Treatment for Aggression and Agitation in Patients With A... | NCT00843518 | Trialant
NCT00843518
Sponsor
Eli Lilly and Company
Status
Completed
Last Update Posted
Nov 29, 2017Actual
Enrollment
132Actual
Phase
Phase 2
Conditions
Alzheimer's Disease
Interventions
LY451395
Placebo
Countries
United States
Protocol Section
Identification Module
NCT ID
NCT00843518
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
12541
Secondary IDs
ID
Type
Description
Link
H6N-MC-LEAQ
Other Identifier
Eli Lilly and Company
Brief Title
Treatment for Aggression and Agitation in Patients With Alzheimer's Disease
Official Title
Assessment of LY451395 for Neuropsychiatric Symptoms of Aggression and Agitation in Alzheimer's Disease
Acronym
Not provided
Organization
Eli Lilly and CompanyINDUSTRY
Status Module
Record Verification Date
Oct 2017
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Feb 2009
Primary Completion Date
Jun 2011Actual
Completion Date
Jun 2011Actual
First Submitted Date
Feb 12, 2009
First Submission Date that Met QC Criteria
Feb 12, 2009
First Posted Date
Feb 13, 2009Estimated
Results Waived
Not provided
Results First Submitted Date
Jul 7, 2016
Results First Submitted that Met QC Criteria
Oct 23, 2017
Results First Posted Date
Nov 29, 2017Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Sep 20, 2011
Certification/Extension First Submitted that Passed QC Review
Sep 20, 2011
Certification/Extension First Posted Date
Sep 26, 2011Estimated
Last Update Submitted Date
Oct 23, 2017
Last Update Posted Date
Nov 29, 2017Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Eli Lilly and CompanyINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The purpose of this study is to determine whether this drug can help symptoms of aggression and agitation in participants with Alzheimer's disease.
Detailed Description
The primary purpose of this study is to help answer the following research questions:
Whether this drug can help symptoms of aggression and agitation in participants with Alzheimer's Disease.
The safety of this drug and any side effects that might be associated with it.
How this drug compares to placebo.
During the 12-week period of this study, the participant will have an equal chance of receiving 1 of the 2 treatment groups: active drug or placebo.
Conditions Module
Conditions
Alzheimer's Disease
Keywords
Agitation and Aggression
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
132Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
LY451395
Experimental
3 milligram (mg) LY451395 orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
Drug: LY451395
Placebo
Placebo Comparator
Placebo orally twice daily for 12 weeks
Drug: Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
LY451395
Drug
3 mg LY451395 orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
LY451395
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Mean Change From Baseline in the 4-Item Agitation/Aggression Subscale of the Neuropsychiatric Inventory (NPI-4 A/A) at Week 12
NPI assessed noncognitive psychopathology in participants with Alzheimer's dementia. A 4-item subscale of the standard 12-item NPI measured the neuropsychiatric symptoms of A/A, with items consisting of agitation/aggression, aberrant motor behavior, irritability/emotional lability, and disinhibition. Scores for each subscale (frequency x severity) were calculated to obtain each item score. The total subscale score ranged from 0 to 48, with higher scores indicating more frequent and/or severe A/A symptoms. If a symptom was not present at all, the site would not enter anything for frequency or severity, and a zero would be imputed for that item. Least Squares (LS) Mean value was adjusted for NPI strata, treatment, pooled site, visit, treatment-by-visit, baseline NPI-4 A/A, and baseline-by-visit interaction.
Baseline, Week 12
Secondary Outcomes
Measure
Description
Time Frame
Mean Change From Baseline in 10-Item Version of Neuropsychiatric Inventory (NPI-10) at Week 12
NPI assessed noncognitive psychopathology in participants with Alzheimer's dementia. A 10-item scale of the standard 12-item NPI measured neuropsychiatric symptoms minus the appetite and sleep disturbance items. Scores for each subscale (frequency × severity) were calculated to obtain the item score. The total subscale score ranged from 0 to 120, with higher scores indicating more frequent and/or severe A/A symptoms. If a symptom was not present at all, the site would not enter anything for frequency or severity, and a zero would be imputed for that item. LS Mean value was adjusted for NPI strata, treatment, pooled site, visit, treatment-by-visit, baseline NPI-10, and baseline-by-visit interaction.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Community-dwelling participants with a diagnosis of probable Alzheimer's disease (AD) based on disease criteria from the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the Alzheimer's Association. Mini Mental State Examination (MMSE) score from 6 to 26 inclusive; Neuropsychiatric Inventory-10 (NPI-10) total score greater than or equal to 10.
