Alzheimer's Disease
Conditions
Keywords
BACE inhibitor
Brief summary
The main purpose of this study is to evaluate the safety and the effect on brain tau of the study drug LY3202626 in participants with mild Alzheimer's disease (AD) dementia.
Interventions
DRUGLY3202626
Administered orally
DRUGPlacebo
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
55 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Present with mild AD dementia based on the National Institute on Aging (NIA) and the Alzheimer's Association (AA) disease diagnostic criteria as determined by a qualified clinician approved by the Sponsor or designee. * Mini-Mental State Examination score of 20 to 26 inclusive at screening visit. * Has a florbetapir PET scan consistent with the presence of amyloid pathology at screening.
Exclusion criteria
* Significant neurological disease affecting the central nervous system (CNS), other than AD, that may affect cognition or ability to complete the study, including but not limited to, other dementias, serious infection of the brain, Parkinson's disease, multiple concussions, or epilepsy or recurrent seizures (except febrile childhood seizures). * Ocular pathology that significantly limits ability to reliably evaluate vision or the retina. * Use of strong inducers of cytochrome P450 3A (CYP3A). * Sensitivity to florbetapir or ¹⁸F-AV-1451. * Contraindication to MRI or PET or poor venous access for blood draws.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in ¹⁸F-AV-1451 Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at 52 Weeks | Baseline, Week 52 | The 18F-AV-1451 PET tracer assesses change from baseline in the pharmacodynamic effect of 3 mg and 12 mg doses of LY3202626 in participants with mild Alzheimer's disease (AD), compared with placebo at Week 52.The SUVr of ¹⁸F-AV-1451 was modeled using analysis of covariance (ANCOVA) to include the fixed, categorical effects of treatment dose, and the continuous, fixed covariate of baseline Tau PET SUVr and age at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Amyloid-Related Imaging Abnormalities (ARIA) | Week 52 | Percentage of participants with presence of amyloid-related imaging abnormalities-edema (ARIA-E, also known as vasogenic edema) and percentage of an increase in amyloid-related imaging abnormalities-hemorrhage (ARIA-H, also known as also known as microhemorrhage) at Week 52 are summarized here. The mixed-effect model for repeated measures (MMRM) analysis was adjusted for fixed effects of treatment, visit (categorical covariate), treatment-by-visit interaction, baseline age, baseline score (continuous covariate) and baseline-by-visit interaction. |
| Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores | Baseline through Week 52 | The Columbia-Suicide Severity Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation is defined as a yes answer to any 1 of 5 suicidal ideation questions, which includes a wish to be dead and 4 different categories of active suicidal ideation. Suicidal behavior is defined as a yes answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation and behavior are defined as treatment-emergent (TE) if not present during the period up through randomization. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module. |
| Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve at Steady State (AUC [T,SS]) of LY3202626 | Week 2, 4, and 12: Predose and Postdose prior to departing; Week 8 and 16: Postdose after arriving and prior to departing; Week 24: Postdose after cognitive testing | PK: AUC \[T,SS\] of LY3202626 |
| Percentage of Participants With Emergent Magnetic Resonance Imaging (MRI) Findings | Week 52 | Percentage of participants with treatment-emergent MRI findings at Week 52 are summarized here. The mixed-effect model for repeated measures (MMRM) analysis was adjusted for fixed effects of treatment, visit (categorical covariate), treatment-by-visit interaction, baseline age, baseline score (continuous covariate) and baseline-by-visit interaction. |
| Change From Baseline on the 13-item Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog₁₃) | Baseline, Week 52 | The ADAS 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 that was used as the primary efficacy measure 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. A mixed model repeated measures (MMRM) was used in analysis. The model included fixed, categorical effects of treatment, visit and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline. |
