IDENTITY-2: Effects of LY450139, on the Progression of Alzheimer's Disease as Compared With Placebo
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT00762411
Collaborator
(none)
1,111
91
2
30.9
12.2
0.4
Study Details
Study Description
Brief Summary
Alzheimer's disease (AD) is a fatal degenerative disease of the brain for which there is no cure. AD causes brain cells to die. AD is thought to be caused by an excess of beta amyloid (β-amyloid), a sticky protein in the brain that forms amyloid plaques. At autopsy, AD patients are required to have these amyloid plaques in the brain in order to have a definitive diagnosis of AD. Inhibiting the enzyme gamma-secretase (γ-secretase) lowers the production of β-amyloid. Semagacestat (LY450139) is a functional γ-secretase inhibitor and was shown to lower β-amyloid in blood and spinal fluid in humans tested thus far and in blood, spinal fluid and brain in animals tested thus far. This study used several different tests to measure the effect of semagacestat on both β-amyloid and amyloid plaques for some patients. The buildup of amyloid plaques was measured by a brain scan that takes a picture of amyloid plaques in the brain. Other tests measured the overall function of the brain and brain size in some patients. In this trial, patients who initially received placebo (inactive sugar pill) were, at a certain point in the study, switched over to active drug, semagacestat. In other words, all patients could eventually receive active drug. Each patient's participation could last approximately 2 years. Patients taking approved AD medications were permitted to participate in this study and continue taking these medications during the study. All patients who completed this study had the option to continue receiving semagacestat by participating in an open label study.
Preliminary results from this study (LFBC) (and another similar study LFAN [NCT00594568]) showed semagacestat did not slow disease progression and was associated with worsening of clinical measures of cognition and the ability to perform activities of daily living. Study drug was stopped in all studies. LFBC, LFAN and open label LFBF (NCT01035138) have been amended to continue collecting safety data, including cognitive scores, for at least seven months. The CT-Registry will reflect results of analyses from the original protocol in addition to those from the amended protocol.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
1111 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Effect of LY450139 a y-Secretase Inhibitor, on the Progression of Alzheimer's Disease as Compared With Placebo
Study Start Date
:
Sep 1, 2008
Actual Primary Completion Date
:
Apr 1, 2011
Actual Study Completion Date
:
Apr 1, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LY450139 Participants received 60 milligrams (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. |
Drug: LY450139
Administered orally once daily.
Other Names:
|
| Placebo Comparator: Placebo 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. |
Drug: Placebo
Administered orally once daily.
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog11) at 76 Weeks [Baseline (randomization), 76 weeks]
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.
- Change From Baseline in Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog11) at 16 Weeks After Cessation of Study Drug [Baseline (randomization), 16 weeks following treatment cessation]
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.
- Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at 76 Weeks [Baseline (randomization), 76 weeks]
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.
- Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at 16 Weeks After Cessation of Study Drug [Baseline (randomization), 16 weeks following treatment cessation]
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.
Secondary Outcome Measures
- Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) at 76 Weeks [Baseline (randomization), 76 weeks]
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.
- Change From Baseline in Neuropsychiatric Inventory (NPI) at 76 Weeks [Baseline (randomization), 76 weeks]
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.
- Change From Baseline in the Resource Utilization in Dementia-Lite (RUD-Lite) up to 76 Weeks [Baseline (randomization), up to 76 weeks]
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.
- 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 [Baseline (randomization), 76 weeks]
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.
- Change From Baseline in Quality of Life in Alzheimer's Disease (QoL-AD) at 76 Weeks [Baseline (randomization), 76 weeks]
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.
- Change From Baseline in Mini Mental State Examination (MMSE) at 76 Weeks [Baseline (randomization), 76 weeks]
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
- Percent Change From Baseline in Amyloid Beta (Aβ) 1-42 Plasma Concentration at 52 Weeks [Baseline (randomization), 52 weeks]
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.
- Change From Baseline in Positron Emission Tomography (PET) Using Fluorine-18 Fluorodeoxyglucose (18F-FDG) at 76 Weeks [Baseline (randomization), 76 weeks]
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.
- Change From Baseline in Hippocampal Volume Using Volumetric Magnetic Resonance Imaging (vMRI) up to 76 Weeks [Baseline (randomization), up to 76 weeks]
The vMRI assessment of right and left hippocampal volume is reported. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator.
- Change From Baseline in Amyloid Imaging Positron Emission Tomography (AV-45 PET) up to 76 Weeks [Baseline (randomization), up to 76 weeks]
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.
- Change From Baseline in Tau Concentration in Spinal Fluid up to 76 Weeks [Baseline (randomization), up to 76 weeks]
Concentration of total tau in spinal fluid. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator.
