| Primary | Primary Cognitive Efficacy Endpoint (ADAS-Cog13) | Change from baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale 13 (ADAS-Cog13) scores. The ADAS-Cog13 is a rater administered instrument that was designed to assess the severity of the dysfunction in the cognitive and noncognitive behaviors characteristic of persons with AD. The cognitive subscale of the ADAS-Cog13 consists of 13 items assessing areas of cognitive function most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, digit cancellation. The ADAS-Cog13 scale ranges from 0 to 85. Higher scores indicate greater disease severity. | Full Analysis Set (FAS): The FAS includes all study subjects who received at least one dose of the study drug, had at least one baseline assessment and any post baseline efficacy assessment. All primary and secondary clinical efficacy analyses are conducted on this population. | Posted | | Least Squares Mean | Standard Error | Score on a scale | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
| | | Title | Denominators | Categories |
|---|
| | | Title | Measurements |
|---|
| - OG0004.40± 0.69
- OG0013.89± 0.69
|
|
| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
|---|
| The null hypothesis was change from baseline (CBL) of ADAS-Cog13 in the ALZ-801 arm was not different from the placebo arm. The alternative hypothesis was that the CBL of ADAS-Cog13 in ALZ-801 arm was different. A Mixed-Effect Model Repeated Measure (MMRM) model was used with fixed terms for treatment, gender, age group, disease severity based on baseline MMSE (≤ 26 vs. > 26), concomitant AD medications, visit, and treatment by visit interaction and baseline ADAS-Cog 13 values as covariates. | MMRM | | 0.6058 | Statistical testing was two-sided at the α=0.05 significance level. Between-treatment group comparison (effect in ALZ-801 minus effect in placebo): LSM difference and p-value. | Least Squares Mean Difference | -0.51 | Standard Error of the Mean | 0.98 | 2-Sided | | | | | |
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| Primary | Incidence, Nature, and Severity of Treatment Emergent Adverse Events (TEAE) | Safety and tolerability as measured by incidence, nature and severity of treatment emergent adverse events (TEAE), serious TEAEs, and TEAEs leading to withdrawal. | Safety Population: subjects who took at least 1 dose of any study drug are included. | Posted | | Count of Participants | | Participants | No | Entire study: approximately 82 weeks. (first dose of study drug until end of Safety Follow-up Visit at 28 +/- 7 days after the last dose (ie, 78-week treatment period plus 4-weeks follow-up after last dose up to total of 82 weeks) | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
| |
| Secondary | Key Secondary Endpoint (A-IADL-W) | Change from baseline in Amsterdam - Instrumental Activities of Daily Living scores calculated using the weighted average method (A-IADL-W score). The A-IADL Questionnaire is a 70-item informant-based computerized questionnaire aimed at detecting deficits in complex functions at the early stages of AD. Instrumental ADL can be described as the activities necessary to function independently in society. These activities include, but are not limited to, cooking, doing finances, and shopping. They are complex everyday tasks, determined by multiple cognitive processes and controlled processing. They can be distinguished from basic ADL, which include basic self-care skills. The A-IADL-W has a score range of 0-100 and is calculated as follows: (sum of all scores / number of questions scored) × 25. For A-IADL-W, higher scores indicates worse functioning or more impairment. | | Posted | | Least Squares Mean | Standard Error | score on a scale | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
|
| Secondary | Key Secondary Endpoint (CDR-SB) | Change from baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) scores. CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; Total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity. | | Posted | | Least Squares Mean | Standard Error | score on a scale | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
| |
| Secondary | Functional Assessment (DAD) | Change from baseline in Disability Assessment for Dementia (DAD)scores. The DAD consists of 40 items with a score range of 0-100 to evaluate the basic and instrumental activities of daily living of subjects with dementia. It is administered through an interview with the caregiver. Higher DAD scores indicate less disability or better function. | | Posted | | Least Squares Mean | Standard Error | score on a scale | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
| |
