Small Molecule · ITI-007

Lumateperone (ITI-007)

ApprovedIntra-Cellular Therapies, Inc. (ITCI)

Oral, once-daily (42 mg) small-molecule antipsychotic/antidepressant marketed as Caplyta. A high-affinity 5-HT2A receptor antagonist that also modulates dopamine D2 receptors (described by the developer as a presynaptic partial agonist / postsynaptic antagonist 'D2 receptor phosphoprotein modulator') and inhibits the serotonin transporter (SERT), with additional D1-receptor / glutamatergic modulation. Developed by Intra-Cellular Therapies; on 6 Nov 2025 the FDA approved it as adjunctive therapy with antidepressants for major depressive disorder in adults, its fourth indication after schizophrenia and bipolar I/II depression. Intra-Cellular Therapies was acquired by Johnson & Johnson (closed 2 Apr 2025).

Also known as: ITI-007, ITI-722, Caplyta, lumateperone, 313368-91-1

Data current as of

Key facts

Modality
Small molecule
Chemical class
butyrophenone, pyridopyrroloquinoxaline
DEA schedule
Unscheduled
Chemistry
Single enantiomer
Mechanism
5-HT2A antagonist
Highest phase
Approved
Lead indication
Schizophrenia
Developer
Intra-Cellular Therapies, Inc. (ITCI)
Trials
16 tracked · 6 recruiting · 722 sites
Next catalyst
1H 2026 — Topline data (Bipolar disorder)

Mechanism of action#

Multi-target small molecule. High-affinity serotonin 5-HT2A receptor antagonist (human pKi 9.3, Ki ~0.50 nM) with comparatively lower affinity at dopamine D2 receptors (pKi 7.5, Ki ~32 nM) where it acts as a presynaptic partial agonist / postsynaptic antagonist (the developer's 'dopamine receptor phosphoprotein modulator' framing), and inhibition of the serotonin transporter (SERT; pKi 7.2, Ki ~63 nM). Also modulates dopamine D1-receptor-dependent glutamatergic signaling. The combined 5-HT2A antagonism plus low/region-selective D2 occupancy and SERT inhibition underlies its low metabolic/EPS burden and proposed antidepressant activity.

0.1 nM1 nM10 nM100 nM5-HT2A5-HT2A — antagonist — Ki 0.5 nMKi 0.5 nMD2D2 — antagonist — Ki 32 nMKi 32 nMSERTSERT — inhibitor — Ki 63 nMKi 63 nM
Binding affinity on a log scale — further left is more potent. Values from the sourced literature (see table).
TargetActionAffinity
5-HT2AprimaryHTR2AAntagonistKi 0.5 nMⓘ
D2DRD2AntagonistKi 32 nMⓘ
SERTSLC6A4InhibitorKi 63 nMⓘ

Formulations#

FormulationRouteRegimenPharmacokinetics
Lumateperone oral capsule (Caplyta)immediate-release capsule (crystalline tosylate salt)
Capsules of 42 mg, 21 mg, and 10.5 mg lumateperone (equivalent to 60/30/15 mg lumateperone tosylate); recommended dose 42 mg once daily, with or without food.
OralOnce dailyt½ 18 h · Tmax 1.5 h · F 4.4%

