Clinical trial • Phase II • Psychiatry

ITI-1284 for Agitation associated with Alzheimer's dementia | Alzheimer's disease

Phase II trial of ITI-1284 for Agitation associated with Alzheimer's dementia | Alzheimer's disease.

Overview

Trial Therapeutic Area
Psychiatry
Trial Disease
Agitation associated with Alzheimer's dementia | Alzheimer's disease
Trial Stage
Phase II
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
31-01-2025
First CTIS Authorization Date
27-05-2025

Trial design

Randomised, active: iti-1284 administered once daily (flexible-dose, sublingual tablets). comparator: placebo tablets matching the iti-1284 10 mg and 20 mg active tablets, administered once daily (double-blind).-controlled Phase II trial across 37 sites in Bulgaria, Croatia, Czechia and others.

Randomised
Yes
Comparator
Active: ITI-1284 administered once daily (flexible-dose, sublingual tablets). Comparator: Placebo tablets matching the ITI-1284 10 mg and 20 mg active tablets, administered once daily (double-blind).
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
183
Trial Duration For Participant
88

Eligibility

Recruits 183 Patients with impaired capacity are included with specific consent/assent provisions: if deemed competent the patient provides signed informed consent; if not competent, consent may be provided by an appropriate person (eg, legally authorized representative) in accordance with local regulations, with the patient’s assent if capable or lack of dissent. Country-specific variants: in Bulgaria caregiver acknowledgment may be required when the patient is competent; in Croatia the patient is required to be deemed competent to provide signed informed consent. Caregivers/LARs and study partner (caregiver) involvement is mandated for attendance at visits..

Vulnerable Population
Patients with impaired capacity are included with specific consent/assent provisions: if deemed competent the patient provides signed informed consent; if not competent, consent may be provided by an appropriate person (eg, legally authorized representative) in accordance with local regulations, with the patient’s assent if capable or lack of dissent. Country-specific variants: in Bulgaria caregiver acknowledgment may be required when the patient is competent; in Croatia the patient is required to be deemed competent to provide signed informed consent. Caregivers/LARs and study partner (caregiver) involvement is mandated for attendance at visits.

Inclusion criteria

  • {"criterion_text":"- 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;"}
  • {"criterion_text":"- Has a Mini Mental State Examination, 2nd Edition™: Standard Version (MMSE-2®:SV) score of 6 to 24 (inclusive) at Screening (Visit 1)"}
  • {"criterion_text":"- 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"}
  • {"criterion_text":"- Male or female, ≥ 55 years of age"}
  • {"criterion_text":"- Has a body mass index (BMI) of 18–40 kg/m2 inclusive"}
  • {"criterion_text":"- Has an onset of symptoms of agitation at least 2 weeks prior to Screening (Visit 1)"}
  • {"criterion_text":"- 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;"}
  • {"criterion_text":"- 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.\tExcessive motor activity (eg, includes pacing, rocking, gesturing, pointing fingers, restlessness, performing repetitious mannerisms); and/or ii.\tVerbal aggression (eg, yelling, speaking in an excessively loud voice, using profanity, screaming, shouting); and/or iii.\tPhysical 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.\tSignificant impairment in ability to perform or participate in daily living activities; c. Agitation is not solely attributable to another psychiatric, medical, or environmental condition"}
  • {"criterion_text":"- 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)"}
  • {"criterion_text":"- 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."}
  • {"criterion_text":"- CGI-S score ≥ 4 at Screening (Visit 1) and Baseline (Visit 2)"}

Exclusion criteria

  • {"criterion_text":"- Agitation symptoms are attributable to concomitant medications, adverse environmental conditions, substance abuse, or active medical or psychiatric conditions as per Investigator’s judgment"}
  • {"criterion_text":"- 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)"}
  • {"criterion_text":"- 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)"}
  • {"criterion_text":"- The patient has known hypersensitivity or intolerance toITI-1284 or lumateperone, or to any of their excipients."}
  • {"criterion_text":"- 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"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- The primary efficacy endpoint is the change from baseline to end of Week 12 in CMAI total score.","definition_or_measurement_approach":"Change from baseline to end of Week 12 in Cohen-Mansfield Agitation Inventory (CMAI) total score."}

Secondary endpoints

  • {"endpoint_text":"- The key secondary efficacy endpoint: change from baseline to end of Week 12 in CGI-S score.","definition_or_measurement_approach":"Change from baseline to end of Week 12 in Clinical Global Impression–Severity (CGI-S) score."}

