← Trials/Trial dossier/NCT00762411

IDENTITY-2

CompletedPhase 3Results posted

Effects of LY450139, on the Progression of Alzheimer's Disease as Compared With Placebo

Effect of LY450139 a y-Secretase Inhibitor, on the Progression of Alzheimer's Disease as Compared With Placebo

Lead sponsor

Eli Lilly and Company

Asset

Semagacestat

Listed sites

Recruiting sites

Enrollment

1,111

actual

Study population

Alzheimer’s disease

Key I/E criteria

•mild-to-moderate AD•MMSE 16-26

Primary endpoints

•ADAS-Cog•ADCS-Activities of Daily Living (ADCS-ADL)

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study ID11271

Secondary IDH6L-MC-LFBCEli Lilly and Company

NCT IDNCT00762411

Timeline

Milestones

Study start2008-09 (month precision)

Study first posted2008-09-30estimated

Primary completion2011-04actual (month precision)

Study completion2011-04actual (month precision)

Results first posted2014-09-25estimated

Last update posted2015-02-16estimated

Assets

Drug assets

Semagacestat

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age55 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Meets criteria for mild to moderate Alzheimer's disease (AD) with Mini-Mental State Examination score of 16 through 26 at visit 1

•Modified Hachinski Ischemia Scale score of less than or equal to 4

•Geriatric Depression Scale score of less than or equal to 6

•A magnetic resonance imaging (MRI) or computerized tomography (CT) scan in the last 2 years with no findings inconsistent with a diagnosis of AD

•If female, must be without menstruation for a least 12 consecutive months or have had both ovaries removed

Exclusion criteria

•Is not capable of swallowing whole oral medication

•Has serious or unstable illnesses

•Does not have a reliable caregiver

•Chronic alcohol and/or drug abuse within the past 5 years

•Has ever had a active vaccination for AD

Endpoints (58)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Memory

Global cognition

Behavior / neuropsychiatric

Amyloid biomarkers

Function / daily living

Tau biomarkers

Neuroimaging

Caregiver / quality of life

Safety / tolerability / PK

Global cognition

8 endpoints

Secondary/protocol endpoint

Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) at 76 Weeks

Time frame:Baseline (randomization), 76 weeks

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Mini Mental State Examination (MMSE) at 76 Weeks

Time frame:Baseline (randomization), 76 weeks

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) at 4 Weeks After Cessation of Study Drug

Time frame:Baseline (randomization), 4 weeks following treatment cessation

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Mini Mental State Examination (MMSE) 4 Weeks After Cessation of Study Drug

Time frame:Baseline (randomization), 4 weeks following treatment cessation

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/registry result

Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) at 76 Weeks

Time frame:Baseline (randomization), 76 weeks

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), units on a scale	Standard error
140 mg LY450139n=22 Participants	3.05	1.10
Placebon=34 Participants	4.00	0.92

p0.294Mixed Models Analysis

Secondary/registry result

Change From Baseline in Mini Mental State Examination (MMSE) at 76 Weeks

Time frame:Baseline (randomization), 76 weeks

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), units on a scale	Standard error
140 mg LY450139n=555 Participants	-3.56	0.38
Placebon=553 Participants	-3.35	0.35

p0.632Mixed Models Analysis

Secondary/registry result

Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) at 4 Weeks After Cessation of Study Drug

Time frame:Baseline (randomization), 4 weeks following treatment cessation

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Secondary/registry result

Change From Baseline in Mini Mental State Examination (MMSE) 4 Weeks After Cessation of Study Drug

Time frame:Baseline (randomization), 4 weeks following treatment cessation

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Memory

16 endpoints

Primary/protocol endpoint

Change From Baseline in Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog11) at 76 Weeks

Time frame:Baseline (randomization), 76 weeks

ADAS-Cog

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog11) at 16 Weeks After Cessation of Study Drug

Time frame:Baseline (randomization), 16 weeks following treatment cessation

ADAS-Cog

change from baseline, improvement

Primary/registry result

Change From Baseline in Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog11) at 76 Weeks

Time frame:Baseline (randomization), 76 weeks

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), units on a scale	Standard error
140 mg LY450139n=555 Participants	7.37	0.79
Placebon=553 Participants	6.77	0.72

p0.560Mixed Models Analysis

Primary/registry result

Change From Baseline in Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog11) at 16 Weeks After Cessation of Study Drug