Are men or women at least 60 years old.
Weight greater than or equal to 45 kilograms (kg).
Have clinically significant and persistent verbal or physical agitation and/or verbal or physical aggression behaviors that are disruptive to daily functioning or potentially harmful and occurred at least 3 days per week over the past 4 weeks prior to study entry.
Understand English.
Have a reliable and actively involved caregiver who must be able to communicate in English and be willing to comply with protocol requirements.
Exclusion Criteria:
Meet DSM-IV-TR or Delirium Rating Scale-Revised-98 criteria for delirium.
Does not score ≤4 on the Modified Hachinski Ischemia Scale for vascular dementia.
Have a magnetic resonance imaging (MRI) or computer tomography (CT) scan on file since the onset of symptoms of AD and performed within the past 24 months that is inconsistent with a diagnosis of AD.
Have a current, required use, or expected use of psychoactive drugs or other medications not allowed in this trial.
Have currently active significant medical, neurological, or psychiatric problems that are not allowed in this trial or other brain disorders.
Have received acetylcholinesterase inhibitor (AChEIs) or memantine for less than 4 months, or have less than 2 months of stable therapy on these treatments by Visit 2.
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
60 Years
Maximum Age
Not provided
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Call 1-877.CTLilly (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM-5PM Easter time (UTC/GMT-5 hours, EST
Eli Lilly and Company
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
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.
Trzepacz PT, Cummings J, Konechnik T, Forrester TD, Chang C, Dennehy EB, Willis BA, Shuler C, Tabas LB, Lyketsos C. Mibampator (LY451395) randomized clinical trial for agitation/aggression in Alzheimer's disease. Int Psychogeriatr. 2013 May;25(5):707-19. doi: 10.1017/S1041610212002141. Epub 2012 Dec 21.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
Study Period 1 lasted 3 to 28 days and included screening tests and procedures (N=205). Study Period 2 was a 12-week, randomized, double-blind treatment period with clinic visits at 3-week intervals and intervening weekly telephone assessments with caregivers (N=132). Study Period 3 was a 1-week, single-blind washout period (N=91).
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
LY451395
3 milligram (mg) LY451395 (mibampator) orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
Mean Change From Baseline in the Neuropsychiatric Inventory (NPI) Depression Domain at Week 12
NPI Depression domain was an item of the standard 12-item NPI that measured depression in participants with Alzheimer's dementia. Scores for each subscale (frequency × severity) were calculated to obtain the item score, which ranged from 0 to 12 with higher scores indicating more frequent and/or severe neuropsychiatric symptoms. If a symptom was not present at all, the site would not enter anything for frequency or severity, and a zero would be imputed for that item. LS Mean value was adjusted for NPI strata, treatment, pooled site, visit, treatment-by-visit, baseline NPI depression, and baseline-by-visit interaction.
Baseline, Week 12
Mean Change From Baseline in the Neuropsychiatric Inventory (NPI) Psychosis Subscale Score at Week 12
The NPI Psychosis subscale score was the sum of the delusions and hallucinations items of the standard 12-item NPI that measured psychosis symptoms in participants with Alzheimer's dementia. Scores for each subscale (frequency x severity) were calculated for each item score and ranged from 0 to 24 with higher scores indicating more frequent and/or severe neuropsychiatric symptoms. LS Mean value was adjusted for NPI strata, treatment, pooled site, visit, treatment-by-visit, baseline NPI psychosis, and baseline-by-visit interaction.
Baseline, Week 12
Mean Change From Baseline in Cohen-Mansfield Agitation Inventory-Community Version (CMAI-C) at Week 12
CMAI-C is the Cohen-Mansfield Agitation Inventory - Community Version, and it contained 36 questions. The first 35 items were rated from 1 (never) to 7 (several times per hour) and the last item asked if there was any other inappropriate behavior, with a free text field to specify the behavior. The total score ranged from 7 to 245 (7 x 35), with higher scores reflecting more severe agitation. LS Mean value was adjusted for NPI strata, treatment, pooled site, visit, treatment-by-visit, baseline CMAI-C, and baseline-by-visit interaction.
