Alzheimer Disease
Conditions
Keywords
Receptor for Advanced Glycation Endproducts (RAGE), ADAS-cog, CDR-sb
Brief summary
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).
Interventions
DRUGAzeliragon
Azeliragon 5 mg capsule administered orally, once daily
DRUGPlacebo
Matching placebo capsule administered orally, once daily
Sponsors
vTv Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 : Change From Baseline in the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog14) at Month 6 | Baseline to 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Change From Baseline in the Amsterdam-Instrumental Activities of Daily Living (Amsterdam-IADL) at Month 6 | Baseline to 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. |
| Part 1: Change From Baseline in the Clinical Dementia Rating Scale-Sum of Boxes (CDR-sb) at Month 6 | Baseline to Month 6 | Clinical Dementia Rating - Sum of box (CDR-sb) scores range from 0 to 18 with higher scores indicating greater cognitive impairment. |
| Part 1: Change From Baseline in the Functional Activities Questionnaire (FAQ) at Month 6 | Baseline to Month 6 | The total FAQ score ranges from 0 to 30, with higher scores indicating greater functional loss. |
| Mean Change From Baseline in the Mini Mental State Exam (MMSE) at Month 6. | Baseline to Month 6 | The MMSE scale range is 0 to 30 with lower scores indicating greater cognitive impairment. |
Other
| Measure | Time frame |
|---|---|
| Count and Percentage of Subjects With Treatment-emergent Adverse Events | Baseline to Month 6 |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Azeliragon Azeliragon 5mg capsule administered orally, once daily for 6 months (Part 1)
Azeliragon: Azeliragon 5 mg capsule administered orally, once daily | 21 |
| Placebo Matching placebo capsule administered orally, once daily for 6 months (Part 1)
Placebo: Matching placebo capsule administered orally, once daily | 22 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Sponsor Request | 0 | 1 |
| Overall Study | Study Terminated by Sponsor | 0 | 3 |
Baseline characteristics
| Characteristic | Azeliragon | Placebo | Total |
|---|---|---|---|
| ADAS-Cog 14 Total Score | 30.8 units on a scale STANDARD_DEVIATION 7.53 | 29.4 units on a scale STANDARD_DEVIATION 8.87 | 30.1 units on a scale STANDARD_DEVIATION 8.17 |
| Age, Continuous | 76.3 years STANDARD_DEVIATION 5.82 | 77.0 years STANDARD_DEVIATION 6.56 | 76.7 years STANDARD_DEVIATION 6.14 |
| ApoE4 Carrier Status Carrier | 12 Participants | 10 Participants | 22 Participants |
| ApoE4 Carrier Status Non-Carrier | 9 Participants | 12 Participants | 21 Participants |
| CDR Global Score CDR Global = 0.5 | 10 Participants | 13 Participants | 23 Participants |
| CDR Global Score CDR Global = 1 | 11 Participants | 9 Participants | 20 Participants |
| CDR Sum of Boxes | 4.7 units on a scale STANDARD_DEVIATION 1.37 | 4.2 units on a scale STANDARD_DEVIATION 2.22 | 4.5 units on a scale STANDARD_DEVIATION 1.85 |
| Education Level Associate's Degree | 1 Participants | 2 Participants | 3 Participants |
| Education Level Bachelor's Degree | 7 Participants | 4 Participants | 11 Participants |
| Education Level High School | 6 Participants | 8 Participants | 14 Participants |
| Education Level Master's Degree | 1 Participants | 4 Participants | 5 Participants |
| Education Level Other (Training, Certifications, etc.) | 1 Participants | 2 Participants | 3 Participants |
| Education Level Some College | 5 Participants | 2 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 21 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| MMSE Total Score | 23.7 units on a scale STANDARD_DEVIATION 1.48 | 23.5 units on a scale STANDARD_DEVIATION 2.24 | 23.6 units on a scale STANDARD_DEVIATION 1.89 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 19 Participants | 22 Participants | 41 Participants |
| Sex: Female, Male Female | 9 Participants | 11 Participants | 20 Participants |
| Sex: Female, Male Male | 12 Participants | 11 Participants | 23 Participants |
| Years Since Diagnosis of AD | 1.9 years STANDARD_DEVIATION 1.16 | 1.8 years STANDARD_DEVIATION 1.24 | 1.9 years STANDARD_DEVIATION 1.19 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 22 |
| other Total, other adverse events | 9 / 21 | 13 / 22 |
| serious Total, serious adverse events | 1 / 21 | 0 / 22 |
Outcome results
Primary
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
Time frame: Baseline to Month 6
Population: The full analysis set (FAS) includes all randomized subjects, whether or not they receive any study medication, and who have at least one post-Baseline assessment. The FAS was used for all hypothesis tests of efficacy.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azeliragon | Part 1 : Change From Baseline in the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog14) at Month 6 | 1.8 score on a scale | Standard Error 0.82 |
| Placebo | Part 1 : Change From Baseline in the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog14) at Month 6 | 0.4 score on a scale | Standard Error 0.69 |
p-value: 0.2057Mixed Models Analysis
Secondary
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.
