Alzheimer's Disease
Conditions
Brief summary
The primary objective of the original study was to assess the safety of semagacestat in Alzheimer's disease (AD) patients during 24 months of open-label treatment. Baseline for the efficacy measures is defined as the baseline for feeder studies LFAN (NCT00594568) and LFBC (NCT00762411). For all safety analyses (adverse events), baseline for patients will be week 0 of this study (LFBF). Preliminary results from LFAN and LFBC showed semagacestat did not slow disease progression and was associated with worsening of clinical measures of cognition and the ability to perform activities of daily living. Study drug was stopped in all studies. Studies LFAN, LFBC and LFBF have been amended to continue collecting safety data, including cognitive scores, for at least seven months. The CT-Registry will reflect results of analyses from the original protocol in addition to those from the amended protocol. Very few participants from LFBC rolled over into LFBF (N = 9). Due to insufficient sample size, the data for LFBC participants who rolled into LFBF were not analyzed.
Interventions
DRUGsemagacestat
140mg administered orally, once daily for 24 months; dose reduction to 100mg or 60 mg possible due to intolerability
Sponsors
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Meets National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable Alzheimer's Disease * Completed semagacestat study LFAN or study LFBC through 88 weeks * Must continue to have a reliable caregiver * Capable of swallowing whole oral medication * Agrees not to participate in other investigational compounds for the duration of study
Exclusion criteria
* Meets LFAN or LFBC study discontinuation criteria at the last visit of the LFAN or LFBC study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog11) at Week 16 After Cessation of Study Drug | Baseline (LFAN randomization), 16 weeks (LFBF) after cessation of study drug | The cognitive subscale of the ADAS (ADAS-Cog11) consists of 11 items assessing areas of function most typically impaired in Alzheimer's Disease (AD): orientation, verbal memory, language, and praxis. The scale ranges from 0 to 70, with higher scores indicating greater disease severity. |
| Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at Week 16 After Cessation of Study Drug | Baseline (LFAN randomization), 16 weeks (LFBF) after cessation of study drug | The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. It measures both basic and instrumental activities of daily living. The total score ranges from 0 to 78, with lower scores indicating greater disease severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Amyloid Imaging Positron Emission Tomography (AV-45-PET) at Week 12 | Baseline (LFAN Randomization), 12 weeks (LFBF) | A radioactive tracer for PET that is a ligand for amyloid called \[18F\]-AV-45. This permits the visualization of amyloid in the brains of Alzheimer's participants. The outcome reported is the composite summary of the standard uptake value ratio for the cerebellar gray matter. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator. Due to insufficient sample size, this analysis was not done. |
| Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog11) at Week 12 | Baseline (LFAN Randomization), 12 weeks (LFBF) | The cognitive subscale of the ADAS (ADAS-Cog11) consists of 11 items assessing areas of function most typically impaired in Alzheimer's Disease (AD): orientation, verbal memory, language, and praxis. The scale ranges from 0 to 70, with higher scores indicating greater disease severity. Least Square (LS) Mean value was controlled for baseline value, age, investigator, and concomitant standard of care (SOC) medication. |
| Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12) at Week 12 | Baseline (LFAN Randomization), 12 weeks (LFBF) | ADAS-Cog12 is the ADAS-Cog11 augmented with the delayed free recall measure, resulting in a total score ranging from 0 to 80. Higher scores indicate greater disease severity. Least Square (LS) Mean value was controlled for baseline value, age, investigator, and concomitant standard of care (SOC) medication. |
| Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog14) at Week 12 | Baseline (LFAN Randomization), 12 weeks (LFBF) | The ADAS-Cog14 is the ADAS-Cog11 augmented with delayed free recall, digit cancellation, and maze completion measures. A score of 0 to 10 for delayed free recall and a conversion code of 0 to 5 for digit cancellation and maze completion provide total score ranges for this extended ADAS-Cog14 of 0 to 90. Higher scores indicate greater disease severity. Least Square (LS) Mean value was controlled for the baseline value, age, investigator, and concomitant standard of care (SOC) medication. |
| Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at Week 12 | Baseline (LFAN Randomization), 12 weeks (LFBF) | The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. It measures both basic and instrumental activities of daily living. The total score ranges from 0 to 78, with lower scores indicating greater disease severity. Least Square (LS) Mean value was controlled for baseline value, age, investigator, and concomitant standard of care (SOC) medication. |
| Mean Concentration of LY450139 | 3 months (pre-dose, 2, 4, and 6 hours after dosing )(LFBF) | — |
| Percent Change From Baseline in Amyloid Beta (Aβ) 1-42 Plasma Concentration at Week 12 | Baseline (LFAN Randomization ), 6 hours pose-dose at Week 12 (LFBF) | Concentration of amino acid peptide known as Aβ 1-42 in plasma. Least Square (LS) Mean value was controlled for baseline value, age, and investigator. |
| Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog14) at Week 16 After Cessation of Study Drug | Baseline (LFAN Randomization), 16 weeks (LFBF) after cessation of study drug | The ADAS-Cog14 is the ADAS-Cog11 augmented with delayed free recall, digit cancellation, and maze completion measures. A score of 0 to 10 for delayed free recall and a conversion code of 0 to 5 for digit cancellation and maze completion provide total score ranges for this extended ADAS-Cog14 of 0 to 90. Higher scores indicate greater disease severity. |
| Change From Baseline in Clinical Dementia Rating Scale (Sum of Boxes) (CDR-SB) at Week 24 | Baseline (LFAN Randomization), 24 weeks (LFBF) | The CDR-SB is a semi-structured interview of participants and their caregivers. The participant's cognitive status is rated in 6 domains of functioning, including memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. A severity score is assigned for each of the 6 domains with total score ranging from 0 to 18. Higher scores indicate greater disease severity. Least Square (LS) Mean value was controlled for baseline value, age, investigator, and concomitant standard of care (SOC) medication. |
| Change From Baseline in Mini-Mental State Examination (MMSE) at Week 24 | Baseline (LFAN Randomization), 24 weeks (LFBF) | The MMSE is a brief screening instrument used to assess cognitive function in elderly participants. It assesses orientation, memory, attention, and ability to name objects, follow verbal and written commands, write a sentence, and copy figures. The total score ranges from 0 to 30, with a lower score indicating greater disease severity. Least Square (LS) Mean value was controlled for baseline value, age, investigator, and concomitant standard of care (SOC) medication. |
| Change From Baseline in Neuropsychiatric Inventory (NPI) at Week 24 | Baseline (LFAN Randomization), 24 weeks (LFBF) | The NPI is a tool for assessing psychopathology in patients with dementia and other neurologic disorders. Information is obtained from a caregiver familiar with the patient's behavior. The score ranges from 12 to 144, with higher scores indicating greater disease severity. Least Square (LS) Mean value was controlled for the baseline value, age, investigator, concomitant standard of care medication. |
| Change From Baseline in EuroQol-5D (EQ-5D) at Week 24 | Baseline (LFAN Randomization), 24 weeks (LFBF) | EQ-5D (proxy version) measures mobility, self-care, usual activities, pain/discomfort, anxiety/depression; each has 3 severity levels (no, some, severe problems) coded to a 1-digit number (1-3). Digits are combined into 5-digit number describing health state. Numbers 1-3 are not added for total score. Visual Analog Scale (VAS) assesses caregiver's impression of participant's overall health state; VAS scores range=0-100, with lower scores indicating greater disease severity. LS Mean value was controlled for baseline value, age, investigator, and concomitant standard of care (SOC) medication. |