Baseline, Week 12
Mean Change From Baseline in Cornell Scale for Depression in Dementia (CSDD) at Week 12
CSDD was a 19-item, clinician-rated scale designed to measure the presence and severity of depressive symptoms in dementia participants. Symptoms were rated as absent, mild/intermittent, or severe. Scores ranged from 0 to 38; scores of 8 or more suggested clinical depression. LS Mean value was adjusted for NPI strata, treatment, pooled site, visit, treatment-by-visit, baseline CSDD, and baseline-by-visit interaction.
Baseline, Week 12
Mean Change From Baseline in Total T-Score in the Frontal System Behaviors Scale (FrSBe) at Week 12
FrSBe was a 46-item, caregiver-rated scale that assessed behaviors associated with damage to the frontal lobes and frontal systems of the brain, including executive function, disinhibition, and apathy. Raw scores were normalized to T-scores based on gender, education, and age. Higher T scores represent a worse outcome. A score of 50 reflects a normative sample, and T scores at or above 65 are considered clinically significant. LS Mean value was adjusted for NPI strata, treatment, pooled site, visit, treatment-by-visit, baseline FrSBe, and baseline-by-visit interaction.
Baseline, Week 12
Mean Change From Baseline in Clinical Global Impression-Severity-Agitation/Aggression (CGI-S-A/A) at Week 12
CGI-S-A/A was a 7-point, single-item rating scale for overall severity of symptoms based on the investigator's general clinical experience with a similar participant population. This Likert scale ranged from 0 (normal) to 7 (most severely ill). LS Mean value was adjusted for NPI strata, treatment, pooled site, visit, treatment-by-visit, baseline CGI-S-A/A, and baseline-by-visit interaction.
Baseline, Week 12
Mean Change From Baseline in Clinical Global Impression-Severity-Global Functioning (CGI-S-GF) at Week 12
CGI-S-GF was a 7-point, single-item rating scale for overall functioning based on the investigator's general clinical experience with a similar participant population. This Likert scale ranged from 0 (normal) to 7 (most severely ill). LS Mean value was adjusted for NPI strata, treatment, pooled site, visit, treatment-by-visit, baseline CGI-S-GF, and baseline-by-visit interaction.
Baseline, Week 12
Mean Change From Baseline in the 14-Item Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog14) at Week 12
ADAS-Cog14, a 14-item rating scale, measured the severity of cognitive dysfunction in persons with AD. Scores ranged from 0 to 90, with a higher score indicating worse cognitive functioning. LS Mean value was adjusted for NPI strata, treatment, pooled site, visit, treatment-by-visit, baseline ADAS-Cog, and baseline-by-visit interaction.
Baseline, Week 12
United States
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
92626
United States
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.
Hamden
Connecticut
06518
United States
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
32806
United States
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
33609
United States
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.
West Palm Beach
Florida
33407
United States
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.
Atlanta
Georgia
30308
United States
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.
Easton
Maryland
21601
United States
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.
Flowood
Mississippi
39232
United States
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.
Toms River
New Jersey
08755
United States
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.
Staten Island
New York
10312
United States
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.
Hickory
North Carolina
28601
United States
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.
Portland
Oregon
97210
United States
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.
Norristown
Pennsylvania
19401
United States
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.
Austin
Texas
78757
United States
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.
Bennington
Vermont
05201
United States
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.
Waukesha
Wisconsin
53188
United States
FG00063 subjects
FG00169 subjects
COMPLETED
FG00043 subjects
FG00149 subjects
NOT COMPLETED
FG00020 subjects
FG00120 subjects
Type
Comment
Reasons
Adverse Event
FG0005 subjects
FG0013 subjects
Death
FG0000 subjects
FG0011 subjects
Lost to Follow-up
FG0002 subjects
FG0013 subjects
Physician Decision
FG0002 subjects
FG0011 subjects
Protocol Violation
FG0002 subjects
FG0015 subjects
Withdrawal by Subject
FG0002 subjects
FG0010 subjects
Caregiver decision
FG0007 subjects
FG0017 subjects
Period 3 (Single-blind Washout)
Type
Comment
Milestone Data
STARTED
FG00042 subjects1 LY451395 participant completed double-blind treatment, but did not enter washout period.
