Lumateperone for Bipolar Mania
Recruiting in Palo Alto (17 mi)
+20 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Intra-Cellular Therapies, Inc.
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 1 jurisdiction
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).
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 traditional treatments.
2451113What 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 compared to a placebo 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.
810121415Is Lumateperone safe for humans?
Lumateperone, also known as Caplyta or ITI-007, is used to treat schizophrenia and depressive episodes in bipolar disorder. It has been shown to reduce inflammation and anxiety-like behavior in animal studies, suggesting it may be safe for humans, but always consult with a healthcare provider for personalized advice.
13679Will 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.
Eligibility Criteria
This trial is for adults aged 18-75 with bipolar I disorder experiencing a manic or mixed episode, possibly with psychotic symptoms. They must meet DSM 5 criteria, have specific scores on the YMRS scale, and be hospitalized due to their current episode. Excluded are those with other primary psychiatric diagnoses, severe substance use disorders (except nicotine), first-time manic episodes, or significant suicidal risk.Inclusion Criteria
I am between 18 and 75 years old.
Participant Groups
The study tests Lumateperone against a placebo in patients with bipolar mania. It's a multi-center trial where participants are randomly assigned to either the medication or placebo without knowing which one they receive (double-blind). The goal is to evaluate the effectiveness of Lumateperone in acute treatment.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Lumateperone 42 mgExperimental Treatment1 Intervention
Lumateperone 42 mg capsules
Group II: PlaceboPlacebo Group1 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)
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Clinical SiteMontclair, CA
Clinical SiteBellflower, CA
Clinical SiteRogers, AR
Clinical SiteCulver City, CA
More Trial Locations
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Who is running the clinical trial?
Intra-Cellular Therapies, Inc.Lead Sponsor
References
Valproate in the treatment of bipolar disorder: literature review and clinical guidelines. [2019]A growing number of uncontrolled and controlled studies performed since the mid-1960s indicate that the antiepileptic drug valproate is effective in the acute and prophylactic treatment of some patients with bipolar disorder, including those inadequately responsive to or intolerant of lithium therapy. Preliminary evidence also suggests that valproate may be particularly likely to have antimanic or mood-stabilizing effects in certain bipolar patients, including those with rapid cycling, dysphoric or mixed mania, and neurologic abnormalities. In this article, studies examining the efficacy of valproate in the treatment of bipolar disorder are reviewed and clinical guidelines for the use of valproate in bipolar patients are presented.
Onychomycosis. New therapies for an old disease. [2018]The newer generation of antifungal agents such as itraconazole and terbinafine are more effective than the older therapies, griseofulvin and ketoconazole, in the treatment of dermatophyte pedal onychomycosis. Itraconazole can be administered as continuous dosing, 200 mg per day for 3 months, or in the form of pulse therapy, 200 mg twice a day for 1 week per month for 3 consecutive months. Terbinafine is given as continuous dosing, 250 mg per day for 3 months.
[Brief history of the development of valproate in bipolar disorders]. [2013]The anticonvulsant properties of N-dipropylacetic acid (valproic acid) were discovered in 1967 by Meunier and Carraz. It very soon became widely used in epilepsy, generally in the form of sodium valproate. Divalproate, an equimolar combination of valproic acid and sodium valproate has been available in the United States for this indication since 1983. The development of this drug for use in bipolar disorders occurred in two stages. Antimanic and prophylactic activity was demonstrated for valpromide, a primary amide of valproic acid (Lambert et al., 1968-71). The preliminary studies conducted by Lambert were not repeated outside France and it was only much later that the efficacy of derivatives of valproic acid in bipolar disorders was demonstrated in studies undertaken in Germany with sodium valproate (Enrich and Von Zerssen, 1980-85), and then in the USA with divalproate in the last decade. The majority of controlled studies were performed with divalproate and demonstrated the efficacy of this drug in monotherapy during manic episodes (Pope et al., 1991) (Bowden et al, 1994), and divalproate was approved by the FDA in 1995 in this indication. The results of the study by Bowden and the findings of other open studies suggest a wider spectrum of activity for divalproate than for lithium with a good efficacy profile in subtypes of mania in which the effects of lithium are mediocre: dysphoric mania, rapid cycling mania and forms of mania secondary to organic brain disease. The prospective studies by Puzynski and Klosiewicz (1984) and by Lambert and Venaud (1992) demonstrated the prophylactic activity of valpromide, with slightly greater efficacy being noted against manic episodes than against depressive episodes. The study by Bowden et al. (2000) shows that good efficacy of divalproate in acute manic episodes in a given patient may be predictive of efficacy of the drug in maintenance therapy. The field of bipolar disorders currently appears much wider and more heterogeneous than has long been held. Current therapeutic strategy is dominated by thymoregulators. In such long-term therapy where poor compliance constitutes a risk factor for treatment failure, use of valproate (valpromide, divalproate) has the twin advantage of being easy to manage and well tolerated in the long-term. During coadministration of thymoregulators, which is often necessary due to their limited individual efficacy, general consensus exists regarding the therapeutic value of combined divalproate and lithium.