- LY450139 Population Pharmacokinetics: Clearance of LY450139 [6 weeks, 12 weeks, and 52 weeks]
Model estimated apparent oral clearance. Clearance is defined as the volume of plasma which is completely cleared of drug (LY450139) per unit time.
- LY450139 Population Pharmacokinetics: Volume of Distribution of LY450139 [6 weeks, 12 weeks, and 52 weeks]
Model-estimated apparent volume of distribution. Volume of distribution is a measure of the extent to which drug distributes in the body.
- Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) at 4 Weeks After Cessation of Study Drug [Baseline (randomization), 4 weeks following treatment cessation]
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.
- Change From Baseline in Neuropsychiatric Inventory (NPI) at 4 Weeks After Cessation of Study Drug [Baseline (randomization), 4 weeks following treatment cessation]
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.
- Change From Baseline in Resource Utilization in Dementia-Lite (RUD-Lite) at 4 Weeks After Cessation of Study Drug [Baseline (randomization), 4 weeks following treatment cessation]
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.
- 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 [Baseline (randomization), 4 weeks following treatment cessation]
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.
- Change From Baseline in Quality of Life in Alzheimer's Disease (QoL-AD) at 4 Weeks After Cessation of Study Drug [Baseline (randomization), 4 weeks following treatment cessation]
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.
- Change From Baseline in Mini Mental State Examination (MMSE) 4 Weeks After Cessation of Study Drug [Baseline (randomization), 4 weeks following treatment cessation]
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.
- Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog12) at 76 Weeks [Baseline (randomization), 76 weeks]
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.
- Change From Baseline in Alzheimer's Disease Assessment Scale (ADAS-Cog14) at 76 Weeks [Baseline (randomization), 76 weeks]
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.
- Change From Baseline in Phosphorylated-Tau (P-tau) Concentration in Spinal Fluid up to 76 Weeks [Baseline (randomization), up to 76 weeks]
Concentration of p-tau in spinal fluid. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator.
- Change From Baseline in Amyloid Beta (Aβ) 1-42 Concentration in Spinal Fluid up to 76 Weeks [Baseline (randomization), up to 76 weeks]
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.
- Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog12) at 16 Weeks After Cessation of Study Drug [Baseline (randomization), 16 weeks following treatment cessation]
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.
- Change From Baseline in Alzheimer's Disease Assessment Scale (ADAS-Cog14) at 16 Weeks After Cessation of Study Drug [Baseline (randomization), 16 weeks following treatment cessation]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
55 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Phoenix | Arizona | United States | 85004 |
| 2 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Costa Mesa | California | United States | 92626 |
| 3 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | La Jolla | California | United States | 92037 |
| 4 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Laguna Hills | California | United States | 92653 |
| 5 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Los Angeles | California | United States | 90036 |
| 6 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Oxnard | California | United States | 93030 |
| 7 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | San Francisco | California | United States | 94109 |
| 8 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Boca Raton | Florida | United States | 33431 |
| 9 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Hallandale Beach | Florida | United States | 33009 |
| 10 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Hollywood | Florida | United States | 33021 |
| 11 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Miami | Florida | United States | 33137 |
| 12 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Orlando | Florida | United States | 32806 |
| 13 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Tampa | Florida | United States | 33609 |
| 14 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | New Orleans | Louisiana | United States | 70131 |
| 15 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Shreveport | Louisiana | United States | 71104 |
| 16 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Hattiesburg | Mississippi | United States | 39401 |
| 17 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Omaha | Nebraska | United States | 68105 |
| 18 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Albany | New York | United States | 12205 |
| 19 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Manhasset | New York | United States | 11030 |
| 20 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Durham | North Carolina | United States | 27710 |
| 21 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Oklahoma City | Oklahoma | United States | 73103 |
| 22 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Philadelphia | Pennsylvania | United States | 19131 |
| 23 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Rio De Janeiro | Brazil | 21020-130 | |
| 24 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Salvador | Brazil | 40301500 | |
| 25 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | São Paulo | Brazil | 040024-002 | |
| 26 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Sofia | Bulgaria | 1527 | |
| 27 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Winnipeg | Manitoba | Canada | R3N 0K6 |
| 28 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Saint John | New Brunswick | Canada | E2L 3L6 |
| 29 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | London | Ontario | Canada | N6C 5J1 |