Other endpoints

  • {"endpoint_text":"- The safety objective of this study is to evaluate the safety and tolerability of ITI-1284 administered once daily compared with placebo in the treatment of psychosis in patients with AD, as assessed by adverse events (AEs), vital signs, electrocardiograms (ECGs), clinical laboratory tests, modified physical examinations, assessment of cognition by Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Columbia-Suicide Severity Rating Scale (C-SSRS) and extrapyramidal symptoms (EPS) as assessed by Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), and Simpson-Angus Scale (SAS).","definition_or_measurement_approach":"Safety/tolerability assessed by AEs, vital signs, ECGs, clinical labs, modified physical exams, ADAS-Cog for cognition, C-SSRS for suicidality, and EPS scales (AIMS, BARS, SAS)."}
  • {"endpoint_text":"- The pharmacokinetic (PK) objective of this study is to evaluate the plasma concentrations of ITI-1284 and its metabolites following SL administration of ITI-1284 once daily.","definition_or_measurement_approach":"Measurement of plasma concentrations of ITI-1284 and metabolites following sublingual (SL) once-daily administration (PK sampling as specified in protocol)."}

Recruitment

Planned Sample Size
183
Recruitment Window Months
22
Consent Approach
Informed consent: if patient is deemed competent the patient signs informed consent; if not competent, consent may be provided by an appropriate person (eg, legally authorized representative) in accordance with local regulations; patient assent is sought if capable or absence of dissent is noted. Country-specific variants: Bulgaria requires caregiver acknowledgment when patient is competent; Croatia requires the patient be deemed competent to provide signed informed consent. Consent and assent forms and supporting materials (including caregiver ICF, adult assent, pregnant partner ICF) are provided in multiple languages (English, Bulgarian, Croatian, Romanian, Spanish, Slovak, Czech, etc) as per submitted documents.

Methods

  • Doctor-to-Patient Letter (K2_Recruitment material_Doctor-to-Patient Letter) – physician-mediated recruitment materials to inform patients.
  • Physician Referral Letter (K2_Recruitment material_Physician Referral Letter) – referral from treating clinicians.
  • Patient Brochure / Patient and Caregiver Study Guide (K2_Recruitment material_Patient Brochure; Patient and Caregiver Study Guide) – patient-facing printed materials.
  • Caregiver Brochure and Caregiver Diary/Diary Instructions (K2_Recruitment material_Caregiver Brochure; D4_Caregiver Documents_Caregiver Diary Instructions) – materials directed at caregivers to support enrolment and study participation.
  • K1_Recruitment arrangements and consent procedure documents (K1_Recruitment procedures; K1_Recruitment arrangements and informed consent procedure) – documented recruitment/consent workflow.
  • Country/language-specific recruitment materials available (versions in BG, RO, HR, ES, SK, CS/CZ, EN) indicating localised approaches.

Geography

Total Number Of Sites
37
Total Number Of Participants
137

Bulgaria

Earliest CTIS Part Ii Submission Date
19-05-2025
Latest Decision Or Authorization Date
30-05-2025
Processing Time Days
11
Number Of Sites
7
Number Of Participants
32

Sites

Site Name
Umbal - Prof. D-R Stoyan Kirkovich AD
Department Name
Department of Psychiatry
Contact Person Name
Georgi Panov
Contact Person Email
dr.georgi.panov@gmail.com
Site Name
Center For Mental Health Prof. N. Shipkovenski EOOD
Department Name
Department "Daily stationary"; floor 6, offices 11, 12 and 13
Contact Person Name
Ana Popova
Contact Person Email
dr.anapopova@gmail.com
Site Name
Medical Center Medconsult Pleven OOD
Contact Person Name
Maria Aleksandrova
Contact Person Email
mcpleven@abv.bg
Site Name
Medical Center Hera EOOD
Contact Person Name
Spiridon Spiridonov
Contact Person Email
spiridon.aleksiev@gmail.com
Site Name
Medical Center Intermedica Ltd.
Contact Person Name
Toni Donchev
Contact Person Email
tonyd@abv.bg
Site Name
Diagnostic And Consultation Centre St.Vrach And St.St. Kuzma And Damian OOD
Contact Person Name
Petya Dimitrova
Contact Person Email
drdimitrova@abv.bg
Site Name
State Psychiatric Hospital Lovech
Department Name
Women Department with 25 beds; Men Department with 30 beds
Contact Person Name
Magdalena Petrakieva
Contact Person Email
megi_petrakieva@abv.bg