Efficacy of itraconazole as a combined continuous/pulse therapy in feline dermatophytosis: preliminary results in nine cases. [2019]This study evaluated the efficacy of itraconazole as a combined continuous/pulse therapy for feline dermatophytosis. Nine cats with dermatophytosis caused by Microsporum canis were treated with itraconazole at 10 mg kg(-1) orally once daily for 28 days and then on an alternate week regimen (1 week off, 1 week on) at the same dosage. Cats were re-evaluated by physical examination and fungal culture at days 28, 42, 56 and 70 if necessary. Treatment was stopped when two consecutive negative fungal cultures were obtained. Eight cats were cured after 56 days, with two negative cultures obtained at days 28 and 42. In one case, a positive culture was obtained at day 28, but negative cultures were achieved at days 42 and 56. This protocol appears to be effective in the treatment of feline dermatophytosis, although these preliminary results should be confirmed by a controlled study.
Potent synergistic in vitro interaction between nonantimicrobial membrane-active compounds and itraconazole against clinical isolates of Aspergillus fumigatus resistant to itraconazole. [2021]To develop new approaches for the treatment of invasive infections caused by Aspergillus fumigatus, the in vitro interactions between itraconazole (ITZ) and seven different nonantimicrobial membrane-active compounds--amiodarone (AMD), amiloride, lidocaine, lansoprazole (LAN), nifedipine (NIF), verapamil, and fluphenazine--against seven ITZ-susceptible and seven ITZ-resistant (ITZ-R) strains were evaluated by the checkerboard microdilution method based on National Committee for Clinical Laboratory Standards M-38A guidelines. The nature and the intensity of the interactions were assessed by a nonparametric approach (fractional inhibitory concentration [FIC] index model), a fully parametric response surface approach (Greco model) of the Loewe additivity no-interaction theory, and the nonparametric (Prichard model) and semiparametric response surface approaches of the Bliss independence (BI) no-interaction theory. Statistically significant synergy was found for the combination of ITZ and AMD and the combination of LAN and NIF, although with different intensities against ITZ-R strains. The FIC index values ranged from 1 to 0.02 for ITZ-AMD, 0.53 to 0.04 for ITZ-LAN, and 0.28 to 0.06 for ITZ-NIF. By use of the BI-based model, the strongest synergy was found for the combination of ITZ with AMD, followed by the combination of ITZ and NIF. The parametric models could not be fit adequately because most of the drugs alone did not show any effect and, thus, no sigmoid dose-response. In general, the combination of ITZ with calcium pump blockers displayed in vitro synergistic activity, primarily against ITZ-R strains, and warrants further investigation.
A randomized, placebo-controlled, multicenter study of divalproex sodium extended release in the treatment of acute mania. [2019]The efficacy and safety of divalproex sodium extended release (divalproex ER) were evaluated in patients hospitalized for acute mania associated with bipolar I disorder, manic or mixed type (DSM-IV-TR criteria).
Impact of initiating long-acting injectable paliperidone palmitate on relapse and hospitalization in patients with bipolar I disorder: A mirror image retrospective study. [2021]Literature assessing the use of long-acting injectable paliperidone palmitate in patients with bipolar I disorder is limited. The aim of this retrospective study was to determine the effectiveness of long-acting injectable paliperidone palmitate treatment on relapse and hospitalization in a real-world setting. Patients with bipolar I disorder aged 18-65 years, who were treated with paliperidone palmitate once-monthly (PP1M) for at least one year, were included. The rate of relapse, hospitalization, and length of hospital stay were collected. Safety outcomes included levels of prolactin, fasting blood sugar, total cholesterol, triglyceride, high density lipoprotein, and low density lipoprotein. The data of 36 patients who met the study criteria were evaluated. Number and length of hospitalizations, number of manic and mixed episodes significantly decreased after PP1M addition. When we compared the prolactin, fasting blood sugar, total cholesterol, triglyceride, high density lipoprotein, and low density lipoprotein levels as an indicator of the safety of treatment, there was no statistically significant change in these values before and after PP1M addition. Our findings suggested PP1M may be effective in reducing manic and mixed episodes. Limitations include a mirror image retrospective design and small sample size.
