ITI-1284 · program
ITI-1284 (deulumateperone) for Agitation in Alzheimer's disease
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), 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.
Development timeline
- UpcomingAnticipated Phase 2 topline for ITI-1284 in agitation associated with Alzheimer's dementia (NCT06651567); primary completion targeted October 2027.
- Intra-Cellular Therapies FY2024 corporate update reports patient enrollment ongoing in the Phase 2 program evaluating ITI-1284 in agitation associated with Alzheimer's disease (alongside the Phase 2 Alzheimer's psychosis program).↗
- Phase 2 agitation-in-Alzheimer's-dementia trial started: NCT06651567 (ITI-1284 10-20 mg sublingual ODT once daily vs placebo, flexible-dose, n~320; primary endpoint CMAI total score at Week 12). Actual study start per ClinicalTrials.gov.
Readouts
- Q4 2027AnticipatedTopline dataNCT06651567
Anticipated Phase 2 topline for ITI-1284 in agitation associated with Alzheimer's dementia (NCT06651567); primary completion targeted October 2027.
Clinical trials in Agitation in Alzheimer's disease
NCT06651567Phase 2Recruitingn=320
A Multicenter, Randomized, Double-blind, Placebo-controlled, Flexible-dose Study of the Efficacy, Safety, and Tolerability of ITI-1284 in Patients With Agitation Associated With Alzheimer's Dementia
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 reports fourth quarter and full-year 2024 financial results - enrollment ongoing in Phase 2 ITI-1284 agitation-in-AD program — Intra-Cellular Therapies, Inc. (GlobeNewswire)
- ITI-1284 in agitation associated with Alzheimer's dementia (Phase 2, NCT06651567) — ClinicalTrials.gov
- Lumateperone (ligand 9099) - binding data at 5-HT2A, D2, and SERT — IUPHAR/BPS Guide to Pharmacology