- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00843518
Treatment for Aggression and Agitation in Patients With Alzheimer's Disease
October 23, 2017 updated by: Eli Lilly and Company
Assessment of LY451395 for Neuropsychiatric Symptoms of Aggression and Agitation in Alzheimer's Disease
The purpose of this study is to determine whether this drug can help symptoms of aggression and agitation in participants with Alzheimer's disease.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
132
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Arizona
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Phoenix, Arizona, United States, 85006
- 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.
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California
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Costa Mesa, California, United States, 92626
- 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.
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Connecticut
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Hamden, Connecticut, United States, 06518
- 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.
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Florida
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Orlando, Florida, United States, 32806
- 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.
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Tampa, Florida, United States, 33609
- 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.
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West Palm Beach, Florida, United States, 33407
- 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.
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Georgia
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Atlanta, Georgia, United States, 30308
- 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.
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Maryland
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Easton, Maryland, United States, 21601
- 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.
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Mississippi
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Flowood, Mississippi, United States, 39232
- 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.
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New Jersey
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Toms River, New Jersey, United States, 08755
- 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.
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New York
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Staten Island, New York, United States, 10312
- 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.
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North Carolina
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Hickory, North Carolina, United States, 28601
- 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.
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Oregon
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Portland, Oregon, United States, 97210
- 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.
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Pennsylvania
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Norristown, Pennsylvania, United States, 19401
- 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.
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Texas
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Austin, Texas, United States, 78757
- 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.
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Vermont
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Bennington, Vermont, United States, 05201
- 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.
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Wisconsin
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Waukesha, Wisconsin, United States, 53188
- 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.
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
60 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: LY451395
3 milligram (mg) LY451395 orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
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3 mg LY451395 orally twice daily for 12 weeks; may have been reduced to 1 mg if participant was unable to tolerate
Other Names:
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Placebo Comparator: Placebo
Placebo orally twice daily for 12 weeks
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Placebo orally twice daily for 12 weeks
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Mean Change From Baseline in the 4-Item Agitation/Aggression Subscale of the Neuropsychiatric Inventory (NPI-4 A/A) at Week 12
Time Frame: Baseline, Week 12
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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.
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Baseline, Week 12
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Mean Change From Baseline in 10-Item Version of Neuropsychiatric Inventory (NPI-10) at Week 12
Time Frame: Baseline, Week 12
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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.
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Baseline, Week 12
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Mean Change From Baseline in the Neuropsychiatric Inventory (NPI) Depression Domain at Week 12
Time Frame: Baseline, Week 12
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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.
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Baseline, Week 12
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Mean Change From Baseline in the Neuropsychiatric Inventory (NPI) Psychosis Subscale Score at Week 12
Time Frame: Baseline, Week 12
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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.
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Baseline, Week 12
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Mean Change From Baseline in Cohen-Mansfield Agitation Inventory-Community Version (CMAI-C) at Week 12
Time Frame: Baseline, Week 12
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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.
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Baseline, Week 12
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Mean Change From Baseline in Cornell Scale for Depression in Dementia (CSDD) at Week 12
Time Frame: Baseline, Week 12
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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.
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Baseline, Week 12
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Mean Change From Baseline in Total T-Score in the Frontal System Behaviors Scale (FrSBe) at Week 12
Time Frame: Baseline, Week 12
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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.
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Baseline, Week 12
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Mean Change From Baseline in Clinical Global Impression-Severity-Agitation/Aggression (CGI-S-A/A) at Week 12
Time Frame: Baseline, Week 12
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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.
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Baseline, Week 12
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Mean Change From Baseline in Clinical Global Impression-Severity-Global Functioning (CGI-S-GF) at Week 12
Time Frame: Baseline, Week 12
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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.
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Baseline, Week 12
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Mean Change From Baseline in the 14-Item Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog14) at Week 12
Time Frame: Baseline, Week 12
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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.
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Baseline, Week 12
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: 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
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
February 1, 2009
Primary Completion (Actual)
June 1, 2011
Study Completion (Actual)
June 1, 2011
Study Registration Dates
First Submitted
February 12, 2009
First Submitted That Met QC Criteria
February 12, 2009
First Posted (Estimate)
February 13, 2009
Study Record Updates
Last Update Posted (Actual)
November 29, 2017
Last Update Submitted That Met QC Criteria
October 23, 2017
Last Verified
October 1, 2017
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Behavioral Symptoms
- Mental Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurologic Manifestations
- Neurobehavioral Manifestations
- Neurocognitive Disorders
- Neurodegenerative Diseases
- Dyskinesias
- Psychomotor Disorders
- Dementia
- Tauopathies
- Aggression
- Psychomotor Agitation
- Alzheimer Disease
Other Study ID Numbers
- 12541
- H6N-MC-LEAQ (Other Identifier: Eli Lilly and Company)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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