Alzheimer's Disease
Conditions
Keywords
beta-secretase inhibitor
Brief summary
The purpose of this Phase 1/Phase 2 study is to evaluate how the body handles the drug and the drug's effect on the body of participants with mild cognitive impairment (MCI) due to Alzheimer's Disease (AD) or mild AD and who test positive for amyloid plaque.
Interventions
DRUGLY2886721
DRUGPlacebo
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Meets criteria for MCI due to AD or Mild AD All participants will be required to undergo assessment via the Mini Mental State Examination (MMSE) scale at screening * Participants with MMSE scores of 20 to 26, inclusive, may be enrolled provided they meet the criteria for mild AD, as follows: * Participant meets the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable AD * Clinical Dementia Rating Scale (CDR) score of 0.5 or 1 * Positive scan for the presence of amyloid beta * Participants with MMSE of 27 to 30, inclusive, may be enrolled as participants with MCI due to AD provided they meet the following criteria: * Gradual and progressive change in memory function as reported by the participant or a caregiver during a period of more than 6 months * Free and Cued Selective Reminding Test with Immediate Recall (FCSRT-IR): free recall ≤22 and total recall ≤46 * Absence of dementia * Preservation of functional independence * Exclusion of other potential (vascular, traumatic, or medical) causes of cognitive decline, where possible * Positive scan for the presence of amyloid beta * Women must be postmenopausal * Men are required to use an approved barrier method of contraception if their partners are pregnant, or of childbearing potential and not using approved contraceptive methods
Exclusion criteria
* Participant in another drug or device study * Have a history of frontotemporal dementia, Lewy body disease, vascular dementia, Huntington's disease, Parkinson's disease, progressive supranuclear palsy (PSNP), or other movement disorder * Participants are not on a stable standard of care (acetylcholinesterase inhibitors, memantine) initiated less than 2 months prior to entry or have less than 4 weeks of stable therapy. Note: Stable standard of care is allowed. * Have had a serious infectious disease affecting the brain in the past 5 years * Have had a serious or repeat head injury * Have significant retinal impairment or disease * Have had a stroke or other circulation problems that are affecting current health * Have had a seizure * Have major depressive disorder and are not on a stable dose of medication. Participants who no longer meet the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (DSM-IV) criteria for major depression may be included * History of schizophrenia, bipolar disorder, or severe mental illness * History of alcohol or drug abuse * Have asthma, chronic obstructive pulmonary disease (COPD), or other breathing disease that is not controlled with medicine * Have human immunodeficiency virus (HIV) or syphilis * Are taking blood thinners
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 12 Weeks in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations | Baseline, 12 weeks | Percent change in lumbar CSF concentrations of Aβ1-40 and Aβ1-42 from baseline at 12 weeks post-dose was calculated. The units for CSF were picograms per milliliter (pg/mL). Least Squares (LS) means of percent change in concentration from baseline was calculated using analysis of covariance (ANCOVA) with baseline as a covariate and treatment as a fixed effect. |