FG00149 subjects
COMPLETED
FG00042 subjects
FG00149 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
LY451395
3 milligram (mg) LY451395 (mibampator) orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
BG001
Placebo
Placebo orally twice daily for 12 weeks
BG002
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00063
BG00169
BG002132
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00077.21± 8.246
BG00177.66± 7.574
BG00277.44± 7.874
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00031
BG00136
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0002
BG0010
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0011
BG002
Region of Enrollment
Number
participants
Title
Denominators
Categories
United States
Title
Measurements
BG00063
BG00169
BG002
Mini Mental State Examination (MMSE)
MMSE assessed cognitive function in elderly participants. The scale ranged from 0 to 30, with higher scores indicating higher cognitive function.
Mean
Standard Deviation
units on a scale
Title
Denominators
Categories
Title
Measurements
BG00016.0± 6.06
BG001
4-Item version of Neuropsychiatric Inventory (NPI-4) of Agitation and Aggression (A/A)
NPI assessed noncognitive psychopathology in participants with Alzheimer's dementia. A 4-item subscale of the standard 12-item NPI measured the neuropsychiatric symptoms of A/A, with items consisting of agitation/aggression, aberrant motor behavior, irritability/emotional lability, and disinhibition. Scores for each subscale (frequency x severity) were calculated to obtain each item score. The total subscale score ranged from 0 to 48, with higher scores indicating more frequent and/or severe A/A symptoms. If a symptom was not present at all then a zero would be imputed for that item.
Mean
Standard Deviation
units on a scale
Title
Denominators
Categories
Title
Measurements
BG00018.8± 8.72
BG001
10-Item version of Neuropsychiatric Inventory (NPI-10)
NPI assessed noncognitive psychopathology in participants with Alzheimer's dementia. A 10-item scale of the standard 12-item NPI measured neuropsychiatric symptoms minus appetite and sleep disturbance. Scores for each subscale (frequency × severity) were calculated to obtain the item score. The total subscale score ranged from 0 to 120, with higher scores indicating more frequent and/or severe A/A symptoms. If a symptom was not present at all, the site would not enter anything for frequency or severity, and a zero would be imputed for that item.
NPI Depression domain was an item of the standard 12-item NPI that measured depression in participants with Alzheimer's dementia. Scores for each subscale (frequency x severity) were calculated to obtain the item score, which ranged from 0 to 12, with higher scores indicating more frequent and/or severe neuropsychiatric symptoms.
The NPI Psychosis subscale score was the sum of the delusions and hallucinations items of the standard 12-item NPI that measured psychosis symptoms in participants with Alzheimer's dementia. Scores for each subscale (frequency x severity) were calculated for each item score and ranged from 0 to 24 with higher scores indicating more frequent and/or severe neuropsychiatric symptoms.
Mean
Standard Deviation
units on a scale
Title
Denominators
Categories
Title
Measurements
BG0003.2± 5.24
BG001
Cohen-Mansfield Agitation Inventory-Community (CMAI-C) Version
CMAI-C is the Cohen-Mansfield Agitation Inventory - Community Version, and it contained 36 questions. The first 35 items were rated from 1 (never) to 7 (several times per hour) and the last item asked if there was any other inappropriate behavior, with a free text field to specify the behavior. The total score ranged from 7 to 245 (7 x 35), with higher scores reflecting more severe agitation.
Mean
Standard Deviation
units on a scale
Title
Denominators
Categories
Title
Measurements
BG00073.6± 22.55
BG001
Cornell Scale for Depression in Dementia (CSDD)
CSDD was a 19-item, clinician-rated scale designed to measure the presence and severity of depressive symptoms in dementia participants. Symptoms were rated as absent, mild/intermittent, or severe. Scores ranged from 0 to 38; scores of 8 or more suggested clinical depression.
Mean
Standard Deviation
units on a scale
Title
Denominators
Categories
Title
Measurements
BG0008.4± 5.40
BG001
Total T-Score in the Frontal System Behaviors (FrSBe) Scale
FrSBe was a 46-item, caregiver-rated scale that assessed behaviors associated with damage to the frontal lobes and frontal systems of the brain, including executive function, disinhibition, and apathy. Raw scores were normalized to T-scores based on gender, education, and age. Higher T scores represent a worse outcome. A score of 50 reflects a normative sample, and T scores at or above 65 are considered clinically significant.
