Lumateperone for Bipolar Mania

Recruiting at 16 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

Trial Summary

What is the purpose of this trial?

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 episodes or manic episodes with mixed features (bipolar mania), with or without psychotic symptoms, according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5).

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.

What data supports the effectiveness of the drug Lumateperone for treating bipolar mania?

Lumateperone has been shown to be effective in treating major depressive episodes in people with bipolar I and II disorders, as it significantly improved symptoms of depression in clinical trials. While the studies focus on depression, the drug's approval for bipolar depression suggests it may have potential benefits for other aspects of bipolar disorder, such as mania. ^{1 2 3 4 5}

Is Lumateperone safe for humans?

Lumateperone is used to treat schizophrenia and depressive episodes in bipolar disorder, and it has been shown to reduce inflammation and anxiety-like behavior in animal studies. While these findings suggest potential safety, more specific human safety data would be needed for a comprehensive understanding. ^{6 7 8 9 10}

What makes the drug Lumateperone unique for treating bipolar mania?

Lumateperone is unique because it works differently from other drugs by targeting multiple neurotransmitter systems in the brain, which may help manage symptoms of bipolar mania more effectively. It is also known for having a favorable side effect profile compared to some other treatments. ^{11 12 13 14 15}

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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+

Findings from Research

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]

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]

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 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 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, 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 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 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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Evaluating lumateperone for its use in treating depressive episodes associated with bipolar I or II disorder in adults. [2023]

2. United States 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. [2022]

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

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

4. Netherlands 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. [2023]

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

The Efficacy of Lumateperone in Patients With Bipolar Depression With Mixed Features. [2023]

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

Lumateperone Normalizes Pathological Levels of Acute Inflammation through Important Pathways Known to Be Involved in Mood Regulation. [2023]

7. Netherlands 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. [2021]

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

A randomized, placebo-controlled, multicenter study of divalproex sodium extended release in the treatment of acute mania. [2019]

9. Denmark pubmed.ncbi.nlm.nih.gov

Valproate in bipolar disorder: 2000 onwards. [2013]

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

Valproate in the treatment of bipolar disorder: literature review and clinical guidelines. [2019]

11. United States 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. [2021]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Synergistic activity of the combination of falcarindiol and itraconazole in vitro against dermatophytes. [2023]

13. England pubmed.ncbi.nlm.nih.gov

Efficacy of itraconazole as a combined continuous/pulse therapy in feline dermatophytosis: preliminary results in nine cases. [2019]

14. Japan pubmed.ncbi.nlm.nih.gov

Antifungal Susceptibility Testing for Microsporum canis from Cats in Japan. [2023]

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

Onychomycosis. New therapies for an old disease. [2018]