ITI-1284 · program
ITI-1284 (deulumateperone) for Generalized anxiety disorder
Indications for ITI-1284: Generalized anxiety disorder · Phase 2 Agitation in Alzheimer's disease · Phase 2 Alzheimer's disease · Phase 2
Phase 2 program of ITI-1284 (deulumateperone), an orally disintegrating sublingual tablet, in generalized anxiety disorder. Two randomized, double-blind, placebo-controlled multicenter Phase 2 trials are recruiting at 10 mg and 20 mg once-daily doses: an adjunctive study in patients with inadequate response to GAD treatment (NCT06480383, n~705, started Aug 2024) and a monotherapy study (NCT06701903, n~570, started Nov 2024), both with primary completion targeted for June 2027. Intra-Cellular Therapies announced initiation of the Phase 2 GAD program in its Feb 2024 corporate update. No topline GAD results have been reported and no FDA designations have been disclosed for the GAD indication. is_lead_indication=false: GAD is one of several ITI-1284 Phase 2 indications (alongside Alzheimer's-related psychosis and agitation), with no GAD-specific lead designation, and the parent compound lumateperone is approved in other indications.
Development timeline
- UpcomingAnticipated Phase 2 topline for monotherapy ITI-1284 in GAD (NCT06701903); primary completion targeted June 2027.
- UpcomingAnticipated Phase 2 topline for adjunctive ITI-1284 in GAD (NCT06480383); primary completion targeted June 2027.
- Second GAD trial started: monotherapy Phase 2 study NCT06701903 (ITI-1284 10 mg / 20 mg sublingual vs placebo, n~570).
- First GAD trial started: adjunctive Phase 2 study NCT06480383 (ITI-1284 10 mg / 20 mg sublingual vs placebo in patients with inadequate response to GAD treatment, n~705).
- Intra-Cellular Therapies announced (FY2023 corporate update) that it had initiated Phase 2 programs evaluating ITI-1284 in generalized anxiety disorder (GAD), with patient enrollment anticipated in 1H 2024.↗
Readouts
- Mid-2027AnticipatedTopline dataNCT06701903
Anticipated Phase 2 topline for monotherapy ITI-1284 in GAD (NCT06701903); primary completion targeted June 2027.
- Mid-2027AnticipatedTopline dataNCT06480383
Anticipated Phase 2 topline for adjunctive ITI-1284 in GAD (NCT06480383); primary completion targeted June 2027.
Clinical trials in Generalized anxiety disorder
NCT06701903Phase 2Recruitingn=570
A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety, and Tolerability of ITI-1284 as Monotherapy Treatment in Patients With Generalized Anxiety Disorder
NCT06480383Phase 2Recruitingn=705
A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety, and Tolerability of ITI-1284 as an Adjunctive Treatment in Patients With Generalized Anxiety Disorder Who Have an Inadequate Response to Generalized Anxiety Disorder Treatment
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| ITI-1284 ODT-SLZydis orally disintegrating tablet (Catalent) 10 mg or 20 mg sublingual orally disintegrating tablet, once daily | Sublingual | Once daily | — |
Mechanism of action
Multi-target small molecule; a deuterated analogue of lumateperone with the same receptor pharmacophore. Acts as a high-affinity serotonin 5-HT2A receptor antagonist with comparatively lower-affinity activity at dopamine D2 receptors (functionally described by the developer as a presynaptic partial agonist / postsynaptic antagonist, a 'dopamine receptor phosphoprotein modulator'), inhibition of the serotonin transporter (SERT), and additional D1-receptor / glutamatergic modulation. No ITI-1284-specific binding constants have been published; deuteration is a metabolic (pharmacokinetic) modification that is not expected to alter target affinities, so the target identities are inherited from lumateperone (IUPHAR ligand 9099). The anxiolytic rationale rests on this combined 5-HT2A antagonism plus low/region-selective D2 occupancy and SERT inhibition.
| Target | Action | Affinity |
|---|---|---|
| 5-HT2AprimaryHTR2A | Antagonist | —ⓘ |
| D2DRD2 | Antagonist | —ⓘ |
| SERTSLC6A4 | Inhibitor | —ⓘ |
← Full ITI-1284 compound page (identity, identifiers, all indications)
Sources
- Intra-Cellular Therapies Announces Expansion of its Pipeline with the Introduction of a New Molecular Entity, ITI-1284 — Intra-Cellular Therapies (GlobeNewswire)
- Intra-Cellular Therapies FY2023 corporate update - initiation of Phase 2 ITI-1284 GAD program — Intra-Cellular Therapies, Inc. (GlobeNewswire)
- ITI-1284 as adjunctive treatment in generalized anxiety disorder (Phase 2, NCT06480383) — ClinicalTrials.gov
- ITI-1284 as monotherapy treatment in generalized anxiety disorder (Phase 2, NCT06701903) — ClinicalTrials.gov
- Lumateperone (ligand 9099) - binding data at 5-HT2A, D2, and SERT — IUPHAR/BPS Guide to Pharmacology