| Change From Baseline in Resource Utilization in Dementia-Lite Questionnaire (RUD-Lite) at Week 12 | Baseline (LFAN Randomization), 12 weeks (LFBF) | RUD-Lite assesses the healthcare resource utilization of participants and their caregivers to determine the level of formal and informal care attributable to Alzheimer's Disease (AD). Information on both caregivers (caregiving time, work status) and participants (accommodation and healthcare resource utilization) is collected from the baseline and follow-up interviews. Reported the change in number of hospitalizations per participant to week 12. |
| Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12) at Week 16 After Cessation of Study Drug | Baseline (LFAN Randomization), 16 weeks (LFBF) after cessation of study drug | ADAS-Cog12 is the ADAS-Cog11 augmented with the delayed free recall measure, resulting in a total score ranging from 0 to 80. Higher scores indicate greater disease severity. |
| Change From Baseline in Hippocampal Volume Using Volumetric Magnetic Resonance Imaging (vMRI) at Week 12 | Baseline (LFAN Randomization), 12 weeks (LFBF) | The vMRI assessment of right hippocampal and left hippocampal volume is reported. Least Square (LS) Mean value was controlled for baseline value, age, and investigator. |
Countries
Australia, Canada, Chile, Finland, France, Germany, Israel, Italy, Japan, Poland, South Africa, Spain, Sweden, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LFAN Placebo/LY140 mg Participants received placebo orally once daily for 76 weeks during study LFAN. At the end of 76 weeks, participants received LY450319 titrated up to 140 mg orally once daily. Participants continued 140 mg LY450319 (LY 140 mg) orally once daily up to 24 months during this extension study (LFBF) | 73 |
| LFAN LY 100 mg/ LY 140 mg Participants received 100 mg LY450319 orally once daily during study LFAN, and 140 mg LY450319 orally once daily up to 24 months during extension study | 60 |
| LFAN LY 140 mg/LY 140 mg Participants received 140 mg LY450319 orally once daily during study LFAN, and 140 mg LY450319 orally once daily up to 24 months during extension study | 47 |
| Total | 180 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 0 | 2 |
| Overall Study | Caregiver Decision | 2 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 1 |
| Overall Study | Sponsor Decision | 66 | 60 | 42 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | LFAN LY 100 mg/ LY 140 mg | LFAN Placebo/LY140 mg | Total | LFAN LY 140 mg/LY 140 mg |
|---|---|---|---|---|
| Age, Continuous | 73.5 years STANDARD_DEVIATION 8.7 | 74.1 years STANDARD_DEVIATION 8.3 | 73.9 years STANDARD_DEVIATION 8.7 | 74.1 years STANDARD_DEVIATION 9.5 |
| Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog11) | 21.1 units on a scale STANDARD_DEVIATION 8.5 | 21.0 units on a scale STANDARD_DEVIATION 8.5 | 21.1 units on a scale STANDARD_DEVIATION 8.7 | 21.5 units on a scale STANDARD_DEVIATION 9.3 |
| Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) | 65.5 units on a scale STANDARD_DEVIATION 9 | 63.7 units on a scale STANDARD_DEVIATION 11.4 | 63.9 units on a scale STANDARD_DEVIATION 10.9 | 62.2 units on a scale STANDARD_DEVIATION 12.2 |
| Race/Ethnicity, Customized Asian | 2 participants | 8 participants | 14 participants | 4 participants |
| Race/Ethnicity, Customized Black or African American | 0 participants | 2 participants | 2 participants | 0 participants |
| Race/Ethnicity, Customized Multi-racial | 0 participants | 2 participants | 3 participants | 1 participants |
| Race/Ethnicity, Customized White | 58 participants | 61 participants | 161 participants | 42 participants |
| Region of Enrollment Australia | 3 participants | 3 participants | 6 participants | 0 participants |
| Region of Enrollment Canada | 5 participants | 4 participants | 12 participants | 3 participants |
| Region of Enrollment Chile | 2 participants | 1 participants | 3 participants | 0 participants |
| Region of Enrollment Finland | 0 participants | 3 participants | 3 participants | 0 participants |
| Region of Enrollment France | 0 participants | 2 participants | 2 participants | 0 participants |
| Region of Enrollment Germany | 5 participants | 8 participants | 18 participants | 5 participants |
| Region of Enrollment Israel | 1 participants | 2 participants | 5 participants | 2 participants |
| Region of Enrollment Italy | 0 participants | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Japan | 2 participants | 6 participants | 11 participants | 3 participants |
| Region of Enrollment Poland | 0 participants | 0 participants | 2 participants | 2 participants |
| Region of Enrollment South Africa | 0 participants | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Spain | 2 participants | 2 participants | 6 participants | 2 participants |
