Trial Outcomes & Findings for A Study of Semagacestat for Alzheimer's Patients (NCT NCT01035138)
NCT ID: NCT01035138
Last Updated: 2014-09-25
Results Overview
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.
COMPLETED
PHASE3
180 participants
Baseline (LFAN randomization), 16 weeks (LFBF) after cessation of study drug
2014-09-25
Participant Flow
Participant milestones
| Measure |
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 milligram (mg) orally once daily. Participants continued 140 mg LY450319 (LY 140 mg) orally once daily up to 24 months during this extension study (LFBF)
|
LFAN LY 100 mg/ LY 140 mg
Participants received 100 mg LY450319 (LY 100 mg) orally once daily during study LFAN, and 140 mg LY450319 orally once daily up to 24 months during this extension study (LFBF)
|
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 this extension study (LFBF)
|
|---|---|---|---|
|
Overall Study
STARTED
|
73
|
60
|
47
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
73
|
60
|
47
|
Reasons for withdrawal
| Measure |
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 milligram (mg) orally once daily. Participants continued 140 mg LY450319 (LY 140 mg) orally once daily up to 24 months during this extension study (LFBF)
|
LFAN LY 100 mg/ LY 140 mg
Participants received 100 mg LY450319 (LY 100 mg) orally once daily during study LFAN, and 140 mg LY450319 orally once daily up to 24 months during this extension study (LFBF)
|
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 this extension study (LFBF)
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
4
|
0
|
2
|
|
Overall Study
Caregiver Decision
|
2
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
0
|
|
Overall Study
Physician Decision
|
0
|
0
|
1
|
|
Overall Study
Sponsor Decision
|
66
|
60
|
42
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
1
|
Baseline Characteristics
A Study of Semagacestat for Alzheimer's Patients
Baseline characteristics by cohort
| Measure |
LFAN Placebo/LY140 mg
n=73 Participants
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)
|
LFAN LY 100 mg/ LY 140 mg
n=60 Participants
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
|
LFAN LY 140 mg/LY 140 mg
n=47 Participants
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
|
Total
n=180 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
74.1 years
STANDARD_DEVIATION 8.3 • n=5 Participants
|
73.5 years
STANDARD_DEVIATION 8.7 • n=7 Participants
|
74.1 years
STANDARD_DEVIATION 9.5 • n=5 Participants
|
73.9 years
STANDARD_DEVIATION 8.7 • n=4 Participants
|
|
Sex: Female, Male
Female
|
39 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
93 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
34 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
87 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
61 participants
n=5 Participants
|
58 participants
n=7 Participants
|
42 participants
n=5 Participants
|
161 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
2 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
8 participants
n=5 Participants
|
2 participants
n=7 Participants
|
4 participants
n=5 Participants
|
14 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Multi-racial
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
3 participants
n=4 Participants
|
|
Region of Enrollment
United States
|
40 participants
n=5 Participants
|
38 participants
n=7 Participants
|
29 participants
n=5 Participants
|
107 participants
n=4 Participants
|
|
Region of Enrollment
Finland
|
3 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
3 participants
n=4 Participants
|
|
Region of Enrollment
Spain
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
6 participants
n=4 Participants
|
|
Region of Enrollment
Chile
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
0 participants
n=5 Participants
|
3 participants
n=4 Participants
|
|
Region of Enrollment
Israel
|
2 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
5 participants
n=4 Participants
|
|
Region of Enrollment
Italy
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=4 Participants
|
|
Region of Enrollment
France
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
2 participants
n=4 Participants
|
|
Region of Enrollment
Canada
|
4 participants
n=5 Participants
|
5 participants
n=7 Participants
|
3 participants
n=5 Participants
|
12 participants
n=4 Participants
|
|
Region of Enrollment
Poland
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
2 participants
n=4 Participants
|
|
Region of Enrollment
Australia
|
3 participants
n=5 Participants
|
3 participants
n=7 Participants
|
0 participants
n=5 Participants
|
6 participants
n=4 Participants
|
|
Region of Enrollment
South Africa
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=4 Participants
|
|
Region of Enrollment
Germany
|
8 participants
n=5 Participants
|
5 participants
n=7 Participants
|
5 participants
n=5 Participants
|
18 participants
n=4 Participants
|
|
Region of Enrollment
Japan
|
6 participants
n=5 Participants
|
2 participants
n=7 Participants
|
3 participants
n=5 Participants
|
11 participants
n=4 Participants
|
|
Region of Enrollment
Sweden
|
0 participants
n=5 Participants
|
2 participants
n=7 Participants
|
1 participants
n=5 Participants
|
3 participants
n=4 Participants
|
|
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog11)
|
21.0 units on a scale
STANDARD_DEVIATION 8.5 • n=5 Participants
|
21.1 units on a scale
STANDARD_DEVIATION 8.5 • n=7 Participants
|
21.5 units on a scale
STANDARD_DEVIATION 9.3 • n=5 Participants
|
21.1 units on a scale
STANDARD_DEVIATION 8.7 • n=4 Participants
|
|
Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL)
|
63.7 units on a scale
STANDARD_DEVIATION 11.4 • n=5 Participants
|
65.5 units on a scale
STANDARD_DEVIATION 9.0 • n=7 Participants
|
62.2 units on a scale
STANDARD_DEVIATION 12.2 • n=5 Participants
|
63.9 units on a scale
STANDARD_DEVIATION 10.9 • n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline (LFAN randomization), 16 weeks (LFBF) after cessation of study drugPopulation: Participants who completed Study LFAN, took at least one dose of study drug in extension study and had both baseline and post-baseline values.