Development timeline#

2010201520202025TodayApproved27 Apr 2026 — readout (met) — FDA approved Caplyta (lumateperone) sNDA adding relapse-prevention data in schizophrenia (Study 304: HR 0.37, 63% lower relapse risk, p=0.0002).27 Apr 2026 — FDA approval — FDA approves CAPLYTA (lumateperone) sNDA for prevention of relapse in schizophrenia6 Nov 2025 — readout (met) — FDA approved Caplyta (lumateperone) as adjunctive therapy with antidepressants for MDD in adults.2 Apr 2025 — Acquisition — Johnson & Johnson acquires Intra-Cellular Therapies13 Feb 2023 — readout (met) — Study 402 positive (42 mg): lumateperone adjunctive to lithium/valproate met the MADRS Week-6 primary in bipolar depression (LSMD -2.4, p=0.02).20 Dec 2021 — readout (met) — FDA approved Caplyta (lumateperone) for bipolar I and II depression in adults, as monotherapy and as adjunctive therapy with lithium or valproate.20 Dec 2019 — readout (met) — FDA approved Caplyta (lumateperone) 42 mg once daily for the treatment of schizophrenia in adults.31 May 2005 — Licensing deal — Intra-Cellular in-licenses lumateperone (ITI-007) from Bristol-Myers SquibbPhase 21 Aug 2013 — phase change — Study 005 (NCT01499563, ITI-007-005) primary completion: positive Phase 2 4-week trial; lumateperone 42 mg met PANSS total primary endpoint vs placebo (-13.2 vs -7.4, p=0.017, ES ~0.4). One of the two positive pivotal efficacy trials cited for the schizophrenia approval (Lieberman et al. 2016).Phase 31 Mar 2027 — upcoming — Anticipated topline of Study 601, the first pivotal Phase 3 of lumateperone for irritability associated with autism spectrum disorder (pediatric); primary endpoint ABC-Irritability at Week 6.1 Mar 2027 — upcoming — Anticipated topline of Study 602, the second pivotal Phase 3 of lumateperone for irritability associated with autism spectrum disorder (pediatric); primary endpoint ABC-Irritability at Week 6.31 May 2026 — upcoming — Anticipated topline from Phase 3 Study 452 (NCT06462612) of lumateperone 42 mg in acute bipolar mania (YMRS at Week 3).31 Mar 2026 — upcoming — Anticipated topline from Phase 3 Study 451 (NCT06462586) of lumateperone 42 mg in acute bipolar mania (YMRS at Week 3).21 Feb 2025 — phase change — Intra-Cellular Therapies FY2024 corporate update: 'in the fourth quarter of 2024, we commenced patient enrollment in two Phase 3 studies in pediatric patients for the treatment of irritability associated with autism spectrum disorder' (Studies 601/602; NCT06690398, NCT06706674).22 Nov 2024 — phase change — Study 601 (NCT06690398, ITI-007-601) Phase 3 in pediatric irritability associated with autism spectrum disorder started; randomized, double-blind, placebo-controlled, n=174, primary endpoint ABC-Irritability at Week 6. Study start date per ClinicalTrials.gov.17 Jul 2024 — phase change — Study 452 (NCT06462612, ITI-007-452) started — second Phase 3 acute bipolar-mania study, same design (lumateperone 42 mg vs placebo, 3-week, YMRS Week 3 primary). CT.gov start date 17 Jul 2024; status RECRUITING. Together the two studies form the pivotal acute-mania package. Intra-Cellular reported both were initiated in Q2 2024 with enrollment ongoing.19 Jun 2024 — phase change — Study 451 (NCT06462586, ITI-007-451) started — first of two Phase 3 acute bipolar-mania studies (manic / mixed episodes of bipolar I). Randomized, double-blind, placebo-controlled; lumateperone 42 mg vs placebo, 3-week treatment, primary endpoint YMRS change at Week 3. CT.gov start date 19 Jun 2024; status RECRUITING.18 Jun 2024 — readout (met) — Study 502 positive: lumateperone + antidepressant met MADRS primary (-4.5 vs placebo, p<0.0001) and CGI-S key secondary at Week 6.16 Apr 2024 — readout (met) — Study 501 positive: lumateperone + antidepressant met MADRS primary (-4.9 vs placebo, p<0.0001) and CGI-S key secondary at Week 6.23 Sept 2021 — readout (met) — Study 404 positive: lumateperone 42 mg monotherapy met the MADRS Week-6 primary in bipolar I/II depression (LSMD -4.6, ES -0.56, p<0.0001).2 Jul 2020 — phase change — Study 402 (NCT02600507), the adjunctive-to-lithium/valproate Phase 3, completed and MET its primary at 42 mg: MADRS LSMD -2.4 vs placebo at Week 6 (p=0.02) and CGI-BP-S depression key secondary (LSMD -0.3, p=0.01). Primary completion 2020-07-02.1 Mar 2019 — phase change — Study 404 (NCT03249376), a global monotherapy Phase 3, completed and MET its primary endpoint: MADRS LSMD -4.6 vs placebo at Week 6 (95% CI -6.34 to -2.83; ES -0.56; p<0.0001), plus CGI-BP-S key secondary. The positive monotherapy pivotal study. Primary completion 2019-03-01.28 Jan 2019 — phase change — Study 401 (NCT02600494), the first US-only monotherapy Phase 3 in bipolar depression, completed but MISSED its MADRS primary endpoint (attributed to high placebo response). Primary completion 2019-01-28.1 Aug 2016 — phase change — Study 302 (NCT02469155, ITI-007-302) primary completion: 6-week, placebo- and active-controlled Phase 3; lumateperone 42 mg did NOT reach statistical significance vs placebo on PANSS total (high placebo response / assay-sensitivity issue), though magnitude of improvement was similar to the positive studies. Negative result captured deliberately.1 Jul 2015 — phase change — Study 301 (NCT02282761, ITI-007-301) primary completion: positive Phase 3 4-week trial; lumateperone 42 mg met PANSS total primary endpoint with a statistically significant drug-placebo difference of -4.2 at Week 4 (Correll et al. 2020, JAMA Psychiatry). Second of the two positive pivotal trials.Filed (NDA)3 Dec 2024 — phase change — Intra-Cellular Therapies submitted the sNDA to FDA for Caplyta (lumateperone) as adjunctive therapy for MDD, based on Studies 501 and 502.
