A study to assess the efficacy and safety of ITI-1284 in the treatment of Agitation Associated with Alzheimer's Dementia
- Conditions
- Agitation Associated with Alzheimer’s Dementia
- Registration Number
- 2024-514680-26-00
- Lead Sponsor
- Intra-Cellular Therapies Inc.
- Brief Summary
The primary efficacy objective is to evaluate the efficacy of ITI-1284 administered once daily compared with placebo in the treatment of agitation in patients with Alzheimer’s dementia, as measured by change from baseline to end of Week 12 in Cohen-Mansfield Agitation Inventory (CMAI) total score.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- Authorised, recruitment pending
- Sex
- Not specified
- Target Recruitment
- 137
Applicable to all EU countries except Bulgaria and Croatia Able to provide consent before the initiation of any study-specific procedures as follows: o If patient is deemed competent to provide informed consent in the judgement of the Investigator, can understand the nature of the trial and protocol requirements, and provide signed informed consent in conjunction with an acknowledgment from the patient’s representative or surrogate (eg, caregiver, family member, friend, partner, Legally Authorized Representative [LAR]); or o If patient is deemed not competent to provide informed consent, with the patient’s assent (if capable) or lack of dissent, consent may be provided by an appropriate person (eg, patient's LAR) in accordance with local regulations; Applicable to Bulgaria only: Able to provide consent before the initiation of any study-specific procedures as follows: o If patient is deemed competent to provide informed consent in the judgment of the Investigator, can understand the nature of the trial and protocol requirements, and provide signed informed consent in conjunction with an acknowledgment from the patient’s caregiver; or o If patient is deemed not competent to provide informed consent, with the patient’s assent (if capable) or lack of dissent, consent may be provided by an appropriate person (eg, patient’s LAR) in accordance with local regulations; Applicable to Croatia only: Able to provide consent before the initiation of any study-specific procedures as follows: o Patient is deemed competent to provide informed consent in the judgment of the Investigator, can understand the nature of the trial and protocol requirements, and provide signed informed consent;
Has a Mini Mental State Examination, 2nd Edition™: Standard Version (MMSE-2®:SV) score of 6 to 24 (inclusive) at Screening (Visit 1)
Lives at home or in an assisted living/long-term care facility and has the ability to visit the clinic as an outpatient if the study is not otherwise being conducted at the assisted living or long-term care facility. a. Patients living at home must not live alone; b. Patients must have been at their current location for at least 4 weeks prior to Screening and plan to remain at the same location for the duration of the trial; c. Patients must be accompanied to and from study visits by a designated caregiver
Male or female, ≥ 55 years of age
Has a body mass index (BMI) of 18–40 kg/m2 inclusive
Has an onset of symptoms of agitation at least 2 weeks prior to Screening (Visit 1)
Meets clinical criteria for Alzheimer’s disease (AD) based on 2011 NIA-AA dementia criteria and biomarker criteria (Jack et al, 2018; Jack et al, 2024) which is either: o Confirmation of high likelihood for amyloid pathology consistent with AD, as confirmed by blood-based biomarker (plasma amyloid beta 42 [Aβ42]/40 ratio and phosphorylated-tau217 [p-tau217]/non-phosphorylated- tau217 [p-tau217 ratio], or plasma Aβ42 and Aβ40 concentrations and determination of the presence of apolipoprotein E [ApoE]-specific peptides) at Screening (Visit 1); or o Confirmation of AD by historical documentation of cerebrospinal fluid (CSF) biomarker (CSF Aβ42/40, CSF p-tau181/Aβ42, or CSF total-tau/Aβ42) or amyloid positron emission tomography (PET) brain scan;