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.
Outcome measures
| Measure |
LFAN Placebo/LY140 mg
n=41 Participants
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)
|
LFAN LY 100 mg/ LY 140 mg
n=40 Participants
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
|
LFAN LY 140 mg/LY 140 mg
n=26 Participants
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
|
|---|---|---|---|
|
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
|
12.5 units on a scale
Standard Deviation 12.82
|
10.5 units on a scale
Standard Deviation 13.62
|
PRIMARY outcome
Timeframe: Baseline (LFAN randomization), 16 weeks (LFBF) after cessation of study drugPopulation: Participants who completed Study LFAN, took at least one dose of study drug in extension study and had both baseline and post-baseline values.
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.
Outcome measures
| Measure |
LFAN Placebo/LY140 mg
n=36 Participants
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)
|
LFAN LY 100 mg/ LY 140 mg
n=33 Participants
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
|
LFAN LY 140 mg/LY 140 mg
n=21 Participants
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
|
|---|---|---|---|
|
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
|
-10.6 units on a scale
Standard Deviation 15.15
|
-5.1 units on a scale
Standard Deviation 11.28
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
LFAN Placebo/LY140 mg
n=11 Participants
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)
|
LFAN LY 100 mg/ LY 140 mg
n=18 Participants
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
|
LFAN LY 140 mg/LY 140 mg
n=7 Participants
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
|
|---|---|---|---|
|
Percent Change From Baseline in Amyloid Beta (Aβ) 1-42 Plasma Concentration at Week 12
|
-5.84 percentage of change
Standard Error 16.03
|
-6.09 percentage of change
Standard Error 9.01
|
14.27 percentage of change
Standard Error 17.37
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
LFAN Placebo/LY140 mg
n=9 Participants
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)
|
LFAN LY 100 mg/ LY 140 mg
n=7 Participants
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
|
LFAN LY 140 mg/LY 140 mg
n=3 Participants
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
|
|---|---|---|---|
|
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
|
-279.29 cubic millimeter (mm³)
Standard Error 77.55
|
22.49 cubic millimeter (mm³)
Standard Error 107.49
|
|
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 81.00
|
-187.16 cubic millimeter (mm³)
Standard Error 65.53
|
-3.86 cubic millimeter (mm³)
Standard Error 99.85
|
SECONDARY outcome
Timeframe: Baseline (LFAN Randomization), 12 weeks (LFBF)Population: Due to insufficient sample size, this analysis was not done.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
LFAN Placebo/LY140 mg
n=65 Participants
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)
|
LFAN LY 100 mg/ LY 140 mg
n=53 Participants
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
|
LFAN LY 140 mg/LY 140 mg
n=43 Participants
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
|
|---|---|---|---|
|
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
|
8.06 units on a scale
Standard Error 1.67
|
11.56 units on a scale
Standard Error 1.79
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
LFAN Placebo/LY140 mg
n=65 Participants
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)
|
LFAN LY 100 mg/ LY 140 mg
n=53 Participants
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
|
LFAN LY 140 mg/LY 140 mg
n=43 Participants
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
|
|---|---|---|---|
|
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12) at Week 12
|
10.35 units on a scale
Standard Error 1.60
|
9.09 units on a scale
Standard Error 1.75
|
12.66 units on a scale
Standard Error 1.88
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
LFAN Placebo/LY140 mg
n=65 Participants
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)
|
LFAN LY 100 mg/ LY 140 mg
n=52 Participants
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
|
LFAN LY 140 mg/LY 140 mg
n=43 Participants
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
|
|---|---|---|---|
|
