ITI-1284 is a novel sublingual rapidly disintegrating tablet being developed by Intra-Cellular Therapies, Inc. for the treatment of agitation associated with Alzheimer's dementia. This is a Phase 2 randomized, double-blind, placebo-controlled study evaluating the efficacy, safety, and tolerability of ITI-1284 in patients with AD-related agitation.
This trial represents Intra-Cellular Therapies' expansion of their ITI-1284 program beyond Alzheimer's disease psychosis (NCT06540833) into the broader behavioral symptom domain of agitation, which affects up to 70% of Alzheimer's patients at some point during their disease course.
Agitation in Alzheimer's disease manifests as inappropriate verbal, physical, or aggressive behaviors that interfere with daily functioning. It includes behaviors such as restlessness, pacing, irritability, and aggression, and represents one of the most challenging aspects of AD care for caregivers and healthcare providers.
| Attribute |
Details |
| NCT Number |
NCT06651567 |
| Sponsor |
Intra-Cellular Therapies, Inc. |
| Drug |
ITI-1284 |
| Phase |
Phase 2 |
| Indication |
Agitation Associated with Alzheimer's Dementia |
| Status |
Recruiting |
| Start Date |
October 22, 2024 |
| Primary Completion |
October 2027 (estimated) |
| Estimated Completion |
November 2027 |
| Total Participants |
320 (estimated) |
| Study Design |
Randomized, double-blind, placebo-controlled, parallel-group |
ITI-1284 is a sublingual rapidly disintegrating tablet administered at doses of 10 mg or 20 mg once daily. The specific molecular target and mechanism of action have not been fully disclosed, but the development suggests it targets neuropsychiatric symptoms in AD through central nervous system modulation.
The sublingual formulation offers several advantages for the AD agitation population:
- Rapid onset: Direct absorption through oral mucosa bypasses first-pass metabolism
- Ease of administration: Rapidly disintegrating tablets are easier for patients with swallowing difficulties
- Improved compliance: Once-daily dosing with sublingual administration may improve adherence
- Reduced GI side effects: Bypasses some gastrointestinal tract exposure
- Quick action: Faster onset may help manage acute agitation episodes
flowchart TD
A["ITI-1284<br/>Sublingual Tablet"] --> B["Absorption via<br/>Oral Mucosa"]
B --> C["Blood-Brain<br/>Barrier"]
C --> D["CNS Target<br/>Engagement"]
D --> E["Modulation of<br/>Neurotransmission"]
E --> F["Reduction in<br/>Agitation Symptoms"]
F --> G["Decreased<br/>Physical Aggression"]
F --> H["Decreased<br/>Verbal Agitation"]
F --> I["Decreased<br/>Restlessness"]
style A fill:#e1f5fe,stroke:#333
style F fill:#c8e6c9,stroke:#333
| Parameter |
Agitation Trial (NCT06651567) |
Psychosis Trial (NCT06540833) |
| Indication |
Agitation Associated with AD |
Psychosis Associated with AD |
| Treatment Duration |
12 weeks |
6 weeks |
| Primary Endpoint |
CMAI total score |
BEHAVE-AD psychosis subscale |
| Eligibility |
NPI-AA ≥4 |
BEHAVE-AD psychosis items ≥2 |
This is a multicenter, randomized, double-blind, placebo-controlled, flexible-dose study conducted in three periods:
- Patient eligibility assessment
- Confirmation of AD diagnosis
- Baseline agitation evaluation
- Patients randomized 1:1 to ITI-1284 or placebo
- Flexible dosing: 10 mg or 20 mg once daily
- Efficacy and safety assessments at multiple timepoints
- Post-treatment safety follow-up visit
- Approximately 30 days after last dose
| Parameter |
Details |
| Randomization |
1:1 (ITI-1284 : Placebo) |
| Treatment Duration |
12 weeks |
| Masking |
Quadruple (participant, care provider, investigator, outcomes assessor) |
| Allocation |
Randomized, parallel-group |
| Primary Endpoint |
Change from baseline in CMAI total score at Week 12 |
- Cohen-Mansfield Agitation Inventory (CMAI) total score change from baseline at Week 12
The CMAI is a validated 29-item caregiver-rating questionnaire to assess agitated behavior in elderly patients. Each item is rated on a 7-point scale of frequency, from "never" (1) to "several times an hour" (7). The minimum possible CMAI total score is 29, and the maximum is 203.
The CMAI assesses three domains of agitation:
- Physical agitation: pacing, rocking, rubbing, kicking, etc.