| Secondary | Global Cognition Assessment (MMSE) | Change from baseline in Mini-Mental State Examination (MMSE) score. The MMSE is a measure of global cognition that is widely used for clinical staging of Alzheimer's Disease. It consists of 11 domains items for a score range of 0-30 to assess general cognitive function. Higher score on MMSE means better cognitive skills. | | Posted | | Least Squares Mean | Standard Error | score on a scale | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
| |
| Other Pre-specified | Imaging Biomarker Endpoint (Hippocampal Volume) | Change from baseline in total (bilateral) hippocampal volume (HV) (uL) as measured by Magnetic Resonance Imaging (MRI). HV atrophy is an early event in AD patients, especially in APOE4/4 homozygotes who show accelerated atrophy compared to APOE3/3 patients with Early AD. HV may be a marker of synaptic loss and neurodegeneration. | The Imaging Biomarker population included all subjects with an evaluable baseline vMRI assessment who had received at least 1 dose of study drug and had at least 1 evaluable post-baseline imaging vMRI assessment. | Posted | | Least Squares Mean | Standard Error | microliters | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
| |
| Other Pre-specified | Imaging Biomarker Endpoint (Cortical Thickness [Whole Cortex]) | Change from baseline in total (bilateral) cortical thickness (mm) as measured by MRI. Brain MRI studies in Alzheimer's Disease patients show progressive cortical atrophy, reflecting progressive neurodegeneration. | Imaging Biomarker Population | Posted | | Least Squares Mean | Standard Error | mm | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
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| Other Pre-specified | Imaging Biomarker Endpoint (Cortical Thickness [Mayo Index]) | Change from baseline in total (bilateral) cortical thickness (mm) as measured by MRI. Brain MRI studies in Alzheimer's Disease patients show progressive cortical atrophy, reflecting progressive neurodegeneration. The Mayo Index refers specifically to the measurement of cortical thickness in the medial temporal lobe. | Imaging Biomarker Population | Posted | | Least Squares Mean | Standard Error | mm | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
| |
| Other Pre-specified | Imaging Biomarker Endpoint (Whole Brain Volume) | Change from baseline in whole brain volume (uL) as measured by Magnetic Resonance Imaging (MRI). | Imaging Biomarker Population | Posted | | Least Squares Mean | Standard Error | microliters | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
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| Other Pre-specified | Imaging Biomarker Endpoint (Ventricular Volume) | Change from baseline in total (bilateral) ventricular volume (uL) as measured by Magnetic Resonance Imaging (MRI). | Imaging Biomarker Population | Posted | | Least Squares Mean | Standard Error | microliters | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
| |
| Other Pre-specified | Imaging Biomarker Endpoint - DTI in Grey Matter Mean Diffusivity - Bilateral Caudate | Change from baseline in Grey Matter Mean Diffusivity (Bilateral Caudate) as measured by Diffusion Tensor Imaging - Magnetic Resonance Imaging (DTI-MRI). The mean diffusivity (MD) is the average of the three main diffusion values (eigenvalues) obtained from the diffusion tensor imaging (DTI). It is expressed as mm2/s. This unit quantifies the average rate of water diffusion across all directions within a tissue, providing an overall measure of tissue microstructural properties. Lower MD value suggests better maintenance of microstructural integrity of a given brain tissue. Positive treatment effects of ALZ-801 on DTI would present as lower mean diffusivity compared with the placebo group. | DTI-MRI Population defined as all participants who had an evaluable baseline DTI-MRI assessment, received at least one dose of study drug, and had at least one evaluable post-baseline DTI-MRI assessment. | Posted | | Least Squares Mean | Standard Error | square millimeters per second (mm²/s) | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
|
| Other Pre-specified | Imaging Biomarker Endpoint - DTI in White Matter Mean Diffusivity (Bilateral Fornix) | Change from baseline in Bilateral Fornix White Matter Mean Diffusivity as measured by Diffusion Tensor Imaging - Magnetic Resonance Imaging (DTI-MRI). The mean diffusivity (MD) is the average of the three main diffusion values (eigenvalues) obtained from the diffusion tensor imaging (DTI). It is expressed as mm2/s. This unit quantifies the average rate of water diffusion across all directions within a tissue, providing an overall measure of tissue microstructural properties. Lower MD value suggests better maintenance of microstructural integrity of a given brain tissue. Positive treatment effects of ALZ-801 on DTI would present as lower mean diffusivity compared with the placebo group. | | Posted | | Least Squares Mean | Standard Error | square millimeters per second (mm²/s) | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