| 30 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Ottawa | Ontario | Canada | K1N 5C8 |
| 31 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Peterborough | Ontario | Canada | K9H2P4 |
| 32 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Toronto | Ontario | Canada | M3B2S7 |
| 33 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Greenfield Park | Quebec | Canada | J4V 2J2 |
| 34 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Montreal | Quebec | Canada | H1T 2M4 |
| 35 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Verdun | Quebec | Canada | H4H 1R3 |
| 36 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Beijing | China | 100853 | |
| 37 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Shanghai | China | 200025 | |
| 38 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Xi'An | China | 710038 | |
| 39 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Montpellier | France | 34295 | |
| 40 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Paris | France | 75651 | |
| 41 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Poitiers | France | 86021 | |
| 42 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Strasbourg | France | 67091 | |
| 43 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Berlin | Germany | 10629 | |
| 44 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Frankfurt | Germany | 60528 | |
| 45 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Hamburg | Germany | 22083 | |
| 46 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Heidelberg | Germany | 69115 | |
| 47 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Mannheim | Germany | 68165 | |
| 48 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Budapest | Hungary | H-1083 | |
| 49 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Esztergom | Hungary | 2500 | |
| 50 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Boggiovara | Italy | 41100 | |
| 51 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Cassino | Italy | 03043 | |
| 52 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Milano | Italy | 20122 | |
| 53 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Parma | Italy | 43100 | |
| 54 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Akita | Japan | 010-0874 | |
| 55 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Fukuoka | Japan | 814-0180 | |
| 56 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Hyogo | Japan | 655-0037 | |
| 57 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Ibaraki | Japan | 305-8576 | |
| 58 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Iwate | Japan | 020-8505 | |
| 59 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Kanagawa | Japan | 251-0038 | |
| 60 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Kumamoto | Japan | 861-8002 | |
| 61 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Kyoto | Japan | 606-0851 | |
| 62 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Nagasaki | Japan | 852-8108 | |
| 63 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Osaka | Japan | 599-8263 | |
| 64 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Saitama | Japan | 344-0036 | |
| 65 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Tokyo | Japan | 113-8655 | |
| 66 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Seoul | Korea, Republic of | 139-707 | |
| 67 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Suwon | Korea, Republic of | 443-721 | |
| 68 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Aguascalientes | Mexico | 20217 | |
| 69 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Monterrey | Mexico | 64710 | |
| 70 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Saltillo | Mexico | 25000 | |
| 71 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Bucharest | Romania | 011241 | |
| 72 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Timisoara | Romania | 300736 | |
| 73 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Ekaterinburg | Russian Federation | 620030 | |
| 74 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Kazan | Russian Federation | 420101 | |
| 75 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Saint Petersburg | Russian Federation | 190021 | |
| 76 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Saratov | Russian Federation | 410028 | |
| 77 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Belgrade | Serbia | 11000 | |
| 78 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Kragujevac | Serbia | 34000 | |
| 79 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Changhua | Taiwan | 500 | |
| 80 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Tainan | Taiwan | 70403 | |
| 81 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Taipei | Taiwan | 111 | |
| 82 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Tao-Yuan | Taiwan | 333 | |
| 83 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Eskisehir | Turkey | 26480 | |
| 84 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Istanbul | Turkey | 34452 | |
| 85 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Izmir | Turkey | 35340 | |
| 86 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Samsun | Turkey | ||
| 87 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Dnipropetrovsk | Ukraine | 49616 | |
| 88 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Donetsk | Ukraine | 83037 | |
| 89 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Kherson | Ukraine | 73488 | |
| 90 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Kyiv | Ukraine | 04080 | |
| 91 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Odesa | Ukraine | 65006 |
Sponsors and Collaborators
- Eli Lilly and Company
Investigators
- Study Director: Call 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559 Mon - Fri 9 AM - 5 PM eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00762411
Other Study ID Numbers:
- 11271
- H6L-MC-LFBC
First Posted:
Sep 30, 2008
Last Update Posted:
Feb 16, 2015
Last Verified:
Jan 1, 2015
Keywords provided by Eli Lilly and Company
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | 140 mg LY450139 | Placebo |
|---|---|---|
| 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 | 553 |
