Trial Outcomes & Findings for Treatment for Aggression and Agitation in Patients With Alzheimer's Disease (NCT NCT00843518)
NCT ID: NCT00843518
Last Updated: 2017-11-29
Results Overview
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.
COMPLETED
PHASE2
132 participants
Baseline, Week 12
2017-11-29
Participant Flow
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).
Participant milestones
| Measure |
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
|
Placebo
Placebo orally twice daily for 12 weeks
|
|---|---|---|
|
Period 2 (Double-blind Treatment)
STARTED
|
63
|
69
|
|
Period 2 (Double-blind Treatment)
COMPLETED
|
43
|
49
|
|
Period 2 (Double-blind Treatment)
NOT COMPLETED
|
20
|
20
|
|
Period 3 (Single-blind Washout)
STARTED
|
42
|
49
|
|
Period 3 (Single-blind Washout)
COMPLETED
|
42
|
49
|
|
Period 3 (Single-blind Washout)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
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
|
Placebo
Placebo orally twice daily for 12 weeks
|
|---|---|---|
|
Period 2 (Double-blind Treatment)
Adverse Event
|
5
|
3
|
|
Period 2 (Double-blind Treatment)
Death
|
0
|
1
|
|
Period 2 (Double-blind Treatment)
Lost to Follow-up
|
2
|
3
|
|
Period 2 (Double-blind Treatment)
Physician Decision
|
2
|
1
|
|
Period 2 (Double-blind Treatment)
Protocol Violation
|
2
|
5
|
|
Period 2 (Double-blind Treatment)
Withdrawal by Subject
|
2
|
0
|
|
Period 2 (Double-blind Treatment)
Caregiver decision
|
7
|
7
|
Baseline Characteristics
Treatment for Aggression and Agitation in Patients With Alzheimer's Disease
Baseline characteristics by cohort
| Measure |
LY451395
n=63 Participants
3 milligram (mg) LY451395 (mibampator) orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
|
Placebo
n=69 Participants
Placebo orally twice daily for 12 weeks
|
Total
n=132 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
77.21 years
STANDARD_DEVIATION 8.246 • n=93 Participants
|
77.66 years
STANDARD_DEVIATION 7.574 • n=4 Participants
|
77.44 years
STANDARD_DEVIATION 7.874 • n=27 Participants
|
|
Sex: Female, Male
Female
|
31 Participants
n=93 Participants
|
36 Participants
n=4 Participants
|
67 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
32 Participants
n=93 Participants
|
33 Participants
n=4 Participants
|
65 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
61 Participants
n=93 Participants
|
69 Participants
n=4 Participants
|
130 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
9 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
15 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
53 Participants
n=93 Participants
|
62 Participants
n=4 Participants
|
115 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
63 participants
n=93 Participants
|
69 participants
n=4 Participants
|
132 participants
n=27 Participants
|
|
Mini Mental State Examination (MMSE)
|
16.0 units on a scale
STANDARD_DEVIATION 6.06 • n=93 Participants
|
18.0 units on a scale
STANDARD_DEVIATION 5.26 • n=4 Participants
|
17.0 units on a scale
STANDARD_DEVIATION 5.72 • n=27 Participants
|
|
4-Item version of Neuropsychiatric Inventory (NPI-4) of Agitation and Aggression (A/A)
|
18.8 units on a scale
STANDARD_DEVIATION 8.72 • n=93 Participants
|
18.1 units on a scale
STANDARD_DEVIATION 8.19 • n=4 Participants
|
18.4 units on a scale
STANDARD_DEVIATION 8.42 • n=27 Participants
|
|
10-Item version of Neuropsychiatric Inventory (NPI-10)
|
31.9 units on a scale
STANDARD_DEVIATION 16.67 • n=93 Participants
|
29.7 units on a scale
STANDARD_DEVIATION 13.22 • n=4 Participants
|
30.7 units on a scale
STANDARD_DEVIATION 14.95 • n=27 Participants
|
|
Neuropsychiatric Inventory (NPI) Depression Domain
|
2.2 units on a scale
STANDARD_DEVIATION 3.10 • n=93 Participants
|
1.8 units on a scale
STANDARD_DEVIATION 2.33 • n=4 Participants
|
2.0 units on a scale
STANDARD_DEVIATION 2.73 • n=27 Participants
|
|
Neuropsychiatric Inventory (NPI) Psychosis Subscale
|
3.2 units on a scale
STANDARD_DEVIATION 5.24 • n=93 Participants
|
2.4 units on a scale
STANDARD_DEVIATION 3.92 • n=4 Participants
|
2.8 units on a scale
STANDARD_DEVIATION 4.60 • n=27 Participants
|
|
Cohen-Mansfield Agitation Inventory-Community (CMAI-C) Version
|
73.6 units on a scale
STANDARD_DEVIATION 22.55 • n=93 Participants
|
64.7 units on a scale
STANDARD_DEVIATION 17.58 • n=4 Participants
|
68.9 units on a scale
STANDARD_DEVIATION 20.52 • n=27 Participants
|
|
