ITI-1284 (deulumateperone)

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.

Formulations#

ITI-1284 (deulumateperone) for Generalized anxiety disorder#

Phase 2RecruitingGeneralized anxiety disorder indication →

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.

ITI-1284 (deulumateperone) for Agitation in Alzheimer's disease#

Phase 2RecruitingAgitation in Alzheimer's disease indication →

Phase 2 program of ITI-1284 (deulumateperone), a sublingual orally disintegrating tablet, in agitation associated with Alzheimer's dementia. One multicenter, randomized, double-blind, placebo-controlled, flexible-dose Phase 2 trial is recruiting (NCT06651567, n~320, started 22 Oct 2024): ITI-1284 10-20 mg once-daily sublingual vs placebo over a 12-week double-blind treatment period, with the Cohen-Mansfield Agitation Inventory (CMAI) total score at Week 12 as the primary endpoint and primary completion targeted for October 2027. Intra-Cellular Therapies' FY2024 corporate update (Feb 2025) reported enrollment ongoing in the Phase 2 agitation-in-AD program. No topline results have been reported and no FDA designations have been disclosed for this indication. is_lead_indication=false: agitation in Alzheimer's dementia is one of several ITI-1284 Phase 2 indications (alongside generalized anxiety disorder and Alzheimer's-related psychosis), with the parent compound lumateperone already approved in other indications.

ITI-1284 (deulumateperone) for Alzheimer's disease#

Phase 2RecruitingAlzheimer's disease indication →

Phase 2 program of ITI-1284 (deulumateperone), an orally disintegrating sublingual tablet, in psychosis associated with Alzheimer's disease. A single multicenter, randomized, double-blind, placebo-controlled, flexible-dose Phase 2 trial is recruiting (NCT06540833, n=370): ITI-1284 10 mg or 20 mg once daily vs placebo over a 6-week treatment period in patients with biomarker-confirmed Alzheimer's disease and psychosis, with the BEHAVE-AD psychosis subscale at Week 6 as the primary outcome. Intra-Cellular Therapies announced initiation of the Phase 2 ITI-1284 psychosis program in its FY2023 corporate update (Feb 2024) and commenced enrollment in 3Q 2024; the trial started 15 Aug 2024 with primary completion targeted for September 2027. No topline results have been reported and no FDA designations have been disclosed for this indication. is_lead_indication=false: AD-related psychosis is one of several ITI-1284 Phase 2 indications (alongside Alzheimer's agitation and generalized anxiety disorder), with no AD-psychosis-specific lead designation, and the parent compound lumateperone is approved in other indications.

Clinical trials#