| COMPLETED | 22 | 34 |
| NOT COMPLETED | 534 | 521 |
| Period Title: Initial Treatment | ||
| STARTED | 22 | 34 |
| COMPLETED | 5 | 8 |
| NOT COMPLETED | 17 | 26 |
| Period Title: Initial Treatment | ||
| STARTED | 312 | 430 |
| COMPLETED | 228 | 312 |
| NOT COMPLETED | 84 | 118 |
Baseline Characteristics
| Arm/Group Title | 140 mg LY450139 | Placebo | Total |
|---|---|---|---|
| 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 Participants | 555 | 553 | 1108 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
73.4
(8.0)
|
73.0
(8.0)
|
73.2
(8.0)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
316
56.9%
|
327
59.1%
|
643
58%
|
| Male |
239
43.1%
|
226
40.9%
|
465
42%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| Caucasian |
358
64.5%
|
354
64%
|
712
64.3%
|
| African |
11
2%
|
8
1.4%
|
19
1.7%
|
| Hispanic |
33
5.9%
|
29
5.2%
|
62
5.6%
|
| East Asian |
150
27%
|
160
28.9%
|
310
28%
|
| West Asian |
3
0.5%
|
2
0.4%
|
5
0.5%
|
| Region of Enrollment (participants) [Number] | |||
| Brazil |
18
3.2%
|
21
3.8%
|
39
3.5%
|
| Bulgaria |
20
3.6%
|
18
3.3%
|
38
3.4%
|
| Canada |
50
9%
|
49
8.9%
|
99
8.9%
|
| China |
22
4%
|
22
4%
|
44
4%
|
| France |
28
5%
|
29
5.2%
|
57
5.1%
|
| Germany |
24
4.3%
|
20
3.6%
|
44
4%
|
| Hungary |
19
3.4%
|
16
2.9%
|
35
3.2%
|
| Italy |
14
2.5%
|
11
2%
|
25
2.3%
|
| Japan |
64
11.5%
|
69
12.5%
|
133
12%
|
| Korea, Republic of |
38
6.8%
|
43
7.8%
|
81
7.3%
|
| Mexico |
26
4.7%
|
24
4.3%
|
50
4.5%
|
| Romania |
20
3.6%
|
17
3.1%
|
37
3.3%
|
| Russian Federation |
15
2.7%
|
19
3.4%
|
34
3.1%
|
| Serbia |
5
0.9%
|
8
1.4%
|
13
1.2%
|
| Taiwan |
25
4.5%
|
24
4.3%
|
49
4.4%
|
| Turkey |
25
4.5%
|
23
4.2%
|
48
4.3%
|
| Ukraine |
19
3.4%
|
20
3.6%
|
39
3.5%
|
| United States |
123
22.2%
|
120
21.7%
|
243
21.9%
|
| Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) Score (n=507, 533) (units on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [units on a scale] |
24.5
(9.1)
|
24.2
(9.1)
|
24.3
(9.1)
|
| Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory Score (n=505, 529) (units on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [units on a scale] |
58.8
(13.3)
|
59.1
(13.8)
|
58.9
(13.5)
|
Outcome Measures
| Title | Change From Baseline in Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog11) at 76 Weeks |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 555 | 553 |
| Least Squares Mean (Standard Error) [units on a scale] |
7.37
(0.79)
|
6.77
(0.72)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 140 mg LY450139, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.560 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Title | Change From Baseline in Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog11) at 16 Weeks After Cessation of Study Drug |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 312 | 430 |
| Least Squares Mean (Standard Error) [units on a scale] |
4.81
(0.70)
|
4.85
(0.63)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 140 mg LY450139, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.959 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Title | Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at 76 Weeks |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 555 | 553 |
| Least Squares Mean (Standard Error) [units on a scale] |
-10.49
(0.98)
|
-9.77
(0.90)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 140 mg LY450139, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.567 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| 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 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 312 | 430 |
| Least Squares Mean (Standard Error) [units on a scale] |
-8.88
(0.93)
|
-7.68
(0.84)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 140 mg LY450139, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.199 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Title | Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) at 76 Weeks |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 22 | 34 |
| Least Squares Mean (Standard Error) [units on a scale] |
3.05
(1.10)
|
4.00
(0.92)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 140 mg LY450139, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.294 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Title | Change From Baseline in Neuropsychiatric Inventory (NPI) at 76 Weeks |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 555 | 553 |
| Least Squares Mean (Standard Error) [units on a scale] |
2.94
(1.04)
|
3.84
(0.95)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 140 mg LY450139, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.477 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Title | Change From Baseline in the Resource Utilization in Dementia-Lite (RUD-Lite) up to 76 Weeks |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 555 | 553 |
| Least Squares Mean (Standard Error) [number of hospitalizations] |
0.72
(0.14)
|
0.82
(0.16)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 140 mg LY450139, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.673 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| 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 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 555 | 553 |
| Least Squares Mean (Standard Error) [units on a scale] |
-4.46
(1.78)
|
-3.38
(1.64)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 140 mg LY450139, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.622 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Title | Change From Baseline in Quality of Life in Alzheimer's Disease (QoL-AD) at 76 Weeks |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 555 | 553 |
| Least Squares Mean (Standard Error) [units on a scale] |
-1.83
(0.47)
|
-1.05
(0.43)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 140 mg LY450139, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.178 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Title | Change From Baseline in Mini Mental State Examination (MMSE) at 76 Weeks |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 555 | 553 |