| Region of Enrollment Sweden | 2 participants | 0 participants | 3 participants | 1 participants |
| Region of Enrollment United States | 38 participants | 40 participants | 107 participants | 29 participants |
| Sex: Female, Male Female | 33 Participants | 39 Participants | 93 Participants | 21 Participants |
| Sex: Female, Male Male | 27 Participants | 34 Participants | 87 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 73 | 3 / 60 | 4 / 47 |
| serious Total, serious adverse events | 6 / 73 | 4 / 60 | 2 / 47 |
Outcome results
Primary
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog11) at Week 16 After Cessation of Study Drug
The cognitive subscale of the ADAS (ADAS-Cog11) consists of 11 items assessing areas of function most typically impaired in Alzheimer's Disease (AD): orientation, verbal memory, language, and praxis. The scale ranges from 0 to 70, with higher scores indicating greater disease severity.
Time frame: Baseline (LFAN randomization), 16 weeks (LFBF) after cessation of study drug
Population: Participants who completed Study LFAN, took at least one dose of study drug in extension study and had both baseline and post-baseline values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LFAN Placebo/LY140 mg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog11) at Week 16 After Cessation of Study Drug | 6.4 units on a scale | Standard Deviation 11.53 |
| LFAN LY 100 mg/ LY 140 mg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog11) at Week 16 After Cessation of Study Drug | 12.5 units on a scale | Standard Deviation 12.82 |
| LFAN LY 140 mg/LY 140 mg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog11) at Week 16 After Cessation of Study Drug | 10.5 units on a scale | Standard Deviation 13.62 |
Primary
Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at Week 16 After Cessation of Study Drug
The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. It measures both basic and instrumental activities of daily living. The total score ranges from 0 to 78, with lower scores indicating greater disease severity.
Time frame: Baseline (LFAN randomization), 16 weeks (LFBF) after cessation of study drug
Population: Participants who completed Study LFAN, took at least one dose of study drug in extension study and had both baseline and post-baseline values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LFAN Placebo/LY140 mg | Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at Week 16 After Cessation of Study Drug | -4.5 units on a scale | Standard Deviation 7.73 |
| LFAN LY 100 mg/ LY 140 mg | Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at Week 16 After Cessation of Study Drug | -10.6 units on a scale | Standard Deviation 15.15 |
| LFAN LY 140 mg/LY 140 mg | Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at Week 16 After Cessation of Study Drug | -5.1 units on a scale | Standard Deviation 11.28 |
Secondary
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog11) at Week 12
The cognitive subscale of the ADAS (ADAS-Cog11) consists of 11 items assessing areas of function most typically impaired in Alzheimer's Disease (AD): orientation, verbal memory, language, and praxis. The scale ranges from 0 to 70, with higher scores indicating greater disease severity. Least Square (LS) Mean value was controlled for baseline value, age, investigator, and concomitant standard of care (SOC) medication.
Time frame: Baseline (LFAN Randomization), 12 weeks (LFBF)
Population: Participants who completed Study LFAN, took at least one dose of study drug in extension study and had both baseline and post-baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LFAN Placebo/LY140 mg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog11) at Week 12 | 9.3 units on a scale | Standard Error 1.52 |
| LFAN LY 100 mg/ LY 140 mg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog11) at Week 12 | 8.06 units on a scale | Standard Error 1.67 |
| LFAN LY 140 mg/LY 140 mg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog11) at Week 12 | 11.56 units on a scale | Standard Error 1.79 |
Secondary
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12) at Week 12
ADAS-Cog12 is the ADAS-Cog11 augmented with the delayed free recall measure, resulting in a total score ranging from 0 to 80. Higher scores indicate greater disease severity. Least Square (LS) Mean value was controlled for baseline value, age, investigator, and concomitant standard of care (SOC) medication.
