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CAPLYTA®

(lumateperone)

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CAPLYTA® (lumateperone)
Medical Information

CAPLYTA - Effect on QT Interval

Last Updated: 05/28/2026

SUMMARY

  • The effect of CAPLYTA on the QT interval was studied in a Thorough QT (TQT) study, designed in accordance with Food and Drug Administration (FDA) guidance, in 29 male and female patients with stable schizophrenia or schizoaffective disorder.1 
    • The TQT study showed no clear signal of any effect of CAPLYTA on the heart rate, atrioventricular (AV) conduction (as measured by the PR interval), or cardiac depolarization (as measured by the QRS duration). There were no new clinically relevant morphological changes demonstrating a signal of concern. Furthermore, there was no signal of any effect of the 42 mg dose on cardiac repolarization.
  • In a 6-week open-label (OL) switching study assessing CAPLYTA in outpatients with stable schizophrenia, no clinically meaningful changes were reported over time in mean or median electrocardiogram (ECG) parameters.2 
    • One patient experienced a QT interval of >60 ms on days 8 and 25, and 2 patients experienced a similar increase on day 56 after resuming the other antipsychotic therapy.
  • In a phase 3 randomized study evaluating lumateperone 28 mg and CAPLYTA 42 mg in patients with schizophrenia, a QT Fridericia-corrected (QTcF) interval of >450 ms was reported in 1 patient in the lumateperone 28 mg group (before and after treatment) and in 1 patient in the placebo group (before treatment).3 
  • In an OL positron emission tomography study evaluating dopamine D2 receptor occupancy at plasma steady state following 2 weeks of treatment with CAPLYTA 42 mg daily in the morning in patients with schizophrenia, no clinically significant changes were reported in ECG parameters.4
  • In a 6-week phase 3 study assessing lumateperone 28 mg and CAPLYTA 42 mg in patients with major depressive episodes (MDEs) associated with bipolar I or bipolar II disorder, no patient experienced a QTcF interval of >480 ms or an increase of >60 ms at any time during the study.5
  • In a 6-month OL extension of the aforementioned phase 3 study with CAPLYTA 42 mg in patients with MDEs associated with bipolar I or bipolar II disorder, no ECG-related treatment-emergent adverse events were reported, and no patient experienced a QTcF interval of >480 ms or a >60 ms increase from baseline at any time.6
  • In a 6-week phase 3 study evaluating lumateperone 28 mg and CAPLYTA 42 mg as adjunctive treatment to lithium or valproate in patients with MDEs associated with bipolar depression, no patient in any group experienced a QTcF interval of >500 ms or an increase of >60 ms from baseline at any time during the study.7
  • In a 6-week phase 3 study assessing CAPLYTA 42 mg adjunctive to antidepressant therapy (ADT) in patients with major depressive disorder (MDD), no patients in the CAPLYTA 42 mg + ADT group and 2 patients in the placebo + ADT group experienced a QTcF interval of ≥480 ms and a >60 ms increase from baseline.8 
  • In a 6-week phase 3 study assessing CAPLYTA 42 mg adjunctive to ADT in patients with MDD, no patients in the CAPLYTA 42 mg + ADT and placebo + ADT groups experienced a QTcF interval of ≥500 ms or a >60 ms increase.9 
  • In a 26-week OL study evaluating CAPLYTA 42 mg adjunctive to ADT in patients with MDD, mean changes in ECG parameters were minimal and not clinically meaningful at the end of the OL treatment period.10,11

CLINICAL DATA

The effect of CAPLYTA on the QT interval was studied in a TQT study designed in accordance with FDA guidance. Cardiac safety, including the QT/QTc interval, was also studied using 12-lead ECG in late-stage clinical trials of CAPLYTA in patients with schizophrenia.1 

The TQT study enrolled 33 male and female patients with stable schizophrenia or schizoaffective disorder. Of these, 32 patients received study treatment and 29 completed the study. The TQT study was a randomized, blinded (except for the positive control moxifloxacin), multisite, 4-arm, crossover study that included placebo, moxifloxacin, and CAPLYTA 42 mg therapeutic and 126 mg supratherapeutic doses that were administered once daily for up to 5 days.1

The study was found to be valid in that the positive control group (moxifloxacin) showed a small change in the corrected QTc duration and met the prespecified criteria for assay sensitivity; the change from baseline in the placebo group was within 3 ms for QTcF, and a bias analysis demonstrated no QT bias.1

The TQT study showed no clear signal of any effect of CAPLYTA on the heart rate, AV conduction (as measured by the PR interval), or cardiac depolarization (as measured by the QRS duration). There was a trend toward a small decrease in the heart rate for the supratherapeutic dose (generally <5 beats per minute). There were no new clinically relevant morphological changes demonstrating a signal of concern. Furthermore, there was no signal of any effect of the 42 mg dose on cardiac repolarization. A concentration-QTcF analysis demonstrated no predictions of clinically relevant effects of the 42 mg dose on cardiac repolarization, with 90% 2-sided upper confidence bounds <10 ms for CAPLYTA and all metabolites.1