| Change From Baseline to 26 Weeks in CSF Aβ1-40 and Aβ1-42 Concentrations | Baseline, 26 weeks | Percent change in lumbar CSF concentrations of Aβ1-40 and Aβ1-42 from baseline at 26 weeks post-dose was to be calculated. The units for CSF were picograms per milliliter (pg/mL). LS means of percent change in concentration from baseline was calculated using ANCOVA with baseline as a covariate and treatment as a fixed effect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 26 Weeks in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) | Baseline, 26 weeks | ADAS-Cog11 is an 11-item instrument measuring impairment in memory (Items 1-4, 7, 11), praxis (Items 4 and 5), orientation (Item 6), and language (Items 8-10). Item 1 ranged 0 (all items recalled correctly)-10 (none recalled correctly); Items 2-5 and 8-11 ranged 0 (all items named, performed, drawn, spoken, remember correctly/clearly)-5 (none correct/not clearly spoken); Item 6 ranged 0 (no incorrect responses)-8 (all incorrect); and Item 7 ranged 0 (all words remembered correctly)-12 (no words remembered correctly) for a total ADAS-Cog11 score of 0-70 with higher scores indicating greater disease severity. A score of 0-10 for delayed free recall and a conversion code of 0-5 for digit cancellation and maze completion was added to the total ADAS-Cog11 score for a total ADAS-Cog14 score ranging 0-90 with higher scores indicating greater impairment. LS means were calculated using Mixed Model Repeated Measures (MMRM) with Treatment + Visit + Treatment\*Visit + Baseline + Baseline\*Visit. |
| Change From Baseline to 26 Weeks in the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) | Baseline, 26 weeks | The CDR-SB is a composite measure of 6 domains of cognitive and functional performance: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Scores ranged from 0 to 18, with higher scores indicating greater impairment. LS means were calculated using MMRM with Treatment + Visit + Treatment\*Visit + Baseline + Baseline\*Visit. |
| Change From Baseline in Plasma Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations | Baseline, 12 weeks, 26 weeks | Percent change in plasma concentrations of Aβ1-40 and Aβ1-42 from baseline at 12 weeks and 26 weeks post-dose was calculated. The units for CSF were picograms per milliliter (pg/mL). |
| Change From Baseline in Cerebrospinal Fluid (CSF) Tau and Phosphorylated Tau (Ptau)-181 Concentrations | Baseline, 12 weeks, 26 weeks | Percent change in lumbar CSF tau and ptau-181 concentrations from baseline at 12 weeks post-dose and 26 weeks post-dose was calculated. The units for CSF were picograms per milliliter (pg/mL). Least Squares (LS) means of percent change in concentration from baseline was calculated using analysis of covariance (ANCOVA) with baseline as a covariate and treatment as a fixed effect. |
| Change From Baseline to 26 Weeks in Mini Mental State Examination (MMSE) | Baseline, 26 weeks | The MMSE (Folstein et al. 1975) is one of the most widely used screening instruments for cognitive impairment. The test consists of five sections (orientation, registration, attention-calculation, recall, and language) and provides a total score ranging from 0 to 30, with lower scores indicative of greater cognitive impairment. LS means were calculated using MMRM with Treatment + Visit + Treatment\*Visit + Baseline + Baseline\*Visit. |
| Change From Baseline to 26 Weeks in Neuropsychological Test Battery (NTB) | Baseline, 26 weeks | The NTB is a composite cognitive measure in clinical Alzheimer's disease studies and is a collection of several written and oral tests that examines verbal and nonverbal brain functions. NTB Z-score typically ranges from -3 to 3, with lower scores suggesting greater cognitive impairment. LS means were calculated using ANCOVA with baseline as a covariate and treatment as a fixed effect. |
Countries
Italy, Japan, Netherlands, Spain, United States
Participant flow
Pre-assignment details
As a result of findings from the I4O-MC-BACJ study (NCT01534273), enrollment was discontinued to the 15 milligrams (mg) arm. The 9 participants already enrolled were allowed to continue study treatment at the 15 mg dose.