| Change From Baseline on the Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living Inventory (ADCS-iADL) | Baseline, Week 52 | The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures both basic and instrumental activities (instrumental activity items 7-23) of daily living by participants. The range for the ADCS-iADL is 0-56 with higher scores reflecting better performance. ADCS-iADL was analyzed using mixed-model repeated measures (MMRM), Least Square (LS) Mean was controlled for treatment, visit, treatment-by-visit interaction, baseline age, baseline score and baseline-by-visit interaction. |
| Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) | Baseline, Week 52 | The iADRS comprises scores form the ADAS-Cog and the ADCS-iADL. The iADRS is calculated as a linear combination of the total scores of the ADAS-Cog13 9score range 0 to 85 with higher scores reflecting worse performance and the ADCS-iADL (score range 0-56 with higher scores reflecting better performance). The iADRS score ranges from 0 to 141 with lower scores indicating worse performance. iADRS was analyzed using mixed-model repeated measures (MMRM); Least Square (LS) Mean was controlled for treatment, visit, treatment-by-visit interaction, baseline age, baseline score and baseline-by-visit interaction. |
| Change From Baseline in Plasma Amyloid Beta Aβ₁-₄₀, ₁-₄₂, and 1-x Concentration | Baseline, Week 52 | A mixed model repeated measures (MMRM) analysis will be used to evaluate the change from baseline to Week 52 in plasma Aβ₁-₄₀, Aβ₁-₄₂, and Aβ 1-x. The model for the fixed effects will include terms for the following independent effects: log transformed baseline plasma Aβ, treatment, visit, treatment-by-visit interaction. |
Countries
Australia, Canada, Japan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 3 mg LY3202626 3 mg LY3202626 administered orally once daily for 52 weeks. | 55 |
| 12 mg LY3202626 12 mg LY3202626 administered orally once daily for 52 weeks. | 128 |
| Placebo Placebo administered orally once daily for 52 weeks. | 133 |
| Total | 316 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 4 | 5 |
| Overall Study | Lack of Efficacy | 0 | 1 | 0 |
| Overall Study | Progressive Disease | 1 | 0 | 0 |
| Overall Study | Site Closed by Sponsor | 1 | 1 | 3 |
| Overall Study | Study Drug Non-Compliance | 0 | 2 | 0 |
| Overall Study | Study Terminated by Sponsor | 29 | 101 | 109 |
| Overall Study | Subject Withdrew Caregiver Circumstances | 2 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 3 |
Baseline characteristics
| Characteristic | Total | Placebo | 12 mg LY3202626 | 3 mg LY3202626 |
|---|---|---|---|---|
| Age, Continuous | 72.86 years STANDARD_DEVIATION 7.36 | 72.54 years STANDARD_DEVIATION 7.8 | 72.73 years STANDARD_DEVIATION 7.15 | 73.91 years STANDARD_DEVIATION 6.72 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 7 Participants | 5 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 270 Participants | 112 Participants | 108 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 33 Participants | 14 Participants | 15 Participants | 4 Participants |
| Flortaucipir Standard Uptake Value Ratio (SUVr) | 1.38 standard uptake value ratio (SUVr) STANDARD_DEVIATION 0.31 | 1.42 standard uptake value ratio (SUVr) STANDARD_DEVIATION 0.35 | 1.36 standard uptake value ratio (SUVr) STANDARD_DEVIATION 0.28 | 1.32 standard uptake value ratio (SUVr) STANDARD_DEVIATION 0.24 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 39 Participants | 13 Participants | 18 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 4 Participants | 5 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 262 Participants | 113 Participants | 104 Participants | 45 Participants |
| Region of Enrollment Australia | 43 Participants | 15 Participants | 23 Participants | 5 Participants |
| Region of Enrollment Canada | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Japan | 37 Participants | 12 Participants | 18 Participants | 7 Participants |
| Region of Enrollment United States | 234 Participants | 105 Participants | 86 Participants | 43 Participants |
| Sex: Female, Male Female | 192 Participants | 77 Participants | 86 Participants | 29 Participants |
| Sex: Female, Male Male | 124 Participants | 56 Participants | 42 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 127 | 0 / 133 |
| other Total, other adverse events | 46 / 55 | 97 / 127 | 91 / 133 |
| serious Total, serious adverse events | 10 / 55 | 8 / 127 | 10 / 133 |
Outcome results
Primary
Change From Baseline in ¹⁸F-AV-1451 Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at 52 Weeks
The 18F-AV-1451 PET tracer assesses change from baseline in the pharmacodynamic effect of 3 mg and 12 mg doses of LY3202626 in participants with mild Alzheimer's disease (AD), compared with placebo at Week 52.The SUVr of ¹⁸F-AV-1451 was modeled using analysis of covariance (ANCOVA) to include the fixed, categorical effects of treatment dose, and the continuous, fixed covariate of baseline Tau PET SUVr and age at baseline.
