ITI-007 · program
Lumateperone (ITI-007) for Autism spectrum disorder
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 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.
Development timeline
- 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.
- 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.
- 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).↗
- 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.
Readouts
- 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.
- 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.
Clinical trials in Autism spectrum disorder
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
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
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
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| 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. | Oral | Once daily | t½ 18 h · Tmax 1.5 h · F 4.4% |
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.
| Target | Action | Affinity |
|---|---|---|
| 5-HT2AprimaryHTR2A | Antagonist | Ki 0.5 nMⓘ |
| D2DRD2 | Antagonist | Ki 32 nMⓘ |
| SERTSLC6A4 | Inhibitor | Ki 63 nMⓘ |
← Full ITI-007 compound page (identity, identifiers, all indications)
Sources
- CAPLYTA (lumateperone) capsules - Prescribing Information — DailyMed / NIH (FDA label)
- 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)
- Lumateperone (ligand 9099) - binding data at 5-HT2A, D2, and SERT — IUPHAR/BPS Guide to Pharmacology
- Study 321 (ITI-007-321): Open-label safety and tolerability of lumateperone in pediatric schizophrenia, bipolar disorder or autism spectrum disorder (NCT06229210) — ClinicalTrials.gov
- Study 601 (ITI-007-601): Lumateperone for irritability associated with autism spectrum disorder in pediatric patients (NCT06690398) — ClinicalTrials.gov
- Study 602 (ITI-007-602): Lumateperone for irritability associated with autism spectrum disorder in pediatric patients (NCT06706674) — ClinicalTrials.gov