ITI-007 · program

Lumateperone (ITI-007) for Bipolar disorder

Phase 3RecruitingJohnson & Johnson (JNJ)

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

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.

Data current as of

Development timeline

Phase 3Jun 2024 – May 2026
  1. UpcomingAnticipated topline from Phase 3 Study 452 (NCT06462612) of lumateperone 42 mg in acute bipolar mania (YMRS at Week 3).
  2. UpcomingAnticipated topline from Phase 3 Study 451 (NCT06462586) of lumateperone 42 mg in acute bipolar mania (YMRS at Week 3).
  3. 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.
  4. 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.

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).

Clinical trials in Bipolar disorder

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 States, Bulgaria, Serbia, Romania)

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 States, Bulgaria, India, Serbia)

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. Lumateperone (ligand 9099) - binding data at 5-HT2A, D2, and SERT — IUPHAR/BPS Guide to Pharmacology
  3. Study 451 (ITI-007-451): Lumateperone in the acute treatment of patients with bipolar mania (NCT06462586) — ClinicalTrials.gov
  4. Study 452 (ITI-007-452): Lumateperone in the treatment of patients with bipolar mania (NCT06462612) — ClinicalTrials.gov