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Effects of LY450139, on the Progression of Alzheimer's Disease as Compared With Placebo (IDENTITY-2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00762411
Recruitment Status : Completed
First Posted : September 30, 2008
Results First Posted : September 25, 2014
Last Update Posted : February 16, 2015
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Alzheimer's Disease
Interventions Drug: LY450139
Drug: Placebo
Enrollment 1111
Recruitment Details  
Pre-assignment Details  
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88. Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Period Title: Initial Treatment
Started 556 555
Intent-to-treat (ITT) 555 [1] 553 [2]
Completed 22 34
Not Completed 534 521
Reason Not Completed
Death             7             6
Adverse Event             132             40
Protocol Violation             4             1
Withdrawal by Subject             65             52
Physician Decision             1             0
Sponsor Decision             293             401
Lost to Follow-up             5             0
Caregiver Decision             21             16
Abnormal Lab/ECG Result             6             4
Entry Criteria Exclusion             0             1
[1]
ITT population included all randomized participants(pts) who received at least 1 dose of study drug.
[2]
ITT population included all randomized participants who received at least 1 dose of study drug.
Period Title: Delayed Start
Started 22 34
Completed 5 8
Not Completed 17 26
Reason Not Completed
Adverse Event             0             4
Protocol Violation             0             1
Sponsor Decision             16             20
Caregiver Decision             1             1
Period Title: Safety Follow Up (SFU)-Optional
Started 312 [1] 430 [1]
Completed 228 312
Not Completed 84 118
Reason Not Completed
Death             1             8
Adverse Event             0             1
Withdrawal by Subject             21             46
Lost to Follow-up             6             1
Caregiver Decision             8             8
No safety visit or SFU             48             54
[1]
SFU was optional; pts entered from initial treatment and delayed start or did not enter SFU.
Arm/Group Title 140 mg LY450139 Placebo Total
Hide Arm/Group Description Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88. Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88. Total of all reporting groups
Overall Number of Baseline Participants 555 553 1108
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 555 participants 553 participants 1108 participants
73.4  (8.0) 73.0  (8.0) 73.2  (8.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 555 participants 553 participants 1108 participants
Female
316
  56.9%
327
  59.1%
643
  58.0%
Male
239
  43.1%
226
  40.9%
465
  42.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 555 participants 553 participants 1108 participants
Caucasian 358 354 712
African 11 8 19
Hispanic 33 29 62
East Asian 150 160 310
West Asian 3 2 5
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 555 participants 553 participants 1108 participants
Brazil 18 21 39
Bulgaria 20 18 38
Canada 50 49 99
China 22 22 44
France 28 29 57
Germany 24 20 44
Hungary 19 16 35
Italy 14 11 25
Japan 64 69 133
Korea, Republic of 38 43 81
Mexico 26 24 50
Romania 20 17 37
Russian Federation 15 19 34
Serbia 5 8 13
Taiwan 25 24 49
Turkey 25 23 48
Ukraine 19 20 39
United States 123 120 243
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) Score (n=507, 533)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 555 participants 553 participants 1108 participants
24.5  (9.1) 24.2  (9.1) 24.3  (9.1)
[1]
Measure Description: The cognitive subscale of the ADAS (ADAS‑Cog11) consists of 11 items assessing areas of function most typically impaired in AD: orientation, verbal memory, language, and praxis. The scale ranges from 0 to 70, with higher scores indicating greater disease severity.
Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory Score (n=505, 529)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 555 participants 553 participants 1108 participants
58.8  (13.3) 59.1  (13.8) 58.9  (13.5)
[1]
Measure Description: The Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Inventory Score is a 23-item inventory developed as a rater-administered questionnaire that should be answered by the participant’s caregiver. The ADCS-ADL measures both basic and instrumental activities of daily living by participants. The total ADCS-ADL score ranges from 0 to 78, with lower scores indicating greater disease severity.
1.Primary Outcome
Title Change From Baseline in Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog11) at 76 Weeks
Hide Description The cognitive subscale of the ADAS (ADAS Cog11) was used as a primary efficacy measure and 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 Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.
Time Frame Baseline (randomization), 76 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication.
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 555 553
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
7.37  (0.79) 6.77  (0.72)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 140 mg LY450139, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.560
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
2.Primary Outcome
Title Change From Baseline in Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog11) at 16 Weeks After Cessation of Study Drug
Hide Description The cognitive subscale of 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 Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.
Time Frame Baseline (randomization), 16 weeks following treatment cessation
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication and had both baseline and post-baseline evaluable data.
