ITI-007 · program

Lumateperone (ITI-007) for Schizophrenia

ApprovedApprovedJohnson & Johnson (JNJ)

Indications for ITI-007: Schizophrenia · Approved Bipolar depression · Approved Bipolar disorder · Phase 3 Autism spectrum disorder · Phase 3 Major depressive disorder · Approved

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.

Data current as of

Development timeline

ApprovedDec 2019 – 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).↗
  2. metFDA approved Caplyta (lumateperone) 42 mg once daily for the treatment of schizophrenia in adults.↗
Phase 3Jul 2015 – Aug 2016
  1. 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.
  2. 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.
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).

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. ↗

Clinical trials in Schizophrenia

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 States, Bulgaria, Poland, Serbia)

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.

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.

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%

Mechanism of action (compound-wide)

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.

TargetActionAffinity
5-HT2AprimaryHTR2AAntagonistKi 0.5 nMⓘ
D2DRD2AntagonistKi 32 nMⓘ
SERTSLC6A4InhibitorKi 63 nMⓘ

← Full ITI-007 compound page (identity, identifiers, all indications)

Sources

  1. CAPLYTA (lumateperone) capsules - Prescribing Information — DailyMed / NIH (FDA label)
  2. Correll et al. 2020 — Efficacy and Safety of Lumateperone for Treatment of Schizophrenia: A Randomized Clinical Trial (Study 301, JAMA Psychiatry) — JAMA Psychiatry / PMC
  3. FDA approves Caplyta (lumateperone) sNDA with relapse-prevention data in schizophrenia (Study 304) — Johnson & Johnson (PR Newswire)
  4. FDA approves Intra-Cellular Therapies' Caplyta (lumateperone) for the treatment of schizophrenia in adults — Intra-Cellular Therapies, Inc. (GlobeNewswire)
  5. Lumateperone (ligand 9099) - binding data at 5-HT2A, D2, and SERT — IUPHAR/BPS Guide to Pharmacology
  6. Safety and tolerability of lumateperone for schizophrenia: pooled analysis of late-phase trials (Study 005/301/302 outcomes) — PMC
  7. Study 005 (ITI-007-005): ITI-007 in schizophrenia (NCT01499563) — ClinicalTrials.gov
  8. Study 301 (ITI-007-301): ITI-007 in schizophrenia (NCT02282761) — ClinicalTrials.gov
  9. Study 302 (ITI-007-302): ITI-007 6-week study in schizophrenia (NCT02469155) — ClinicalTrials.gov
  10. Study 304 (ITI-007-304): lumateperone for prevention of relapse in schizophrenia (NCT04959032) — ClinicalTrials.gov