Cornell Scale for Depression in Dementia (CSDD)
|
8.4 units on a scale
STANDARD_DEVIATION 5.40 • n=93 Participants
|
8.0 units on a scale
STANDARD_DEVIATION 4.63 • n=4 Participants
|
8.2 units on a scale
STANDARD_DEVIATION 4.99 • n=27 Participants
|
|
Total T-Score in the Frontal System Behaviors (FrSBe) Scale
|
92.4 units on a scale
STANDARD_DEVIATION 22.50 • n=93 Participants
|
89.1 units on a scale
STANDARD_DEVIATION 18.50 • n=4 Participants
|
90.7 units on a scale
STANDARD_DEVIATION 22.11 • n=27 Participants
|
|
Clinical Global Impression-Severity-Agitation/Aggressive (CGI-S-A/A)
|
4.1 units on a scale
STANDARD_DEVIATION 0.68 • n=93 Participants
|
4.1 units on a scale
STANDARD_DEVIATION 0.69 • n=4 Participants
|
4.1 units on a scale
STANDARD_DEVIATION 0.68 • n=27 Participants
|
|
Clinical Global Impression-Severity-Global Functioning (CGI-S-GF)
|
4.1 units on a scale
STANDARD_DEVIATION 0.88 • n=93 Participants
|
4.0 units on a scale
STANDARD_DEVIATION 0.78 • n=4 Participants
|
4.1 units on a scale
STANDARD_DEVIATION 0.82 • n=27 Participants
|
|
14-Item Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog14)
|
43.3 units on a scale
STANDARD_DEVIATION 20.42 • n=93 Participants
|
40.0 units on a scale
STANDARD_DEVIATION 18.07 • n=4 Participants
|
41.6 units on a scale
STANDARD_DEVIATION 19.22 • n=27 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 12Population: 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.
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.
Outcome measures
| Measure |
LY451395
n=43 Participants
3 milligram (mg) LY451395 (mibampator) orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
|
Placebo
n=50 Participants
Placebo orally twice daily for 12 weeks
|
|---|---|---|
|
Mean Change From Baseline in the 4-Item Agitation/Aggression Subscale of the Neuropsychiatric Inventory (NPI-4 A/A) at Week 12
|
-5.4 units on a scale
Standard Error 1.21
|
-6.2 units on a scale
Standard Error 1.12
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: 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.
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.
Outcome measures
| Measure |
LY451395
n=43 Participants
3 milligram (mg) LY451395 (mibampator) orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
|
Placebo
n=50 Participants
Placebo orally twice daily for 12 weeks
|
|---|---|---|
|
Mean Change From Baseline in 10-Item Version of Neuropsychiatric Inventory (NPI-10) at Week 12
|
-8.2 units on a scale
Standard Error 2.08
|
-9.3 units on a scale
Standard Error 1.93
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: 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.
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.
Outcome measures
| Measure |
LY451395
n=43 Participants
3 milligram (mg) LY451395 (mibampator) orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
|
Placebo
n=50 Participants
Placebo orally twice daily for 12 weeks
|
|---|---|---|
|
Mean Change From Baseline in the Neuropsychiatric Inventory (NPI) Depression Domain at Week 12
|
-0.2 units on a scale
Standard Error 0.34
|
-1.0 units on a scale
Standard Error 0.32
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: 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.
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.
Outcome measures
| Measure |
LY451395
n=43 Participants
3 milligram (mg) LY451395 (mibampator) orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
|
Placebo
n=50 Participants
Placebo orally twice daily for 12 weeks
|
|---|---|---|
|
Mean Change From Baseline in the Neuropsychiatric Inventory (NPI) Psychosis Subscale Score at Week 12
|
-0.4 units on a scale
Standard Error 0.58
|
-0.4 units on a scale
Standard Error 0.54
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: 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.
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.
Outcome measures
| Measure |
LY451395
n=42 Participants
3 milligram (mg) LY451395 (mibampator) orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
|
Placebo
n=50 Participants
Placebo orally twice daily for 12 weeks
|
|---|---|---|
|
Mean Change From Baseline in Cohen-Mansfield Agitation Inventory-Community Version (CMAI-C) at Week 12
|
-7.2 units on a scale
Standard Error 1.98
|
-4.1 units on a scale
Standard Error 1.79
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: 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.
