This is 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

The study will be conducted in 3 periods:

• Screening Period (up to 4 weeks) during which patient eligibility will be assessed;
• Double-blind Treatment Period (12 weeks) during which all patients will be randomized in a 1:1 ratio to receive either ITI-1284 or placebo;
• Safety Follow-up Period (30 days) during which all patients will return for a safety follow-up visit approximately 30 days after the last dose of study drug.

Inclusion Criteria:

• Can understand the nature of the trial and protocol requirements and provide signed informed consent, if in the judgement of the Investigator is deemed competent to provide consent or if patient is deemed not competent to provide informed consent, with the patient's assent (if capable), consent may be provided by an appropriate person (eg, patient's Legally Authorized Representative [LAR]) before the initiation of any study-specific procedures in accordance with local regulations;

• Meets clinical criteria for Alzheimer's disease based on 2011 National Institute of Aging-Alzheimer's Association (NIA-AA) dementia criteria and biomarker criteria and either:

  • Has a high likelihood for amyloid pathology consistent with Alzheimer's disease, as confirmed by blood-based biomarker at Screening; or
  • Has historical documentation of cerebrospinal fluid (CSF) biomarker or amyloid positron emission tomography (PET) brain scan;

• Meets all criteria for agitation according to the International Psychogeriatric Association (IPA) consensus definition

• Has clinically meaningful agitation defined as a Neuropsychiatric Inventory-Agitation/Aggression (NPI-AA) domain total score of ≥ 4 at both Screening and Baseline;

• CGI-S score ≥ 4 at Screening and Baseline;

• Has Mini-Mental State Examination, 2nd Edition™: Standard Version (MMSE-2®:SV) score of 6 to 24 at Screening;

Exclusion Criteria:

• Agitation symptoms are attributable to concomitant medications, adverse environmental conditions, substance abuse, or active medical or psychiatric conditions as per Investigator's judgment;

• Has been diagnosed with one or more of the following psychiatric conditions:

  • Schizophrenia, schizoaffective disorder, or other psychotic disorder that is not related to Alzheimer's dementia;
  • Bipolar disorder;
  • Major depressive disorder, unless it is considered stable and treated for at least 8 weeks prior to Screening;

• Has a significant risk for suicidal behavior during the course of their participation in the study, or is considered to be an imminent danger to themselves or others, in the opinion of the investigator, and/or as assessed by Columbia Suicide Severity Rating Scale (C-SSRS); or the patient has had 1 or more suicide attempts within the 2 years prior to Screening;

• The patient has known hypersensitivity or intolerance to ITI-1284 or lumateperone, or to any of their excipients.