Lumateperone for Major Depressive Disorder
Recruiting in Palo Alto (17 mi)
+31 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Intra-Cellular Therapies, Inc.
Must be taking: Antidepressants
Disqualifiers: Schizophrenia, Bipolar, Anxiety, others
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?
This trial is testing lumateperone, a medication that may help people with depression who haven't improved with other treatments. The study includes patients diagnosed with Major Depressive Disorder who haven't responded well to their current antidepressants. Lumateperone works by balancing brain chemicals that affect mood, potentially improving depressive symptoms.
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 Lumateperone safe for humans?
How is the drug lumateperone different from other treatments for major depressive disorder?
Lumateperone is unique because it is a first-in-class drug that simultaneously affects serotonin, dopamine, and glutamate systems in the brain, which is different from most other treatments that typically target only one or two of these pathways. It is also taken orally and has been shown to improve a wide range of depression symptoms in people with bipolar disorder, suggesting potential benefits for major depressive disorder.35678
Eligibility Criteria
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.
I am between 18 and 65 years old.
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
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Trial Timeline
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)
Treatment Details
Interventions
- Lumateperone (Other)
- Placebo (Placebo)
Trial OverviewThe 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.
Participant Groups
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Lumateperone 42 mgExperimental Treatment1 Intervention
Group II: PlaceboPlacebo Group1 Intervention
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Clinical SiteKansas City, KS
Clinical SitePico Rivera, CA
Clinical SitePhiladelphia, PA
Clinical SiteClermont, FL
More Trial Locations
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Who Is Running the Clinical Trial?
Intra-Cellular Therapies, Inc.Lead Sponsor
References
Lumateperone: a new treatment approach for neuropsychiatric disorders. [2019]Lumateperone tosylate (ITI-007 tosylate, ITI-722) is a first-in-class investigational drug which acts syn-ergistically through multiple systems (serotonergic, dopaminergic and glutamatergic), thus representing a unique approach for the therapeutic management of a range of neuropsychiatric disorders. It possesses a potent antagonistic activity at 5-hydroxytryptamine (serotonin) 2A (5-HT2A) receptors and also binds to dopamine (D1, D2) receptors with partial agonism at presynaptic D2 receptors and postsynaptic antagonism. Further, preclinical data demonstrated that lumateperone uniquely acts as an indirect modulator of glutamatergic phosphoprotein with D1-dependent augmentation of both NMDA and AMPA activity via the mammalian target of rapamycin (mTOR) pathway, mechanisms thought to predict potent and rapid antidepressant effects. Previous results of schizophrenia efficacy studies found robust improvements in depressive as well as psychotic symptoms for those patients who were comorbidly depressed. In various clinical trials to date, the safety profile of lumateperone was found to be similar to that of placebo. These promising results and strong performance in phase II studies point to the potential of lumateperone to display potent and rapid antidepressant effects in patients suffering from a range of mood disorders. Currently, this novel drug is in phase III of its clinical development for schizophrenia, agitation associated with dementia and bipolar depression.
Evidence on the New Drug Lumateperone (ITI-007) for Psychiatric and Neurological Disorders. [2021]Lumateperone (ITI-007) is a tosylate salt with binding affinities to receptors implicated in the therapeutic actions of antipsychotic medications, including the serotonin 5HT2A receptors, dopamine D2 and D1 receptors and the serotonin transporter. It has a unique mechanism of action because it simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, implicated in serious mental illness. It can be considered a multi-target-directed ligand and a multifunctional modulator of serotoninergic system with possible precognitive, antipsychotic, antidepressant and anxiolytic properties. Lumateperone has been investigated as a novel agent for the treatment of schizophrenia, but it represents a new potential option for other psychiatric and neurological diseases, such as behavioural symptoms of dementia or Alzheimer's disease, sleep disturbances, bipolar depression. Besides, it has demonstrated a favourable safety profile without significant extrapyramidal side effects, hyperprolactinemia or changes in cardiometabolic or endocrine factors versus placebo. Additional studies are warranted to confirm and examine the benefit of lumateperone and possible therapeutic targets. This paper is a comprehensive and thorough summary of the most important findings and potential future role of this particular compound in personalized treatments.