Participants by arm
| Arm | Count |
|---|---|
| 15 mg LY2886721 LY2886721: 15 milligrams (mg), capsules, administered orally, once daily for 26 weeks. | 9 |
| 35 mg LY2886721 LY2886721: 35 mg, capsules, administered orally, once daily for 26 weeks. | 23 |
| 70 mg LY2886721 LY2886721: 70 mg, capsules, administered orally, once daily for 26 weeks. | 18 |
| Placebo Placebo: 1 placebo capsule, administered orally, once daily for 26 weeks. | 20 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 3 | 1 |
| Overall Study | Physician Decision | 0 | 1 | 0 | 0 |
| Overall Study | Sponsor Decision | 1 | 14 | 13 | 12 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | 15 mg LY2886721 | 35 mg LY2886721 | 70 mg LY2886721 | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 65.59 years STANDARD_DEVIATION 7.569 | 72.50 years STANDARD_DEVIATION 8.378 | 70.23 years STANDARD_DEVIATION 8.603 | 67.73 years STANDARD_DEVIATION 7.126 | 69.66 years STANDARD_DEVIATION 8.201 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 3 Participants | 3 Participants | 0 Participants | 6 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 9 Participants | 20 Participants | 15 Participants | 20 Participants | 64 Participants |
| Region of Enrollment Japan | 0 Participants | 3 Participants | 2 Participants | 0 Participants | 5 Participants |
| Region of Enrollment Netherlands | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 5 Participants |
| Region of Enrollment United States | 8 Participants | 19 Participants | 15 Participants | 18 Participants | 60 Participants |
| Sex: Female, Male Female | 5 Participants | 10 Participants | 7 Participants | 11 Participants | 33 Participants |
| Sex: Female, Male Male | 4 Participants | 13 Participants | 11 Participants | 9 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 9 | 13 / 23 | 16 / 18 | 15 / 20 |
| serious Total, serious adverse events | 1 / 9 | 2 / 23 | 0 / 18 | 0 / 20 |
Outcome results
Primary
Change From Baseline to 12 Weeks in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations
Percent change in lumbar CSF concentrations of Aβ1-40 and Aβ1-42 from baseline at 12 weeks post-dose was calculated. The units for CSF were picograms per milliliter (pg/mL). Least Squares (LS) means of percent change in concentration from baseline was calculated using analysis of covariance (ANCOVA) with baseline as a covariate and treatment as a fixed effect.
Time frame: Baseline, 12 weeks
Population: All randomized participants with evaluable post-baseline CSF Aβ1-40 or Aβ1-42 data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 15 mg LY2886721 | Change From Baseline to 12 Weeks in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations | Aβ1-40 | -31.8 percent change in Aβ1-40 and Aβ1-42 | Standard Error 7.35 |
| 15 mg LY2886721 | Change From Baseline to 12 Weeks in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations | Aβ1-42 | -34.4 percent change in Aβ1-40 and Aβ1-42 | Standard Error 7.27 |
| 35 mg LY2886721 | Change From Baseline to 12 Weeks in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations | Aβ1-42 | -52.0 percent change in Aβ1-40 and Aβ1-42 | Standard Error 6.8 |
| 35 mg LY2886721 | Change From Baseline to 12 Weeks in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations | Aβ1-40 | -57.7 percent change in Aβ1-40 and Aβ1-42 | Standard Error 6.67 |
| 70 mg LY2886721 | Change From Baseline to 12 Weeks in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations | Aβ1-40 | -58.9 percent change in Aβ1-40 and Aβ1-42 | Standard Error 8.73 |
| 70 mg LY2886721 | Change From Baseline to 12 Weeks in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations | Aβ1-42 | -60.7 percent change in Aβ1-40 and Aβ1-42 | Standard Error 8.42 |
| Placebo | Change From Baseline to 12 Weeks in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations | Aβ1-40 | 3.7 percent change in Aβ1-40 and Aβ1-42 | Standard Error 5.96 |
| Placebo | Change From Baseline to 12 Weeks in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations | Aβ1-42 | 6.5 percent change in Aβ1-40 and Aβ1-42 | Standard Error 6.06 |
Primary
Change From Baseline to 26 Weeks in CSF Aβ1-40 and Aβ1-42 Concentrations
Percent change in lumbar CSF concentrations of Aβ1-40 and Aβ1-42 from baseline at 26 weeks post-dose was to be calculated. The units for CSF were picograms per milliliter (pg/mL). LS means of percent change in concentration from baseline was calculated using ANCOVA with baseline as a covariate and treatment as a fixed effect.
Time frame: Baseline, 26 weeks
Population: Zero participants analyzed. CSF Aβ1-40 and Aβ1-42 concentrations data was not collected for analysis at 26 weeks.