Time frame: Baseline (LFAN Randomization), 12 weeks (LFBF)
Population: Participants who completed Study LFAN, took at least one dose of study drug in extension study and had both baseline and post-baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LFAN Placebo/LY140 mg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12) at Week 12 | 10.35 units on a scale | Standard Error 1.6 |
| LFAN LY 100 mg/ LY 140 mg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12) at Week 12 | 9.09 units on a scale | Standard Error 1.75 |
| LFAN LY 140 mg/LY 140 mg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12) at Week 12 | 12.66 units on a scale | Standard Error 1.88 |
Secondary
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12) at Week 16 After Cessation of Study Drug
ADAS-Cog12 is the ADAS-Cog11 augmented with the delayed free recall measure, resulting in a total score ranging from 0 to 80. Higher scores indicate greater disease severity.
Time frame: Baseline (LFAN Randomization), 16 weeks (LFBF) after cessation of study drug
Population: Participants who completed Study LFAN, took at least one dose of study drug in extension study and had both baseline and post-baseline values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LFAN Placebo/LY140 mg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12) at Week 16 After Cessation of Study Drug | 6.7 units on a scale | Standard Deviation 12.05 |
| LFAN LY 100 mg/ LY 140 mg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12) at Week 16 After Cessation of Study Drug | 12.6 units on a scale | Standard Deviation 13.11 |
| LFAN LY 140 mg/LY 140 mg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12) at Week 16 After Cessation of Study Drug | 11.2 units on a scale | Standard Deviation 14.97 |
Secondary
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog14) at Week 12
The ADAS-Cog14 is the ADAS-Cog11 augmented with delayed free recall, digit cancellation, and maze completion measures. A score of 0 to 10 for delayed free recall and a conversion code of 0 to 5 for digit cancellation and maze completion provide total score ranges for this extended ADAS-Cog14 of 0 to 90. Higher scores indicate greater disease severity. Least Square (LS) Mean value was controlled for the baseline value, age, investigator, and concomitant standard of care (SOC) medication.
Time frame: Baseline (LFAN Randomization), 12 weeks (LFBF)
Population: Participants who completed Study LFAN, took at least one dose of study drug in extension study and had both baseline and post-baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LFAN Placebo/LY140 mg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog14) at Week 12 | 11.31 units on a scale | Standard Error 1.78 |
| LFAN LY 100 mg/ LY 140 mg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog14) at Week 12 | 10.02 units on a scale | Standard Error 1.99 |
| LFAN LY 140 mg/LY 140 mg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog14) at Week 12 | 14.50 units on a scale | Standard Error 2.1 |
Secondary
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog14) at Week 16 After Cessation of Study Drug
The ADAS-Cog14 is the ADAS-Cog11 augmented with delayed free recall, digit cancellation, and maze completion measures. A score of 0 to 10 for delayed free recall and a conversion code of 0 to 5 for digit cancellation and maze completion provide total score ranges for this extended ADAS-Cog14 of 0 to 90. Higher scores indicate greater disease severity.
Time frame: Baseline (LFAN Randomization), 16 weeks (LFBF) after cessation of study drug
Population: Participants who completed Study LFAN, took at least one dose of study drug in extension study and had both baseline and post-baseline values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LFAN Placebo/LY140 mg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog14) at Week 16 After Cessation of Study Drug | 7.7 units on a scale | Standard Deviation 13.21 |
| LFAN LY 100 mg/ LY 140 mg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog14) at Week 16 After Cessation of Study Drug | 14.1 units on a scale | Standard Deviation 14.66 |
| LFAN LY 140 mg/LY 140 mg | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog14) at Week 16 After Cessation of Study Drug | 13.3 units on a scale | Standard Deviation 16.93 |
Secondary
Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at Week 12
The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. It measures both basic and instrumental activities of daily living. The total score ranges from 0 to 78, with lower scores indicating greater disease severity. Least Square (LS) Mean value was controlled for baseline value, age, investigator, and concomitant standard of care (SOC) medication.