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 312 430
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
4.81  (0.70) 4.85  (0.63)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 140 mg LY450139, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.959
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
3.Primary Outcome
Title Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at 76 Weeks
Hide Description The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures both basic and instrumental activities of daily living by participants. The total score ranges from 0 to 78, with lower scores indicating greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.
Time Frame Baseline (randomization), 76 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication.
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 555 553
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-10.49  (0.98) -9.77  (0.90)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 140 mg LY450139, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.567
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
4.Primary Outcome
Title Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at 16 Weeks After Cessation of Study Drug
Hide Description The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures both basic and instrumental activities of daily living by participants. The total score ranges from 0 to 78, with lower scores indicating greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.
Time Frame Baseline (randomization), 16 weeks following treatment cessation
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication and had both baseline and post-baseline evaluable data.
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 312 430
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-8.88  (0.93) -7.68  (0.84)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 140 mg LY450139, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.199
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) at 76 Weeks
Hide Description CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.
Time Frame Baseline (randomization), 76 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication and had both baseline and post-baseline evaluable data.
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 22 34
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
3.05  (1.10) 4.00  (0.92)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 140 mg LY450139, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.294
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Neuropsychiatric Inventory (NPI) at 76 Weeks
Hide Description NPI assesses psychopathology in participants with dementia and other neurologic disorders. Information is obtained from a caregiver familiar with the participant's behavior. Total score ranges from 12 to 144; higher scores indicate greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.
Time Frame Baseline (randomization), 76 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication.
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 555 553
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
2.94  (1.04) 3.84  (0.95)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 140 mg LY450139, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.477
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in the Resource Utilization in Dementia-Lite (RUD-Lite) up to 76 Weeks
Hide Description Assesses healthcare resource utilization (formal and informal care). Information gathered on both caregivers (care-giving time, work status) and participants (accommodation and healthcare resource utilization) was gathered from baseline and follow-up interviews. Reported number of hospitalizations per participant up to 76 weeks. Least Squares (LS) Mean value was controlled for age and investigator.
Time Frame Baseline (randomization), up to 76 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication, last observation carried forward (LOCF).
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 555 553
Least Squares Mean (Standard Error)
Unit of Measure: number of hospitalizations
0.72  (0.14) 0.82  (0.16)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 140 mg LY450139, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.673
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
8.Secondary Outcome
Title 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
Hide Description 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. Numerals 1-3 are not added for total score. VAS assesses caregiver's impression of participant's overall health state; scores range: 0 to 100. Lower scores indicate greater disease severity. Least Squares (LS) Mean value controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.
Time Frame Baseline (randomization), 76 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication.
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 555 553
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-4.46  (1.78) -3.38  (1.64)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 140 mg LY450139, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.622
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in Quality of Life in Alzheimer's Disease (QoL-AD) at 76 Weeks
Hide Description Assess QoL for AD: participant rates mood, relationships, memory, finances, physical condition, and overall QoL assessment. Each of 13 items, rated on a 4-point scale. Sum of items=total score (range: 13 to 52). Higher scores indicate greater QoL. Participant's primary caregiver asked to complete same measure. Least Squares (LS) Mean value controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.
Time Frame Baseline (randomization), 76 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication.
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 555 553
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.83  (0.47) -1.05  (0.43)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 140 mg LY450139, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.178
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in Mini Mental State Examination (MMSE) at 76 Weeks
Hide Description MMSE is a brief screening instrument used to assess cognitive function (orientation, memory, attention, ability to name objects, follow verbal/written commands, write a sentence, and copy figures) in elderly participants. Total score ranges from 0 to 30; lower score indicates greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication
Time Frame Baseline (randomization), 76 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication.
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 555 553
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-3.56  (0.38) -3.35  (0.35)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 140 mg LY450139, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.632
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
11.Secondary Outcome
Title Percent Change From Baseline in Amyloid Beta (Aβ) 1-42 Plasma Concentration at 52 Weeks
Hide Description Concentration of amino acid peptide known as Aβ 1-42 in plasma. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator.
Time Frame Baseline (randomization), 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication.
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 555 553
Least Squares Mean (Standard Error)
Unit of Measure: picogram per milliliter (pg/mL)
-16.03  (28.33) 76.37  (24.73)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 140 mg LY450139, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline in Positron Emission Tomography (PET) Using Fluorine-18 Fluorodeoxyglucose (18F-FDG) at 76 Weeks
Hide Description Measurement of local cerebral glucose metabolism by PET using the radioactive tracer 18F-FDG. The outcome reported is the composite summary of the standard uptake value ratio (SUVR) normalized to the Pons. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator.