Secondary
Change From Baseline in Cerebrospinal Fluid (CSF) Tau and Phosphorylated Tau (Ptau)-181 Concentrations
Percent change in lumbar CSF tau and ptau-181 concentrations from baseline at 12 weeks post-dose and 26 weeks post-dose was calculated. The units for CSF were picograms per milliliter (pg/mL). Least Squares (LS) means of percent change in concentration from baseline was calculated using analysis of covariance (ANCOVA) with baseline as a covariate and treatment as a fixed effect.
Time frame: Baseline, 12 weeks, 26 weeks
Population: All randomized participants at 12 weeks with evaluable post-baseline CSF Tau or Ptau data.~Zero participants analyzed for 26 week CSF Tau or Ptau as data was not collected for analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 15 mg LY2886721 | Change From Baseline in Cerebrospinal Fluid (CSF) Tau and Phosphorylated Tau (Ptau)-181 Concentrations | CSF Tau, Week 12 | 14.3 percent change in tau and ptau-181 | Standard Error 6.06 |
| 15 mg LY2886721 | Change From Baseline in Cerebrospinal Fluid (CSF) Tau and Phosphorylated Tau (Ptau)-181 Concentrations | CSF Ptau, Week 12 | 0.7 percent change in tau and ptau-181 | Standard Error 4.81 |
| 35 mg LY2886721 | Change From Baseline in Cerebrospinal Fluid (CSF) Tau and Phosphorylated Tau (Ptau)-181 Concentrations | CSF Ptau, Week 12 | 1.7 percent change in tau and ptau-181 | Standard Error 4.01 |
| 35 mg LY2886721 | Change From Baseline in Cerebrospinal Fluid (CSF) Tau and Phosphorylated Tau (Ptau)-181 Concentrations | CSF Tau, Week 12 | 2.6 percent change in tau and ptau-181 | Standard Error 5.42 |
| 70 mg LY2886721 | Change From Baseline in Cerebrospinal Fluid (CSF) Tau and Phosphorylated Tau (Ptau)-181 Concentrations | CSF Tau, Week 12 | 6.8 percent change in tau and ptau-181 | Standard Error 7.49 |
| 70 mg LY2886721 | Change From Baseline in Cerebrospinal Fluid (CSF) Tau and Phosphorylated Tau (Ptau)-181 Concentrations | CSF Ptau, Week 12 | 4.3 percent change in tau and ptau-181 | Standard Error 5.41 |
| Placebo | Change From Baseline in Cerebrospinal Fluid (CSF) Tau and Phosphorylated Tau (Ptau)-181 Concentrations | CSF Tau, Week 12 | -4.4 percent change in tau and ptau-181 | Standard Error 4.63 |
| Placebo | Change From Baseline in Cerebrospinal Fluid (CSF) Tau and Phosphorylated Tau (Ptau)-181 Concentrations | CSF Ptau, Week 12 | -3.6 percent change in tau and ptau-181 | Standard Error 3.4 |
Secondary
Change From Baseline in Plasma Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations
Percent change in plasma concentrations of Aβ1-40 and Aβ1-42 from baseline at 12 weeks and 26 weeks post-dose was calculated. The units for CSF were picograms per milliliter (pg/mL).