Time frame: Baseline (LFAN Randomization), 12 weeks (LFBF)
Population: Participants who completed Study LFAN, took at least one dose of study drug in extension study and had both baseline and post-baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LFAN Placebo/LY140 mg | Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at Week 12 | -12.34 units on a scale | Standard Error 2.11 |
| LFAN LY 100 mg/ LY 140 mg | Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at Week 12 | -8.22 units on a scale | Standard Error 2.36 |
| LFAN LY 140 mg/LY 140 mg | Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at Week 12 | -8.74 units on a scale | Standard Error 2.67 |
Secondary
Change From Baseline in Amyloid Imaging Positron Emission Tomography (AV-45-PET) at Week 12
A radioactive tracer for PET that is a ligand for amyloid called \[18F\]-AV-45. This permits the visualization of amyloid in the brains of Alzheimer's participants. The outcome reported is the composite summary of the standard uptake value ratio for the cerebellar gray matter. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator. Due to insufficient sample size, this analysis was not done.
Time frame: Baseline (LFAN Randomization), 12 weeks (LFBF)
Population: Due to insufficient sample size, this analysis was not done.
Secondary
Change From Baseline in Clinical Dementia Rating Scale (Sum of Boxes) (CDR-SB) at Week 24
The CDR-SB is a semi-structured interview of participants and their caregivers. The participant's cognitive status is rated in 6 domains of functioning, including memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. A severity score is assigned for each of the 6 domains with total score ranging from 0 to 18. Higher scores indicate greater disease severity. Least Square (LS) Mean value was controlled for baseline value, age, investigator, and concomitant standard of care (SOC) medication.
Time frame: Baseline (LFAN Randomization), 24 weeks (LFBF)
Population: Participants who completed Study LFAN, took at least one dose of study drug in extension study and had both baseline and post-baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LFAN Placebo/LY140 mg | Change From Baseline in Clinical Dementia Rating Scale (Sum of Boxes) (CDR-SB) at Week 24 | 4.18 units on a scale | Standard Error 0.53 |
| LFAN LY 100 mg/ LY 140 mg | Change From Baseline in Clinical Dementia Rating Scale (Sum of Boxes) (CDR-SB) at Week 24 | 2.99 units on a scale | Standard Error 0.58 |
| LFAN LY 140 mg/LY 140 mg | Change From Baseline in Clinical Dementia Rating Scale (Sum of Boxes) (CDR-SB) at Week 24 | 3.39 units on a scale | Standard Error 0.65 |
Secondary
Change From Baseline in EuroQol-5D (EQ-5D) at Week 24
EQ-5D (proxy version) measures mobility, self-care, usual activities, pain/discomfort, anxiety/depression; each has 3 severity levels (no, some, severe problems) coded to a 1-digit number (1-3). Digits are combined into 5-digit number describing health state. Numbers 1-3 are not added for total score. Visual Analog Scale (VAS) assesses caregiver's impression of participant's overall health state; VAS scores range=0-100, with lower scores indicating greater disease severity. LS Mean value was controlled for baseline value, age, investigator, and concomitant standard of care (SOC) medication.
Time frame: Baseline (LFAN Randomization), 24 weeks (LFBF)
Population: Participants who completed Study LFAN, took at least one dose of study drug in extension study and had both baseline and post-baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LFAN Placebo/LY140 mg | Change From Baseline in EuroQol-5D (EQ-5D) at Week 24 | 0.76 units on a scale | Standard Error 3.19 |
| LFAN LY 100 mg/ LY 140 mg | Change From Baseline in EuroQol-5D (EQ-5D) at Week 24 | -2.23 units on a scale | Standard Error 3.38 |
| LFAN LY 140 mg/LY 140 mg | Change From Baseline in EuroQol-5D (EQ-5D) at Week 24 | -14.44 units on a scale | Standard Error 3.67 |
Secondary
Change From Baseline in Hippocampal Volume Using Volumetric Magnetic Resonance Imaging (vMRI) at Week 12
The vMRI assessment of right hippocampal and left hippocampal volume is reported. Least Square (LS) Mean value was controlled for baseline value, age, and investigator.