Mean
Standard Deviation
units on a scale
Title
Denominators
Categories
Title
Measurements
BG00092.4± 22.50
BG001
Clinical Global Impression-Severity-Agitation/Aggressive (CGI-S-A/A)
CGI-S-A/A was a 7-point, single-item rating scale for overall severity of symptoms based on the investigator's general clinical experience with a similar participant population. This Likert scale ranged from 0 (normal) to 7 (most severely ill).
Mean
Standard Deviation
units on a scale
Title
Denominators
Categories
Title
Measurements
BG0004.1± 0.68
BG001
Clinical Global Impression-Severity-Global Functioning (CGI-S-GF)
CGI-S-GF was a 7-point, single-item rating scale for overall functioning based on the investigator's general clinical experience with a similar participant population. This Likert scale ranged from 0 (normal) to 7 (most severely ill).
ADAS-Cog14, a 14-item rating scale, measured the severity of cognitive dysfunction in persons with Alzheimer's disease (AD). Scores ranged from 0 to 90, with a higher score indicating worse cognitive functioning.
Mean
Standard Deviation
units on a scale
Title
Denominators
Categories
Title
Measurements
BG00043.3± 20.42
BG001
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Mean Change From Baseline in the 4-Item Agitation/Aggression Subscale of the Neuropsychiatric Inventory (NPI-4 A/A) at Week 12
NPI assessed noncognitive psychopathology in participants with Alzheimer's dementia. A 4-item subscale of the standard 12-item NPI measured the neuropsychiatric symptoms of A/A, with items consisting of agitation/aggression, aberrant motor behavior, irritability/emotional lability, and disinhibition. Scores for each subscale (frequency x severity) were calculated to obtain each item score. The total subscale score ranged from 0 to 48, with higher scores indicating more frequent and/or severe A/A symptoms. If a symptom was not present at all, the site would not enter anything for frequency or severity, and a zero would be imputed for that item. Least Squares (LS) Mean value was adjusted for NPI strata, treatment, pooled site, visit, treatment-by-visit, baseline NPI-4 A/A, and baseline-by-visit interaction.
The analysis population included all randomized participants and was a modified intent-to-treat (ITT) population defined as having both a baseline and at least 1 post-baseline measure.
Posted
Least Squares Mean
Standard Error
units on a scale
Baseline, Week 12
ID
Title
Description
OG000
LY451395
3 milligram (mg) LY451395 (mibampator) orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
OG001
Placebo
Placebo orally twice daily for 12 weeks
Units
Counts
Participants
OG00043
OG00150
Title
Denominators
Categories
Title
Measurements
OG000-5.4± 1.21
OG001-6.2± 1.12
Secondary
Mean Change From Baseline in 10-Item Version of Neuropsychiatric Inventory (NPI-10) at Week 12
NPI assessed noncognitive psychopathology in participants with Alzheimer's dementia. A 10-item scale of the standard 12-item NPI measured neuropsychiatric symptoms minus the appetite and sleep disturbance items. Scores for each subscale (frequency × severity) were calculated to obtain the item score. The total subscale score ranged from 0 to 120, with higher scores indicating more frequent and/or severe A/A symptoms. If a symptom was not present at all, the site would not enter anything for frequency or severity, and a zero would be imputed for that item. LS Mean value was adjusted for NPI strata, treatment, pooled site, visit, treatment-by-visit, baseline NPI-10, and baseline-by-visit interaction.
The analysis population included all randomized participants and was a modified intent-to-treat (ITT) population defined as having both a baseline and at least 1 post-baseline measure.