Time frame:Baseline (randomization), 16 weeks following treatment cessation

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), units on a scale	Standard error
140 mg LY450139n=312 Participants	4.81	0.70
Placebon=430 Participants	4.85	0.63

p0.959Mixed Models Analysis

Secondary/protocol endpoint

Change From Baseline in Quality of Life in Alzheimer's Disease (QoL-AD) at 76 Weeks

Time frame:Baseline (randomization), 76 weeks

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Quality of Life in Alzheimer's Disease (QoL-AD) at 4 Weeks After Cessation of Study Drug

Time frame:Baseline (randomization), 4 weeks following treatment cessation

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog12) at 76 Weeks

Time frame:Baseline (randomization), 76 weeks

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Alzheimer's Disease Assessment Scale (ADAS-Cog14) at 76 Weeks

Time frame:Baseline (randomization), 76 weeks

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog12) at 16 Weeks After Cessation of Study Drug

Time frame:Baseline (randomization), 16 weeks following treatment cessation

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Alzheimer's Disease Assessment Scale (ADAS-Cog14) at 16 Weeks After Cessation of Study Drug

Time frame:Baseline (randomization), 16 weeks following treatment cessation

ADAS-Cog

change from baseline, improvement

Secondary/registry result

Change From Baseline in Quality of Life in Alzheimer's Disease (QoL-AD) at 76 Weeks

Time frame:Baseline (randomization), 76 weeks

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), units on a scale	Standard error
140 mg LY450139n=555 Participants	-1.83	0.47
Placebon=553 Participants	-1.05	0.43

p0.178Mixed Models Analysis

Secondary/registry result

Change From Baseline in Quality of Life in Alzheimer's Disease (QoL-AD) at 4 Weeks After Cessation of Study Drug

Time frame:Baseline (randomization), 4 weeks following treatment cessation

change from baseline, improvement

Secondary/registry result

Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog12) at 76 Weeks

Time frame:Baseline (randomization), 76 weeks

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), units on a scale	Standard error
140 mg LY450139n=22 Participants	10.09	3.29
Placebon=34 Participants	10.34	2.67

p0.929Mixed Models Analysis

Secondary/registry result

Change From Baseline in Alzheimer's Disease Assessment Scale (ADAS-Cog14) at 76 Weeks

Time frame:Baseline (randomization), 76 weeks

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), units on a scale	Standard error
140 mg LY450139n=555 Participants	9.23	0.90
Placebon=553 Participants	8.32	0.82

p0.437Mixed Models Analysis

Secondary/registry result

Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog12) at 16 Weeks After Cessation of Study Drug

Time frame:Baseline (randomization), 16 weeks following treatment cessation

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), units on a scale	Standard error
140 mg LY450139n=312 Participants	5.33	0.74
Placebon=430 Participants	5.14	0.67

p0.805Mixed Models Analysis

Secondary/registry result

Change From Baseline in Alzheimer's Disease Assessment Scale (ADAS-Cog14) at 16 Weeks After Cessation of Study Drug

Time frame:Baseline (randomization), 16 weeks following treatment cessation

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), units on a scale	Standard error
140 mg LY450139n=312 Participants	6.00	0.82
Placebon=430 Participants	5.89	0.73

p0.893Mixed Models Analysis

Function / daily living

4 endpoints

Primary/protocol endpoint

Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at 76 Weeks

Time frame:Baseline (randomization), 76 weeks

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at 16 Weeks After Cessation of Study Drug

Time frame:Baseline (randomization), 16 weeks following treatment cessation

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Primary/registry result

Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at 76 Weeks

Time frame:Baseline (randomization), 76 weeks

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), units on a scale	Standard error
140 mg LY450139n=555 Participants	-10.49	0.98
Placebon=553 Participants	-9.77	0.90

p0.567Mixed Models Analysis

Primary/registry result

Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at 16 Weeks After Cessation of Study Drug

Time frame:Baseline (randomization), 16 weeks following treatment cessation

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), units on a scale	Standard error
140 mg LY450139n=312 Participants	-8.88	0.93
Placebon=430 Participants	-7.68	0.84

p0.199Mixed Models Analysis

Behavior / neuropsychiatric

8 endpoints

Secondary/protocol endpoint

Change From Baseline in Neuropsychiatric Inventory (NPI) at 76 Weeks

Time frame:Baseline (randomization), 76 weeks

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in the EuroQol 5-Dimensional Health-Related Quality of Life Scale Proxy Version (EQ-5D Proxy) Visual Analog Scale (VAS) at 76 Weeks