Time frame: Baseline (LFAN Randomization), 12 weeks (LFBF)
Population: Participants who completed Study LFAN, took at least one dose of study drug in extension study and had both baseline and post-baseline values.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LFAN Placebo/LY140 mg | Change From Baseline in Hippocampal Volume Using Volumetric Magnetic Resonance Imaging (vMRI) at Week 12 | Left hippocampal volume | -115.39 cubic millimeter (mm³) | Standard Error 83.61 |
| LFAN Placebo/LY140 mg | Change From Baseline in Hippocampal Volume Using Volumetric Magnetic Resonance Imaging (vMRI) at Week 12 | Right hippocampal volume | -141.79 cubic millimeter (mm³) | Standard Error 81 |
| LFAN LY 100 mg/ LY 140 mg | Change From Baseline in Hippocampal Volume Using Volumetric Magnetic Resonance Imaging (vMRI) at Week 12 | Left hippocampal volume | -279.29 cubic millimeter (mm³) | Standard Error 77.55 |
| LFAN LY 100 mg/ LY 140 mg | Change From Baseline in Hippocampal Volume Using Volumetric Magnetic Resonance Imaging (vMRI) at Week 12 | Right hippocampal volume | -187.16 cubic millimeter (mm³) | Standard Error 65.53 |
| LFAN LY 140 mg/LY 140 mg | Change From Baseline in Hippocampal Volume Using Volumetric Magnetic Resonance Imaging (vMRI) at Week 12 | Left hippocampal volume | 22.49 cubic millimeter (mm³) | Standard Error 107.49 |
| LFAN LY 140 mg/LY 140 mg | Change From Baseline in Hippocampal Volume Using Volumetric Magnetic Resonance Imaging (vMRI) at Week 12 | Right hippocampal volume | -3.86 cubic millimeter (mm³) | Standard Error 99.85 |
Secondary
Change From Baseline in Mini-Mental State Examination (MMSE) at Week 24
The MMSE is a brief screening instrument used to assess cognitive function in elderly participants. It assesses orientation, memory, attention, and ability to name objects, follow verbal and written commands, write a sentence, and copy figures. The total score ranges from 0 to 30, with a lower score indicating greater disease severity. Least Square (LS) Mean value was controlled for baseline value, age, investigator, and concomitant standard of care (SOC) medication.
Time frame: Baseline (LFAN Randomization), 24 weeks (LFBF)
Population: Participants who completed Study LFAN, took at least one dose of study drug in extension study and had both baseline and post-baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LFAN Placebo/LY140 mg | Change From Baseline in Mini-Mental State Examination (MMSE) at Week 24 | -4.67 units on a scale | Standard Error 0.78 |
| LFAN LY 100 mg/ LY 140 mg | Change From Baseline in Mini-Mental State Examination (MMSE) at Week 24 | -4.15 units on a scale | Standard Error 0.85 |
| LFAN LY 140 mg/LY 140 mg | Change From Baseline in Mini-Mental State Examination (MMSE) at Week 24 | -4.84 units on a scale | Standard Error 0.91 |
Secondary
Change From Baseline in Neuropsychiatric Inventory (NPI) at Week 24
The NPI is a tool for assessing psychopathology in patients with dementia and other neurologic disorders. Information is obtained from a caregiver familiar with the patient's behavior. The score ranges from 12 to 144, with higher scores indicating greater disease severity. Least Square (LS) Mean value was controlled for the baseline value, age, investigator, concomitant standard of care medication.