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.
Outcome measures
| Measure |
LY451395
n=39 Participants
3 milligram (mg) LY451395 (mibampator) orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
|
Placebo
n=47 Participants
Placebo orally twice daily for 12 weeks
|
|---|---|---|
|
Mean Change From Baseline in Cornell Scale for Depression in Dementia (CSDD) at Week 12
|
-2.5 units on a scale
Standard Error 0.59
|
-2.7 units on a scale
Standard Error 0.54
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: 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.
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.
Outcome measures
| Measure |
LY451395
n=42 Participants
3 milligram (mg) LY451395 (mibampator) orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
|
Placebo
n=49 Participants
Placebo orally twice daily for 12 weeks
|
|---|---|---|
|
Mean Change From Baseline in Total T-Score in the Frontal System Behaviors Scale (FrSBe) at Week 12
|
-2.2 units on a scale
Standard Error 2.02
|
2.3 units on a scale
Standard Error 1.88
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: 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.
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.
Outcome measures
| Measure |
LY451395
n=43 Participants
3 milligram (mg) LY451395 (mibampator) orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
|
Placebo
n=50 Participants
Placebo orally twice daily for 12 weeks
|
|---|---|---|
|
Mean Change From Baseline in Clinical Global Impression-Severity-Agitation/Aggression (CGI-S-A/A) at Week 12
|
-0.7 units on a scale
Standard Error 0.15
|
-0.6 units on a scale
Standard Error 0.14
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: 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.
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.
Outcome measures
| Measure |
LY451395
n=43 Participants
3 milligram (mg) LY451395 (mibampator) orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
|
Placebo
n=50 Participants
Placebo orally twice daily for 12 weeks
|
|---|---|---|
|
Mean Change From Baseline in Clinical Global Impression-Severity-Global Functioning (CGI-S-GF) at Week 12
|
-0.2 units on a scale
Standard Error 0.11
|
-0.03 units on a scale
Standard Error 0.11
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: 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.
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.
Outcome measures
| Measure |
LY451395
n=43 Participants
3 milligram (mg) LY451395 (mibampator) orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
|
Placebo
n=49 Participants
Placebo orally twice daily for 12 weeks
|
|---|---|---|
|
Mean Change From Baseline in the 14-Item Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog14) at Week 12
|
-0.1 units on a scale
Standard Error 0.98
|
-0.6 units on a scale
Standard Error 0.92
|
Adverse Events
LY451395 Acute Treatment
Placebo Acute Treatment
LY451395 Washout
Placebo Washout
LY451395 Post-Study
Placebo Post-Study
Serious adverse events
| Measure |
LY451395 Acute Treatment
n=63 participants at risk
3 milligram (mg) LY451395 orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate.
|
Placebo Acute Treatment
n=69 participants at risk
Placebo orally twice daily for 12 weeks
|
LY451395 Washout
n=42 participants at risk
A 1-week single-blind washout period after the acute period, during which time all randomized participants received placebo.
|
Placebo Washout
n=49 participants at risk
A 1-week single-blind washout period after the acute period, during time which all randomized participants received placebo.
|
LY451395 Post-Study
n=63 participants at risk
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.
|
Placebo Post-Study
n=69 participants at risk
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.
|
|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Pancreatic pseudocyst
|
1.6%
1/63 • Number of events 1
|
0.00%
0/69
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
|
General disorders
Non-cardiac chest pain
|
1.6%
1/63 • Number of events 1
|
0.00%
0/69
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/63
|
1.4%
1/69 • Number of events 1
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
|
Infections and infestations
Pneumonia
|
1.6%
1/63 • Number of events 1
|
1.4%
1/69 • Number of events 1
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
|
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
|
0.00%
0/63
|
0.00%
0/69
|
0.00%
0/42
|
0.00%
0/49
|
1.6%
1/63 • Number of events 1
|
0.00%
0/69
|
|
Musculoskeletal and connective tissue disorders
Spinal column stenosis
|
0.00%
0/63
|
1.4%
1/69 • Number of events 1
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
|
Nervous system disorders
Haemorrhage intracranial
|
0.00%
0/63
|
1.4%
1/69 • Number of events 1
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
|
Nervous system disorders
Presyncope
|
0.00%
0/63
|
1.4%
1/69 • Number of events 1
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
|
Nervous system disorders
Transient ischaemic attack
|
1.6%
1/63 • Number of events 1
|
0.00%
0/69
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
|
Psychiatric disorders
Psychotic disorder
|
1.6%
1/63 • Number of events 1
|
0.00%
0/69
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
Other adverse events
| Measure |
LY451395 Acute Treatment
n=63 participants at risk
3 milligram (mg) LY451395 orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate.