Time frame:Baseline (randomization), 76 weeks

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Neuropsychiatric Inventory (NPI) at 4 Weeks After Cessation of Study Drug

Time frame:Baseline (randomization), 4 weeks following treatment cessation

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in EuroQol 5-Dimensional Health-Related Quality of Life Scale Proxy Version (EQ-5D Proxy) Visual Analog Scale (VAS) at 4 Weeks After Cessation of Study Drug

Time frame:Baseline (randomization), 4 weeks following treatment cessation

change from baseline, improvement

Secondary/registry result

Change From Baseline in Neuropsychiatric Inventory (NPI) at 76 Weeks

Time frame:Baseline (randomization), 76 weeks

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), units on a scale	Standard error
140 mg LY450139n=555 Participants	2.94	1.04
Placebon=553 Participants	3.84	0.95

p0.477Mixed Models Analysis

Secondary/registry result

Change From Baseline in the EuroQol 5-Dimensional Health-Related Quality of Life Scale Proxy Version (EQ-5D Proxy) Visual Analog Scale (VAS) at 76 Weeks

Time frame:Baseline (randomization), 76 weeks

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), units on a scale	Standard error
140 mg LY450139n=555 Participants	-4.46	1.78
Placebon=553 Participants	-3.38	1.64

p0.622Mixed Models Analysis

Secondary/registry result

Change From Baseline in Neuropsychiatric Inventory (NPI) at 4 Weeks After Cessation of Study Drug

Time frame:Baseline (randomization), 4 weeks following treatment cessation

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/registry result

Change From Baseline in EuroQol 5-Dimensional Health-Related Quality of Life Scale Proxy Version (EQ-5D Proxy) Visual Analog Scale (VAS) at 4 Weeks After Cessation of Study Drug

Time frame:Baseline (randomization), 4 weeks following treatment cessation

change from baseline, improvement

Amyloid biomarkers

6 endpoints

Secondary/protocol endpoint

Percent Change From Baseline in Amyloid Beta (Aβ) 1-42 Plasma Concentration at 52 Weeks

Time frame:Baseline (randomization), 52 weeks

percent change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Amyloid Imaging Positron Emission Tomography (AV-45 PET) up to 76 Weeks

Time frame:Baseline (randomization), up to 76 weeks

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Amyloid Beta (Aβ) 1-42 Concentration in Spinal Fluid up to 76 Weeks

Time frame:Baseline (randomization), up to 76 weeks

change from baseline, improvement

Secondary/registry result

Percent Change From Baseline in Amyloid Beta (Aβ) 1-42 Plasma Concentration at 52 Weeks

Time frame:Baseline (randomization), 52 weeks

percent change from baseline, improvement

Posted result

Group	Value (least_squares_mean), picogram per milliliter (pg/mL)	Standard error
140 mg LY450139n=555 Participants	-16.03	28.33
Placebon=553 Participants	76.37	24.73

p0.009ANCOVA

Secondary/registry result

Change From Baseline in Amyloid Imaging Positron Emission Tomography (AV-45 PET) up to 76 Weeks

Time frame:Baseline (randomization), up to 76 weeks

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), ratio	Standard error
140 mg LY450139n=555 Participants	-0.36	0.23
Placebon=553 Participants	0.16	0.11

p0.326ANCOVA

Secondary/registry result

Change From Baseline in Amyloid Beta (Aβ) 1-42 Concentration in Spinal Fluid up to 76 Weeks

Time frame:Baseline (randomization), up to 76 weeks

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), picogram per milliliter (pg/mL)	Standard error
140 mg LY450139n=555 Participants	19.20	26.03
Placebon=553 Participants	-21.39	35.35

p0.417ANCOVA

Tau biomarkers

4 endpoints

Secondary/protocol endpoint

Change From Baseline in Tau Concentration in Spinal Fluid up to 76 Weeks

Time frame:Baseline (randomization), up to 76 weeks

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Phosphorylated-Tau (P-tau) Concentration in Spinal Fluid up to 76 Weeks