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
|
10.02 units on a scale
Standard Error 1.99
|
14.50 units on a scale
Standard Error 2.10
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
LFAN Placebo/LY140 mg
n=60 Participants
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)
|
LFAN LY 100 mg/ LY 140 mg
n=50 Participants
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
|
LFAN LY 140 mg/LY 140 mg
n=36 Participants
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
|
|---|---|---|---|
|
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
|
-8.22 units on a scale
Standard Error 2.36
|
-8.74 units on a scale
Standard Error 2.67
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
LFAN Placebo/LY140 mg
n=46 Participants
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)
|
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
|
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
|
|---|---|---|---|
|
Mean Concentration of LY450139
Pre-dose (n=7)
|
1.81 nanogram/milliliter (ng/mL)
Geometric Coefficient of Variation 124
|
—
|
—
|
|
Mean Concentration of LY450139
2 hours after dosing (n=46)
|
1160 nanogram/milliliter (ng/mL)
Geometric Coefficient of Variation 66.9
|
—
|
—
|
|
Mean Concentration of LY450139
4 hours after dosing (n=44)
|
679 nanogram/milliliter (ng/mL)
Geometric Coefficient of Variation 41.9
|
—
|
—
|
|
Mean Concentration of LY450139
6 hours after dosing (n=41)
|
341 nanogram/milliliter (ng/mL)
Geometric Coefficient of Variation 52.6
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (LFAN Randomization), 16 weeks (LFBF) after cessation of study drugPopulation: Participants who completed Study LFAN, took at least one dose of study drug in extension study and had both baseline and post-baseline values.
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.
Outcome measures
| Measure |
LFAN Placebo/LY140 mg
n=41 Participants
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)
|
LFAN LY 100 mg/ LY 140 mg
n=40 Participants
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
|
LFAN LY 140 mg/LY 140 mg
n=26 Participants
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
|
|---|---|---|---|
|
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
|
12.6 units on a scale
Standard Deviation 13.11
|
11.2 units on a scale
Standard Deviation 14.97
|
SECONDARY outcome
Timeframe: Baseline (LFAN Randomization), 16 weeks (LFBF) after cessation of study drugPopulation: Participants who completed Study LFAN, took at least one dose of study drug in extension study and had both baseline and post-baseline values.
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.
Outcome measures
| Measure |
LFAN Placebo/LY140 mg
n=41 Participants
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)
|
LFAN LY 100 mg/ LY 140 mg
n=40 Participants
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
|
LFAN LY 140 mg/LY 140 mg
n=26 Participants
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
|
|---|---|---|---|
|
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
|
14.1 units on a scale
Standard Deviation 14.66
|
13.3 units on a scale
Standard Deviation 16.93
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
LFAN Placebo/LY140 mg
n=63 Participants
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)
|
LFAN LY 100 mg/ LY 140 mg
n=52 Participants
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
|
LFAN LY 140 mg/LY 140 mg
n=39 Participants
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
|
|---|---|---|---|
|
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
|
2.99 units on a scale
Standard Error 0.58
|
3.39 units on a scale
Standard Error 0.65
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
LFAN Placebo/LY140 mg
n=62 Participants
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)
|
LFAN LY 100 mg/ LY 140 mg
n=51 Participants
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
|
LFAN LY 140 mg/LY 140 mg
n=41 Participants
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
|
|---|---|---|---|
|
Change From Baseline in Mini-Mental State Examination (MMSE) at Week 24
|
-4.67 units on a scale
Standard Error 0.78
|
-4.15 units on a scale
Standard Error 0.85
|
-4.84 units on a scale
Standard Error 0.91
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