Meets all of the following criteria for agitation according to the International Psychogeriatric Association (IPA) consensus definition (Sano et al, 2024) at Screening (Visit 1): a. Exhibits one or more of the following persistently or frequently recurring (ie, for a period of ≥ 2 weeks) behaviors associated with observed/inferred evidence of emotional distress (eg, rapid changes in mood, irritability, outbursts): i. Excessive motor activity (eg, includes pacing, rocking, gesturing, pointing fingers, restlessness, performing repetitious mannerisms); and/or ii. Verbal aggression (eg, yelling, speaking in an excessively loud voice, using profanity, screaming, shouting); and/or iii. Physical aggression (eg, grabbing, shoving, pushing, resisting, hitting others, kicking objects or people, scratching, biting, throwing objects, hitting self, slamming doors, tearing things, and destroying property); b. Behaviors produces excess disability, which in the Investigator’s judgment are beyond that due to the cognitive impairment and include at least one of the following: i. Significant impairment in interpersonal relationships; ii. Significant impairment in other aspects of social functioning; or iii. Significant impairment in ability to perform or participate in daily living activities; c. Agitation is not solely attributable to another psychiatric, medical, or environmental condition
Has clinically meaningful agitation defined as a Neuropsychiatric Inventory–Agitation/Aggression (NPI-AA) domain total score of ≥ 4 (frequency × severity) at both Screening (Visit 1) and Baseline (Visit 2)
Meets criteria for CMAI Factor 1 (verbally and physically aggressive behavior [eg, cursing, screaming, biting, hitting, kicking]) at Screening (Visit 1) and Baseline (Visit 2 ) as specified in Protocol Section 8.1.5: a. ≥ 1 aggressive behavior(s) occurring several times per week; b. ≥ 2 aggressive behaviors occurring once or twice per week; or c. ≥ 3 aggressive behaviors occurring less than once per week.
CGI-S score ≥ 4 at Screening (Visit 1) and Baseline (Visit 2)
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: a. Schizophrenia, schizoaffective disorder, or other psychotic disorder that is not related to Alzheimer’s dementia; b. Bipolar disorder; c. Major depressive disorder, unless it is considered stable and treated for at least 8 weeks prior to Screening (Visit 1)
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 2 years prior to Screening (Visit 1)
The patient has known hypersensitivity or intolerance toITI-1284 or lumateperone, or to any of their excipients.
Has had an insufficient response, based on the Investigator’s judgment, to 2 or more previous antipsychotic medications for the treatment of dementia-related agitation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method The primary efficacy endpoint is the change from baseline to end of Week 12 in CMAI total score. The primary efficacy endpoint is the change from baseline to end of Week 12 in CMAI total score.
- Secondary Outcome Measures
Name Time Method The key secondary efficacy endpoint: change from baseline to end of Week 12 in CGI-S score. The key secondary efficacy endpoint: change from baseline to end of Week 12 in CGI-S score.
Trial Locations
- Locations (34)
Umbal - Prof. D-R Stoyan Kirkovich AD
🇧🇬Stara Zagora, Bulgaria
Center For Mental Health Prof. N. Shipkovenski EOOD
🇧🇬Sofia, Bulgaria
Medical Center Medconsult Pleven OOD
🇧🇬Pleven, Bulgaria
Medical Center Hera EOOD
🇧🇬Sofiya, Bulgaria
Medical Center Intermedica Ltd.
🇧🇬Sofia, Bulgaria
Diagnostic And Consultation Centre St.Vrach And St.St. Kuzma And Damian OOD
🇧🇬Sofiya, Bulgaria
State Psychiatric Hospital Lovech
🇧🇬Lovech, Bulgaria
Clinic for psychiatry Sveti Ivan
🇭🇷Grad Zagreb, Croatia
University Hospital Centre Zagreb
🇭🇷Zagreb, Croatia
Klinika za psihijatriju Vrapce
🇭🇷Grad Zagreb, Croatia
Scroll for more (24 remaining)Umbal - Prof. D-R Stoyan Kirkovich AD🇧🇬Stara Zagora, BulgariaGeorgi PanovSite contact+359888454634dr.georgi.panov@gmail.com