A Phase 2 interventional study of LY451395 and Placebo in Alzheimer's Disease, sponsored by Eli Lilly and Company. Completed at 17 sites in United States. Open to participants aged 60 Years and older. Per ClinicalTrials.gov, last updated 2017-11-29.
Sponsored by Eli Lilly and Company · Phase 2, Interventional, and Treatment
The purpose of this study is to determine whether this drug can help symptoms of aggression and agitation in participants with Alzheimer's disease.
The primary purpose of this study is to help answer the following research questions:
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.
3,678 studies on the registry are indexed under Alzheimer Disease; 872 are open to participants now.
This study's enrollment of 132 is above the median of 70 across 2,808 interventional studies indexed under Alzheimer Disease.
Browse Alzheimer Disease studies →Eli Lilly and Company is the lead sponsor of 2,048 studies on the registry; 140 are open to participants now.
Of its 521 completed or terminated interventional studies of FDA-regulated products, 341 (65%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
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 orally twice daily for 12 weeks
Drug: Placebo
3 mg LY451395 orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
Also known as: mibampator
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
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.
Time frame: Baseline, Week 12
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.
Time frame: Baseline, Week 12
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline, Week 12
| Milestone | LY451395 | Placebo |
|---|---|---|
| Started | 63 | 69 |
| Completed | 43 | 49 |
| Not completed | 20 | 20 |
| Withdrew: Adverse event | 5 | 3 |
| Withdrew: Death | 0 | 1 |
| Withdrew: Lost to follow-up | 2 | 3 |
| Withdrew: Physician decision | 2 | 1 |
| Withdrew: Protocol violation | 2 | 5 |
| Withdrew: Withdrawal by subject | 2 | 0 |
| Withdrew: Caregiver decision | 7 | 7 |
| Milestone | LY451395 | Placebo |
|---|---|---|
| Started | 42 | 49 |
| Completed | 42 | 49 |
| Not completed | 0 | 0 |
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.
| units on a scale | LY451395 | Placebo |
|---|---|---|
| Mean Change From Baseline in the 4-Item Agitation/Aggression Subscale of the Neuropsychiatric Inventory (NPI-4 A/A) at Week 12 | -5.4 ± 1.21 | -6.2 ± 1.12 |
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.
| units on a scale | LY451395 | Placebo |
|---|---|---|
| Mean Change From Baseline in 10-Item Version of Neuropsychiatric Inventory (NPI-10) at Week 12 | -8.2 ± 2.08 | -9.3 ± 1.93 |
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.
| units on a scale | LY451395 | Placebo |
|---|---|---|
| Mean Change From Baseline in the Neuropsychiatric Inventory (NPI) Depression Domain at Week 12 | -0.2 ± 0.34 | -1.0 ± 0.32 |
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.
| units on a scale | LY451395 | Placebo |
|---|---|---|
| Mean Change From Baseline in the Neuropsychiatric Inventory (NPI) Psychosis Subscale Score at Week 12 | -0.4 ± 0.58 | -0.4 ± 0.54 |
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.
| units on a scale | LY451395 | Placebo |
|---|---|---|
| Mean Change From Baseline in Cohen-Mansfield Agitation Inventory-Community Version (CMAI-C) at Week 12 | -7.2 ± 1.98 | -4.1 ± 1.79 |
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.
| units on a scale | LY451395 | Placebo |
|---|---|---|
| Mean Change From Baseline in Cornell Scale for Depression in Dementia (CSDD) at Week 12 | -2.5 ± 0.59 | -2.7 ± 0.54 |
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.
| units on a scale | LY451395 | Placebo |
|---|---|---|
| Mean Change From Baseline in Total T-Score in the Frontal System Behaviors Scale (FrSBe) at Week 12 | -2.2 ± 2.02 | 2.3 ± 1.88 |
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.
| units on a scale | LY451395 | Placebo |
|---|---|---|
| Mean Change From Baseline in Clinical Global Impression-Severity-Agitation/Aggression (CGI-S-A/A) at Week 12 | -0.7 ± 0.15 | -0.6 ± 0.14 |
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.
| units on a scale | LY451395 | Placebo |
|---|---|---|
| Mean Change From Baseline in Clinical Global Impression-Severity-Global Functioning (CGI-S-GF) at Week 12 | -0.2 ± 0.11 | -0.03 ± 0.11 |
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.