Phase change Readout Event UpcomingHover a marker for details.
Phase 3Jul 2015 – Mar 2027
  1. UpcomingAnticipated topline of Study 601, the first pivotal Phase 3 of lumateperone for irritability associated with autism spectrum disorder (pediatric); primary endpoint ABC-Irritability at Week 6.Autism spectrum disorder
  2. UpcomingAnticipated topline of Study 602, the second pivotal Phase 3 of lumateperone for irritability associated with autism spectrum disorder (pediatric); primary endpoint ABC-Irritability at Week 6.Autism spectrum disorder
  3. UpcomingAnticipated topline from Phase 3 Study 452 (NCT06462612) of lumateperone 42 mg in acute bipolar mania (YMRS at Week 3).Bipolar disorder
  4. UpcomingAnticipated topline from Phase 3 Study 451 (NCT06462586) of lumateperone 42 mg in acute bipolar mania (YMRS at Week 3).Bipolar disorder
  5. Intra-Cellular Therapies FY2024 corporate update: 'in the fourth quarter of 2024, we commenced patient enrollment in two Phase 3 studies in pediatric patients for the treatment of irritability associated with autism spectrum disorder' (Studies 601/602; NCT06690398, NCT06706674).Autism spectrum disorder↗
  6. Study 601 (NCT06690398, ITI-007-601) Phase 3 in pediatric irritability associated with autism spectrum disorder started; randomized, double-blind, placebo-controlled, n=174, primary endpoint ABC-Irritability at Week 6. Study start date per ClinicalTrials.gov.Autism spectrum disorder
  7. Study 452 (NCT06462612, ITI-007-452) started — second Phase 3 acute bipolar-mania study, same design (lumateperone 42 mg vs placebo, 3-week, YMRS Week 3 primary). CT.gov start date 17 Jul 2024; status RECRUITING. Together the two studies form the pivotal acute-mania package. Intra-Cellular reported both were initiated in Q2 2024 with enrollment ongoing.Bipolar disorder
  8. Study 451 (NCT06462586, ITI-007-451) started — first of two Phase 3 acute bipolar-mania studies (manic / mixed episodes of bipolar I). Randomized, double-blind, placebo-controlled; lumateperone 42 mg vs placebo, 3-week treatment, primary endpoint YMRS change at Week 3. CT.gov start date 19 Jun 2024; status RECRUITING.Bipolar disorder
  9. metStudy 502 positive: lumateperone + antidepressant met MADRS primary (-4.5 vs placebo, p<0.0001) and CGI-S key secondary at Week 6.Major depressive disorder↗
  10. metStudy 501 positive: lumateperone + antidepressant met MADRS primary (-4.9 vs placebo, p<0.0001) and CGI-S key secondary at Week 6.Major depressive disorder↗
  11. metStudy 404 positive: lumateperone 42 mg monotherapy met the MADRS Week-6 primary in bipolar I/II depression (LSMD -4.6, ES -0.56, p<0.0001).Bipolar depression↗
  12. Study 402 (NCT02600507), the adjunctive-to-lithium/valproate Phase 3, completed and MET its primary at 42 mg: MADRS LSMD -2.4 vs placebo at Week 6 (p=0.02) and CGI-BP-S depression key secondary (LSMD -0.3, p=0.01). Primary completion 2020-07-02.Bipolar depression↗
  13. Study 404 (NCT03249376), a global monotherapy Phase 3, completed and MET its primary endpoint: MADRS LSMD -4.6 vs placebo at Week 6 (95% CI -6.34 to -2.83; ES -0.56; p<0.0001), plus CGI-BP-S key secondary. The positive monotherapy pivotal study. Primary completion 2019-03-01.Bipolar depression↗
  14. Study 401 (NCT02600494), the first US-only monotherapy Phase 3 in bipolar depression, completed but MISSED its MADRS primary endpoint (attributed to high placebo response). Primary completion 2019-01-28.Bipolar depression
  15. Study 302 (NCT02469155, ITI-007-302) primary completion: 6-week, placebo- and active-controlled Phase 3; lumateperone 42 mg did NOT reach statistical significance vs placebo on PANSS total (high placebo response / assay-sensitivity issue), though magnitude of improvement was similar to the positive studies. Negative result captured deliberately.Schizophrenia
  16. Study 301 (NCT02282761, ITI-007-301) primary completion: positive Phase 3 4-week trial; lumateperone 42 mg met PANSS total primary endpoint with a statistically significant drug-placebo difference of -4.2 at Week 4 (Correll et al. 2020, JAMA Psychiatry). Second of the two positive pivotal trials.Schizophrenia
ApprovedMay 2005 – Apr 2026
  1. metFDA approved Caplyta (lumateperone) sNDA adding relapse-prevention data in schizophrenia (Study 304: HR 0.37, 63% lower relapse risk, p=0.0002).Schizophrenia↗
  2. FDA approvalFDA approves CAPLYTA (lumateperone) sNDA for prevention of relapse in schizophreniaSchizophrenia↗
  3. metFDA approved Caplyta (lumateperone) as adjunctive therapy with antidepressants for MDD in adults.Major depressive disorder↗
  4. AcquisitionJohnson & Johnson acquires Intra-Cellular Therapies↗
  5. metStudy 402 positive (42 mg): lumateperone adjunctive to lithium/valproate met the MADRS Week-6 primary in bipolar depression (LSMD -2.4, p=0.02).Bipolar depression↗
  6. metFDA approved Caplyta (lumateperone) for bipolar I and II depression in adults, as monotherapy and as adjunctive therapy with lithium or valproate.Bipolar depression↗
  7. metFDA approved Caplyta (lumateperone) 42 mg once daily for the treatment of schizophrenia in adults.Schizophrenia↗
  8. Licensing dealIntra-Cellular in-licenses lumateperone (ITI-007) from Bristol-Myers Squibb↗
Filed (NDA)Dec 2024
  1. Intra-Cellular Therapies submitted the sNDA to FDA for Caplyta (lumateperone) as adjunctive therapy for MDD, based on Studies 501 and 502.Major depressive disorder↗
Phase 2Aug 2013
  1. Study 005 (NCT01499563, ITI-007-005) primary completion: positive Phase 2 4-week trial; lumateperone 42 mg met PANSS total primary endpoint vs placebo (-13.2 vs -7.4, p=0.017, ES ~0.4). One of the two positive pivotal efficacy trials cited for the schizophrenia approval (Lieberman et al. 2016).Schizophrenia