Time Frame Baseline (randomization), 76 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication and had both baseline and post-baseline evaluable data.
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 74 80
Least Squares Mean (Standard Error)
Unit of Measure: ratio
-0.13  (0.05) -0.08  (0.03)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 140 mg LY450139, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.426
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
13.Secondary Outcome
Title Change From Baseline in Hippocampal Volume Using Volumetric Magnetic Resonance Imaging (vMRI) up to 76 Weeks
Hide Description The vMRI assessment of right and left hippocampal volume is reported. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator.
Time Frame Baseline (randomization), up to 76 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication, last observation carried forward (LOCF).
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 555 553
Least Squares Mean (Standard Error)
Unit of Measure: cubic millimeter (mm^3)
Right Hippocampal Volume -158.50  (29.44) -73.60  (24.18)
Left Hippocampal Volume -84.41  (61.96) -111.27  (49.22)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 140 mg LY450139, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.101
Comments This is the p-value for the Right Hippocampal Volume.
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 140 mg LY450139, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.772
Comments This is the p-value for the Left Hippocampal Volume.
Method ANCOVA
Comments [Not Specified]
14.Secondary Outcome
Title Change From Baseline in Amyloid Imaging Positron Emission Tomography (AV-45 PET) up to 76 Weeks
Hide Description 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 (SUVR) normalized to the cerebellar gray matter. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator.
Time Frame Baseline (randomization), up to 76 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication, last observation carried forward (LOCF).
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 555 553
Least Squares Mean (Standard Error)
Unit of Measure: ratio
-0.36  (0.23) 0.16  (0.11)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 140 mg LY450139, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.326
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
15.Secondary Outcome
Title Change From Baseline in Tau Concentration in Spinal Fluid up to 76 Weeks
Hide Description Concentration of total tau in spinal fluid. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator.
Time Frame Baseline (randomization), up to 76 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication, last observation carried forward (LOCF).
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 555 553
Least Squares Mean (Standard Error)
Unit of Measure: picogram per milliliter (pg/mL)
-11.60  (39.39) 117.88  (53.58)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 140 mg LY450139, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.117
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
16.Secondary Outcome
Title LY450139 Population Pharmacokinetics: Clearance of LY450139
Hide Description Model estimated apparent oral clearance. Clearance is defined as the volume of plasma which is completely cleared of drug (LY450139) per unit time.
Time Frame 6 weeks, 12 weeks, and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized to LY450139 with sufficient dosing information and concentration data to allow estimation of pharmacokinetic parameters.
Arm/Group Title 140 mg LY450139
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Overall Number of Participants Analyzed 517
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: liters per hour (L/h)
18.9
(26.6%)
17.Secondary Outcome
Title LY450139 Population Pharmacokinetics: Volume of Distribution of LY450139
Hide Description Model-estimated apparent volume of distribution. Volume of distribution is a measure of the extent to which drug distributes in the body.
Time Frame 6 weeks, 12 weeks, and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized to LY450139 with sufficient dosing information and concentration data to allow estimation of pharmacokinetic parameters.
Arm/Group Title 140 mg LY450139
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Overall Number of Participants Analyzed 517
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: liters (L)
66.1
(26.2%)
18.Secondary Outcome
Title Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) at 4 Weeks After Cessation of Study Drug
Hide Description Semi-structured interview. Participant's cognitive status rated across 6 domains of functioning: memory, orientation, judgment/problem solving, community affairs, home/hobbies, personal care. Severity score assigned for each of 6 domains; total score (SB) ranges: 0 to 18. Higher scores=greater disease severity. Least Squares Mean value controlled for baseline value, age, investigator, visit, and concomitant standard of care medication. LY450139 dosing stopped due to evidence of dose-dependent cognitive/functional worsening. Participants followed off-dose for 32 weeks, but CDR-SB not assessed.
Time Frame Baseline (randomization), 4 weeks following treatment cessation
Hide Outcome Measure Data
Hide Analysis Population Description
August 2010: all dosing was stopped after protocol-specified interim review showed dose-dependent cognitive/functional worsening of LY450139-treated participants. Participants were followed off-dose for 32 weeks. No analysis was performed at 4 weeks after cessation of drug since this outcome measure was not assessed during the follow-up period.
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
19.Secondary Outcome
Title Change From Baseline in Neuropsychiatric Inventory (NPI) at 4 Weeks After Cessation of Study Drug
Hide Description NPI assesses psychopathology in participants with dementia and other neurologic disorders. Information is obtained from a caregiver familiar with participant's behavior. Total score ranges from 12 to 144; higher scores indicate greater disease severity. The Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication. All LY450139 dosing stopped due to evidence of dose-dependent cognitive/functional worsening. Participants were followed off-dose for 32 weeks, but NPI was not assessed.
