Overview
ITI-1284 is a novel sublingual rapidly disintegrating tablet being developed by Intra-Cellular Therapies, Inc. for the treatment of psychosis associated with Alzheimer's disease (AD). This is a Phase 2 randomized, double-blind, placebo-controlled study evaluating the efficacy, safety, and tolerability of ITI-1284 in patients with AD psychosis[@clinicaltrialsgov].
Intra-Cellular Therapies is best known for developing cariprazine (Vraylar®), an FDA-approved antipsychotic for schizophrenia, bipolar disorder, and major depressive disorder. This trial represents their entry into the Alzheimer's disease psychosis (ADP) space[@itcinc].
Alzheimer's disease psychosis affects approximately 25-50% of patients with Alzheimer's disease, manifesting as visual or auditory hallucinations, delusions, and other psychotic symptoms. This represents a significant unmet medical need with no FDA-approved treatments specifically for ADP[@ipapsychosis2024].
| Attribute | Details |
|-----------|---------|
| NCT Number | NCT06540833 |
| Sponsor | Intra-Cellular Therapies, Inc. |
| Drug | ITI-1284 |
| Phase | Phase 2 |
| Indication | Psychosis Associated with Alzheimer's Disease |
| Status | Recruiting |
| Start Date | August 15, 2024 |
| Primary Completion | September 2027 (estimated) |
| Estimated Completion | October 2027 |
| Total Participants | 370 (estimated) |
| Study Design | Randomized, double-blind, placebo-controlled, parallel-group |
Mechanism of Action
Drug Profile
...Overview
ITI-1284 is a novel sublingual rapidly disintegrating tablet being developed by Intra-Cellular Therapies, Inc. for the treatment of psychosis associated with Alzheimer's disease (AD). This is a Phase 2 randomized, double-blind, placebo-controlled study evaluating the efficacy, safety, and tolerability of ITI-1284 in patients with AD psychosis[@clinicaltrialsgov].
Intra-Cellular Therapies is best known for developing cariprazine (Vraylar®), an FDA-approved antipsychotic for schizophrenia, bipolar disorder, and major depressive disorder. This trial represents their entry into the Alzheimer's disease psychosis (ADP) space[@itcinc].
Alzheimer's disease psychosis affects approximately 25-50% of patients with Alzheimer's disease, manifesting as visual or auditory hallucinations, delusions, and other psychotic symptoms. This represents a significant unmet medical need with no FDA-approved treatments specifically for ADP[@ipapsychosis2024].
| Attribute | Details |
|-----------|---------|
| NCT Number | NCT06540833 |
| Sponsor | Intra-Cellular Therapies, Inc. |
| Drug | ITI-1284 |
| Phase | Phase 2 |
| Indication | Psychosis Associated with Alzheimer's Disease |
| Status | Recruiting |
| Start Date | August 15, 2024 |
| Primary Completion | September 2027 (estimated) |
| Estimated Completion | October 2027 |
| Total Participants | 370 (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.
Sublingual Administration Advantages
The sublingual formulation offers several advantages for the AD psychosis 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 exposureMolecular Mechanism
Mermaid diagram (expand to render)
Comparison with Other AD Psychosis Treatments
| Drug | Company | Formulation | Phase | Status |
|------|---------|-------------|-------|--------|
| ITI-1284 | Intra-Cellular Therapies | Sublingual tablet | Phase 2 | Recruiting |
| ACP-204 | ACADIA Pharmaceuticals | Oral | Phase 2/3 | Recruiting |
| Pimavanserin | ACADIA | Oral | Phase 3 | FDA Approved (PDP only) |
| Risperidone | Generic | Oral | Generic | Off-label |
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 psychosis evaluation
Period 2: Double-Blind Treatment (6 weeks)
- Patients randomized 1:1 to ITI-1284 or placebo
- Flexible dosing: 10 mg or 20 mg once daily
- Efficacy and safety assessments
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 | 6 weeks |
| Masking | Quadruple (participant, care provider, investigator, outcomes assessor) |
| Allocation | Randomized, parallel-group |
| Primary Endpoint | Change from baseline in BEHAVE-AD psychosis subscale at Week 6 |
Efficacy Endpoints
Primary Endpoint
- BEHAVE-AD psychosis subscale score change from baseline at Week 6
The BEHAVE-AD is a comprehensive rating scale for behavioral symptoms in AD that includes:
- Paranoid and delusional ideations domain: 7 items
- Hallucinations domain: 5 items
- Scoring: 0 (not present) to 3 (present, generally with emotional and physical component)
- Maximum psychosis subscale score: 36 points[@behavead]
Secondary Endpoints
- Clinical Global Impression - Severity (CGI-S) score at Week 6[@cgis]
- Safety and tolerability assessments
- Pharmacokinetic evaluations
Patient Population
Inclusion Criteria