Time frame: Baseline, 12 weeks, 26 weeks
Population: All randomized participants with evaluable post-baseline CSF Aβ1-40 or Aβ1-42 data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 mg LY2886721 | Change From Baseline in Plasma Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations | Aβ1-40, Week 12 | -73.4 percent change in Aβ1-40 and Aβ1-42 | Standard Deviation 6.22 |
| 15 mg LY2886721 | Change From Baseline in Plasma Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations | Aβ1-40, Week 26 | -72.3 percent change in Aβ1-40 and Aβ1-42 | Standard Deviation 11.5 |
| 15 mg LY2886721 | Change From Baseline in Plasma Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations | Aβ1-42, Week 12 | -63.4 percent change in Aβ1-40 and Aβ1-42 | Standard Deviation 6.11 |
| 15 mg LY2886721 | Change From Baseline in Plasma Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations | Aβ1-42, Week 26 | -65.1 percent change in Aβ1-40 and Aβ1-42 | Standard Deviation 8.85 |
| 35 mg LY2886721 | Change From Baseline in Plasma Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations | Aβ1-40, Week 26 | -85.0 percent change in Aβ1-40 and Aβ1-42 | Standard Deviation 3.89 |
| 35 mg LY2886721 | Change From Baseline in Plasma Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations | Aβ1-42, Week 12 | -71.1 percent change in Aβ1-40 and Aβ1-42 | Standard Deviation 8.38 |
| 35 mg LY2886721 | Change From Baseline in Plasma Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations | Aβ1-42, Week 26 | -75.0 percent change in Aβ1-40 and Aβ1-42 | Standard Deviation 4.33 |
| 35 mg LY2886721 | Change From Baseline in Plasma Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations | Aβ1-40, Week 12 | -80.8 percent change in Aβ1-40 and Aβ1-42 | Standard Deviation 8.07 |
| 70 mg LY2886721 | Change From Baseline in Plasma Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations | Aβ1-42, Week 12 | -78.2 percent change in Aβ1-40 and Aβ1-42 | Standard Deviation 5.08 |
| 70 mg LY2886721 | Change From Baseline in Plasma Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations | Aβ1-40, Week 26 | -89.1 percent change in Aβ1-40 and Aβ1-42 | — |
| 70 mg LY2886721 | Change From Baseline in Plasma Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations | Aβ1-42, Week 26 | -80.8 percent change in Aβ1-40 and Aβ1-42 | — |
| 70 mg LY2886721 | Change From Baseline in Plasma Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations | Aβ1-40, Week 12 | -88.1 percent change in Aβ1-40 and Aβ1-42 | Standard Deviation 2.66 |
| Placebo | Change From Baseline in Plasma Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations | Aβ1-42, Week 26 | 1.82 percent change in Aβ1-40 and Aβ1-42 | Standard Deviation 9.98 |
| Placebo | Change From Baseline in Plasma Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations | Aβ1-40, Week 26 | 0.944 percent change in Aβ1-40 and Aβ1-42 | Standard Deviation 22.6 |
| Placebo | Change From Baseline in Plasma Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations | Aβ1-40, Week 12 | 1.90 percent change in Aβ1-40 and Aβ1-42 | Standard Deviation 15 |
| Placebo | Change From Baseline in Plasma Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations | Aβ1-42, Week 12 | 0.541 percent change in Aβ1-40 and Aβ1-42 | Standard Deviation 10.1 |
Secondary
Change From Baseline to 26 Weeks in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog)
ADAS-Cog11 is an 11-item instrument measuring impairment in memory (Items 1-4, 7, 11), praxis (Items 4 and 5), orientation (Item 6), and language (Items 8-10). Item 1 ranged 0 (all items recalled correctly)-10 (none recalled correctly); Items 2-5 and 8-11 ranged 0 (all items named, performed, drawn, spoken, remember correctly/clearly)-5 (none correct/not clearly spoken); Item 6 ranged 0 (no incorrect responses)-8 (all incorrect); and Item 7 ranged 0 (all words remembered correctly)-12 (no words remembered correctly) for a total ADAS-Cog11 score of 0-70 with higher scores indicating greater disease severity. A score of 0-10 for delayed free recall and a conversion code of 0-5 for digit cancellation and maze completion was added to the total ADAS-Cog11 score for a total ADAS-Cog14 score ranging 0-90 with higher scores indicating greater impairment. LS means were calculated using Mixed Model Repeated Measures (MMRM) with Treatment + Visit + Treatment\*Visit + Baseline + Baseline\*Visit.