Time Frame Baseline (randomization), 4 weeks following treatment cessation
Hide Outcome Measure Data
Hide Analysis Population Description
August 2010: all dosing was stopped after protocol-specified interim review showed dose-dependent cognitive/functional worsening of LY450139-treated participants. Participants were followed off-dose for 32 weeks. No analysis was performed at 4 weeks after cessation of drug since this outcome measure was not assessed during the follow-up period.
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
20.Secondary Outcome
Title Change From Baseline in Resource Utilization in Dementia-Lite (RUD-Lite) at 4 Weeks After Cessation of Study Drug
Hide Description Assesses healthcare resource utilization (formal and informal care). Information gathered on both care-giving time, work status) and participants (accommodation, healthcare resource utilization) is collected. Reported number of participant hospitalizations. Least Squares (LS) Mean value controlled for age and investigator. All LY450139 dosing was stopped due to evidence of dose-dependent cognitive/functional worsening. Participants were followed off-dose for 32 weeks, but RUD-Lite was not assessed.
Time Frame Baseline (randomization), 4 weeks following treatment cessation
Hide Outcome Measure Data
Hide Analysis Population Description
August 2010: all dosing was stopped after protocol-specified interim review showed dose-dependent cognitive/functional worsening of LY450139-treated participants. Participants were followed off-dose for 32 weeks. No analysis was performed at 4 weeks after cessation of drug since this outcome measure was not assessed during the follow-up period.
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
21.Secondary Outcome
Title 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
Hide Description EQ-5D (proxy version) measures mobility, self-care, usual activities, pain/discomfort, anxiety/depression. 3 severity levels: no, some, severe problems. VAS assesses caregiver's impression of participant's health state; score ranges: 0 to 100. Lower scores=greater disease severity. Least Squares (LS) Mean value controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication. All LY450139 dosing was stopped due to evidence of dose-dependent cognitive/functional worsening. Participants were followed off-dose for 32 weeks, but EQ-5D VAS was not assessed.
Time Frame Baseline (randomization), 4 weeks following treatment cessation
Hide Outcome Measure Data
Hide Analysis Population Description
August 2010: all dosing was stopped after protocol-specified interim review showed dose-dependent cognitive/functional worsening of LY450139-treated participants. Participants were followed off-dose for 32 weeks. No analysis was performed at 4 weeks after cessation of drug since this outcome measure was not assessed during the follow-up period.
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
22.Secondary Outcome
Title Change From Baseline in Quality of Life in Alzheimer's Disease (QoL-AD) at 4 Weeks After Cessation of Study Drug
Hide Description Assess QoL for AD; participant rates mood, relationships, memory, finances, physical condition, and overall QoL assessment. Each of 13 items rated on a 4-point scale. Sum of items=total score (range: 13-52). Higher scores=greater QoL. Participant's primary caregiver asked to complete same measure. Least Squares Mean value controlled for baseline, age, investigator, visit, and concomitant standard of care (SOC) medication. All LY450139 dosing was stopped due to evidence of dose-dependent cognitive/functional worsening. Participants were followed off-dose for 32 weeks, but QoL-AD not assessed.
Time Frame Baseline (randomization), 4 weeks following treatment cessation
Hide Outcome Measure Data
Hide Analysis Population Description
August 2010: all dosing was stopped after protocol-specified interim review showed dose-dependent cognitive/functional worsening of LY450139-treated participants. Participants were followed off-dose for 32 weeks. No analysis was performed at 4 weeks after cessation of drug since this outcome measure was not assessed during the follow-up period.
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
23.Secondary Outcome
Title Change From Baseline in Mini Mental State Examination (MMSE) 4 Weeks After Cessation of Study Drug
Hide Description Used to assess cognitive function (orientation, memory, attention, ability to name objects, follow verbal/written commands, write a sentence, and copy figures) in elderly participants. Total score ranges: 0 to 30. Lower score indicates greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication. All LY450139 dosing was stopped due to evidence of dose-dependent cognitive/functional worsening. Participants were followed off-dose for 32 weeks, but MMSE was not assessed.
Time Frame Baseline (randomization), 4 weeks following treatment cessation
Hide Outcome Measure Data
Hide Analysis Population Description
August 2010: all dosing was stopped after protocol-specified interim review showed dose-dependent cognitive/functional worsening of LY450139-treated participants. Participants were followed off-dose for 32 weeks. No analysis was performed at 4 weeks after cessation of drug since this outcome measure was not assessed during the follow-up period.