LFAN Placebo/LY140 mg
n=18 Participants
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)
|
LFAN LY 100 mg/ LY 140 mg
n=23 Participants
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
|
LFAN LY 140 mg/LY 140 mg
n=9 Participants
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
|
|---|---|---|---|
|
Change From Baseline in Neuropsychiatric Inventory (NPI) at Week 24
|
1.87 units on a scale
Standard Error 4.68
|
1.94 units on a scale
Standard Error 3.62
|
3.62 units on a scale
Standard Error 6.43
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
LFAN Placebo/LY140 mg
n=62 Participants
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)
|
LFAN LY 100 mg/ LY 140 mg
n=54 Participants
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
|
LFAN LY 140 mg/LY 140 mg
n=42 Participants
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
|
|---|---|---|---|
|
Change From Baseline in EuroQol-5D (EQ-5D) at Week 24
|
0.76 units on a scale
Standard Error 3.19
|
-2.23 units on a scale
Standard Error 3.38
|
-14.44 units on a scale
Standard Error 3.67
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
LFAN Placebo/LY140 mg
n=5 Participants
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)
|
LFAN LY 100 mg/ LY 140 mg
n=3 Participants
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
|
LFAN LY 140 mg/LY 140 mg
n=3 Participants
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
|
|---|---|---|---|
|
Change From Baseline in Resource Utilization in Dementia-Lite Questionnaire (RUD-Lite) at Week 12
|
1.80 number of hospitalizations
Standard Deviation 1.92
|
0.67 number of hospitalizations
Standard Deviation 0.58
|
0.33 number of hospitalizations
Standard Deviation 0.58
|
Adverse Events
LFAN Placebo/LY140 mg
LFAN LY 100 mg/ LY 140 mg
LFAN LY 140 mg/LY 140 mg
Serious adverse events
| Measure |
LFAN Placebo/LY140 mg
n=73 participants at risk
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)
|
LFAN LY 100 mg/ LY 140 mg
n=60 participants at risk
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
|
LFAN LY 140 mg/LY 140 mg
n=47 participants at risk
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
|
|---|---|---|---|
|
Psychiatric disorders
Mania
|
1.4%
1/73 • Number of events 1
|
0.00%
0/60
|
0.00%
0/47
|
|
Gastrointestinal disorders
Gastrointestinal Haemorrhage
|
1.4%
1/73 • Number of events 1
|
0.00%
0/60
|
0.00%
0/47
|
|
Hepatobiliary disorders
Cholecystitis Acute
|
1.4%
1/73 • Number of events 2
|
0.00%
0/60
|
0.00%
0/47
|
|
Hepatobiliary disorders
Hepatic Cyst Ruptured
|
0.00%
0/73
|
1.7%
1/60 • Number of events 1
|
0.00%
0/47
|
|
Injury, poisoning and procedural complications
Femur Fracture
|
1.4%
1/73 • Number of events 1
|
0.00%
0/60
|
0.00%
0/47
|
|
Musculoskeletal and connective tissue disorders
Spinal Column Stenosis
|
0.00%
0/73
|
0.00%
0/60
|
2.1%
1/47 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma
|
1.4%
1/73 • Number of events 1
|
0.00%
0/60
|
0.00%
0/47
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous Cell Carcinoma Of Skin
|
0.00%
0/73
|
1.7%
1/60 • Number of events 1
|
0.00%
0/47
|
|
Nervous system disorders
Ischaemic Stroke
|
0.00%
0/73
|
1.7%
1/60 • Number of events 1
|
0.00%
0/47
|
|
Nervous system disorders
Syncope
|
0.00%
0/73
|
1.7%
1/60 • Number of events 1
|
0.00%
0/47
|
|
Psychiatric disorders
Aggression
|
0.00%
0/73
|
0.00%
0/60
|
2.1%
1/47 • Number of events 1
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/73
|
1.7%
1/60 • Number of events 1
|
0.00%
0/47
|
|
Psychiatric disorders
Confusional State
|
1.4%
1/73 • Number of events 1
|
0.00%
0/60
|
0.00%
0/47
|
Other adverse events
| Measure |
LFAN Placebo/LY140 mg
n=73 participants at risk
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)
|
LFAN LY 100 mg/ LY 140 mg
n=60 participants at risk
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
|
LFAN LY 140 mg/LY 140 mg
n=47 participants at risk
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
|
|---|---|---|---|
|
Injury, poisoning and procedural complications
Contusion
|
1.4%
1/73 • Number of events 1
|
3.3%
2/60 • Number of events 2
|
6.4%
3/47 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Hair Colour Changes
|
5.5%
4/73 • Number of events 4
|
1.7%
1/60 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60