Time frame: Baseline to Month 6
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azeliragon | Mean Change From Baseline in the Mini Mental State Exam (MMSE) at Month 6. | -1.8 score on a scale | Standard Error 0.41 |
| Placebo | Mean Change From Baseline in the Mini Mental State Exam (MMSE) at Month 6. | -1.7 score on a scale | Standard Error 0.43 |
Secondary
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.
Time frame: Baseline to Month 6
Population: The full analysis set (FAS) includes all randomized subjects, whether or not they receive any study medication, and who have at least one post-Baseline assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azeliragon | Part 1: Change From Baseline in the Amsterdam-Instrumental Activities of Daily Living (Amsterdam-IADL) at Month 6 | 6.2 score on a scale | Standard Error 1.99 |
| Placebo | Part 1: Change From Baseline in the Amsterdam-Instrumental Activities of Daily Living (Amsterdam-IADL) at Month 6 | 9.3 score on a scale | Standard Error 2.37 |
Secondary
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.
Time frame: Baseline to Month 6
Population: The full analysis set (FAS) includes all randomized subjects, whether or not they receive any study medication, and who have at least one post-Baseline assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azeliragon | Part 1: Change From Baseline in the Clinical Dementia Rating Scale-Sum of Boxes (CDR-sb) at Month 6 | 0.6 score on a scale | Standard Error 0.29 |
| Placebo | Part 1: Change From Baseline in the Clinical Dementia Rating Scale-Sum of Boxes (CDR-sb) at Month 6 | 1.3 score on a scale | Standard Error 0.36 |
Secondary
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.
Time frame: Baseline to Month 6
Population: The full analysis set (FAS) includes all randomized subjects, whether or not they receive any study medication, and who have at least one post-Baseline assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Azeliragon | Part 1: Change From Baseline in the Functional Activities Questionnaire (FAQ) at Month 6 | -0.5 score on a scale | Standard Error 0.84 |
| Placebo | Part 1: Change From Baseline in the Functional Activities Questionnaire (FAQ) at Month 6 | 2.8 score on a scale | Standard Error 0.84 |
Other Pre-specified
Count and Percentage of Subjects With Treatment-emergent Adverse Events
Time frame: Baseline to Month 6
Population: The safety set (SAF) includes all subjects who receive any study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Azeliragon | Count and Percentage of Subjects With Treatment-emergent Adverse Events | Subjects with at least 1 adverse event | 16 Participants |
| Azeliragon | Count and Percentage of Subjects With Treatment-emergent Adverse Events | Subjects with at least 1 serious adverse event | 1 Participants |
| Azeliragon | Count and Percentage of Subjects With Treatment-emergent Adverse Events | Subjects who had drug withdrawn due to AE | 2 Participants |
| Placebo | Count and Percentage of Subjects With Treatment-emergent Adverse Events | Subjects with at least 1 adverse event | 16 Participants |
| Placebo | Count and Percentage of Subjects With Treatment-emergent Adverse Events | Subjects with at least 1 serious adverse event | 0 Participants |
| Placebo | Count and Percentage of Subjects With Treatment-emergent Adverse Events | Subjects who had drug withdrawn due to AE | 0 Participants |