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
24.Secondary Outcome
Title Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog12) at 76 Weeks
Hide Description ADAS-Cog12 is ADAS‑Cog11 augmented with delayed free recall measure, resulting in a total score ranging from 0 to 80. Higher scores indicate greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.
Time Frame Baseline (randomization), 76 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication and had both baseline and post-baseline evaluable data.
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 22 34
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
10.09  (3.29) 10.34  (2.67)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 140 mg LY450139, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.929
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
25.Secondary Outcome
Title Change From Baseline in Alzheimer's Disease Assessment Scale (ADAS-Cog14) at 76 Weeks
Hide Description ADAS-Cog14 is 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 Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.
Time Frame Baseline (randomization), 76 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication.
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 555 553
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
9.23  (0.90) 8.32  (0.82)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 140 mg LY450139, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.437
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
26.Secondary Outcome
Title Change From Baseline in Phosphorylated-Tau (P-tau) Concentration in Spinal Fluid up to 76 Weeks
Hide Description Concentration of p-tau in spinal fluid. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator.
Time Frame Baseline (randomization), up to 76 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication, last observation carried forward (LOCF).
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 555 553
Least Squares Mean (Standard Error)
Unit of Measure: picogram per milliliter (pg/mL)
7.94  (3.06) 14.75  (4.68)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 140 mg LY450139, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.318
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
27.Secondary Outcome
Title Change From Baseline in Amyloid Beta (Aβ) 1-42 Concentration in Spinal Fluid up to 76 Weeks
Hide Description Concentration of an amino acid peptide known as Aβ 1-42 in spinal fluid. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator.
Time Frame Baseline (randomization), up to 76 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication, last observation carried forward (LOCF).
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 555 553
Least Squares Mean (Standard Error)
Unit of Measure: picogram per milliliter (pg/mL)
19.20  (26.03) -21.39  (35.35)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 140 mg LY450139, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.417
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
28.Secondary Outcome
Title Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog12) at 16 Weeks After Cessation of Study Drug
Hide Description ADAS-Cog12 is ADAS‑Cog11 augmented with delayed free recall measure, resulting in a total score ranging from 0 to 80. Higher scores indicate greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.
Time Frame Baseline (randomization), 16 weeks following treatment cessation
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication and had both baseline and post-baseline evaluable data.
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 312 430
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
5.33  (0.74) 5.14  (0.67)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 140 mg LY450139, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.805
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
29.Secondary Outcome
Title Change From Baseline in Alzheimer's Disease Assessment Scale (ADAS-Cog14) at 16 Weeks After Cessation of Study Drug
Hide Description ADAS-Cog14 is 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 Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, concomitant standard of care (SOC) medication.
Time Frame Baseline (randomization), 16 weeks following treatment cessation
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication and had both baseline and post-baseline evaluable data.
Arm/Group Title 140 mg LY450139 Placebo
Hide Arm/Group Description:
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
Overall Number of Participants Analyzed 312 430
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
6.00  (0.82) 5.89  (0.73)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 140 mg LY450139, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.893
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo- (Initial Treatment Period [NT]) 140 mg LY450139- NT Placebo- (Delayed Start Period [DO]) 140 mg LY450139- DO Placebo-Safety Follow Up Period (SFU) 140 mg LY450139 - SFU
Hide Arm/Group Description Participants received placebo orally once daily for the first 76 weeks. Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 76. After Week 76, participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88. After Week 76, participants received 140 mg LY450139 orally once daily until Week 88. For SFU, study drug had been stopped and period was optional to enter; Participants entered from Placebo initial treatment or delayed start or did not enter SFU. For SFU, study drug had been stopped and period was optional to enter; Participants entered from 140 mg LY450139 initial treatment or delayed start or did not enter SFU.
