Overview
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[@clinicaltrialsgov].
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[@ipaagitation].
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 |
...Overview
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[@clinicaltrialsgov].
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[@ipaagitation].
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 |
Mechanism of Action
Drug Profile
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.
Sublingual Administration Advantages
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 episodesMolecular Mechanism
Mermaid diagram (expand to render)
Distinction from Psychosis Trial (NCT06540833)
| 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 |
Trial Design
Study Structure
This is a multicenter, randomized, double-blind, placebo-controlled, flexible-dose study conducted in three periods:
Period 1: Screening (up to 4 weeks)
- Patient eligibility assessment
- Confirmation of AD diagnosis
- Baseline agitation evaluation
Period 2: Double-Blind Treatment (12 weeks)
- 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
Period 3: Safety Follow-up (30 days)
- Post-treatment safety follow-up visit
- Approximately 30 days after last dose
Key Study Parameters
| 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 |
Efficacy Endpoints
Primary Endpoint
- 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[@cmai].
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.
Secondary Endpoints
- Clinical Global Impression-Severity (CGI-S) Score at Week 12
- Safety and tolerability assessments
- Pharmacokinetic evaluations
- Caregiver burden assessments
Patient Population
Inclusion Criteria
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
3. 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 ScreeningExclusion Criteria
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)
3. 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 lumateperoneKey Eligibility Summary
| 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 |
Safety Considerations
Expected Adverse Effects
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
Safety Monitoring
The trial includes:
- Regular efficacy and safety assessments during treatment period
- 30-day safety follow-up after last dose
- Independent Data Monitoring Committee (DMC)
Advantages of ITI-1284
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)Clinical Development Context
Unmet Need in AD Agitation
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 |
Relationship to ITI-1284 Psychosis Trial
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:
United States
- 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
International Sites
- 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
- Phone: +1 (646) 440-9333
- Email: ITCIClinicalTrials@itci-inc.com
Cross-Links to NeuroWiki
- [Agitation in Alzheimer's Disease](/diseases/agitation-alzheimers) — Target indication
- [Alzheimer's Disease](/diseases/alzheimers-disease) — Disease context
- [Alzheimer's Disease Psychosis](/diseases/alzheimer-disease-psychosis) — Related indication
- [Intra-Cellular Therapies](/companies/intra-cellular-therapies) — Sponsor](/companies/intra-cellular-therapies)
- [ITI-1284 for AD Psychosis (NCT06540833)](/clinical-trials/iti-1284-alzheimers-psychosis-nct06540833) — Related trial
- [Cariprazine](/therapeutics/cariprazine) — Related compound from same company](/therapeutics)
- [Lumateperone](/therapeutics/lumateperone) — Related compound (chemical analog)
External Links
- [ClinicalTrials.gov - NCT06651567](https://clinicaltrials.gov/show/NCT06651567)
- [Cohen-Mansfield Agitation Inventory](https://pubmed.ncbi.nlm.nih.gov/21248774/)
- [IPA Consensus on Agitation in Dementia](https://pubmed.ncbi.nlm.nih.gov/22860226/)
References
[ClinicalTrials.gov - NCT06651567 (2024)](https://clinicaltrials.gov/show/NCT06651567)
[The Cohen-Mansfield Agitation Inventory: a comprehensive psychometric assessment. Am J Geriatr Psychiatry. 2011 (2011)](https://pubmed.ncbi.nlm.nih.gov/21248774/)
[Agitation in older persons with dementia: a report from the IPA. CNS Drugs. 1998 (1998)](https://pubmed.ncbi.nlm.nih.gov/22860226/)
[Reliability and validity of the Chinese version of the Cohen-Mansfield Agitation Inventory in residents with dementia. Int J Nurs Stud. 2011 (2011)](https://pubmed.ncbi.nlm.nih.gov/20869050/)