Croatia

Earliest CTIS Part Ii Submission Date
19-05-2025
Latest Decision Or Authorization Date
02-06-2025
Processing Time Days
14
Number Of Sites
4
Number Of Participants
15

Sites

Site Name
Clinic for psychiatry Sveti Ivan
Department Name
Psychiatry
Contact Person Name
Igor Filipčić
Contact Person Email
igor.filipcic@pbsvi.hr
Site Name
University Hospital Centre Zagreb
Department Name
Neurology
Contact Person Name
Fran Borovečki
Contact Person Email
fbor@mef.hr
Site Name
University Hospital Centre Zagreb
Department Name
Neurology
Contact Person Name
Nataša Klepac
Contact Person Email
natasaklepac@gmail.com
Site Name
Klinika za psihijatriju Vrapce
Department Name
Psychiatry
Contact Person Name
Ninoslav Mimica

Czechia

Earliest CTIS Part Ii Submission Date
12-05-2025
Latest Decision Or Authorization Date
23-10-2025
Processing Time Days
164
Number Of Sites
7
Number Of Participants
31

Sites

Site Name
Clintrial s.r.o.
Department Name
Psychiatry
Contact Person Name
Zdeněk Šolle
Contact Person Email
zdenek.solle@clintrial.cz
Site Name
Neurohk s.r.o.
Department Name
Neurology
Contact Person Name
Martin Vališ
Contact Person Email
valismar@seznam.cz
Site Name
Fakultni Nemocnice U Sv Anny V Brne
Department Name
Neurology
Contact Person Name
Lenka Krajčovičová
Contact Person Email
lenka.krajcovicova@fnusa.cz
Site Name
Neuropsychiatrie s.r.o.
Department Name
Neurology
Contact Person Name
Jakub Hort
Contact Person Email
jakub.hort@gmail.com
Site Name
Neuroterapie KH s.r.o.
Department Name
Psychiatry
Contact Person Name
Slavomír Pietrucha
Contact Person Email
slavomir.pietrucha@seznam.cz
Site Name
A-Shine s.r.o.
Department Name
Psychiatry
Contact Person Name
Luboš Janů
Contact Person Email
lubos.janu@seznam.cz
Site Name
Neurohk s.r.o. / other listed Czech site

Romania

Earliest CTIS Part Ii Submission Date
06-05-2025
Latest Decision Or Authorization Date
02-06-2025
Processing Time Days
27
Number Of Sites
6
Number Of Participants
16

Sites

Site Name
Spitalul Universitar De Urgenta Militar Central Dr. Carol Davila
Department Name
Psihiatrie
Contact Person Name
Octavian Vasiliu
Contact Person Email
octavvasiliu@yahoo.com
Site Name
Spitalul Clinic De Psihiatrie Prof.Dr.Alexandru Obregia
Department Name
Sectia Cinica Psihiatrie 9
Contact Person Name
Adela Ciobanu
Contact Person Email
adela.ciobanu@yahoo.com
Site Name
Carpe Diem S.R.L.
Department Name
Psihiatrie III
Contact Person Name
Cosmina Muntean
Contact Person Email
97cosmina@gmail.com
Site Name
Spitalul Clinic De Psihiatrie Si Neurologie Brasov
Department Name
Psihiatrie Clinica III
Contact Person Name
Petru Ifteni
Contact Person Email
petru_ifteni@yahoo.com
Site Name
Centru De Evaluare Si Tratament A Toxicodependentelor Pentru Tineri Sf. Stelian
Department Name
Psihiatrie
Contact Person Name
Traian Barbu
Contact Person Email
trabar98@yahoo.com
Site Name
Spitalul Clinic De Psihiatrie Prof.Dr.Alexandru Obregia
Department Name
Mental Health Center
Contact Person Name
Mihaela Rosca
Contact Person Email
mihaelarosca@gmail.com

Spain

Earliest CTIS Part Ii Submission Date
13-05-2025
Latest Decision Or Authorization Date
28-05-2025
Processing Time Days
15
Number Of Sites
6
Number Of Participants
23

