ITI-1284 · program
ITI-1284 (deulumateperone) for 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), 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.
Development timeline
- UpcomingAnticipated Phase 2 topline for ITI-1284 in psychosis associated with Alzheimer's disease (NCT06540833); primary completion targeted September 2027.
- Phase 2 Alzheimer's-disease psychosis trial started: NCT06540833, a multicenter, randomized, double-blind, placebo-controlled, flexible-dose study of ITI-1284 10 mg / 20 mg once-daily sublingual ODT vs placebo (n=370), 6-week treatment, primary outcome BEHAVE-AD psychosis subscale at Week 6.
- Intra-Cellular Therapies announced (FY2023 corporate update) that it had initiated Phase 2 programs evaluating ITI-1284, including in psychosis associated with Alzheimer's disease, with patient enrollment anticipated to commence in 2Q 2024.↗
Readouts
- 2H 2027AnticipatedTopline dataNCT06540833
Anticipated Phase 2 topline for ITI-1284 in psychosis associated with Alzheimer's disease (NCT06540833); primary completion targeted September 2027.
Clinical trials in Alzheimer's disease
NCT06540833Phase 2Recruitingn=370
A Multicenter, Randomized, Double-blind, Placebo-controlled, Flexible-dose Study to Assess the Efficacy, Safety, and Tolerability of ITI-1284 in Patients With Psychosis Associated With Alzheimer's Disease
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 in patients with psychosis associated with Alzheimer's disease (Phase 2, NCT06540833) — ClinicalTrials.gov
- Lumateperone (ligand 9099) - binding data at 5-HT2A, D2, and SERT — IUPHAR/BPS Guide to Pharmacology