All-Cause Mortality
Placebo- (Initial Treatment Period [NT]) 140 mg LY450139- NT Placebo- (Delayed Start Period [DO]) 140 mg LY450139- DO Placebo-Safety Follow Up Period (SFU) 140 mg LY450139 - SFU
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--    
Hide Serious Adverse Events
Placebo- (Initial Treatment Period [NT]) 140 mg LY450139- NT Placebo- (Delayed Start Period [DO]) 140 mg LY450139- DO Placebo-Safety Follow Up Period (SFU) 140 mg LY450139 - SFU
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   60/555 (10.81%)      92/556 (16.55%)      7/34 (20.59%)      1/22 (4.55%)      22/430 (5.12%)      20/312 (6.41%)    
Blood and lymphatic system disorders             
Anaemia folate deficiency  1  0/555 (0.00%)  0 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 1/430 (0.23%)  1 0/312 (0.00%)  0
Cardiac disorders             
Angina pectoris  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Aortic valve stenosis  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 1/312 (0.32%)  1
Atrial fibrillation  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Bradycardia  1  0/555 (0.00%)  0 2/556 (0.36%)  2 0/34 (0.00%)  0 0/22 (0.00%)  0 1/430 (0.23%)  1 0/312 (0.00%)  0
Cardiac arrest  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 1/430 (0.23%)  1 0/312 (0.00%)  0
Cardiac failure  1  0/555 (0.00%)  0 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 1/430 (0.23%)  1 0/312 (0.00%)  0
Cardiac failure acute  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Myocardial infarction  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Myocardial ischaemia  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 2/430 (0.47%)  2 0/312 (0.00%)  0
Ear and labyrinth disorders             
Vertigo  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Eye disorders             
Cataract  1  2/555 (0.36%)  2 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 1/430 (0.23%)  1 0/312 (0.00%)  0
Retinal artery occlusion  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Gastrointestinal disorders             
Abdominal pain  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Abdominal pain upper  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 1/22 (4.55%)  1 0/430 (0.00%)  0 1/312 (0.32%)  1
Colitis ischaemic  1  1/555 (0.18%)  1 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Colonic polyp  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 1/312 (0.32%)  1
Diarrhoea  1  0/555 (0.00%)  0 2/556 (0.36%)  2 1/34 (2.94%)  1 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Diverticulum intestinal  1  0/555 (0.00%)  0 0/556 (0.00%)  0 1/34 (2.94%)  1 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Duodenal ulcer  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 1/430 (0.23%)  1 0/312 (0.00%)  0
Enteritis  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 1/430 (0.23%)  1 0/312 (0.00%)  0
Enterocolitis  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Gastrointestinal disorder  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Gastrointestinal haemorrhage  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Haematemesis  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Haematochezia  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Haemorrhoids  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Intestinal obstruction  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Pancreatitis  1  1/555 (0.18%)  1 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Pancreatitis acute  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Upper gastrointestinal haemorrhage  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Vomiting  1  0/555 (0.00%)  0 0/556 (0.00%)  0 1/34 (2.94%)  1 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
General disorders             
Accidental death  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Chest pain  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Death  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 1/430 (0.23%)  1 0/312 (0.00%)  0
Sudden cardiac death  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Hepatobiliary disorders             
Bile duct stone  1  0/555 (0.00%)  0 1/556 (0.18%)  2 0/34 (0.00%)  0 1/22 (4.55%)  1 0/430 (0.00%)  0 1/312 (0.32%)  1
Cholangitis  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Cholecystitis  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Cholecystitis acute  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Cholecystitis chronic  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Cholelithiasis  1  1/555 (0.18%)  1 2/556 (0.36%)  2 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 1/312 (0.32%)  1
Hepatitis toxic  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Jaundice cholestatic  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Infections and infestations             
Anal abscess  1  0/555 (0.00%)  0 2/556 (0.36%)  2 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Appendicitis  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 1/430 (0.23%)  1 0/312 (0.00%)  0
Bronchitis  1  0/555 (0.00%)  0 2/556 (0.36%)  2 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 1/312 (0.32%)  1
Bronchopneumonia  1  0/555 (0.00%)  0 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 1/430 (0.23%)  1 0/312 (0.00%)  0
Clostridial infection  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Clostridium difficile colitis  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Cystitis  1  0/555 (0.00%)  0 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 1/430 (0.23%)  1 0/312 (0.00%)  0
Diabetic gangrene  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Gastroenteritis  1  0/555 (0.00%)  0 2/556 (0.36%)  2 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Meningitis bacterial  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Pneumonia  1  2/555 (0.36%)  2 12/556 (2.16%)  13 0/34 (0.00%)  0 0/22 (0.00%)  0 2/430 (0.47%)  2 1/312 (0.32%)  1