Lumateperone: New Drug or Same Old Drug With a New Dress? [2021]Lumateperone (Caplyta®) is a drug recently approved by the U.S. Food and Drug Administration for the treatment of schizophrenia. But is it a new drug with promise, or a similar drug with new wrappings? This drug, similar to other second- and third-generation serotonin dopamine antagonists, is a potent antagonist at higher serotonin 2A receptors as well as brief binding to dopamine 1 and dopamine 2 (D2) receptors, but also has partial agonism at presynaptic D2 and indirect modulation of N-Methyl-D-aspartic acid (NMDA) and alpha-amino-3-hydroxy-5-methyl-isoxazolepropionic acid (AMPA) of the glutamine receptors. The current article reviews the putative effects of this novel mechanism of action on symptoms of schizophrenia as discussed in Phase II and III trials. A case study applies the information to a clinical situation. [Journal of Psychosocial Nursing and Mental Health Services, 58(6), 9-12.].
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]In a phase 3 randomized double-blind placebo-controlled study, the authors investigated the efficacy and safety of 42 mg/day of lumateperone in patients with bipolar I or bipolar II disorder experiencing a major depressive episode.
Lumateperone: First Approval. [2021]Lumateperone (Caplyta®) is a novel, orally available agent developed by Intra-Cellular Therapies (under a license from Bristol-Myers Squibb) for the treatment of schizophrenia and other neuropsychiatric and neurological disorders. Lumateperone is a first-in-class selective and simultaneous modulator of serotonin, dopamine and glutamate. In December 2019, lumateperone received its first global approval in the USA for the treatment of schizophrenia in adults. The drug is also under clinical development for bipolar depression, behavioural disorders associated with dementia and Alzheimer's disease, sleep maintenance insomnia and major depressive disorders. This article summarizes the milestones in the development of lumateperone leading to this first approval for the treatment of schizophrenia.
The Efficacy of Lumateperone in Patients With Bipolar Depression With Mixed Features. [2023]Objective: A post hoc analysis of a phase 3, randomized, double-blind, placebo-controlled outpatient study investigated efficacy of lumateperone 42 mg in patients with bipolar I or bipolar II disorder and experiencing a major depressive episode (MDE) stratified by the presence of mixed features.
The efficacy of lumateperone on symptoms of depression in bipolar I and bipolar II disorder: Secondary and post hoc analyses. [2023]A recent Phase 3, randomized, double-blind, placebo-controlled study established that lumateperone 42-mg monotherapy significantly improved symptoms of depression in patients with bipolar depression. This manuscript reports prespecified secondary and post hoc efficacy analyses. Patients with bipolar I or bipolar II disorder experiencing a major depressive episode were randomized 1:1 to lumateperone 42 mg or placebo, administered orally once daily for 6 weeks. Prespecified analyses evaluated change from baseline to Day 43 in individual Montgomery-Åsberg Depression Rating Scale (MADRS) item scores in the modified intent-to-treat population (mITT) and bipolar I and bipolar II disorder subgroups. Post hoc analyses investigated the MADRS anhedonia factor and categorical shifts in MADRS item scores. In the mITT, there was significant improvement from baseline to Day 43 with lumateperone 42 mg compared with placebo for all 10 MADRS items; most MADRS items significantly improved in subgroups with bipolar I (9 items) and bipolar II disorder (8 items). A significantly higher proportion of patients receiving lumateperone compared with placebo shifted from baseline MADRS item score ≥4 to ≤2 at end of treatment in Reported Sadness, Reduced Sleep, Concentration Difficulties, Lassitude, Inability to Feel, and Pessimistic Thoughts. Lumateperone significantly improved the MADRS anhedonia factor from baseline to Day 43 compared with placebo in the mITT (effect size, -0.47) and subgroups with bipolar I (-0.36) and bipolar II disorder (-0.90). Lumateperone 42 mg treatment significantly improved depression symptoms compared with placebo, with consistent efficacy across a broad range of symptoms in people with bipolar I and bipolar II disorder.
Evaluating lumateperone for its use in treating depressive episodes associated with bipolar I or II disorder in adults. [2023]Lumateperone is a novel antipsychotic medication that has recently received approval by the United States Food and Drug Administration for treatment of major depressive episodes of type I and II bipolar disorder. It is approved for use as monotherapy or as an adjunctive treatment to lithium or valproic acid.