Time frame:Baseline (randomization), up to 76 weeks

change from baseline, improvement

Secondary/registry result

Change From Baseline in Tau Concentration in Spinal Fluid up to 76 Weeks

Time frame:Baseline (randomization), up to 76 weeks

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), picogram per milliliter (pg/mL)	Standard error
140 mg LY450139n=555 Participants	-11.60	39.39
Placebon=553 Participants	117.88	53.58

p0.117ANCOVA

Secondary/registry result

Change From Baseline in Phosphorylated-Tau (P-tau) Concentration in Spinal Fluid up to 76 Weeks

Time frame:Baseline (randomization), up to 76 weeks

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), picogram per milliliter (pg/mL)	Standard error
140 mg LY450139n=555 Participants	7.94	3.06
Placebon=553 Participants	14.75	4.68

p0.318ANCOVA

Neuroimaging

4 endpoints

Secondary/protocol endpoint

Change From Baseline in Positron Emission Tomography (PET) Using Fluorine-18 Fluorodeoxyglucose (18F-FDG) at 76 Weeks

Time frame:Baseline (randomization), 76 weeks

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Hippocampal Volume Using Volumetric Magnetic Resonance Imaging (vMRI) up to 76 Weeks

Time frame:Baseline (randomization), up to 76 weeks

change from baseline, improvement

Secondary/registry result

Change From Baseline in Positron Emission Tomography (PET) Using Fluorine-18 Fluorodeoxyglucose (18F-FDG) at 76 Weeks

Time frame:Baseline (randomization), 76 weeks

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), ratio	Standard error
140 mg LY450139n=74 Participants	-0.13	0.05
Placebon=80 Participants	-0.08	0.03

p0.426ANCOVA

Secondary/registry result

Change From Baseline in Hippocampal Volume Using Volumetric Magnetic Resonance Imaging (vMRI) up to 76 Weeks

Time frame:Baseline (randomization), up to 76 weeks

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), cubic millimeter (mm^3)	Standard error
140 mg LY450139Right Hippocampal Volumen=555 Participants	-158.50	29.44
Left Hippocampal Volumen=555 Participants	-84.41	61.96
PlaceboRight Hippocampal Volumen=553 Participants	-73.60	24.18
Left Hippocampal Volumen=553 Participants	-111.27	49.22

p0.101ANCOVA

p0.772ANCOVA

Caregiver / quality of life

4 endpoints

Secondary/protocol endpoint

Change From Baseline in the Resource Utilization in Dementia-Lite (RUD-Lite) up to 76 Weeks

Time frame:Baseline (randomization), up to 76 weeks

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Resource Utilization in Dementia-Lite (RUD-Lite) at 4 Weeks After Cessation of Study Drug

Time frame:Baseline (randomization), 4 weeks following treatment cessation

change from baseline, improvement

Secondary/registry result

Change From Baseline in the Resource Utilization in Dementia-Lite (RUD-Lite) up to 76 Weeks

Time frame:Baseline (randomization), up to 76 weeks

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), number of hospitalizations	Standard error
140 mg LY450139n=555 Participants	0.72	0.14
Placebon=553 Participants	0.82	0.16

p0.673ANCOVA

Secondary/registry result

Change From Baseline in Resource Utilization in Dementia-Lite (RUD-Lite) at 4 Weeks After Cessation of Study Drug

Time frame:Baseline (randomization), 4 weeks following treatment cessation

change from baseline, improvement

Safety / tolerability / PK

4 endpoints

Secondary/protocol endpoint

LY450139 Population Pharmacokinetics: Clearance of LY450139

Time frame:6 weeks, 12 weeks, and 52 weeks

descriptive

Secondary/protocol endpoint

LY450139 Population Pharmacokinetics: Volume of Distribution of LY450139

Time frame:6 weeks, 12 weeks, and 52 weeks

descriptive

Secondary/registry result

LY450139 Population Pharmacokinetics: Clearance of LY450139

Time frame:6 weeks, 12 weeks, and 52 weeks

descriptive

Posted result

Group	Value (geometric_mean), liters per hour (L/h)	Geometric coefficient of variation
140 mg LY450139n=517 Participants	18.9	26.6

Secondary/registry result

LY450139 Population Pharmacokinetics: Volume of Distribution of LY450139

Time frame:6 weeks, 12 weeks, and 52 weeks

descriptive

Posted result

Group	Value (geometric_mean), liters (L)	Geometric coefficient of variation
140 mg LY450139n=517 Participants	66.1	26.2

Publications (2)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.