Lumateperone (ITI-007) for Schizophrenia#

ApprovedApprovedSchizophrenia indication →

Schizophrenia is lumateperone's original and lead indication. The FDA approved Caplyta (lumateperone) 42 mg once daily for the treatment of schizophrenia in adults on 20 December 2019 (Intra-Cellular Therapies announced it 23 December 2019). Efficacy was demonstrated in two positive 4-week, randomized, double-blind, placebo-controlled pivotal trials: Study 005 (NCT01499563; n=335; PANSS total LSMD for the 42 mg dose -13.2 vs -7.4 placebo, p=0.017, effect size ~0.4; Lieberman et al. 2016) and Study 301 (NCT02282761; n=450; drug-placebo PANSS difference -4.2, statistically significant at Week 4; Correll et al. 2020, JAMA Psychiatry). A third Phase 3 study, Study 302 (NCT02469155; n=696; 6-week), did NOT separate from placebo on PANSS (attributed to a high placebo response / assay sensitivity), and is tracked here for completeness. On 27 April 2026 the FDA approved a supplemental NDA (Study 304, NCT04959032, a randomized-withdrawal relapse-prevention trial) adding long-term relapse-prevention data to the label (hazard ratio 0.37, a 63% reduction in relapse risk vs placebo, p=0.0002; 84% relapse-free over six months). Originated by Intra-Cellular Therapies; following J&J's acquisition of ITCI (closed 2 Apr 2025), Caplyta is now marketed by Johnson & Johnson Innovative Medicine. is_lead_indication=true because schizophrenia was the first (lead) approved indication.

Readouts

  • 2026-04-27ReportedRegulatorymetNCT04959032

    FDA approved Caplyta (lumateperone) sNDA adding relapse-prevention data in schizophrenia (Study 304: HR 0.37, 63% lower relapse risk, p=0.0002). ↗

  • 2019-12-20ReportedRegulatorymet

    FDA approved Caplyta (lumateperone) 42 mg once daily for the treatment of schizophrenia in adults. ↗

Lumateperone (ITI-007) for Bipolar disorder#

Phase 3RecruitingBipolar disorder indication →

Active Phase 3 development program for lumateperone (Caplyta) 42 mg once daily in the ACUTE treatment of manic episodes or manic episodes with mixed features associated with bipolar I disorder (bipolar mania) — a label-expansion effort distinct from lumateperone's existing approvals. Intra-Cellular Therapies initiated two multicenter, randomized, double-blind, placebo-controlled Phase 3 acute-mania studies in Q2 2024: Study 451 (NCT06462586) and Study 452 (NCT06462612). Each randomizes ~350 patients (YMRS total >=20 at entry) 1:1 to lumateperone 42 mg or placebo over a 3-week double-blind period, with the PRIMARY endpoint the change from baseline in the Young Mania Rating Scale (YMRS) total score at Week 3 (key secondary CGI-BP-S). Both verified RECRUITING on ClinicalTrials.gov; estimated primary completion is March 2026 (Study 451) and May 2026 (Study 452); no topline results have been reported as of June 2026. Lumateperone is already FDA-approved for schizophrenia and for bipolar I/II DEPRESSION (mono + adjunctive; that depression indication is a separate program), so mania is an incremental indication. Originated by Intra-Cellular Therapies, which Johnson & Johnson acquired (closed 2 Apr 2025); the program is now sponsored by Johnson & Johnson Innovative Medicine. is_lead_indication=false because schizophrenia was the original (lead) approved indication.

Readouts

  • 2H 2026AnticipatedTopline dataNCT06462612

    Anticipated topline from Phase 3 Study 452 (NCT06462612) of lumateperone 42 mg in acute bipolar mania (YMRS at Week 3).

  • 1H 2026AnticipatedTopline dataNCT06462586

    Anticipated topline from Phase 3 Study 451 (NCT06462586) of lumateperone 42 mg in acute bipolar mania (YMRS at Week 3).

Lumateperone (ITI-007) for Autism spectrum disorder#

Phase 3RecruitingAutism spectrum disorder indication →

Active Phase 3 program evaluating lumateperone (Caplyta) for irritability associated with autism spectrum disorder in pediatric patients (ages 5-17). Intra-Cellular Therapies disclosed commencing patient enrollment in the fourth quarter of 2024 in two pivotal Phase 3 studies: Study 601 (NCT06690398) and Study 602 (NCT06706674). Each is a randomized, double-blind, placebo-controlled, multicenter study (n=174) randomizing patients 1:1:1 to lumateperone high dose (42 mg/day for ages 13-17), lumateperone low dose (21 mg/day for ages 13-17), or placebo over a 6-week double-blind period, with the Aberrant Behavior Checklist - Irritability (ABC-I) subscale at Week 6 as the primary endpoint. A separate 26-week open-label pediatric safety/tolerability study (NCT06229210) enrolls ASD-irritability patients alongside pediatric schizophrenia and bipolar disorder. Both pivotal trials are recruiting with estimated primary completion around March 2027; no efficacy readouts have occurred yet. is_lead_indication=false because schizophrenia is lumateperone's lead/original approved indication.