|
Placebo Acute Treatment
n=69 participants at risk
Placebo orally twice daily for 12 weeks
|
LY451395 Washout
n=42 participants at risk
A 1-week single-blind washout period after the acute period, during which time all randomized participants received placebo.
|
Placebo Washout
n=49 participants at risk
A 1-week single-blind washout period after the acute period, during time which all randomized participants received placebo.
|
LY451395 Post-Study
n=63 participants at risk
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.
|
Placebo Post-Study
n=69 participants at risk
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.
|
|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Constipation
|
3.2%
2/63 • Number of events 2
|
2.9%
2/69 • Number of events 2
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
|
Gastrointestinal disorders
Diarrhoea
|
4.8%
3/63 • Number of events 4
|
4.3%
3/69 • Number of events 6
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
|
Gastrointestinal disorders
Eructation
|
0.00%
0/63
|
2.9%
2/69 • Number of events 2
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
|
Gastrointestinal disorders
Nausea
|
4.8%
3/63 • Number of events 3
|
4.3%
3/69 • Number of events 3
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
|
General disorders
Fatigue
|
4.8%
3/63 • Number of events 3
|
1.4%
1/69 • Number of events 1
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
|
General disorders
Gait disturbance
|
0.00%
0/63
|
2.9%
2/69 • Number of events 2
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
|
Infections and infestations
Gingival infection
|
0.00%
0/63
|
0.00%
0/69
|
0.00%
0/42
|
2.0%
1/49 • Number of events 1
|
0.00%
0/63
|
0.00%
0/69
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/63
|
2.9%
2/69 • Number of events 2
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
|
Infections and infestations
Upper respiratory tract infection
|
4.8%
3/63 • Number of events 3
|
1.4%
1/69 • Number of events 1
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
|
Infections and infestations
Urinary tract infection
|
1.6%
1/63 • Number of events 1
|
2.9%
2/69 • Number of events 2
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
|
Infections and infestations
Vaginal infection
|
3.2%
1/31 • Number of events 1
|
0.00%
0/36
|
0.00%
0/22
|
0.00%
0/27
|
0.00%
0/31
|
0.00%
0/36
|
|
Injury, poisoning and procedural complications
Face injury
|
0.00%
0/63
|
0.00%
0/69
|
0.00%
0/42
|
2.0%
1/49 • Number of events 1
|
0.00%
0/63
|
0.00%
0/69
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/63
|
1.4%
1/69 • Number of events 1
|
0.00%
0/42
|
2.0%
1/49 • Number of events 1
|
0.00%
0/63
|
0.00%
0/69
|
|
Injury, poisoning and procedural complications
Joint injury
|
0.00%
0/63
|
0.00%
0/69
|
0.00%
0/42
|
2.0%
1/49 • Number of events 1
|
0.00%
0/63
|
0.00%
0/69
|
|
Injury, poisoning and procedural complications
Laceration
|
0.00%
0/63
|
0.00%
0/69
|
0.00%
0/42
|
2.0%
1/49 • Number of events 1
|
0.00%
0/63
|
0.00%
0/69
|
|
Investigations
Blood uric acid increased
|
0.00%
0/63
|
0.00%
0/69
|
2.4%
1/42 • Number of events 1
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
|
Investigations
Prostatic specific antigen increased
|
0.00%
0/32
|
3.0%
1/33 • Number of events 1
|
0.00%
0/20
|
0.00%
0/22
|
0.00%
0/32
|
0.00%
0/33
|
|
Metabolism and nutrition disorders
Decreased appetite
|
3.2%
2/63 • Number of events 2
|
1.4%
1/69 • Number of events 1
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/63
|
2.9%
2/69 • Number of events 2
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
|
Nervous system disorders
Dizziness
|
1.6%
1/63 • Number of events 2
|
4.3%
3/69 • Number of events 3
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
|
Nervous system disorders
Headache
|
3.2%
2/63 • Number of events 2
|
1.4%
1/69 • Number of events 1
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
|
Nervous system disorders
Lethargy
|
4.8%
3/63 • Number of events 3
|
1.4%
1/69 • Number of events 1
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
|
Nervous system disorders
Tremor
|
4.8%
3/63 • Number of events 3
|
1.4%
1/69 • Number of events 1
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
|
Psychiatric disorders
Insomnia
|
3.2%
2/63 • Number of events 2
|
2.9%
2/69 • Number of events 2
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.8%
3/63 • Number of events 3
|
4.3%
3/69 • Number of events 3
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
3.2%
2/63 • Number of events 2
|
0.00%
0/69
|
0.00%
0/42
|
0.00%
0/49
|
0.00%
0/63
|
0.00%
0/69
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60