Time frame: Baseline (LFAN Randomization), 24 weeks (LFBF)
Population: Participants who completed Study LFAN, took at least one dose of study drug in extension study and had both baseline and post-baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LFAN Placebo/LY140 mg | Change From Baseline in Neuropsychiatric Inventory (NPI) at Week 24 | 1.87 units on a scale | Standard Error 4.68 |
| LFAN LY 100 mg/ LY 140 mg | Change From Baseline in Neuropsychiatric Inventory (NPI) at Week 24 | 1.94 units on a scale | Standard Error 3.62 |
| LFAN LY 140 mg/LY 140 mg | Change From Baseline in Neuropsychiatric Inventory (NPI) at Week 24 | 3.62 units on a scale | Standard Error 6.43 |
Secondary
Change From Baseline in Resource Utilization in Dementia-Lite Questionnaire (RUD-Lite) at Week 12
RUD-Lite assesses the healthcare resource utilization of participants and their caregivers to determine the level of formal and informal care attributable to Alzheimer's Disease (AD). Information on both caregivers (caregiving time, work status) and participants (accommodation and healthcare resource utilization) is collected from the baseline and follow-up interviews. Reported the change in number of hospitalizations per participant to week 12.
Time frame: Baseline (LFAN Randomization), 12 weeks (LFBF)
Population: Participants who completed Study LFAN, took at least one dose of study drug in extension study and had both baseline and post-baseline values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LFAN Placebo/LY140 mg | Change From Baseline in Resource Utilization in Dementia-Lite Questionnaire (RUD-Lite) at Week 12 | 1.80 number of hospitalizations | Standard Deviation 1.92 |
| LFAN LY 100 mg/ LY 140 mg | Change From Baseline in Resource Utilization in Dementia-Lite Questionnaire (RUD-Lite) at Week 12 | 0.67 number of hospitalizations | Standard Deviation 0.58 |
| LFAN LY 140 mg/LY 140 mg | Change From Baseline in Resource Utilization in Dementia-Lite Questionnaire (RUD-Lite) at Week 12 | 0.33 number of hospitalizations | Standard Deviation 0.58 |
Secondary
Mean Concentration of LY450139
Time frame: 3 months (pre-dose, 2, 4, and 6 hours after dosing )(LFBF)
Population: Participants who completed Study LFAN, took study drug in extension study and had pharmacokinetics measurements.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LFAN Placebo/LY140 mg | Mean Concentration of LY450139 | Pre-dose (n=7) | 1.81 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 124 |
| LFAN Placebo/LY140 mg | Mean Concentration of LY450139 | 2 hours after dosing (n=46) | 1160 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 66.9 |
| LFAN Placebo/LY140 mg | Mean Concentration of LY450139 | 4 hours after dosing (n=44) | 679 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 41.9 |
| LFAN Placebo/LY140 mg | Mean Concentration of LY450139 | 6 hours after dosing (n=41) | 341 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 52.6 |
Secondary
Percent Change From Baseline in Amyloid Beta (Aβ) 1-42 Plasma Concentration at Week 12
Concentration of amino acid peptide known as Aβ 1-42 in plasma. Least Square (LS) Mean value was controlled for baseline value, age, and investigator.
Time frame: Baseline (LFAN Randomization ), 6 hours pose-dose at Week 12 (LFBF)
Population: Participants who completed Study LFAN, took at least one dose of study drug in extension study and had both baseline and post-baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LFAN Placebo/LY140 mg | Percent Change From Baseline in Amyloid Beta (Aβ) 1-42 Plasma Concentration at Week 12 | -5.84 percentage of change | Standard Error 16.03 |
| LFAN LY 100 mg/ LY 140 mg | Percent Change From Baseline in Amyloid Beta (Aβ) 1-42 Plasma Concentration at Week 12 | -6.09 percentage of change | Standard Error 9.01 |
| LFAN LY 140 mg/LY 140 mg | Percent Change From Baseline in Amyloid Beta (Aβ) 1-42 Plasma Concentration at Week 12 | 14.27 percentage of change | Standard Error 17.37 |