially at higher serum levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valproate in bipolar disorder: 2000 onwards. Bowden, CL., Singh, V.[2013]

In a study of 377 hospitalized patients with acute mania associated with bipolar I disorder, divalproex sodium extended release (divalproex ER) showed significant efficacy compared to placebo, with 48% of patients experiencing at least a 50% improvement in mania symptoms by day 21.

Divalproex ER was associated with improvements in specific symptoms such as reduced need for sleep and increased energy, while side effects included somnolence and dizziness, indicating it is generally safe for treating mania episodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, placebo-controlled, multicenter study of divalproex sodium extended release in the treatment of acute mania. Bowden, CL., Swann, AC., Calabrese, JR., et al.[2019]

Lumateperone, used for treating schizophrenia and bipolar depression, has been shown to reduce elevated levels of proinflammatory cytokines in mice, suggesting it may help alleviate depressive symptoms linked to inflammation.

In addition to its neurotransmitter modulation, lumateperone appears to enhance blood-brain barrier integrity and reduce anxiety-like behaviors in rodents, indicating its potential broader effects on mental health beyond just neurotransmitter activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lumateperone Normalizes Pathological Levels of Acute Inflammation through Important Pathways Known to Be Involved in Mood Regulation. Dutheil, S., Watson, LS., Davis, RE., et al.[2023]

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 study of 36 patients with bipolar I disorder treated with long-acting injectable paliperidone palmitate for at least one year, there was a significant reduction in the number and length of hospitalizations and manic episodes.

Safety assessments showed no significant changes in prolactin levels or other metabolic markers, suggesting that paliperidone palmitate is a safe option for managing bipolar I disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of initiating long-acting injectable paliperidone palmitate on relapse and hospitalization in patients with bipolar I disorder: A mirror image retrospective study. Caliskan, AM., Calisir, S., Caliskan, S., et al.[2021]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40874771/

Dose-response efficacy and safety of lumateperone in ... Results: Three randomized controlled trials involving 1454 patients showed that a 42-mg daily dose of lumateperone significantly improved ...

2. jnj.com jnj.com/media-center/press-releases/fda-approval-of-caplyta-lumateperone-has-the-potential-to-reset-treatment-expectations-offering-hope-for-remission-in-adults-with-major-depressive-disorder

FDA approval of CAPLYTA® (lumateperone) has the ... CAPLYTA®, added to an antidepressant, demonstrated robust efficacy for the treatment of MDD in the primary endpoint, the MADRS Total score, with ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06462612

NCT06462612 | Study of Lumateperone in the Treatment ... This is a multicenter, randomized, double-blind, placebo-controlled, study in the acute treatment of patients with a diagnosis of bipolar I disorder with manic ...

4. caplytahcp.com caplytahcp.com/bipolar/primary-efficacy

Primary Efficacy - Bipolar Depression - Caplyta HCP Explore the data on the efficacy of CAPLYTA in adults with bipolar depression. Please see full Prescribing Information, including Boxed WARNINGS.

5. 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 ...

6. caplytahcp.com caplytahcp.com/long-term-data

Long-Term Safety Data | CAPLYTA® (lumateperone) Patients on CAPLYTA sustained treatment over 6 months1,2. 9 out of 10 patients chose to continue into the open-label safety extension, and 85% stayed on ...

7. 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 ...