Time frame: Baseline, 26 weeks
Population: All randomized participants with evaluable ADAS-Cog data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 15 mg LY2886721 | Change From Baseline to 26 Weeks in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) | 1.1 units on a scale | Standard Error 2.77 |
| 35 mg LY2886721 | Change From Baseline to 26 Weeks in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) | 0.6 units on a scale | Standard Error 2.48 |
| 70 mg LY2886721 | Change From Baseline to 26 Weeks in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) | 0.6 units on a scale | Standard Error 7.41 |
| Placebo | Change From Baseline to 26 Weeks in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) | 1.3 units on a scale | Standard Error 2.44 |
Secondary
Change From Baseline to 26 Weeks in Mini Mental State Examination (MMSE)
The MMSE (Folstein et al. 1975) is one of the most widely used screening instruments for cognitive impairment. The test consists of five sections (orientation, registration, attention-calculation, recall, and language) and provides a total score ranging from 0 to 30, with lower scores indicative of greater cognitive impairment. LS means were calculated using MMRM with Treatment + Visit + Treatment\*Visit + Baseline + Baseline\*Visit.
Time frame: Baseline, 26 weeks
Population: All randomized participants with evaluable MMSE data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 15 mg LY2886721 | Change From Baseline to 26 Weeks in Mini Mental State Examination (MMSE) | -0.7 units on a scale | Standard Error 0.87 |
| 35 mg LY2886721 | Change From Baseline to 26 Weeks in Mini Mental State Examination (MMSE) | -1.8 units on a scale | Standard Error 0.81 |
| 70 mg LY2886721 | Change From Baseline to 26 Weeks in Mini Mental State Examination (MMSE) | 0.2 units on a scale | Standard Error 2.41 |
| Placebo | Change From Baseline to 26 Weeks in Mini Mental State Examination (MMSE) | -3.0 units on a scale | Standard Error 0.77 |
Secondary
Change From Baseline to 26 Weeks in Neuropsychological Test Battery (NTB)
The NTB is a composite cognitive measure in clinical Alzheimer's disease studies and is a collection of several written and oral tests that examines verbal and nonverbal brain functions. NTB Z-score typically ranges from -3 to 3, with lower scores suggesting greater cognitive impairment. LS means were calculated using ANCOVA with baseline as a covariate and treatment as a fixed effect.
Time frame: Baseline, 26 weeks
Population: All randomized participants with evaluable NTB data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 15 mg LY2886721 | Change From Baseline to 26 Weeks in Neuropsychological Test Battery (NTB) | -0.039 units on a scale | Standard Error 0.1096 |
| 35 mg LY2886721 | Change From Baseline to 26 Weeks in Neuropsychological Test Battery (NTB) | -0.161 units on a scale | Standard Error 0.1165 |
| 70 mg LY2886721 | Change From Baseline to 26 Weeks in Neuropsychological Test Battery (NTB) | 0.424 units on a scale | Standard Error 0.3156 |
| Placebo | Change From Baseline to 26 Weeks in Neuropsychological Test Battery (NTB) | -0.262 units on a scale | Standard Error 0.1028 |
Secondary
Change From Baseline to 26 Weeks in the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB)
The CDR-SB is a composite measure of 6 domains of cognitive and functional performance: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Scores ranged from 0 to 18, with higher scores indicating greater impairment. LS means were calculated using MMRM with Treatment + Visit + Treatment\*Visit + Baseline + Baseline\*Visit.
Time frame: Baseline, 26 weeks
Population: All randomized participants with evaluable CDR-SB data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 15 mg LY2886721 | Change From Baseline to 26 Weeks in the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) | 0.80 units on a scale | Standard Error 0.432 |
| 35 mg LY2886721 | Change From Baseline to 26 Weeks in the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) | 0.52 units on a scale | Standard Error 0.395 |
| 70 mg LY2886721 | Change From Baseline to 26 Weeks in the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) | 1.50 units on a scale | Standard Error 1.013 |
| Placebo | Change From Baseline to 26 Weeks in the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) | 1.19 units on a scale | Standard Error 0.402 |