- Verbal agitation: screaming, demanding, complaining, etc.
- Aggressive agitation: hitting, pushing, biting, etc.
- Clinical Global Impression-Severity (CGI-S) Score at Week 12
- Safety and tolerability assessments
- Pharmacokinetic evaluations
- Caregiver burden assessments
- Can understand the nature of the trial and protocol requirements and provide signed informed consent, or consent from a Legally Authorized Representative (LAR)
- Meets clinical criteria for Alzheimer's disease based on 2011 NIA-AA criteria AND either:
- High likelihood for amyloid pathology confirmed by blood-based biomarker at Screening; OR
- Documented confirmation of AD by CSF biomarker or amyloid 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
- MMSE-2:SV score of 6-24 at Screening
- Agitation symptoms are attributable to concomitant medications, adverse environmental conditions, substance abuse, or active medical or psychiatric conditions
- 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 stable and treated for at least 8 weeks)
- Has significant risk for suicidal behavior, or has had 1 or more suicide attempts within 2 years
- Has known hypersensitivity or intolerance to ITI-1284 or lumateperone
| Parameter |
Requirement |
| Age |
≥55 years |
| Diagnosis |
Alzheimer's disease with clinically meaningful agitation |
| MMSE Score |
6-24 (inclusive) |
| NPI-AA Domain |
≥4 |
| CGI-S |
≥4 |
Based on the drug class and patient population, potential adverse effects may include:
- Gastrointestinal: Nausea, dry mouth
- CNS: Headache, dizziness, somnolence, sedation
- Cardiovascular: Orthostatic hypotension
- General: Fatigue, insomnia
The trial includes:
- Regular efficacy and safety assessments during treatment period
- 30-day safety follow-up after last dose
- Independent Data Monitoring Committee (DMC)
- Sublingual formulation: Easy administration for patients with swallowing difficulties
- Rapidly disintegrating: Quick absorption
- Once-daily dosing: Simplified regimen
- Flexible dosing: 10 mg or 20 mg based on response and tolerability
- Non-dopamine blockade: Lower risk of extrapyramidal symptoms (compared to typical antipsychotics)
Agitation in Alzheimer's disease represents a significant challenge:
- Prevalence: Up to 70% of AD patients experience agitation during disease course
- Impact:
- Increased healthcare costs
- Earlier institutionalization
- Severe caregiver stress and burnout
- Reduced quality of life for patients
- Treatment gap: No FDA-approved treatments specifically for AD agitation
¶ Current Treatment Landscape
| Treatment |
Limitations |
| Risperidone |
Extrapyramidal symptoms, stroke risk, boxed warning |
| Quetiapine |
Sedation, metabolic effects, limited efficacy data |
| Aripiprazole |
Mixed efficacy results |
| Pimavanserin |
FDA-approved only for Parkinson's disease psychosis |
| Non-pharmacological |
Resource-intensive, variable efficacy |
This agitation trial (NCT06651267) runs in parallel with the Alzheimer's disease psychosis trial (NCT06540833). Both trials:
- Use the same drug (ITI-1284 10mg/20mg sublingual)
- Are sponsored by Intra-Cellular Therapies
- Use similar study designs and eligibility criteria
- Share the same mechanism of action
The key difference is the target symptom:
- Agitation: Behaviors (pacing, aggression, restlessness)
- Psychosis: False beliefs and perceptions (delusions, hallucinations)
¶ Sites and Recruitment
The trial is actively recruiting at multiple sites across:
- California: Anaheim, Costa Mesa, Garden Grove
- Florida: Boca Raton, Bonita Springs, Brandon, Delray Beach, Doral, Hialeah, Homestead, Maitland (2 locations), Miami (7 locations), Orlando (2 locations), Tampa (2 locations), West Palm Beach
- Massachusetts: Boston
- Nevada: Las Vegas
- New Jersey: Toms River
- North Carolina: Raleigh
- Texas: San Antonio
- Bulgaria: Lovech, Pleven, Sofia (4 locations), Stara Zagora
- Croatia: Zagreb (4 locations)
- Czechia: Brno, Choceň, Kutná Hora, Pilsen, Prague (2 locations)
- Romania: Bucharest (4 locations), Sânpetru, Sibiu
- Serbia: Belgrade (2 locations), Kovin, Niš, Novi Kneževac
- Slovakia: Banská Bystrica, Bratislava, Košice, Krompachy, Svidník, Vranov nad Topľou
- Spain: Albacete, Barcelona, Málaga, Zamora, Zaragoza