Able to understand the nature of the trial and provide informed consent (or LAR consent)
Meets clinical criteria for AD 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 criteria for psychosis per IPA provisional consensus definition at Screening and Baseline
Scoring ≥2 on any item of BEHAVE-AD Part A (Paranoid and Delusional Ideation) or Part B (Hallucinations) at Screening and Baseline
CGI-S score ≥4 at Screening and Baseline
MMSE-2:SV score of 6-24 at Screening
Has a designated caregiverExclusion Criteria
Psychotic symptoms primarily attributable to delirium, substance abuse, or another general-medical condition
Psychiatric diagnoses including schizophrenia, schizoaffective disorder, bipolar disorder
Risk for suicidal behavior or suicide attempts within 2 years
Unable to discontinue other drugs with psychotropic properties
Hospitalized or receiving skilled nursing care
Significant unstable medical conditions
In hospice or end-of-life careKey Eligibility Summary
| Parameter | Requirement |
|-----------|-------------|
| Age | ≥55 years |
| Diagnosis | Alzheimer's disease with psychosis |
| MMSE Score | 6-24 (inclusive) |
| BEHAVE-AD | ≥2 on psychosis items |
| CGI-S | ≥4 |
| Caregiver | Required |
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:
- Weekly 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
No dopamine blockade: Lower risk of extrapyramidal symptomsClinical Development Context
Unmet Need in AD Psychosis
Alzheimer's disease psychosis represents a significant challenge in neurodegenerative disease care:
- Prevalence: 25-50% of AD patients develop psychosis
- Impact:
- Faster cognitive decline
- Earlier nursing home placement
- Increased mortality risk
- Severe caregiver burden
- Treatment gap: No FDA-approved treatments specifically for ADP
Current Treatment Landscape
| Treatment | Limitations |
|-----------|-------------|
| Risperidone | Extrapyramidal symptoms, stroke risk in elderly |
| Quetiapine | Sedation, metabolic effects |
| Aripiprazole | Limited efficacy data in ADP |
| Pimavanserin | FDA-approved only for Parkinson's disease psychosis |
Sites and Recruitment
The trial is actively recruiting at multiple sites across:
United States
- California: Anaheim, Costa Mesa, Lafayette, Newport Beach, Orange
- Florida: Brandon, Coral Springs, Delray Beach, Doral, Homestead, Maitland, Miami (6 locations), Orlando, Sarasota, Tampa (2 locations)
- New Jersey: Toms River
- North Carolina: Charlotte
- Texas: Cypress, San Antonio
- Washington: Bellevue
International Sites
- Bulgaria: Blagoevgrad, Cherven Bryag, Sofia (4 locations), Stara Zagora, Vratsa
- Croatia: Zagreb (3 locations)
- Czech Republic: Brno (2 locations), Hradec Králové, Prague
- Poland: Bydgoszcz, Ścinawa
- Romania: Bucharest (4 locations), Galati, Sibiu
- Serbia: Belgrade, Kovin, Kragujevac, Niš, Novi Kneževac
- Slovakia: Banská Bystrica, Bratislava, Košice (2 locations), Krompachy, Vranov nad Topľou
- Spain: Albacete, Madrid (not yet recruiting), Zamora (not yet recruiting), Zaragoza
- Phone: +1 (646) 440-9333
- Email: ITCIClinicalTrials@itc-inc.com
Cross-Links to NeuroWiki
- [Alzheimer's Disease Psychosis](/diseases/alzheimer-disease-psychosis) — Target indication
- [Psychosis in Neurodegenerative Diseases](/diseases/psychosis-neurodegenerative) — Disease context
- [Intra-Cellular Therapies](/companies/intra-cellular-therapies) — Sponsor](/companies/intra-cellular-therapies)
- [Cariprazine](/therapeutics/cariprazine) — Related compound from same company](/therapeutics)
- [Pimavanserin](/clinical-trials/pimavanserin-parkinsons-psychosis) — Related compound](/proteins/parkin)
- [ACP-204](/clinical-trials/acp-204-alzheimers-psychosis) — Competing AD psychosis drug
External Links
- [ClinicalTrials.gov - NCT06540833](https://clinicaltrials.gov/show/NCT06540833)
- [Intra-Cellular Therapies Pipeline](https://www.itc-inc.com/pipeline/)](/companies/intra-cellular-therapies)
- [BEHAVE-AD Scale](https://pubmed.ncbi.nlm.nih.gov/8123008/)
- [IPA Psychosis Definition in NCD](https://pubmed.ncbi.nlm.nih.gov/38489612/)
References
[ClinicalTrials.gov - NCT06540833 (2024)](https://clinicaltrials.gov/show/NCT06540833)
[Intra-Cellular Therapies Corporate Pipeline (2024)](https://www.itc-inc.com/pipeline/)
[International Psychogeriatric Association provisional consensus definition of psychosis in major or mild neurocognitive disorder. Am J Geriatr Psychiatry. 2024 (2024)](https://pubmed.ncbi.nlm.nih.gov/38489612/)
[The Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). Arch Gen Psychiatry. 1994 (1994)](https://pubmed.ncbi.nlm.nih.gov/8123008/)
[Clinical Global Impression Scale - an overview (n.d.)](https://pubmed.ncbi.nlm.nih.gov/8149188/)