Time frame: Baseline, Week 52
Population: All participants who received at least one dose of study drug, and have baseline and at least one post-baseline scan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 mg LY3202626 | Change From Baseline in ¹⁸F-AV-1451 Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at 52 Weeks | 0.02 Standard Uptake Value Ratio (SUVr) | Standard Deviation 0.04 |
| 12 mg LY3202626 | Change From Baseline in ¹⁸F-AV-1451 Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at 52 Weeks | 0.03 Standard Uptake Value Ratio (SUVr) | Standard Deviation 0.04 |
| Placebo | Change From Baseline in ¹⁸F-AV-1451 Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at 52 Weeks | 0.01 Standard Uptake Value Ratio (SUVr) | Standard Deviation 0.08 |
p-value: 0.418ANCOVA
p-value: 0.231ANCOVA
Secondary
Change From Baseline in Plasma Amyloid Beta Aβ₁-₄₀, ₁-₄₂, and 1-x Concentration
A mixed model repeated measures (MMRM) analysis will be used to evaluate the change from baseline to Week 52 in plasma Aβ₁-₄₀, Aβ₁-₄₂, and Aβ 1-x. The model for the fixed effects will include terms for the following independent effects: log transformed baseline plasma Aβ, treatment, visit, treatment-by-visit interaction.
Time frame: Baseline, Week 52
Population: All participants who received at least one dose of study drug, and have baseline and at least one post-baseline measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 3 mg LY3202626 | Change From Baseline in Plasma Amyloid Beta Aβ₁-₄₀, ₁-₄₂, and 1-x Concentration | Amyloid Beta 1-40 | -157.3 nanograms per liter (ng/L) | Standard Deviation 65.6 |
| 3 mg LY3202626 | Change From Baseline in Plasma Amyloid Beta Aβ₁-₄₀, ₁-₄₂, and 1-x Concentration | Amyloid Beta | -258.7 nanograms per liter (ng/L) | Standard Deviation 64 |
| 3 mg LY3202626 | Change From Baseline in Plasma Amyloid Beta Aβ₁-₄₀, ₁-₄₂, and 1-x Concentration | Amyloid Beta 1-42 | -46.3 nanograms per liter (ng/L) | Standard Deviation 38.7 |
| 12 mg LY3202626 | Change From Baseline in Plasma Amyloid Beta Aβ₁-₄₀, ₁-₄₂, and 1-x Concentration | Amyloid Beta 1-40 | -149.3 nanograms per liter (ng/L) | Standard Deviation 38 |
| 12 mg LY3202626 | Change From Baseline in Plasma Amyloid Beta Aβ₁-₄₀, ₁-₄₂, and 1-x Concentration | Amyloid Beta | -286.1 nanograms per liter (ng/L) | Standard Deviation 85.9 |
| 12 mg LY3202626 | Change From Baseline in Plasma Amyloid Beta Aβ₁-₄₀, ₁-₄₂, and 1-x Concentration | Amyloid Beta 1-42 | -50.0 nanograms per liter (ng/L) | Standard Deviation 34.1 |
| Placebo | Change From Baseline in Plasma Amyloid Beta Aβ₁-₄₀, ₁-₄₂, and 1-x Concentration | Amyloid Beta | -12.0 nanograms per liter (ng/L) | Standard Deviation 80.5 |
| Placebo | Change From Baseline in Plasma Amyloid Beta Aβ₁-₄₀, ₁-₄₂, and 1-x Concentration | Amyloid Beta 1-42 | 0.0 nanograms per liter (ng/L) | Standard Deviation 5.8 |
| Placebo | Change From Baseline in Plasma Amyloid Beta Aβ₁-₄₀, ₁-₄₂, and 1-x Concentration | Amyloid Beta 1-40 | -17.0 nanograms per liter (ng/L) | Standard Deviation 38.2 |
Comparison: Amyloid Beta 1-42p-value: <0.001ANCOVA
Comparison: Amyloid Beta 1-42p-value: <0.001ANCOVA
Comparison: Amyloid Betap-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Comparison: Amyloid Beta 1-40p-value: <0.001ANCOVA
Comparison: Amyloid Beta 1-40p-value: <0.001ANCOVA
