Proof-of-concept, Open-label Study in Patients With Early Alzheimer's Disease

Study Overview
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Brief Summary
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A Phase 2a study in men and women with early Alzheimer's disease to evaluate the pharmacodynamics, pharmacokinetics and safety of obicetrapib therapy.

Detailed Description
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This study will be a proof of concept, Phase 2a study in patients with early Alzheimer's disease (clinical diagnosis of Alzheimer's disease Stage 3 or 4 based on the National Institute on Aging Alzheimer's Association Research Framework criteria) to evaluate the Pharmacodynamic, cognitive effects, Pharmacokinetic, and safety and tolerability of obicetrapib therapy.

Official Title
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A Phase 2a, Proof-of-Concept, Open-Label Study to Evaluate the Pharmacodynamics, Pharmacokinetics, and Safety of Obicetrapib in Patients With Early Alzheimer's Disease (Hetero/Homozygote APOE4 Carriers)

Conditions
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Early Alzheimer's Disease

Intervention / Treatment
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* Drug: Obicetrapib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: men & women 50-75 years post-menopausal or women not of child-bearing potential diagnosis of Alzheimer's disease based on National Institute for Aging: Biomarker classification A+T+N+ or A+T+N- Clinical Stage 3 or 4 with Clinical Dementia Rating score >/= 0.5 & </= 1; mini-mental state examination (MMSE) score >/=20 Have an APOE genotype of E4/E4 or E3/E4 not on or on stabilized AD medication Patient & study partner willing to sign consent Exclusion Criteria: Other than AD, disorder that may impair cognition Contra-indication for MRI History of neurological, psychiatric or mental conditions; history stroke MI Type 1 diabetes & Type 2 with HbA1c>8% BP > 150/90 mmHg renal or hepatic impaired hyperaldosteronism cancer depression laboratory abnormalities not able to undergo lumbar puncture taking certain medications including lipid altering

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 10mg obicetrapib tablets<br>10mg obicetrapib (5mg tablets) administered orally daily for 24 weeks | Drug: Obicetrapib<br>* 10mg obicetrapib<br>* Other names: TA-8995;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apolipoproteins in plasma | Change from baseline to week 24 | 24 weeks | 
| Apolipoproteins in CSF | Change from baseline to week 24 | 24 weeks | 
| HDL particle concentration in plasma | Change from baseline to week 24 | 24 weeks | 
| HDL particle concentration in CSF | Change from baseline to week 24 | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma levels of obicetrapib | Change from baseline to steady-state blood levels of obicetrapib | 24 weeks | 
| CSF levels of obicetrapib | Change from baseline to steady-state CSF levels of obicetrapib | 24 weeks |