Pneumonia staphylococcal  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Pyelonephritis acute  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Salmonella sepsis  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Sepsis  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Septic shock  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Staphylococcal infection  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Urinary tract infection  1  3/555 (0.54%)  3 4/556 (0.72%)  4 1/34 (2.94%)  1 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Urosepsis  1  2/555 (0.36%)  2 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Injury, poisoning and procedural complications             
Accidental overdose  1  0/555 (0.00%)  0 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 1/430 (0.23%)  1 0/312 (0.00%)  0
Ankle fracture  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Fall  1  3/555 (0.54%)  3 3/556 (0.54%)  3 0/34 (0.00%)  0 0/22 (0.00%)  0 1/430 (0.23%)  1 0/312 (0.00%)  0
Femoral neck fracture  1  2/555 (0.36%)  3 2/556 (0.36%)  2 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Femur fracture  1  0/555 (0.00%)  0 2/556 (0.36%)  2 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Fractured sacrum  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Heat exhaustion  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Hip fracture  1  0/555 (0.00%)  0 2/556 (0.36%)  2 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Humerus fracture  1  0/555 (0.00%)  0 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 1/312 (0.32%)  1
Lower limb fracture  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 1/430 (0.23%)  1 0/312 (0.00%)  0
Patella fracture  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Post lumbar puncture syndrome  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Radius fracture  1  0/555 (0.00%)  0 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 1/430 (0.23%)  1 0/312 (0.00%)  0
Rib fracture  1  1/555 (0.18%)  1 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Spinal compression fracture  1  0/555 (0.00%)  0 2/556 (0.36%)  2 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 2/312 (0.64%)  2
Subdural haematoma  1  1/555 (0.18%)  1 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Thoracic vertebral fracture  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Upper limb fracture  1  0/555 (0.00%)  0 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 1/312 (0.32%)  1
Investigations             
Blood glucose increased  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Medical observation  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Metabolism and nutrition disorders             
Decreased appetite  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Dehydration  1  2/555 (0.36%)  2 3/556 (0.54%)  3 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Diabetes mellitus  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Food intolerance  1  0/555 (0.00%)  0 0/556 (0.00%)  0 1/34 (2.94%)  1 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Hypokalaemia  1  0/555 (0.00%)  0 0/556 (0.00%)  0 1/34 (2.94%)  1 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Musculoskeletal and connective tissue disorders             
Back pain  1  0/555 (0.00%)  0 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 1/312 (0.32%)  1
Foot deformity  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Intervertebral disc protrusion  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Lumbar spinal stenosis  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 1/312 (0.32%)  1
Muscular weakness  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Osteitis  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Osteoarthritis  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Rhabdomyolysis  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Rheumatoid arthritis  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Basal cell carcinoma  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Bile duct cancer  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Breast cancer  1  0/555 (0.00%)  0 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 1/312 (0.32%)  1
Breast cancer metastatic  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Colon cancer  1  1/555 (0.18%)  1 3/556 (0.54%)  3 0/34 (0.00%)  0 0/22 (0.00%)  0 2/430 (0.47%)  2 0/312 (0.00%)  0
Endometrial cancer  1  1/328 (0.30%)  1 0/317 (0.00%)  0 0/20 (0.00%)  0 0/12 (0.00%)  0 0/251 (0.00%)  0 0/184 (0.00%)  0
Hepatic cancer metastatic  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Keratoacanthoma  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Lung adenocarcinoma  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Lung cancer metastatic  1  0/555 (0.00%)  0 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 1/430 (0.23%)  1 0/312 (0.00%)  0
Lung neoplasm malignant  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Neurilemmoma  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Neuroendocrine carcinoma  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Non-small cell lung cancer  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Oesophageal carcinoma  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Pancreatic carcinoma  1  0/555 (0.00%)  0 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 1/430 (0.23%)  1 0/312 (0.00%)  0
Squamous cell carcinoma  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 1/312 (0.32%)  1
Squamous cell carcinoma of skin  1  1/555 (0.18%)  1 3/556 (0.54%)  3 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 1/312 (0.32%)  1
Nervous system disorders             
Cerebral haemorrhage  1  2/555 (0.36%)  2 2/556 (0.36%)  2 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Cerebral infarction  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 1/312 (0.32%)  1
Coma  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Convulsion  1  1/555 (0.18%)  1 3/556 (0.54%)  3 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 1/312 (0.32%)  1