Secondary
Change From Baseline on the 13-item Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog₁₃)
The ADAS 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 that was used as the primary efficacy measure 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. A mixed model repeated measures (MMRM) was used in analysis. The model included fixed, categorical effects of treatment, visit and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.
Time frame: Baseline, Week 52
Population: All participants who received at least one dose of study drug, and have baseline and at least one post-baseline ADAS-Cog₁₃ measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 3 mg LY3202626 | Change From Baseline on the 13-item Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog₁₃) | 3.05 units on a scale | Standard Error 1.4 |
| 12 mg LY3202626 | Change From Baseline on the 13-item Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog₁₃) | 1.88 units on a scale | Standard Error 1.33 |
| Placebo | Change From Baseline on the 13-item Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog₁₃) | 2.97 units on a scale | Standard Error 1.51 |
p-value: 0.97Mixed Model Repeated Measures
p-value: 0.586Mixed Model Repeated Meausres
Secondary
Change From Baseline on the Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living Inventory (ADCS-iADL)
The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures both basic and instrumental activities (instrumental activity items 7-23) of daily living by participants. The range for the ADCS-iADL is 0-56 with higher scores reflecting better performance. ADCS-iADL was analyzed using mixed-model repeated measures (MMRM), Least Square (LS) Mean was controlled for treatment, visit, treatment-by-visit interaction, baseline age, baseline score and baseline-by-visit interaction.
Time frame: Baseline, Week 52
Population: All participants who received at least one dose of study drug, and have baseline and at least one post-baseline ADCS-iADL measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 3 mg LY3202626 | Change From Baseline on the Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living Inventory (ADCS-iADL) | -3.97 units on a scale | Standard Error 1.34 |
| 12 mg LY3202626 | Change From Baseline on the Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living Inventory (ADCS-iADL) | -4.63 units on a scale | Standard Error 1.24 |
| Placebo | Change From Baseline on the Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living Inventory (ADCS-iADL) | -7.32 units on a scale | Standard Error 1.38 |
p-value: 0.088ANCOVA
p-value: 0.15ANCOVA
Secondary
Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS)
The iADRS comprises scores form the ADAS-Cog and the ADCS-iADL. The iADRS is calculated as a linear combination of the total scores of the ADAS-Cog13 9score range 0 to 85 with higher scores reflecting worse performance and the ADCS-iADL (score range 0-56 with higher scores reflecting better performance). The iADRS score ranges from 0 to 141 with lower scores indicating worse performance. iADRS was analyzed using mixed-model repeated measures (MMRM); Least Square (LS) Mean was controlled for treatment, visit, treatment-by-visit interaction, baseline age, baseline score and baseline-by-visit interaction.