The supratherapeutic dose of 126 mg produced a small QTcF increase (peak mean increase in placebo-corrected QTcF change from baseline in the by-time-point analysis of 20.0 ms [90% upper confidence interval, 24.8 ms]). The point estimate of the predicted mean ΔΔQTcF increase ranged from 8.5 to 11.7 ms, with 90% 2-sided upper confidence bounds of 11.3 to 17.1 ms. These effects on QTc are of the same order of magnitude as those of moxifloxacin and other approved medications.1


Summary of Clinical Studies of CAPLYTA
Study Objective and Design
Patients and Treatment Groups
Outcomes
Schizophrenia
Correll et al (2021)2 conducted a 6-week OL switching study (Study 303), comprising of 6 weeks of treatment followed by a 2-week safety follow-up, to assess the short-term safety and tolerability of CAPLYTA in outpatients with stable schizophrenia who transitioned from a prior antipsychotic therapy.
  • Patients (N=301) were switched to CAPLYTA 42 mg for 6 weeks; this was followed by a 2-week safety follow-up period during which the previous antipsychotic therapy was resumed.
  • No clinically meaningful changes were reported over time in mean or median ECG parameters.
  • The mean±SD QTcF interval was 407.5±19.2 ms at baseline, with a mean±SD change of
    -1.1±12.6 ms at day 42. No patients experienced a QTcF interval exceeding 500 ms.
  • One patient experienced a QT interval of >60 ms on days 8 and 25, and 2 patients experienced a similar increase on day 56 after resuming the other antipsychotic therapy.
Correll et al (2020)3 conducted a phase 3, randomized, double-blind, placebo-controlled study (Study 301) to evaluate the efficacy and safety of CAPLYTA in patients with schizophrenia, comprising of a 4-week treatment followed by a 2-week safety follow-up.
  • Patients were randomized (1:1:1) to receive lumateperone 28 mg 
    (n=150), CAPLYTA 42 mg (n=150), or placebo (n=149)
  • There were no clinically meaningful changes from baseline or differences observed in ECG findings between the CAPLYTA and placebo groups.
  • A QTcF interval of >450 ms was reported in 1 patient in the lumateperone 28 mg group (before and after treatment) and in 1 patient in the placebo group (before treatment).
  • No patients experienced a QTcF interval of >500 ms or an increase of >60 ms from baseline.
Vanover et al (2019)4 conducted an OL PET study (Study 008) to evaluate the D2RO at plasma steady state following 2 weeks of treatment with CAPLYTA daily in the morning in patients with schizophrenia.
  • All enrolled patients (N=10) had been taken off their previous antipsychotic medication to establish a drug-free baseline using a 2-week washout period. During the study, 9 patients received lorazepam as a concomitant psychotropic medication.
  • No clinically significant changes were reported in ECG parameters.
Bipolar Depression
A randomized, double-blind, placebo-controlled, multicenter, phase 3 study (Study 401) assessed efficacy of CAPLYTA in Part A, comprising of a 6-week treatment period followed by a 2-week safety follow-up, and evaluated long-term safety and tolerability of CAPLYTA in its OLE (Part B), which included 6 months of treatment followed by a 2-week safety follow-up, in patients with MDEs associated with bipolar I or II disorder.5,6
  • In Part A, patients were randomized to receive lumateperone 28 mg (n=183), CAPLYTA 42 mg (n=185), or placebo (n=186).
  • In Part B, eligible patients received CAPLYTA 42 mg (N=127).
  • Part A:
    • No patients experienced a QTcF interval of >480 ms or an increase of >60 ms at any time during the study.
  • Part B:
    • No ECG-related TEAEs were reported, and no patients experienced a QTcF interval of >480 ms or a >60 ms increase from baseline at any time.
Suppes et al (2023)7 conducted a phase 3, randomized, double-blind, placebo-controlled, multicenter study (Study 402) to evaluate the efficacy and safety of CAPLYTA as adjunctive treatment to lithium or valproate in patients with MDEs associated with bipolar depression, comprising of a 6-week treatment followed by a 2-week safety follow-up.
  • Patients were randomized (1:1:1) to receive lumateperone 28 mg (n=176), CAPLYTA 42 mg (n=177), or placebo (n=175).
  • In any group, no patients experienced a QTcF interval of >500 ms or an increase of >60 ms from baseline at any time during the study.
MDD
Durgam et al (2025)8 conducted a phase 3, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study (Study 501) to assess the efficacy and safety of CAPLYTA adjunctive to ADT in patients with MDD who had an inadequate response to ADT, comprising of a 6-week treatment followed by a 2-week safety follow-up.
  • Patients were randomized (1:1) to receive either CAPLYTA 42 mg (n=242) or placebo (n=243) as adjunctive treatment to ADT.
  • No patients in the CAPLYTA 42 mg + ADT group experienced a QTcF interval of ≥480 ms or a >60 ms increase from baseline.
  • In the placebo + ADT group, 1 patient each experienced a QTcF interval of ≥480 ms and a >60 ms increase from baseline; however, no patients experienced a QTcF interval of ≥500 ms.
Durgam et al (2025)9 conducted a phase 3, randomized, double-blind, placebo-controlled, multicenter, international study (Study 502) to evaluate the efficacy and safety of CAPLYTA adjunctive to ADT in patients with MDD who had an inadequate response to ADT, comprising of a 6-week treatment followed by a 2-week safety follow-up.
  • Patients were randomized (1:1) to receive either CAPLYTA 42 mg (n=242) or placebo (n=238) as adjunctive treatment to ADT.
  • No patients in either group experienced a QTcF interval of ≥500 ms or a >60 ms increase.
Durgam et al (2026)10 conducted a 26-week, OL extension, multicenter, international study (Study 503) to evaluate the long-term safety and tolerability of CAPLYTA adjunctive to ADT in adult patients with MDD, comprising of a 26-week treatment followed by a 2-week safety follow-up.11
  • Patients received CAPLYTA 42 mg (n=809) as adjunctive treatment to ADT.
  • Mean changes in ECG parameters were minimal and not clinically meaningful at the end of the OL treatment period.
  • No patients met the PCS criteria for QTcF ≥500 ms, QTcB ≥500 ms, or PR interval ≥250 ms.
  • Two patients (0.3%) had QTcF ≥480 ms and 1 patient (0.1%) had a QTcF increase of >60 ms.
  • A few ECG-related TEAEs were reported among patients who met PCS ECG criteria, most of which were resolved with continued study drug administration.
  • Among patients who met PCS ECG criteria, 5 experienced potentially associated ECG TEAEs.
Abbreviations: ADT, antidepressant therapy; D2RO, dopamine D2 receptor occupancy; ECG, electrocardiogram; MDD, major depressive disorder; MDE, major depressive episode; OL, open-label; OLE, open-label extension; PCS, potentially clinically significant; PET, positron emission tomography; QTcB, QT Bazett-corrected; QTcF, QT Fridericia-corrected; SD, standard deviation; TEAE, treatment-emergent adverse event.