Readouts

  • 1H 2027AnticipatedTopline dataNCT06690398

    Anticipated topline of Study 601, the first pivotal Phase 3 of lumateperone for irritability associated with autism spectrum disorder (pediatric); primary endpoint ABC-Irritability at Week 6.

  • 1H 2027AnticipatedTopline dataNCT06706674

    Anticipated topline of Study 602, the second pivotal Phase 3 of lumateperone for irritability associated with autism spectrum disorder (pediatric); primary endpoint ABC-Irritability at Week 6.

Lumateperone (ITI-007) for Major depressive disorder#

ApprovedApprovedMajor depressive disorder indication →

FDA approved Caplyta (lumateperone) 42 mg once daily on 6 Nov 2025 as adjunctive therapy with antidepressants for major depressive disorder in adults. Approval (an sNDA, submitted 3 Dec 2024) was supported by two positive pivotal Phase 3 trials, Study 501 (NCT04985942) and Study 502 (NCT05061706), each showing a statistically significant MADRS separation from placebo at Week 6 (-4.9 / ES 0.61 and -4.5 / ES 0.56, both p<0.0001) plus a significant CGI-S key secondary, with a 6-month open-label extension (Study 503, NCT05061719) showing 80% response / 65% remission. This is MDD-specific; the compound was already approved for schizophrenia and for bipolar I/II depression. Originated by Intra-Cellular Therapies, which J&J acquired (closed 2 Apr 2025); Caplyta is now marketed by Johnson & Johnson Innovative Medicine. is_lead_indication=false because schizophrenia was the original (lead) approved indication.

Readouts

  • 2025-11-06ReportedRegulatorymet

    FDA approved Caplyta (lumateperone) as adjunctive therapy with antidepressants for MDD in adults. ↗

  • 2024-06-18ReportedTopline datametNCT05061706

    Study 502 positive: lumateperone + antidepressant met MADRS primary (-4.5 vs placebo, p<0.0001) and CGI-S key secondary at Week 6. ↗

  • 2024-04-16ReportedTopline datametNCT04985942

    Study 501 positive: lumateperone + antidepressant met MADRS primary (-4.9 vs placebo, p<0.0001) and CGI-S key secondary at Week 6. ↗

Lumateperone (ITI-007) for Bipolar depression#

ApprovedApprovedBipolar depression indication →

FDA approved Caplyta (lumateperone) 42 mg once daily on 20 Dec 2021 for the treatment of depressive episodes associated with bipolar I or bipolar II disorder in adults, both as MONOTHERAPY and as ADJUNCTIVE therapy with lithium or valproate. At the time it was the first and only FDA-approved treatment for both bipolar I and bipolar II depression as monotherapy and adjunctive therapy. Approval was supported by two positive Phase 3 placebo-controlled studies: the monotherapy Study 404 (NCT03249376), which met its MADRS Week-6 primary (LSMD vs placebo -4.6; ES -0.56; p<0.0001) and CGI-BP-S key secondary, and the adjunctive Study 402 (NCT02600507), in which lumateperone 42 mg added to lithium or valproate met its MADRS Week-6 primary (LSMD -2.4; p=0.02) and the CGI-BP-S depression key secondary (LSMD -0.3; p=0.01). An earlier US-only monotherapy trial (Study 401, NCT02600494) had missed its primary endpoint. is_lead_indication=false because schizophrenia was the original (lead) approved indication. Originated by Intra-Cellular Therapies; Caplyta is now marketed by Johnson & Johnson Innovative Medicine following the ITCI acquisition (closed 2 Apr 2025).

Readouts

  • 2023-02-13ReportedFull resultsmetNCT02600507

    Study 402 positive (42 mg): lumateperone adjunctive to lithium/valproate met the MADRS Week-6 primary in bipolar depression (LSMD -2.4, p=0.02). ↗

  • 2021-12-20ReportedRegulatorymet

    FDA approved Caplyta (lumateperone) for bipolar I and II depression in adults, as monotherapy and as adjunctive therapy with lithium or valproate. ↗

  • 2021-09-23ReportedFull resultsmetNCT03249376

    Study 404 positive: lumateperone 42 mg monotherapy met the MADRS Week-6 primary in bipolar I/II depression (LSMD -4.6, ES -0.56, p<0.0001). ↗

Clinical trials#

NCT06706674ITI-007-602Phase 3Recruitingn=174

Study 602: A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Assess the Efficacy and Safety of Lumateperone in the Treatment of Irritability Associated With Autism Spectrum Disorder in Pediatric Patients 5 to 17 Years of Age

Started Dec 2024· 39 sites across 1 country

United States

NCT06690398ITI-007-601Phase 3Recruitingn=174

Study 601: A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Assess the Efficacy and Safety of Lumateperone in the Treatment of Irritability Associated With Autism Spectrum Disorder in Pediatric Patients 5 to 17 Years of Age