Dementia alzheimer's type  1  2/555 (0.36%)  2 2/556 (0.36%)  2 1/34 (2.94%)  1 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Encephalopathy  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Guillain-barre syndrome  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Haemorrhage intracranial  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Haemorrhagic stroke  1  1/555 (0.18%)  1 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Hydrocephalus  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Loss of consciousness  1  2/555 (0.36%)  2 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 1/430 (0.23%)  1 0/312 (0.00%)  0
Normal pressure hydrocephalus  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Status epilepticus  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Syncope  1  4/555 (0.72%)  4 5/556 (0.90%)  5 1/34 (2.94%)  1 0/22 (0.00%)  0 1/430 (0.23%)  1 1/312 (0.32%)  1
Thalamus haemorrhage  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Psychiatric disorders             
Aggression  1  1/555 (0.18%)  1 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Agitation  1  1/555 (0.18%)  1 2/556 (0.36%)  2 1/34 (2.94%)  1 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Confusional state  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Delirium  1  0/555 (0.00%)  0 2/556 (0.36%)  2 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Hallucination  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Suicidal ideation  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Renal and urinary disorders             
Calculus ureteric  1  1/555 (0.18%)  1 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Nephrolithiasis  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Renal failure  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Renal failure acute  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Urethral caruncle  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Reproductive system and breast disorders             
Prostatitis  1  0/227 (0.00%)  0 1/239 (0.42%)  1 0/14 (0.00%)  0 0/10 (0.00%)  0 0/179 (0.00%)  0 1/128 (0.78%)  1
Respiratory, thoracic and mediastinal disorders             
Choking  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Chronic obstructive pulmonary disease  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Hypoxia  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Respiratory arrest  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Skin and subcutaneous tissue disorders             
Dermatitis  1  0/555 (0.00%)  0 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 1/312 (0.32%)  1
Hyperhidrosis  1  0/555 (0.00%)  0 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 1/430 (0.23%)  1 0/312 (0.00%)  0
Rash papular  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Urticaria  1  0/555 (0.00%)  0 0/556 (0.00%)  0 1/34 (2.94%)  1 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Social circumstances             
Activities of daily living impaired  1  0/555 (0.00%)  0 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 1/312 (0.32%)  1
Vascular disorders             
Aortic dissection  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 1/312 (0.32%)  1
Arteriosclerosis obliterans  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Deep vein thrombosis  1  0/555 (0.00%)  0 1/556 (0.18%)  1 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Haematoma  1  1/555 (0.18%)  1 0/556 (0.00%)  0 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Hypertension  1  1/555 (0.18%)  1 0/556 (0.00%)  0 1/34 (2.94%)  1 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo- (Initial Treatment Period [NT]) 140 mg LY450139- NT Placebo- (Delayed Start Period [DO]) 140 mg LY450139- DO Placebo-Safety Follow Up Period (SFU) 140 mg LY450139 - SFU
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   130/555 (23.42%)      258/556 (46.40%)      6/34 (17.65%)      0/22 (0.00%)      0/430 (0.00%)      0/312 (0.00%)    
Gastrointestinal disorders             
Diarrhoea  1  33/555 (5.95%)  42 58/556 (10.43%)  72 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Hiatus hernia  1  0/555 (0.00%)  0 0/556 (0.00%)  0 2/34 (5.88%)  2 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Nausea  1  19/555 (3.42%)  24 49/556 (8.81%)  53 2/34 (5.88%)  2 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Vomiting  1  17/555 (3.06%)  22 33/556 (5.94%)  46 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Infections and infestations             
Nasopharyngitis  1  22/555 (3.96%)  24 28/556 (5.04%)  31 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Urinary tract infection  1  0/555 (0.00%)  0 0/556 (0.00%)  0 3/34 (8.82%)  3 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Investigations             
Prostatic specific antigen increased  1  0/227 (0.00%)  0 0/239 (0.00%)  0 1/14 (7.14%)  1 0/10 (0.00%)  0 0/179 (0.00%)  0 0/128 (0.00%)  0
Weight decreased  1  16/555 (2.88%)  16 42/556 (7.55%)  42 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Metabolism and nutrition disorders             
Decreased appetite  1  16/555 (2.88%)  16 52/556 (9.35%)  53 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Nervous system disorders             
Dizziness  1  15/555 (2.70%)  15 30/556 (5.40%)  32 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Headache  1  24/555 (4.32%)  29 40/556 (7.19%)  45 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Skin and subcutaneous tissue disorders             
Hair colour changes  1  4/555 (0.72%)  4 53/556 (9.53%)  53 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Rash erythematous  1  5/555 (0.90%)  6 36/556 (6.47%)  42 0/34 (0.00%)  0 0/22 (0.00%)  0 0/430 (0.00%)  0 0/312 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.1
All dosing for 4-week post-study drug cessation timeframe outcome measures stopped after protocol-specified interim review showed dose-dependent cognitive/functional worsening for LY450139 participants. No assessments made during 32-week follow up.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00762411    
Other Study ID Numbers: 11271
H6L-MC-LFBC ( Other Identifier: Eli Lilly and Company )
First Submitted: September 26, 2008
First Posted: September 30, 2008
Results First Submitted: November 6, 2013
Results First Posted: September 25, 2014
Last Update Posted: February 16, 2015