Posted
Least Squares Mean
Standard Error
units on a scale
Baseline, Week 12
ID
Title
Description
OG000
LY451395
3 milligram (mg) LY451395 (mibampator) orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
OG001
Placebo
Placebo orally twice daily for 12 weeks
Secondary
Mean Change From Baseline in the Neuropsychiatric Inventory (NPI) Depression Domain at Week 12
NPI Depression domain was an item of the standard 12-item NPI that measured depression in participants with Alzheimer's dementia. Scores for each subscale (frequency × severity) were calculated to obtain the item score, which ranged from 0 to 12 with higher scores indicating more frequent and/or severe neuropsychiatric symptoms. If a symptom was not present at all, the site would not enter anything for frequency or severity, and a zero would be imputed for that item. LS Mean value was adjusted for NPI strata, treatment, pooled site, visit, treatment-by-visit, baseline NPI depression, and baseline-by-visit interaction.
The analysis population included all randomized participants and was a modified intent-to-treat (ITT) population defined as having both a baseline and at least 1 post-baseline measure.
Posted
Least Squares Mean
Standard Error
units on a scale
Baseline, Week 12
ID
Title
Description
OG000
LY451395
3 milligram (mg) LY451395 (mibampator) orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
OG001
Placebo
Placebo orally twice daily for 12 weeks
Secondary
Mean Change From Baseline in the Neuropsychiatric Inventory (NPI) Psychosis Subscale Score at Week 12
The NPI Psychosis subscale score was the sum of the delusions and hallucinations items of the standard 12-item NPI that measured psychosis symptoms in participants with Alzheimer's dementia. Scores for each subscale (frequency x severity) were calculated for each item score and ranged from 0 to 24 with higher scores indicating more frequent and/or severe neuropsychiatric symptoms. LS Mean value was adjusted for NPI strata, treatment, pooled site, visit, treatment-by-visit, baseline NPI psychosis, and baseline-by-visit interaction.
The analysis population included all randomized participants and was a modified intent-to-treat (ITT) population defined as having both a baseline and at least 1 post-baseline measure.
Posted
Least Squares Mean
Standard Error
units on a scale
Baseline, Week 12
ID
Title
Description
OG000
LY451395
3 milligram (mg) LY451395 (mibampator) orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
OG001
Placebo
Placebo orally twice daily for 12 weeks
Units
Counts
Secondary
Mean Change From Baseline in Cohen-Mansfield Agitation Inventory-Community Version (CMAI-C) at Week 12
CMAI-C is the Cohen-Mansfield Agitation Inventory - Community Version, and it contained 36 questions. The first 35 items were rated from 1 (never) to 7 (several times per hour) and the last item asked if there was any other inappropriate behavior, with a free text field to specify the behavior. The total score ranged from 7 to 245 (7 x 35), with higher scores reflecting more severe agitation. LS Mean value was adjusted for NPI strata, treatment, pooled site, visit, treatment-by-visit, baseline CMAI-C, and baseline-by-visit interaction.
The analysis population included all randomized participants and was a modified intent-to-treat (ITT) population defined as having both a baseline and at least 1 post-baseline measure.
Posted
Least Squares Mean
Standard Error
units on a scale
Baseline, Week 12
ID
Title
Description
OG000
LY451395
3 milligram (mg) LY451395 (mibampator) orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
OG001
Placebo
Placebo orally twice daily for 12 weeks
Units
Counts
Secondary
Mean Change From Baseline in Cornell Scale for Depression in Dementia (CSDD) at Week 12
CSDD was a 19-item, clinician-rated scale designed to measure the presence and severity of depressive symptoms in dementia participants. Symptoms were rated as absent, mild/intermittent, or severe. Scores ranged from 0 to 38; scores of 8 or more suggested clinical depression. LS Mean value was adjusted for NPI strata, treatment, pooled site, visit, treatment-by-visit, baseline CSDD, and baseline-by-visit interaction.
The analysis population included all randomized participants and was a modified intent-to-treat (ITT) population defined as having both a baseline and at least 1 post-baseline measure.
Posted
Least Squares Mean
Standard Error
units on a scale
Baseline, Week 12
ID
Title
Description
OG000
LY451395
3 milligram (mg) LY451395 (mibampator) orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
OG001
Placebo
Placebo orally twice daily for 12 weeks
Units
Counts
Participants
Secondary
Mean Change From Baseline in Total T-Score in the Frontal System Behaviors Scale (FrSBe) at Week 12
FrSBe was a 46-item, caregiver-rated scale that assessed behaviors associated with damage to the frontal lobes and frontal systems of the brain, including executive function, disinhibition, and apathy. Raw scores were normalized to T-scores based on gender, education, and age. Higher T scores represent a worse outcome. A score of 50 reflects a normative sample, and T scores at or above 65 are considered clinically significant. LS Mean value was adjusted for NPI strata, treatment, pooled site, visit, treatment-by-visit, baseline FrSBe, and baseline-by-visit interaction.