Started Nov 2024· 37 sites across 1 country

United States

NCT06462612ITI-007-452Phase 3Recruitingn=350

Study 452: A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Lumateperone in the Acute Treatment of Patients With Manic Episodes or Manic Episodes With Mixed Features Associated With Bipolar I Disorder (Bipolar Mania)

Started Jul 2024· Primary completion May 2026· 35 sites across 4 countries

United StatesBulgariaSerbiaRomania

NCT06462586ITI-007-451Phase 3Recruitingn=350

Study 451: A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Lumateperone in the Acute Treatment of Patients With Manic Episodes or Manic Episodes With Mixed Features Associated With Bipolar I Disorder (Bipolar Mania)

Started Jun 2024· Primary completion Mar 2026· 42 sites across 5 countries

United StatesBulgariaIndiaSerbia

NCT06229210ITI-007-321Phase 3Recruitingn=500

An Open-label, Multicenter Trial to Assess the Safety and Tolerability of Lumateperone in the Treatment of Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder

Started Jan 2024· 50 sites across 2 countries

United StatesSerbia

Show all 16 trials

NCT05850689ITI-007-505Phase 3Recruitingn=470

Study 505: A Randomized, Double-Blind, Placebo-controlled Multicenter Study to Assess the Efficacy and Safety of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder

Started May 2023· Primary completion Sept 2026· 60 sites across 7 countries

United StatesIndiaBulgariaSerbia

NCT05061706ITI-007-502Phase 3Completedn=480

Study 502: A Randomized, Double-Blind, Placebo-controlled Multicenter Study to Assess the Efficacy and Safety of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder

Started Sept 2021· Primary completion Apr 2024· 50 sites across 7 countries

United StatesPolandArgentinaGermany

metprimaryMADRS total score change from baseline to Day 43 (Week 6), lumateperone 42 mg + ADT vs placebo + ADT — LSMD -4.5; ES 0.56 (<0.0001)

Primary MADRS endpoint met: statistically significant, clinically meaningful separation from placebo at Week 6. n=480, 1:1. Second pivotal study.

metsecondaryCGI-S (severity) change from baseline at Week 6 — ES 0.51 (<0.0001)

Key secondary CGI-S endpoint met with statistical significance.

NCT04985942ITI-007-501Phase 3Completedn=485

Study 501: A Randomized, Double-Blind, Placebo-controlled Multicenter Study to Assess the Efficacy and Safety of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder

Started Jul 2021· Primary completion Feb 2024· 54 sites across 6 countries

IndiaUnited StatesBulgariaSlovakia

metsecondaryCGI-S (severity) change from baseline at Week 6 — ES 0.67 (<0.0001)

Key secondary CGI-S endpoint met with statistical significance.

metprimaryMADRS total score change from baseline to Day 43 (Week 6), lumateperone 42 mg + ADT vs placebo + ADT — LSMD -4.9 (lumateperone -14.7 vs placebo -9.8); ES 0.61 (<0.0001)

Primary MADRS endpoint met: statistically significant, clinically meaningful separation from placebo at Week 6 in patients with inadequate antidepressant response. n=485, 1:1.

NCT04959032ITI-007-304Phase 3Completedn=228

Study 304: A Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Lumateperone for the Prevention of Relapse in Patients With Schizophrenia

Started Jul 2021· Primary completion Jul 2024· 43 sites across 4 countries

United StatesBulgariaPolandSerbia

metprimaryTime to first symptomatic relapse, randomized-withdrawal phase (lumateperone 42 mg n=110 vs placebo n=114) — hazard ratio 0.37 (63% lower relapse risk vs placebo); 84% relapse-free over 6 months (0.0002)

Relapse-prevention (randomized-withdrawal) Phase 3 trial: 18-week open-label stabilization on lumateperone 42 mg, then double-blind randomization to continue lumateperone (n=110) or switch to placebo (n=114) for up to 26 weeks. Lumateperone significantly prolonged time to relapse (HR 0.37, 63% risk reduction, p=0.0002). Supported the 27 Apr 2026 sNDA relapse-prevention labeling update. CT.gov hasResults=false at time of capture; efficacy from J&J/ITCI approval PR.

NCT03249376ITI-007-404Phase 3Completedn=381

Study 404: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Assess the Efficacy and Safety of Lumateperone Monotherapy in the Treatment of Patients With Major Depressive Episodes Associated With Bipolar I or Bipolar II Disorder (Bipolar Depression) Conducted Globally

Started Nov 2017· Primary completion Mar 2019· 47 sites across 6 countries

United StatesBulgariaUkraineRussia

metsecondaryCGI-BP-S (Clinical Global Impression-Bipolar-Severity) total score change at Week 6 — ES -0.46 (<0.001)

Key secondary CGI-BP-S endpoint met with statistical significance; CGI-BP-S depression subscale also significantly improved.

metprimaryMADRS total score change from baseline to Day 43 (Week 6), lumateperone 42 mg monotherapy vs placebo — LSMD -4.6 (95% CI -6.34 to -2.83); ES -0.56 (<0.0001)

Primary MADRS endpoint met: lumateperone 42 mg monotherapy produced a statistically significant, clinically meaningful improvement vs placebo at Week 6 in adults with bipolar I or II depression. The positive monotherapy pivotal study supporting the 2021 bipolar-depression approval.