| units on a scale | LY451395 | Placebo |
|---|---|---|
| Mean Change From Baseline in the 14-Item Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog14) at Week 12 | -0.1 ± 0.98 | -0.6 ± 0.92 |
Non-serious events are listed at a 2% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| LY451395 Acute Treatment | — | 5/63 (7.9%) | 24/63 (38.1%) |
| Placebo Acute Treatment | — | 4/69 (5.8%) | 24/69 (34.8%) |
| LY451395 Washout | — | 0/42 (0%) | 1/42 (2.4%) |
| Placebo Washout | — | 0/49 (0%) | 2/49 (4.1%) |
| LY451395 Post-Study | — | 1/63 (1.6%) | 0/63 (0%) |
| Placebo Post-Study | — | 0/69 (0%) | 0/69 (0%) |
| Event | LY451395 Acute Treatment | Placebo Acute Treatment | LY451395 Washout | Placebo Washout | LY451395 Post-Study | Placebo Post-Study |
|---|---|---|---|---|---|---|
| Pancreatic pseudocystGastrointestinal disorders | 1/63 | 0/69 | 0/42 | 0/49 | 0/63 | 0/69 |
| Non-cardiac chest painGeneral disorders | 1/63 | 0/69 | 0/42 | 0/49 | 0/63 | 0/69 |
| PneumoniaInfections and infestations | 1/63 | 1/69 | 0/42 | 0/49 | 0/63 | 0/69 |
| Diabetes mellitus inadequate controlMetabolism and nutrition disorders | 0/63 | 0/69 | 0/42 | 0/49 | 1/63 | 0/69 |
| Transient ischaemic attackNervous system disorders | 1/63 | 0/69 | 0/42 | 0/49 | 0/63 | 0/69 |
| Psychotic disorderPsychiatric disorders | 1/63 | 0/69 | 0/42 | 0/49 | 0/63 | 0/69 |
| DiverticulitisInfections and infestations | 0/63 | 1/69 | 0/42 | 0/49 | 0/63 | 0/69 |
| Spinal column stenosisMusculoskeletal and connective tissue disorders | 0/63 | 1/69 | 0/42 | 0/49 | 0/63 | 0/69 |
| Haemorrhage intracranialNervous system disorders | 0/63 | 1/69 | 0/42 | 0/49 | 0/63 | 0/69 |
| PresyncopeNervous system disorders | 0/63 | 1/69 | 0/42 | 0/49 | 0/63 | 0/69 |
| Event | LY451395 Acute Treatment | Placebo Acute Treatment | LY451395 Washout | Placebo Washout | LY451395 Post-Study | Placebo Post-Study |
|---|---|---|---|---|---|---|
| DiarrhoeaGastrointestinal disorders | 3/63 | 3/69 | 0/42 | 0/49 | 0/63 | 0/69 |
| NauseaGastrointestinal disorders | 3/63 | 3/69 | 0/42 | 0/49 | 0/63 | 0/69 |
| FatigueGeneral disorders | 3/63 | 1/69 | 0/42 | 0/49 | 0/63 | 0/69 |
| Upper respiratory tract infectionInfections and infestations | 3/63 | 1/69 | 0/42 | 0/49 | 0/63 | 0/69 |
| LethargyNervous system disorders | 3/63 | 1/69 | 0/42 | 0/49 | 0/63 | 0/69 |
| TremorNervous system disorders | 3/63 | 1/69 | 0/42 | 0/49 | 0/63 | 0/69 |
| CoughRespiratory, thoracic and mediastinal disorders | 3/63 | 3/69 | 0/42 | 0/49 | 0/63 | 0/69 |
| DizzinessNervous system disorders | 1/63 | 3/69 | 0/42 | 0/49 | 0/63 | 0/69 |
| Vaginal infectionInfections and infestations | 1/31 | 0/36 | 0/22 | 0/27 | 0/31 | 0/36 |
| ConstipationGastrointestinal disorders | 2/63 | 2/69 | 0/42 | 0/49 | 0/63 | 0/69 |
| Age, Continuous(years) | LY451395 | Placebo | Total |
|---|---|---|---|
| Mean | 77.21 ± 8.246 | 77.66 ± 7.574 | 77.44 ± 7.874 |
| Sex: Female, Male(Participants) | LY451395 | Placebo | Total |
|---|---|---|---|
| Female | 31 | 36 | 67 |
| Male | 32 | 33 | 65 |
| Ethnicity (NIH/OMB)(Participants) | LY451395 | Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 2 | 0 | 2 |
| Not Hispanic or Latino | 61 | 69 | 130 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | LY451395 | Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 1 | 1 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 9 | 6 | 15 |
| White | 53 | 62 | 115 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 1 | 0 | 1 |
| Region of Enrollment(participants) | LY451395 | Placebo | Total |
|---|---|---|---|
| United States | 63 | 69 | 132 |
| Mini Mental State Examination (MMSE)(units on a scale) | LY451395 | Placebo | Total |
|---|---|---|---|
| Mean | 16.0 ± 6.06 | 18.0 ± 5.26 | 17.0 ± 5.72 |
| 4-Item version of Neuropsychiatric Inventory (NPI-4) of Agitation and Aggression (A/A)(units on a scale) | LY451395 | Placebo | Total |
|---|---|---|---|
| Mean | 18.8 ± 8.72 | 18.1 ± 8.19 | 18.4 ± 8.42 |
| 10-Item version of Neuropsychiatric Inventory (NPI-10)(units on a scale) | LY451395 | Placebo | Total |
|---|---|---|---|
| Mean | 31.9 ± 16.67 | 29.7 ± 13.22 | 30.7 ± 14.95 |
8 further baseline measures are reported on the registry.
This study is completed, as verified in Oct 2017. You cannot join it, but the record below documents what was studied.
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