Literature Search

A literature search of MEDLINE®, EMBASE®, BIOSIS Previews®, and DERWENT® (and/or other resources, including internal/external databases) was conducted on 06 May 2026.

 

References

Show
1 Data on File. CAPLYTA. Integrated Safety Summary. Intra-Cellular Therapies, Inc; 2019.  
2 Correll CU, Vanover KE, Davis RE, et al. Safety and tolerability of lumateperone 42 mg: an open-label antipsychotic switch study in outpatients with stable schizophrenia. Schizophr Res. 2021;228:198-205.  
3 Correll CU, Davis RE, Weingart M, et al. Efficacy and safety of lumateperone for treatment of schizophrenia: a randomized clinical trial. JAMA Psychiatry. 2020;77(4):349-358.  
4 Vanover KE, Davis RE, Zhou Y, et al. Dopamine D2 receptor occupancy of lumateperone (ITI-007): a Positron Emission Tomography Study in patients with schizophrenia. Neuropsychopharmacology. 2019;44(3):598-605.  
5 Correll CU, Durgam S, Kozauer SG, et al. Lumateperone monotherapy for major depressive episodes associated with bipolar disorder: efficacy and safety in a randomized placebo-controlled trial. [published online ahead of print July 23, 2025]. Int Clin Psychopharmacol. doi:10.1097/yic.0000000000000597.  
6 Tohen M, Durgam S, Kozauer SG, et al. Long-term safety and tolerability of lumateperone 42 mg in patients with bipolar disorder: results from a 6-month open-label extension study. Int Clin Psychopharmacol. 2026;41(2):130-137.  
7 Suppes T, Durgam S, Kozauer SG, et al. Adjunctive lumateperone (ITI‐007) in the treatment of bipolar depression: results from a randomized placebo‐controlled clinical trial. Bipolar Disord. 2023;25(6):478-488.  
8 Durgam S, Earley WR, Kozauer SG, et al. Lumateperone as adjunctive therapy in patients with major depressive disorder: results from a randomized, double-blind, phase 3 trial. J Clin Psychiatry. 2025;86(4):25m15848.  
9 Durgam S, Earley WR, Kozauer SG, et al. Adjunctive lumateperone in patients with major depressive disorder: results from a randomized, double-blind, phase 3 trial. Am J Psychiatry. 2025;182(12):1072-1082.  
10 Durgam S, Earley WR, Kozauer SG, et al. Long-term adjunctive lumateperone 42 mg treatment in major depressive disorder: results from a 6-month open-label extension study. Eur Neuropsychopharmacol. 2026;108:112786.  
11 Data on File. CAPLYTA. Final Clinical Study Report of Study 503. Intra-Cellular Therapies, Inc; 2025.  

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