| |
| Other Pre-specified | Imaging Biomarker Endpoint - White Matter Fractional Anisotropy (Bilateral Fornix) | Change from baseline in Bilateral Fornix White Matter Fractional Anisotropy as measured by Diffusion Tensor Imaging - Magnetic Resonance Imaging (DTI-MRI). Fractional anisotropy (FA) is a unitless, scalar value that measures the degree of anisotropic (directional) water diffusion within a voxel, ranging from 0 to 1. A value of 0 indicates perfectly isotropic (equal in all directions) diffusion, while a value of 1 indicates perfectly anisotropic (directional) diffusion. Higher FA value suggests better maintenance of microstructural integrity of a given brain tissue. Positive treatment effects of ALZ-801 on DTI would present as higher FA in the ALZ-801 group compared with the placebo group. | | Posted | | Least Squares Mean | Standard Error | Units on a scale (fractions 0-1) | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
| |
| Other Pre-specified | Cognitive Efficacy Endpoint (ADAS-Cog 13) - MCI Subgroup | Change from baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale 13 (ADAS-cog 13) scores at 78 weeks. The ADAS-Cog13 is a rater administered instrument that was designed to assess the severity of the dysfunction in the cognitive and noncognitive behaviors characteristic of persons with AD. The cognitive subscale of the ADAS-Cog13 consists of 13 items assessing areas of cognitive function most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, digit cancellation. The ADAS-Cog13 scale ranges from 0 to 85. Higher scores indicate greater disease severity. | FAS MCI subgroup: all study subjects in the MCI subgroup who received at least one dose of the study drug, had at least one baseline assessment and any post baseline efficacy assessment. | Posted | | Least Squares Mean | Standard Error | Score on a scale | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
|
| Other Pre-specified | Cognitive Efficacy Endpoint (ADAS-Cog 13) - Mild Alzheimer's Disease(Mild AD) Subgroup | Change from baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale 13 (ADAS-cog 13) scores at 78 weeks. The ADAS-Cog13 is a rater administered instrument that was designed to assess the severity of the dysfunction in the cognitive and noncognitive behaviors characteristic of persons with AD. The cognitive subscale of the ADAS-Cog13 consists of 13 items assessing areas of cognitive function most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, digit cancellation. The ADAS-Cog13 scale ranges from 0 to 85. Higher scores indicate greater disease severity. | FAS Mild AD subgroup: all study subjects in the Mild AD subgroup who received at least one dose of the study drug, had at least one baseline assessment and any post baseline efficacy assessment. | Posted | | Least Squares Mean | Standard Error | score on a scale | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
|
| Other Pre-specified | A-IADL-W - MCI Subgroup | Change from baseline in Amsterdam - Instrumental Activities of Daily Living scores calculated using the weighted average method (A-IADL-W score). The A-IADL Questionnaire is a 70-item informant-based computerized questionnaire aimed at detecting deficits in complex functions at the early stages of AD. Instrumental ADL can be described as the activities necessary to function independently in society. These activities include, but are not limited to, cooking, doing finances, and shopping. They are complex everyday tasks, determined by multiple cognitive processes and controlled processing. They can be distinguished from basic ADL, which include basic self-care skills. The A-IADL-W has a score range of 0-100 and is calculated as follows: (sum of all scores / number of questions scored) × 25. For A-IADL-W, higher scores indicates worse functioning or more impairment. | | Posted | | Least Squares Mean | Standard Error | score on a scale | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
|
| Other Pre-specified | A-IADL-W - Mild AD Subgroup | Change from baseline in Amsterdam - Instrumental Activities of Daily Living scores calculated using the weighted average method (A-IADL-W score). The A-IADL Questionnaire is a 70-item informant-based computerized questionnaire aimed at detecting deficits in complex functions at the early stages of AD. Instrumental ADL can be described as the activities necessary to function independently in society. These activities include, but are not limited to, cooking, doing finances, and shopping. They are complex everyday tasks, determined by multiple cognitive processes and controlled processing. They can be distinguished from basic ADL, which include basic self-care skills. The A-IADL-W has a score range of 0-100 and is calculated as follows: (sum of all scores / number of questions scored) × 25. For A-IADL-W, higher scores indicates worse functioning or more impairment. | | Posted | | Least Squares Mean | Standard Error | score on a scale | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