NCT02600507ITI-007-402Phase 3Completedn=529

Study 402: Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Assess the Efficacy and Safety of ITI-007 (Lumateperone) Adjunctive to Lithium or Valproate in the Treatment of Patients With Major Depressive Episodes Associated With Bipolar I or Bipolar II Disorder

Started Mar 2016· Primary completion Jul 2020· 71 sites across 5 countries

United StatesBulgariaUkraineRussia

metprimaryMADRS total score change from baseline to Week 6, lumateperone 42 mg adjunctive to lithium/valproate vs placebo — LSMD -2.4 (0.02)

Primary MADRS endpoint met for the 42 mg arm: statistically significant improvement over placebo when added to lithium or valproate at Week 6. The 28 mg arm showed only numerical improvement (LSMD -1.7, p=0.10, not significant). The positive adjunctive pivotal study supporting the 2021 bipolar-depression approval.

metsecondaryCGI-BP-S depression subscore change at Week 6 (lumateperone 42 mg adjunctive) — LSMD -0.3 (0.01)

Key secondary CGI-BP-S depression subscore endpoint met with statistical significance for the 42 mg arm.

NCT02600494ITI-007-401Phase 3Completedn=554

Study 401: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study With an Open-Label Extension to Assess the Efficacy and Safety of ITI-007 (Lumateperone) Monotherapy in the Treatment of Patients With Major Depressive Episodes Associated With Bipolar I or Bipolar II Disorder

Started Dec 2015· Primary completion Jan 2019· 55 sites across 1 country

United States

missedprimaryMADRS total score change from baseline at Week 6, lumateperone monotherapy vs placebo (US-only study)

First, US-only monotherapy Phase 3 in bipolar depression; the MADRS primary endpoint was NOT met, attributed to an unusually high placebo response. Negative result captured deliberately. The later global Study 404 was the positive monotherapy trial used for approval.

NCT02469155ITI-007-302Phase 3Completedn=696

Study 302: A Randomized, Double-Blind, Placebo- and Active-Controlled, Multi-Center Study to Assess the Antipsychotic Efficacy of ITI-007 After 6 Weeks of Treatment in Patients With Schizophrenia

Started Jun 2015· Primary completion Aug 2016· 11 sites across 1 country

United States

missedprimaryPANSS total score change from baseline at Week 6, lumateperone 42 mg vs placebo

Negative/failed pivotal Phase 3 trial (6-week, placebo- and active-controlled; n=696): the difference between lumateperone 42 mg and placebo on PANSS total did NOT reach statistical significance, attributed to a high placebo response / assay-sensitivity issue (magnitude of improvement was nonetheless similar to the positive studies). Captured deliberately as a negative result. Registry dates month-level (2015-06 start, 2016-08 primary completion); day set to 01.

NCT02282761ITI-007-301Phase 3Completedn=450

Study 301: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Assess the Antipsychotic Efficacy of ITI-007 in Patients With Schizophrenia

Started Nov 2014· Primary completion Jul 2015· 11 sites across 1 country

United States

metprimaryPANSS total score change from baseline to Day 28 (Week 4), lumateperone 42 mg vs placebo — drug-placebo difference -4.2 (<0.05)

Positive pivotal Phase 3 trial (1:1:1 lumateperone 42 mg / 28 mg / placebo; n=450): lumateperone 42 mg met the PANSS total primary endpoint with a statistically significant drug-placebo difference of -4.2 at Week 4. Second of two pivotal trials supporting the 2019 schizophrenia approval (Correll et al. 2020, JAMA Psychiatry). Registry dates month-level (2014-11 start, 2015-07 primary completion); day set to 01.

NCT01499563ITI-007-005Phase 2Completedn=335

Study 005: A Randomized, Double-blind, Placebo-controlled, Multi-center Study to Assess the Antipsychotic Efficacy of ITI-007 in Patients With Schizophrenia

Started Dec 2011· Primary completion Aug 2013· 8 sites across 1 country

United States

metprimaryPANSS total score change from baseline to Day 28 (Week 4), lumateperone 42 mg vs placebo — LSMD lumateperone 42 mg -13.2 vs placebo -7.4 (drug-placebo difference ~ -5.8); ES ~0.4 (0.017)

Positive Phase 2 trial: lumateperone 42 mg met the PANSS total primary endpoint at Week 4 (also included a 84 mg arm and a risperidone 4 mg active-control arm). One of two pivotal trials supporting the 2019 schizophrenia approval (Lieberman et al. 2016). Registered on CT.gov as Phase 2. Dates are month-level on the registry (2011-12 start, 2013-08 primary completion); day set to 01.

NCT05061719ITI-007-503Phase 3Completed

Study 503: An Open-label Study of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder

· 109 sites across 11 countries

United StatesBulgariaPolandIndia

metsecondaryLong-term response and remission over 26 weeks (open-label extension) — 80% response; 65% remission (MADRS total <=10) at 6 months

6-month open-label safety/extension study: 80% of patients responded and 65% achieved remission at 6 months; supported the long-term safety/efficacy package for the MDD sNDA.

Conference coverage#

ITI-007 appears in 12 CNS Pulse conference abstracts:

+ 4 more.