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 Normalizes Pathological Levels of Acute Inflammation through Important Pathways Known to Be Involved in Mood Regulation. [2023]Lumateperone is indicated for the treatment of schizophrenia in adults and for depressive episodes associated with bipolar I or II disorder (bipolar depression) in adults, as monotherapy and as adjunctive therapy with lithium or valproate (Calabrese et al., 2021). It is currently under evaluation for the treatment of major depressive disorder (www.ClinicalTrials.gov). Lumateperone acts by selectively modulating serotonin, dopamine, and glutamate neurotransmission in the brain. However, other mechanisms could be involved in the actions of lumateperone, and because of the connection between the immune system and psychiatric health, we hypothesized that lumateperone might improve symptoms of depression, at least in part, by normalizing pathologic inflammation. Here, we show that in male and female C57BL/6 mice subjected to an acute immune challenge, lumateperone reduced aberrantly elevated levels of key proinflammatory cytokines (e.g., IL-1β, IL-6, and TNF-α) in both brain and serum; lumateperone also reduced proinflammatory cytokines in male mice under acute behavioral stress. Further, we demonstrate that lumateperone altered key genes/pathways involved in maintaining tissue integrity and supporting blood-brain barrier function, such as claudin-5 and intercellular adhesion molecule 1. In addition, in acutely stressed male Sprague Dawley rats, lumateperone conferred anxiolytic- and antianhedonic-like properties while enhancing activity in the mammalian target of rapamycin complex 1 pathway in the PFC. Together, our preclinical findings indicate that lumateperone, in addition to its ability to modulate multiple neurotransmitter systems, could also act by reducing the impact of acute inflammatory challenges.SIGNIFICANCE STATEMENT Lumateperone is indicated in adults to treat schizophrenia and depressive episodes associated with bipolar I or II disorder, as monotherapy and adjunctive therapy with lithium or valproate. Because aberrant immune system activity is associated with increased depressive symptoms, the relationship between lumateperone and immune function was studied. Here, lumateperone reduced the levels of proinflammatory cytokines that were increased following an immune challenge or stress in mice. Additionally, lumateperone altered genes and pathways that maintain blood-brain barrier integrity, restored an index of blood-brain barrier function, reduced anxiety-like behavior in rodents, and enhanced mammalian target of rapamycin complex 1 pathway signaling in the PFC. These results highlight the anti-inflammatory actions of lumateperone and describe how lumateperone may reduce immune pathophysiology, which is associated with depressive symptoms.
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.
Antifungal Susceptibility Testing for Microsporum canis from Cats in Japan. [2023]Control of infection caused by Microsporum canis in pet animals are important for prevention of zoonosis. Treatments for animal dermatophytosis have generally consisted of itraconazole (ITZ) and terbinafine (TRF); however, a TRF-resistant M. canis strain from a case of feline dermatophytosis has been reported. In the present study, we examined the in vitro susceptibility of clinical isolates of M. canis to new antifungal drugs, such as ravuconazole (RVZ) and luliconazole (LCZ). The results indicated that RVZ and LCZ are more effective than ITZ and TRF. Therefore, oral administration of RVZ or topical application of LCZ may serve as new treatment options.
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.
Synergistic activity of the combination of falcarindiol and itraconazole in vitro against dermatophytes. [2023]Previous studies have shown that natural polyacetylene alcohols, such as falcarindiol (FADOH), have good antifungal effects on plant fungi. While its effect on fungi that infect humans remains to be explored. In our study, checkerboard microdilution, drop-plate assay, and time-growth method were employed to analyze the interactions between FADOH and itraconazole (ITC) in vitro against dermatophytes, including 12 Trichophyton rubrum (T. rubrum), 12 Trichophyton mentagrophytes (T. mentagrophytes), and 6 Microsporum canis (M. canis). The results showed that the combination of FADOH and ITC exhibited synergistic and additive activity against 86.7% of all tested dermatophytes. FADOH had an excellent synergistic effect on ITC against T. rubrum and T. mentagrophytes; the synergistic rates were 66.7% and 58.3%, respectively. On the contrary, FADOH combined with ITC showed poor synergistic inhibitory activity (16.7%) against M. canis. Moreover, the additive rates of these two drugs against T. rubrum, T. mentagrophytes, and M. canis were 25%, 41.7%, and 33.3%, respectively. No antagonistic interactions were observed. The drop-plate assay and time-growth curves confirmed that the combination of FADOH and ITC had a potent synergistic antifungal effect. The in vitro synergistic effect of FADOH and ITC against dermatophytes is reported here for the first time. Our findings suggest the potential use of FADOH as an effective antifungal drug in the combined therapy of dermatophytoses caused especially by T. rubrum and T. mentagrophytes.
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.
Illuminating Hope for Mental Health: A Drug Review on Lumateperone. [2023]This drug review provides a comprehensive analysis of a novel antipsychotic called lumateperone, marketed as Caplyta. Lumateperone gained FDA approval in 2019 for treating schizophrenia and later, in 2021, for treating bipolar depression. The review begins by delving into lumateperone's mechanism of action, which involves the partial agonism of the dopamine D2 receptor as well as its unique effects on the dopamine transporter, N-methyl-D-aspartate (NMDA) receptor, and serotonin transporter. Additionally, the study examines lumateperone's distinctive pharmacokinetics. Moreover, this review assesses lumateperone's metabolic profile and highlights its favorable outcomes regarding mean body weight, BMI, and waist circumference, surpassing those of other second-generation antipsychotic medications. The study explicitly emphasizes the efficacy and safety of lumateperone in treating schizophrenia and bipolar depression associated with bipolar I and II disorders. An extensive investigation of multiple clinical trials provides compelling evidence of lumateperone's advantages over existing antipsychotic medications. The review also acknowledges the limitations of lumateperone compared to other antipsychotics. In conclusion, this drug review underscores the importance of further research to uncover the additional limitations of lumateperone while acknowledging its promising benefits and potential for advancing treatment options.