|
| Other Pre-specified | CDR-SB - MCI Subgroup | Change from baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) scores. CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; Total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity. | | Posted | | Least Squares Mean | Standard Error | score on a scale | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
| |
| Other Pre-specified | CDR-SB - Mild AD Subgroup | Change from baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) scores. CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; Total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity. | | Posted | | Least Squares Mean | Standard Error | score on a scale | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
| |
| Other Pre-specified | Functional Assessment (DAD) - MCI Subgroup | Change from baseline in Disability Assessment for Dementia (DAD)scores. The DAD consists of 40 items with a score range of 0-100 to evaluate the basic and instrumental activities of daily living of subjects with dementia. It is administered through an interview with the caregiver. Higher DAD scores indicate less disability or better function. | | Posted | | Least Squares Mean | Standard Error | score on a scale | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
| |
| Other Pre-specified | Functional Assessment (DAD) - Mild AD Subgroup | Change from baseline in Disability Assessment for Dementia (DAD)scores. The DAD consists of 40 items with a score range of 0-100 to evaluate the basic and instrumental activities of daily living of subjects with dementia. It is administered through an interview with the caregiver. Higher DAD scores indicate less disability or better function. | | Posted | | Least Squares Mean | Standard Error | score on a scale | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
| |
| Other Pre-specified | Global Cognition Assessment (MMSE) - MCI Subgroup | Change from baseline in Mini-Mental State Examination (MMSE) score. The MMSE is a measure of global cognition that is widely used for clinical staging of Alzheimer's Disease. It consists of 11 domains items for a score range of 0-30 to assess general cognitive function. Higher score on MMSE means better cognitive skills. | | Posted | | Least Squares Mean | Standard Error | Score on a scale | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
| |
| Other Pre-specified | Global Cognition Assessment (MMSE) - Mild AD Subgroup | Change from baseline in Mini-Mental State Examination (MMSE) score. The MMSE is a measure of global cognition that is widely used for clinical staging of Alzheimer's Disease. It consists of 11 domains items for a score range of 0-30 to assess general cognitive function. Higher score on MMSE means better cognitive skills. | | Posted | | Least Squares Mean | Standard Error | score on a scale | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
| |
| Other Pre-specified | Hippocampal Volume (MCI Subgroup) | Change from baseline in total (bilateral) hippocampal volume (HV) (uL) as measured by Magnetic Resonance Imaging (MRI). HV atrophy is an early event in AD patients, especially in APOE4/4 homozygotes who show accelerated atrophy compared to APOE3/3 patients with Early AD. HV may be a marker of synaptic loss and neurodegeneration. | Imaging Biomarker Population MCI Subgroup: this population included all subjects in the MCI subgroup with an evaluable baseline vMRI assessment who had received at least 1 dose of study drug and had at least 1 evaluable post-baseline imaging vMRI assessment. | Posted | | Least Squares Mean | Standard Error | microliters | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
| |
| Other Pre-specified | Hippocampal Volume (Mild AD Subgroup) | Change from baseline in total (bilateral) hippocampal volume (HV) (uL) as measured by Magnetic Resonance Imaging (MRI). HV atrophy is an early event in AD patients, especially in APOE4/4 homozygotes who show accelerated atrophy compared to APOE3/3 patients with Early AD. HV may be a marker of synaptic loss and neurodegeneration. | Imaging Biomarker Population Mild AD Subgroup: this population included all subjects with an evaluable baseline vMRI assessment who had received at least 1 dose of study drug and had at least 1 evaluable post-baseline imaging vMRI assessment. | Posted | | Least Squares Mean | Standard Error | microliters | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
| |
| Other Pre-specified | Cortical Thickness (Whole Cortex) (MCI Subgroup) | Change from baseline in total (bilateral) cortical thickness (mm) as measured by MRI. Brain MRI studies in Alzheimer's Disease patients show progressive cortical atrophy, reflecting progressive neurodegeneration. | Imaging Biomarker Population MCI Subgroup | Posted | | Least Squares Mean | Standard Error | mm | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