| Least Squares Mean (Standard Error) [units on a scale] |
-3.56
(0.38)
|
-3.35
(0.35)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 140 mg LY450139, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.632 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Title | Percent Change From Baseline in Amyloid Beta (Aβ) 1-42 Plasma Concentration at 52 Weeks |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 555 | 553 |
| Least Squares Mean (Standard Error) [picogram per milliliter (pg/mL)] |
-16.03
(28.33)
|
76.37
(24.73)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 140 mg LY450139, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.009 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in Positron Emission Tomography (PET) Using Fluorine-18 Fluorodeoxyglucose (18F-FDG) at 76 Weeks |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 74 | 80 |
| Least Squares Mean (Standard Error) [ratio] |
-0.13
(0.05)
|
-0.08
(0.03)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 140 mg LY450139, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.426 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in Hippocampal Volume Using Volumetric Magnetic Resonance Imaging (vMRI) up to 76 Weeks |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 555 | 553 |
| Right Hippocampal Volume |
-158.50
(29.44)
|
-73.60
(24.18)
|
| Left Hippocampal Volume |
-84.41
(61.96)
|
-111.27
(49.22)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 140 mg LY450139, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.101 |
| Comments | This is the p-value for the Right Hippocampal Volume. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 140 mg LY450139, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.772 |
| Comments | This is the p-value for the Left Hippocampal Volume. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in Amyloid Imaging Positron Emission Tomography (AV-45 PET) up to 76 Weeks |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 555 | 553 |
| Least Squares Mean (Standard Error) [ratio] |
-0.36
(0.23)
|
0.16
(0.11)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 140 mg LY450139, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.326 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in Tau Concentration in Spinal Fluid up to 76 Weeks |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 555 | 553 |
| Least Squares Mean (Standard Error) [picogram per milliliter (pg/mL)] |
-11.60
(39.39)
|
117.88
(53.58)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 140 mg LY450139, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.117 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | LY450139 Population Pharmacokinetics: Clearance of LY450139 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|
| 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. |
| Measure Participants | 517 |
| Geometric Mean (Geometric Coefficient of Variation) [liters per hour (L/h)] |
18.9
(26.6)
|
| Title | LY450139 Population Pharmacokinetics: Volume of Distribution of LY450139 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|
| 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. |
| Measure Participants | 517 |
| Geometric Mean (Geometric Coefficient of Variation) [liters (L)] |
66.1
(26.2)
|
| Title | Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) at 4 Weeks After Cessation of Study Drug |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 0 | 0 |
| Title | Change From Baseline in Neuropsychiatric Inventory (NPI) at 4 Weeks After Cessation of Study Drug |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 0 | 0 |
| Title | Change From Baseline in Resource Utilization in Dementia-Lite (RUD-Lite) at 4 Weeks After Cessation of Study Drug |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 0 | 0 |
| 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 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 0 | 0 |
| Title | Change From Baseline in Quality of Life in Alzheimer's Disease (QoL-AD) at 4 Weeks After Cessation of Study Drug |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 0 | 0 |
| Title | Change From Baseline in Mini Mental State Examination (MMSE) 4 Weeks After Cessation of Study Drug |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 0 | 0 |
| Title | Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog12) at 76 Weeks |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 22 | 34 |
| Least Squares Mean (Standard Error) [units on a scale] |
10.09
(3.29)
|
10.34
(2.67)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 140 mg LY450139, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.929 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Title | Change From Baseline in Alzheimer's Disease Assessment Scale (ADAS-Cog14) at 76 Weeks |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 555 | 553 |
| Least Squares Mean (Standard Error) [units on a scale] |
9.23
(0.90)
|
8.32
(0.82)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 140 mg LY450139, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.437 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Title | Change From Baseline in Phosphorylated-Tau (P-tau) Concentration in Spinal Fluid up to 76 Weeks |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 555 | 553 |
| Least Squares Mean (Standard Error) [picogram per milliliter (pg/mL)] |
7.94
(3.06)
|
14.75
(4.68)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 140 mg LY450139, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.318 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in Amyloid Beta (Aβ) 1-42 Concentration in Spinal Fluid up to 76 Weeks |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 555 | 553 |
| Least Squares Mean (Standard Error) [picogram per milliliter (pg/mL)] |
19.20
(26.03)
|
-21.39
(35.35)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 140 mg LY450139, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.417 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog12) at 16 Weeks After Cessation of Study Drug |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 312 | 430 |