Sites

Site Name
Hospital Germans Trias I Pujol
Department Name
Neurology
Contact Person Name
Pau Pastor Muñoz
Contact Person Email
pastorpau@gmail.com
Site Name
Clinica Montecanal S.L.
Department Name
Neurology
Contact Person Name
Antonio Oliveros Cid
Site Name
Hospital Quironsalud Malaga
Department Name
Neurology
Contact Person Name
Jesus Manuel Romero Imbroda
Site Name
Hospital General Universitario De Albacete
Department Name
Geriatrics
Contact Person Name
Pedro Abizanda Soler
Contact Person Email
pabizanda@sescam.jccm.es
Site Name
Complejo Asistencial De Zamora Hospital Provincial De Zamora
Department Name
Psychiatry and Mental Health Service
Contact Person Name
Manuel Angel Franco Martin
Contact Person Email
mfrancom@saludcastillayleon.es
Site Name
Hospital Universitario De Getafe
Department Name
Geriatrics
Contact Person Name
Leocadio Rodriguez Mañas

Slovakia

Earliest CTIS Part Ii Submission Date
14-05-2025
Latest Decision Or Authorization Date
27-05-2025
Processing Time Days
13
Number Of Sites
7
Number Of Participants
20

Sites

Site Name
Epamed s.r.o.
Department Name
Psychiatry, correct address is: Hlavna 68, 040 01 Kosice
Contact Person Name
Eva Palova
Contact Person Email
palovae@hotmail.com
Site Name
MUDr. Beata Dupejova neurologicka ambulancia s.r.o.
Department Name
Neurology
Contact Person Name
Beata Dupejova
Contact Person Email
dupejova@gmail.com
Site Name
University Hospital Bratislava
Department Name
Neurology
Contact Person Name
Peter Turcani
Contact Person Email
turcani1@gmail.com
Site Name
Neures s.r.o.
Department Name
Neurology
Contact Person Name
Renata Smikova
Contact Person Email
renata.smikova@gmail.com
Site Name
Crystal Comfort s.r.o.
Department Name
Psychiatry
Contact Person Name
Dagmar Breznoscakova
Contact Person Email
dbreznoscakova@gmail.com
Site Name
Centrum Zdravia R.B.K. s.r.o.
Department Name
Psychiatry
Contact Person Name
Rastislav Korba
Contact Person Email
rastislav.korba@gmail.com
Site Name
Additional listed Slovak site

Sponsor

Primary sponsor

Full Name
Intra-Cellular Therapies Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
IQVIA Limited
Responsibilities
ECG, Rater Training, Scale Delivery, scale licensure and Rater Oversight and Interventions Services; and multiple operational duties (codes 1,2,3,5,6,8,12,13,15)
Name
PPD Development LP
Responsibilities
PK testing; operational support (code 15, code 4)
Name
Propharma Group LLC
Responsibilities
Operational support (code 8)
Name
Medidata Solutions Inc.
Responsibilities
Electronic data capture / study platform services (code 7)

Third parties

  • {"country":"Germany","full_name":"Catalent Germany Schorndorf GmbH","duties_or_roles":"code 14","organisation_type":"Pharmaceutical company"}
  • {"country":"France","full_name":"Cerba","duties_or_roles":"Ethanol testing (EU); code 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Propharma Group LLC","duties_or_roles":"code 8","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"code 7","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Multiple services: codes 1, 12, 13, 15 (ECG, Rater Training, Scale Delivery, scale licensure and Rater Oversight and Interventions Services), 2, 3, 5, 6, 8","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"code 4","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"PK testing; code 4","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"C2n Diagnostics LLC","duties_or_roles":"AD Biomarker testing; code 4","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
ITI-1284
Active Substance
ITI-1284
Modality
Small molecule
Routes Of Administration
Sublingual use
Route
Sublingual
Dose Levels
10 mg | 20 mg
Frequency
Once daily
Maximum Dose
20 mg
Investigational Product Name
ITI-1284
Active Substance
ITI-1284
Modality
Small molecule
Routes Of Administration
Sublingual use
Route
Sublingual
Dose Levels
10 mg | 20 mg
Frequency
Once daily
Maximum Dose
20 mg
Investigational Product Name
Placebo tablets matching the ITI-1284 10 mg and 20 mg active tablets
Modality
Other
Dose Levels
Placebo matching 10 mg and 20 mg tablets
Frequency
Once daily (matching active)

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