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| Other Pre-specified | Cortical Thickness (Whole Cortex) (Mild AD Subgroup) | Change from baseline in total (bilateral) cortical thickness (mm) as measured by MRI. Brain MRI studies in Alzheimer's Disease patients show progressive cortical atrophy, reflecting progressive neurodegeneration. | Imaging Biomarker Population Mild AD Subgroup | Posted | | Least Squares Mean | Standard Error | mm | | Baseline to Week 78 | | | | ID | Title | Description |
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| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
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| Other Pre-specified | Cortical Thickness (Mayo Index) (MCI Subgroup) | Change from baseline in total (bilateral) cortical thickness (mm) as measured by MRI. Brain MRI studies in Alzheimer's Disease patients show progressive cortical atrophy, reflecting progressive neurodegeneration. The Mayo Index refers specifically to the measurement of cortical thickness in the medial temporal lobe versus the whole cortex. | Imaging Biomarker Population MCI Subgroup | Posted | | Least Squares Mean | Standard Error | mm | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
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| Other Pre-specified | Cortical Thickness (Mayo Index) (Mild AD Subgroup) | Change from baseline in total (bilateral) cortical thickness (mm) as measured by MRI. Brain MRI studies in Alzheimer's Disease patients show progressive cortical atrophy, reflecting progressive neurodegeneration. The Mayo Index refers specifically to the measurement of cortical thickness in the medial temporal lobe versus the whole cortex. | Imaging Biomarker Population Mild AD Subgroup | Posted | | Least Squares Mean | Standard Error | mm | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
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| Other Pre-specified | Whole Brain Volume (MCI Subgroup) | Change from baseline in whole brain volume (uL) as measured by Magnetic Resonance Imaging (MRI). | Imaging Biomarker Population MCI Subgroup | Posted | | Least Squares Mean | Standard Error | microliters | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
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| Other Pre-specified | Whole Brain Volume (Mild AD Subgroup) | Change from baseline in whole brain volume (uL) as measured by Magnetic Resonance Imaging (MRI). | Imaging Biomarker Population Mild AD Subgroup | Posted | | Least Squares Mean | Standard Error | microliters | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
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| Other Pre-specified | Ventricular Volume (MCI Subgroup) | Change from baseline in total (bilateral) ventricular volume (uL) as measured by Magnetic Resonance Imaging (MRI). | Imaging Biomarker Population MCI Subgroup | Posted | | Least Squares Mean | Standard Error | microliters | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
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| Other Pre-specified | Ventricular Volume (Mild AD Subgroup) | Change from baseline in total (bilateral) ventricular volume (uL) as measured by Magnetic Resonance Imaging (MRI). | Imaging Biomarker Population Mild AD Subgroup | Posted | | Least Squares Mean | Standard Error | microliters | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
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| Post-Hoc | Cerebellar Volume | Change from baseline in total (bilateral) cerebellar volume (uL) as measured by Magnetic Resonance Imaging (MRI). | Imaging Biomarker Population | Posted | | Least Squares Mean | Standard Error | microliters | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
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| Post-Hoc | Cerebellar Volume (MCI Subgroup) | Change from baseline in total (bilateral) cerebellar volume (uL) as measured by Magnetic Resonance Imaging (MRI). | Imaging Biomarker Population MCI Subgroup | Posted | | Least Squares Mean | Standard Error | microliters | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
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| Post-Hoc | Cerebellar Volume (Mild AD Subgroup) | Change from baseline in total (bilateral) cerebellar volume (uL) as measured by Magnetic Resonance Imaging (MRI). | Imaging Biomarker Population Mild AD Subgroup | Posted | | Least Squares Mean | Standard Error | microliters | | Baseline to Week 78 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID | | OG001 | ALZ-801 | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID |
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