| Least Squares Mean (Standard Error) [units on a scale] |
5.33
(0.74)
|
5.14
(0.67)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 140 mg LY450139, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.805 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Title | Change From Baseline in Alzheimer's Disease Assessment Scale (ADAS-Cog14) at 16 Weeks After Cessation of Study Drug |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 312 | 430 |
| Least Squares Mean (Standard Error) [units on a scale] |
6.00
(0.82)
|
5.89
(0.73)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 140 mg LY450139, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.893 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
Adverse Events
| Time Frame | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||
| 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 | ||||||
| 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 (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||
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 (10.8%) | 92/556 (16.5%) | 7/34 (20.6%) | 1/22 (4.5%) | 22/430 (5.1%) | 20/312 (6.4%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| Anaemia folate deficiency | 0/555 (0%) | 0 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 1/430 (0.2%) | 1 | 0/312 (0%) | 0 |
| Cardiac disorders | ||||||||||||
| Angina pectoris | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Aortic valve stenosis | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 1/312 (0.3%) | 1 |
| Atrial fibrillation | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Bradycardia | 0/555 (0%) | 0 | 2/556 (0.4%) | 2 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 1/430 (0.2%) | 1 | 0/312 (0%) | 0 |
| Cardiac arrest | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 1/430 (0.2%) | 1 | 0/312 (0%) | 0 |
| Cardiac failure | 0/555 (0%) | 0 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 1/430 (0.2%) | 1 | 0/312 (0%) | 0 |
| Cardiac failure acute | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Myocardial infarction | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Myocardial ischaemia | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 2/430 (0.5%) | 2 | 0/312 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||||||
| Vertigo | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Eye disorders | ||||||||||||
| Cataract | 2/555 (0.4%) | 2 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 1/430 (0.2%) | 1 | 0/312 (0%) | 0 |
| Retinal artery occlusion | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||
| Abdominal pain | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Abdominal pain upper | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 1/22 (4.5%) | 1 | 0/430 (0%) | 0 | 1/312 (0.3%) | 1 |
| Colitis ischaemic | 1/555 (0.2%) | 1 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Colonic polyp | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 1/312 (0.3%) | 1 |
| Diarrhoea | 0/555 (0%) | 0 | 2/556 (0.4%) | 2 | 1/34 (2.9%) | 1 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Diverticulum intestinal | 0/555 (0%) | 0 | 0/556 (0%) | 0 | 1/34 (2.9%) | 1 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Duodenal ulcer | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 1/430 (0.2%) | 1 | 0/312 (0%) | 0 |
| Enteritis | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 1/430 (0.2%) | 1 | 0/312 (0%) | 0 |
| Enterocolitis | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Gastrointestinal disorder | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Gastrointestinal haemorrhage | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Haematemesis | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Haematochezia | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Haemorrhoids | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Intestinal obstruction | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Pancreatitis | 1/555 (0.2%) | 1 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Pancreatitis acute | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Upper gastrointestinal haemorrhage | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Vomiting | 0/555 (0%) | 0 | 0/556 (0%) | 0 | 1/34 (2.9%) | 1 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| General disorders | ||||||||||||
| Accidental death | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Chest pain | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Death | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 1/430 (0.2%) | 1 | 0/312 (0%) | 0 |
| Sudden cardiac death | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Hepatobiliary disorders | ||||||||||||
| Bile duct stone | 0/555 (0%) | 0 | 1/556 (0.2%) | 2 | 0/34 (0%) | 0 | 1/22 (4.5%) | 1 | 0/430 (0%) | 0 | 1/312 (0.3%) | 1 |
| Cholangitis | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Cholecystitis | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Cholecystitis acute | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Cholecystitis chronic | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Cholelithiasis | 1/555 (0.2%) | 1 | 2/556 (0.4%) | 2 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 1/312 (0.3%) | 1 |
| Hepatitis toxic | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Jaundice cholestatic | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Infections and infestations | ||||||||||||
| Anal abscess | 0/555 (0%) | 0 | 2/556 (0.4%) | 2 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Appendicitis | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 1/430 (0.2%) | 1 | 0/312 (0%) | 0 |
| Bronchitis | 0/555 (0%) | 0 | 2/556 (0.4%) | 2 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 1/312 (0.3%) | 1 |
| Bronchopneumonia | 0/555 (0%) | 0 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 1/430 (0.2%) | 1 | 0/312 (0%) | 0 |
| Clostridial infection | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Clostridium difficile colitis | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Cystitis | 0/555 (0%) | 0 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 1/430 (0.2%) | 1 | 0/312 (0%) | 0 |