Time frame: Baseline, Week 52
Population: All participants who received at least one dose of study drug, and have baseline and at least one post-baseline iADRS measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 3 mg LY3202626 | Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) | -6.01 units on a scale | Standard Error 2.07 |
| 12 mg LY3202626 | Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) | -6.45 units on a scale | Standard Error 1.9 |
| Placebo | Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) | -10.32 units on a scale | Standard Error 2.15 |
p-value: 0.153ANCOVA
p-value: 0.176ANCOVA
Secondary
Percentage of Participants With Amyloid-Related Imaging Abnormalities (ARIA)
Percentage of participants with presence of amyloid-related imaging abnormalities-edema (ARIA-E, also known as vasogenic edema) and percentage of an increase in amyloid-related imaging abnormalities-hemorrhage (ARIA-H, also known as also known as microhemorrhage) at Week 52 are summarized here. The mixed-effect model for repeated measures (MMRM) analysis was adjusted for fixed effects of treatment, visit (categorical covariate), treatment-by-visit interaction, baseline age, baseline score (continuous covariate) and baseline-by-visit interaction.
Time frame: Week 52
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 3 mg LY3202626 | Percentage of Participants With Amyloid-Related Imaging Abnormalities (ARIA) | Presence of Vasogenic Edema | 0.0 percentage of participants |
| 3 mg LY3202626 | Percentage of Participants With Amyloid-Related Imaging Abnormalities (ARIA) | Increase in Microhemorrhages | 4.7 percentage of participants |
| 12 mg LY3202626 | Percentage of Participants With Amyloid-Related Imaging Abnormalities (ARIA) | Presence of Vasogenic Edema | 0.0 percentage of participants |
| 12 mg LY3202626 | Percentage of Participants With Amyloid-Related Imaging Abnormalities (ARIA) | Increase in Microhemorrhages | 6.3 percentage of participants |
| Placebo | Percentage of Participants With Amyloid-Related Imaging Abnormalities (ARIA) | Presence of Vasogenic Edema | 1.6 percentage of participants |
| Placebo | Percentage of Participants With Amyloid-Related Imaging Abnormalities (ARIA) | Increase in Microhemorrhages | 7.5 percentage of participants |
Comparison: Vasogenic Edemap-value: 1Fisher Exact
Comparison: Vasogenic Edemap-value: 0.457Fisher Exact
Comparison: Increase in Microhemorrhagep-value: 0.703Fisher Exact
Comparison: Increase in Microhemorrhagep-value: 1Fisher Exact
Secondary
Percentage of Participants With Emergent Magnetic Resonance Imaging (MRI) Findings
Percentage of participants with treatment-emergent MRI findings at Week 52 are summarized here. The mixed-effect model for repeated measures (MMRM) analysis was adjusted for fixed effects of treatment, visit (categorical covariate), treatment-by-visit interaction, baseline age, baseline score (continuous covariate) and baseline-by-visit interaction.