Sources#

  1. Adjunctive lumateperone (ITI-007) in the treatment of bipolar depression: results from a randomized placebo-controlled clinical trial (Study 402) — Bipolar Disorders (Yatham et al. 2023; PMID 36779257)
  2. CAPLYTA (lumateperone) capsules - Prescribing Information — DailyMed / NIH (FDA label)
  3. Correll et al. 2020 — Efficacy and Safety of Lumateperone for Treatment of Schizophrenia: A Randomized Clinical Trial (Study 301, JAMA Psychiatry) — JAMA Psychiatry / PMC
  4. Efficacy and Safety of Lumateperone for Major Depressive Episodes Associated With Bipolar I or Bipolar II Disorder: A Phase 3 Randomized Placebo-Controlled Trial (Study 404) — American Journal of Psychiatry (Calabrese et al. 2021)
  5. FDA approval of Caplyta (lumateperone) for adjunctive MDD in adults — Johnson & Johnson (PR Newswire)
  6. FDA approves CAPLYTA (lumateperone) sNDA with robust new data supporting reduced risk of relapse in schizophrenia — Johnson & Johnson
  7. FDA approves Intra-Cellular Therapies' Caplyta (lumateperone) for the treatment of schizophrenia in adults — Intra-Cellular Therapies, Inc. (GlobeNewswire)
  8. Intra-Cellular Therapies announces positive Phase 3 topline results from Study 501 (adjunctive MDD) — Intra-Cellular Therapies, Inc. (GlobeNewswire)
  9. Intra-Cellular Therapies announces positive topline results in second Phase 3 trial (Study 502, adjunctive MDD) — Intra-Cellular Therapies, Inc. (GlobeNewswire)
  10. Intra-Cellular Therapies announces U.S. FDA approval of Caplyta (lumateperone) for the treatment of bipolar depression in adults — Intra-Cellular Therapies, Inc. (GlobeNewswire)
Show all 33 sources
  1. Intra-Cellular Therapies reports Q4 and full-year 2024 financial results (commenced enrollment in two Phase 3 pediatric ASD-irritability studies in Q4 2024) — Intra-Cellular Therapies, Inc. (GlobeNewswire)
  2. Intra-Cellular Therapies submits sNDA to FDA for Caplyta (lumateperone) for adjunctive MDD — Intra-Cellular Therapies, Inc. (GlobeNewswire)
  3. Johnson & Johnson Closes Landmark Intra-Cellular Therapies, Inc. Acquisition to Solidify Neuroscience Leadership — Johnson & Johnson
  4. Lumateperone — Wikipedia
  5. Lumateperone (ligand 9099) - binding data at 5-HT2A, D2, and SERT — IUPHAR/BPS Guide to Pharmacology
  6. Lumateperone: First Approval — Drugs (Springer Nature)
  7. Safety and tolerability of lumateperone for schizophrenia: pooled analysis of late-phase trials (Study 005/301/302 outcomes) — PMC
  8. Study 005 (ITI-007-005): ITI-007 in schizophrenia (NCT01499563) — ClinicalTrials.gov
  9. Study 301 (ITI-007-301): ITI-007 in schizophrenia (NCT02282761) — ClinicalTrials.gov
  10. Study 302 (ITI-007-302): ITI-007 6-week study in schizophrenia (NCT02469155) — ClinicalTrials.gov
  11. Study 304 (ITI-007-304): lumateperone for prevention of relapse in schizophrenia (NCT04959032) — ClinicalTrials.gov
  12. Study 321 (ITI-007-321): Open-label safety and tolerability of lumateperone in pediatric schizophrenia, bipolar disorder or autism spectrum disorder (NCT06229210) — ClinicalTrials.gov
  13. Study 401 (ITI-007-401): ITI-007 monotherapy for bipolar depression (NCT02600494) — ClinicalTrials.gov
  14. Study 402 (ITI-007-402): ITI-007 adjunctive to lithium or valproate for bipolar depression (NCT02600507) — ClinicalTrials.gov
  15. Study 404 (ITI-007-404): Lumateperone monotherapy for bipolar depression, conducted globally (NCT03249376) — ClinicalTrials.gov
  16. Study 451 (ITI-007-451): Lumateperone in the acute treatment of patients with bipolar mania (NCT06462586) — ClinicalTrials.gov
  17. Study 452 (ITI-007-452): Lumateperone in the treatment of patients with bipolar mania (NCT06462612) — ClinicalTrials.gov
  18. Study 501 (ITI-007-501): Lumateperone as adjunctive therapy in MDD (NCT04985942) — ClinicalTrials.gov
  19. Study 502 (ITI-007-502): Lumateperone as adjunctive therapy in MDD (NCT05061706) — ClinicalTrials.gov
  20. Study 503 (ITI-007-503): Open-label lumateperone as adjunctive therapy in MDD (NCT05061719) — ClinicalTrials.gov
  21. Study 505 (ITI-007-505): Lumateperone as adjunctive therapy in MDD (NCT05850689) — ClinicalTrials.gov
  22. Study 601 (ITI-007-601): Lumateperone for irritability associated with autism spectrum disorder in pediatric patients (NCT06690398) — ClinicalTrials.gov
  23. Study 602 (ITI-007-602): Lumateperone for irritability associated with autism spectrum disorder in pediatric patients (NCT06706674) — ClinicalTrials.gov