| Diabetic gangrene | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Gastroenteritis | 0/555 (0%) | 0 | 2/556 (0.4%) | 2 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Meningitis bacterial | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Pneumonia | 2/555 (0.4%) | 2 | 12/556 (2.2%) | 13 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 2/430 (0.5%) | 2 | 1/312 (0.3%) | 1 |
| Pneumonia staphylococcal | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Pyelonephritis acute | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Salmonella sepsis | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Sepsis | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Septic shock | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Staphylococcal infection | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Urinary tract infection | 3/555 (0.5%) | 3 | 4/556 (0.7%) | 4 | 1/34 (2.9%) | 1 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Urosepsis | 2/555 (0.4%) | 2 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||
| Accidental overdose | 0/555 (0%) | 0 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 1/430 (0.2%) | 1 | 0/312 (0%) | 0 |
| Ankle fracture | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Fall | 3/555 (0.5%) | 3 | 3/556 (0.5%) | 3 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 1/430 (0.2%) | 1 | 0/312 (0%) | 0 |
| Femoral neck fracture | 2/555 (0.4%) | 3 | 2/556 (0.4%) | 2 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Femur fracture | 0/555 (0%) | 0 | 2/556 (0.4%) | 2 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Fractured sacrum | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Heat exhaustion | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Hip fracture | 0/555 (0%) | 0 | 2/556 (0.4%) | 2 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Humerus fracture | 0/555 (0%) | 0 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 1/312 (0.3%) | 1 |
| Lower limb fracture | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 1/430 (0.2%) | 1 | 0/312 (0%) | 0 |
| Patella fracture | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Post lumbar puncture syndrome | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Radius fracture | 0/555 (0%) | 0 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 1/430 (0.2%) | 1 | 0/312 (0%) | 0 |
| Rib fracture | 1/555 (0.2%) | 1 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Spinal compression fracture | 0/555 (0%) | 0 | 2/556 (0.4%) | 2 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 2/312 (0.6%) | 2 |
| Subdural haematoma | 1/555 (0.2%) | 1 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Thoracic vertebral fracture | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Upper limb fracture | 0/555 (0%) | 0 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 1/312 (0.3%) | 1 |
| Investigations | ||||||||||||
| Blood glucose increased | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Medical observation | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||
| Decreased appetite | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Dehydration | 2/555 (0.4%) | 2 | 3/556 (0.5%) | 3 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Diabetes mellitus | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Food intolerance | 0/555 (0%) | 0 | 0/556 (0%) | 0 | 1/34 (2.9%) | 1 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Hypokalaemia | 0/555 (0%) | 0 | 0/556 (0%) | 0 | 1/34 (2.9%) | 1 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Back pain | 0/555 (0%) | 0 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 1/312 (0.3%) | 1 |
| Foot deformity | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Intervertebral disc protrusion | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Lumbar spinal stenosis | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 1/312 (0.3%) | 1 |
| Muscular weakness | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Osteitis | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Osteoarthritis | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Rhabdomyolysis | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Rheumatoid arthritis | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||
| Basal cell carcinoma | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Bile duct cancer | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Breast cancer | 0/555 (0%) | 0 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 1/312 (0.3%) | 1 |
| Breast cancer metastatic | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Colon cancer | 1/555 (0.2%) | 1 | 3/556 (0.5%) | 3 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 2/430 (0.5%) | 2 | 0/312 (0%) | 0 |
| Endometrial cancer | 1/328 (0.3%) | 1 | 0/317 (0%) | 0 | 0/20 (0%) | 0 | 0/12 (0%) | 0 | 0/251 (0%) | 0 | 0/184 (0%) | 0 |
| Hepatic cancer metastatic | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Keratoacanthoma | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Lung adenocarcinoma | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Lung cancer metastatic | 0/555 (0%) | 0 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 1/430 (0.2%) | 1 | 0/312 (0%) | 0 |
| Lung neoplasm malignant | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Neurilemmoma | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Neuroendocrine carcinoma | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Non-small cell lung cancer | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Oesophageal carcinoma | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Pancreatic carcinoma | 0/555 (0%) | 0 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 1/430 (0.2%) | 1 | 0/312 (0%) | 0 |
| Squamous cell carcinoma | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 1/312 (0.3%) | 1 |
| Squamous cell carcinoma of skin | 1/555 (0.2%) | 1 | 3/556 (0.5%) | 3 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 1/312 (0.3%) | 1 |
| Nervous system disorders | ||||||||||||
