Study of Azeliragon in Patients With Mild Alzheimer's Disease and Impaired Glucose Tolerance

Study Overview
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Brief Summary
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This is a study to evaluate the efficacy and safety of azeliragon in patients with mild Alzheimer's disease and impaired glucose tolerance. Patients will receive either azeliragon or placebo with a patient's participation lasting approximately 9 months (in Part 1) or 21 months (in Part 2).

Official Title
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Randomized, Double-blind, Placebo-controlled, Multicenter Studies to Evaluate the Safety and Efficacy of Azeliragon as a Treatment for Subjects With Mild Alzheimer's Disease and Impaired Glucose Tolerance

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: Azeliragon
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of probable Alzheimer Disease (AD) with documented evidence of progression of disease Mini Mental State Examination (MMSE) score of 21-26, inclusive Clinical Dementia Rating global score of 0.5 or 1 Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog14) of 10 or more Brain magnetic resonance imaging (MRI) consistent with the diagnosis of probable AD Concurrent use of cholinesterase inhibitor or memantine with stable dose for at least 2 months prior to screening Hemoglobin A1c (HbA1c) 6.5% - 9.5%, inclusive Caregiver willing to participate and be able to attend clinic visits with patient Ability to ingest oral medications Exclusion Criteria: Significant neurological or psychiatric disease other than Alzheimer's disease Previous clinical trial participation within 90 days of screening Previous exposure to putative disease modifying therapy for Alzheimer's disease within 1 year of screening History of cancer within the last 5 years except adequately treated cervical carcinoma in-situ, cutaneous basal cell or squamous cell cancer, or non-progressive prostate cancer not requiring current treatment Women of childbearing potential Uncontrolled blood pressure and/or blood pressure above 140/90 Participants receiving medications that may negatively impact cognitive function History of diabetic ketoacidosis within the past year History of chronic pancreatitis Stage 4 kidney disease Use of insulin therapy

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Azeliragon<br>Azeliragon 5mg capsule administered orally, once daily for 6 months (Part 1) or 18 months (Part 2) | Drug: Azeliragon<br>* Azeliragon 5 mg capsule administered orally, once daily<br>* Other names: TTP488;|
| Placebo Comparator: Placebo<br>Matching placebo capsule administered orally, once daily for 6 months (Part 1) or 18 months (Part 2) | Drug: Placebo<br>* Matching placebo capsule administered orally, once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 : Change From Baseline in the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog14) at Month 6 | The Alzheimer's Disease Assessment Scale - Cognitive Subscale 14 Item (ADAS-cog14) scoring range is from 0 to 90, with higher scores indicating greater cognitive impairment | Baseline to Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Change From Baseline in the Amsterdam-Instrumental Activities of Daily Living (Amsterdam-IADL) at Month 6 | The Amsterdam-Instrumental Activities of Daily Living score is calculated from a questionnaire consisting of 70 items in seven categories using an item response theory method of scoring. Scores range from 20 to 80 where lower scores indicate greater functional impairment. | Baseline to Month 6 | 
| Part 1: Change From Baseline in the Clinical Dementia Rating Scale-Sum of Boxes (CDR-sb) at Month 6 | Clinical Dementia Rating - Sum of box (CDR-sb) scores range from 0 to 18 with higher scores indicating greater cognitive impairment. | Baseline to Month 6 | 
| Part 1: Change From Baseline in the Functional Activities Questionnaire (FAQ) at Month 6 | The total FAQ score ranges from 0 to 30, with higher scores indicating greater functional loss. | Baseline to Month 6 | 
| Mean Change From Baseline in the Mini Mental State Exam (MMSE) at Month 6. | The MMSE scale range is 0 to 30 with lower scores indicating greater cognitive impairment. | Baseline to Month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CDR-sb, Receptor for Advanced Glycation Endproducts (RAGE), ADAS-cog