Time frame: Week 52
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 3 mg LY3202626 | Percentage of Participants With Emergent Magnetic Resonance Imaging (MRI) Findings | Lacunar Infarct | 0.0 percentage of participants |
| 3 mg LY3202626 | Percentage of Participants With Emergent Magnetic Resonance Imaging (MRI) Findings | Cortical Superficial Siderous | 0.0 percentage of participants |
| 3 mg LY3202626 | Percentage of Participants With Emergent Magnetic Resonance Imaging (MRI) Findings | White Matter Disease | 2.4 percentage of participants |
| 3 mg LY3202626 | Percentage of Participants With Emergent Magnetic Resonance Imaging (MRI) Findings | Cortical Infarct | 2.4 percentage of participants |
| 3 mg LY3202626 | Percentage of Participants With Emergent Magnetic Resonance Imaging (MRI) Findings | Other Infarct | 0.0 percentage of participants |
| 12 mg LY3202626 | Percentage of Participants With Emergent Magnetic Resonance Imaging (MRI) Findings | Cortical Superficial Siderous | 1.3 percentage of participants |
| 12 mg LY3202626 | Percentage of Participants With Emergent Magnetic Resonance Imaging (MRI) Findings | White Matter Disease | 1.3 percentage of participants |
| 12 mg LY3202626 | Percentage of Participants With Emergent Magnetic Resonance Imaging (MRI) Findings | Cortical Infarct | 0.0 percentage of participants |
| 12 mg LY3202626 | Percentage of Participants With Emergent Magnetic Resonance Imaging (MRI) Findings | Lacunar Infarct | 0.0 percentage of participants |
| 12 mg LY3202626 | Percentage of Participants With Emergent Magnetic Resonance Imaging (MRI) Findings | Other Infarct | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Emergent Magnetic Resonance Imaging (MRI) Findings | Other Infarct | 1.6 percentage of participants |
| Placebo | Percentage of Participants With Emergent Magnetic Resonance Imaging (MRI) Findings | Lacunar Infarct | 1.6 percentage of participants |
| Placebo | Percentage of Participants With Emergent Magnetic Resonance Imaging (MRI) Findings | White Matter Disease | 1.6 percentage of participants |
| Placebo | Percentage of Participants With Emergent Magnetic Resonance Imaging (MRI) Findings | Cortical Superficial Siderous | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Emergent Magnetic Resonance Imaging (MRI) Findings | Cortical Infarct | 0.0 percentage of participants |
Comparison: White Matter Diseasep-value: 1Fisher Exact
Comparison: White Matter Diseasep-value: 1Fisher Exact
p-value: 0.404Fisher Exact
Comparison: Cortical Superficial Siderousp-value: 1Fisher Exact
p-value: 1Fisher Exact
Comparison: Lacunar Infarctp-value: 0.457Fisher Exact
Comparison: Other Infarctp-value: 1Fisher Exact
Comparison: Other Infarctp-value: 0.457Fisher Exact
Secondary
Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores
The Columbia-Suicide Severity Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation is defined as a yes answer to any 1 of 5 suicidal ideation questions, which includes a wish to be dead and 4 different categories of active suicidal ideation. Suicidal behavior is defined as a yes answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation and behavior are defined as treatment-emergent (TE) if not present during the period up through randomization. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module.
Time frame: Baseline through Week 52
Population: All participants who received at least one dose of study drug and had at least one post-baseline C-SSRS measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 3 mg LY3202626 | Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores | TE Suicidal Behavior | 1.82 percentage of participants |
| 3 mg LY3202626 | Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores | TE Suicidal Ideation | 7.27 percentage of participants |
| 12 mg LY3202626 | Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores | TE Suicidal Ideation | 7.09 percentage of participants |
| 12 mg LY3202626 | Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores | TE Suicidal Behavior | 0.79 percentage of participants |
| Placebo | Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores | TE Suicidal Behavior | 0.00 percentage of participants |
| Placebo | Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores | TE Suicidal Ideation | 3.76 percentage of participants |
Comparison: Treatment Emergent Suicidal Ideationp-value: 0.452Fisher Exact
p-value: 0.279Fisher Exact
Comparison: Emergence of Suicidal Behaviorp-value: 0.293Fisher Exact
Comparison: Emergence of Suicidal Behaviorp-value: 0.486Fisher Exact
Secondary
Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve at Steady State (AUC [T,SS]) of LY3202626
PK: AUC \[T,SS\] of LY3202626
Time frame: Week 2, 4, and 12: Predose and Postdose prior to departing; Week 8 and 16: Postdose after arriving and prior to departing; Week 24: Postdose after cognitive testing
Population: All participants who received at least one dose of study drug and have evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 3 mg LY3202626 | Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve at Steady State (AUC [T,SS]) of LY3202626 | 158 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 55.1 |
| 12 mg LY3202626 | Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve at Steady State (AUC [T,SS]) of LY3202626 | 641 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 58 |