| Cerebral haemorrhage | 2/555 (0.4%) | 2 | 2/556 (0.4%) | 2 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Cerebral infarction | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 1/312 (0.3%) | 1 |
| Coma | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Convulsion | 1/555 (0.2%) | 1 | 3/556 (0.5%) | 3 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 1/312 (0.3%) | 1 |
| Dementia alzheimer's type | 2/555 (0.4%) | 2 | 2/556 (0.4%) | 2 | 1/34 (2.9%) | 1 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Encephalopathy | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Guillain-barre syndrome | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Haemorrhage intracranial | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Haemorrhagic stroke | 1/555 (0.2%) | 1 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Hydrocephalus | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Loss of consciousness | 2/555 (0.4%) | 2 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 1/430 (0.2%) | 1 | 0/312 (0%) | 0 |
| Normal pressure hydrocephalus | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Status epilepticus | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Syncope | 4/555 (0.7%) | 4 | 5/556 (0.9%) | 5 | 1/34 (2.9%) | 1 | 0/22 (0%) | 0 | 1/430 (0.2%) | 1 | 1/312 (0.3%) | 1 |
| Thalamus haemorrhage | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Psychiatric disorders | ||||||||||||
| Aggression | 1/555 (0.2%) | 1 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Agitation | 1/555 (0.2%) | 1 | 2/556 (0.4%) | 2 | 1/34 (2.9%) | 1 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Confusional state | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Delirium | 0/555 (0%) | 0 | 2/556 (0.4%) | 2 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Hallucination | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Suicidal ideation | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||
| Calculus ureteric | 1/555 (0.2%) | 1 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Nephrolithiasis | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Renal failure | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Renal failure acute | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Urethral caruncle | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||||
| Prostatitis | 0/227 (0%) | 0 | 1/239 (0.4%) | 1 | 0/14 (0%) | 0 | 0/10 (0%) | 0 | 0/179 (0%) | 0 | 1/128 (0.8%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Choking | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Chronic obstructive pulmonary disease | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Hypoxia | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Respiratory arrest | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||
| Dermatitis | 0/555 (0%) | 0 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 1/312 (0.3%) | 1 |
| Hyperhidrosis | 0/555 (0%) | 0 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 1/430 (0.2%) | 1 | 0/312 (0%) | 0 |
| Rash papular | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Urticaria | 0/555 (0%) | 0 | 0/556 (0%) | 0 | 1/34 (2.9%) | 1 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Social circumstances | ||||||||||||
| Activities of daily living impaired | 0/555 (0%) | 0 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 1/312 (0.3%) | 1 |
| Vascular disorders | ||||||||||||
| Aortic dissection | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 1/312 (0.3%) | 1 |
| Arteriosclerosis obliterans | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Deep vein thrombosis | 0/555 (0%) | 0 | 1/556 (0.2%) | 1 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Haematoma | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Hypertension | 1/555 (0.2%) | 1 | 0/556 (0%) | 0 | 1/34 (2.9%) | 1 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
Other (Not Including 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 | 130/555 (23.4%) | 258/556 (46.4%) | 6/34 (17.6%) | 0/22 (0%) | 0/430 (0%) | 0/312 (0%) | ||||||
| Gastrointestinal disorders | ||||||||||||
| Diarrhoea | 33/555 (5.9%) | 42 | 58/556 (10.4%) | 72 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Hiatus hernia | 0/555 (0%) | 0 | 0/556 (0%) | 0 | 2/34 (5.9%) | 2 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Nausea | 19/555 (3.4%) | 24 | 49/556 (8.8%) | 53 | 2/34 (5.9%) | 2 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Vomiting | 17/555 (3.1%) | 22 | 33/556 (5.9%) | 46 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Infections and infestations | ||||||||||||
| Nasopharyngitis | 22/555 (4%) | 24 | 28/556 (5%) | 31 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Urinary tract infection | 0/555 (0%) | 0 | 0/556 (0%) | 0 | 3/34 (8.8%) | 3 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Investigations | ||||||||||||
| Prostatic specific antigen increased | 0/227 (0%) | 0 | 0/239 (0%) | 0 | 1/14 (7.1%) | 1 | 0/10 (0%) | 0 | 0/179 (0%) | 0 | 0/128 (0%) | 0 |
| Weight decreased | 16/555 (2.9%) | 16 | 42/556 (7.6%) | 42 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||
| Decreased appetite | 16/555 (2.9%) | 16 | 52/556 (9.4%) | 53 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Nervous system disorders | ||||||||||||
| Dizziness | 15/555 (2.7%) | 15 | 30/556 (5.4%) | 32 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Headache | 24/555 (4.3%) | 29 | 40/556 (7.2%) | 45 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||
| Hair colour changes | 4/555 (0.7%) | 4 | 53/556 (9.5%) | 53 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
| Rash erythematous | 5/555 (0.9%) | 6 | 36/556 (6.5%) | 42 | 0/34 (0%) | 0 | 0/22 (0%) | 0 | 0/430 (0%) | 0 | 0/312 (0%) | 0 |
Limitations/Caveats
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.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Eli Lilly and Company |
| Phone | 800-545-5979 |
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00762411
Other Study ID Numbers:
- 11271
- H6L-MC-LFBC
First Posted:
Sep 30, 2008
Last Update Posted:
Feb 16, 2015
Last Verified:
Jan 1, 2015