The analysis population included all randomized participants and was a modified intent-to-treat (ITT) population defined as having both a baseline and at least 1 post-baseline measure.
Posted
Least Squares Mean
Standard Error
units on a scale
Baseline, Week 12
ID
Title
Description
OG000
LY451395
3 milligram (mg) LY451395 (mibampator) orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
OG001
Placebo
Placebo orally twice daily for 12 weeks
Units
Counts
Secondary
Mean Change From Baseline in Clinical Global Impression-Severity-Agitation/Aggression (CGI-S-A/A) at Week 12
CGI-S-A/A was a 7-point, single-item rating scale for overall severity of symptoms based on the investigator's general clinical experience with a similar participant population. This Likert scale ranged from 0 (normal) to 7 (most severely ill). LS Mean value was adjusted for NPI strata, treatment, pooled site, visit, treatment-by-visit, baseline CGI-S-A/A, and baseline-by-visit interaction.
The analysis population included all randomized participants and was a modified intent-to-treat (ITT) population defined as having both a baseline and at least 1 post-baseline measure.
Posted
Least Squares Mean
Standard Error
units on a scale
Baseline, Week 12
ID
Title
Description
OG000
LY451395
3 milligram (mg) LY451395 (mibampator) orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
OG001
Placebo
Placebo orally twice daily for 12 weeks
Units
Counts
Participants
Secondary
Mean Change From Baseline in Clinical Global Impression-Severity-Global Functioning (CGI-S-GF) at Week 12
CGI-S-GF was a 7-point, single-item rating scale for overall functioning based on the investigator's general clinical experience with a similar participant population. This Likert scale ranged from 0 (normal) to 7 (most severely ill). LS Mean value was adjusted for NPI strata, treatment, pooled site, visit, treatment-by-visit, baseline CGI-S-GF, and baseline-by-visit interaction.
The analysis population included all randomized participants and was a modified intent-to-treat (ITT) population defined as having both a baseline and at least 1 post-baseline measure.
Posted
Least Squares Mean
Standard Error
units on a scale
Baseline, Week 12
ID
Title
Description
OG000
LY451395
3 milligram (mg) LY451395 (mibampator) orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
OG001
Placebo
Placebo orally twice daily for 12 weeks
Units
Counts
Participants
Secondary
Mean Change From Baseline in the 14-Item Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog14) at Week 12
ADAS-Cog14, a 14-item rating scale, measured the severity of cognitive dysfunction in persons with AD. Scores ranged from 0 to 90, with a higher score indicating worse cognitive functioning. LS Mean value was adjusted for NPI strata, treatment, pooled site, visit, treatment-by-visit, baseline ADAS-Cog, and baseline-by-visit interaction.
The analysis population included all randomized participants and was a modified intent-to-treat (ITT) population defined as having both a baseline and at least 1 post-baseline measure.
Posted
Least Squares Mean
Standard Error
units on a scale
Baseline, Week 12
ID
Title
Description
OG000
LY451395
3 milligram (mg) LY451395 (mibampator) orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
OG001
Placebo
Placebo orally twice daily for 12 weeks
Units
Counts
Participants
Time Frame
Not provided
Description
Not provided
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
LY451395 Acute Treatment
3 milligram (mg) LY451395 orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate.
5
63
24
63
EG001
Placebo Acute Treatment
Placebo orally twice daily for 12 weeks
4
69
24
69
EG002
LY451395 Washout
A 1-week single-blind washout period after the acute period, during which time all randomized participants received placebo.
0
42
1
42
EG003
Placebo Washout
A 1-week single-blind washout period after the acute period, during time which all randomized participants received placebo.
0
49
2
49
EG004
LY451395 Post-Study
The 30-day period after a participant had taken the last dose of study drug, during which time serious adverse event (SAE) information was collected.
1
63
0
63
EG005
Placebo Post-Study
The 30-day period after a participant had taken the last dose of study drug, during which time serious adverse event (SAE) information was collected.