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Efficacy, Safety, and Tolerability of AVP-786 for the Treatment of Agitation in Participants With Dementia of the Alzheimer's Type

Primary Purpose

Agitation in Participants With Dementia of the Alzheimer's Type

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
AVP-786-18
Placebo
AVP-786-28
AVP-786-42.63
Sponsored by
Otsuka Pharmaceutical Development & Commercialization, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Agitation in Participants With Dementia of the Alzheimer's Type

Eligibility Criteria

50 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosis of probable Alzheimer's Disease (AD) according to the 2011 National Institute on Aging-Alzheimer's Association (NIA-AA) working groups criteria
  • The participant has clinically significant, moderate/severe agitation at the time of screening and for at least 2 weeks prior to randomization
  • The diagnosis of agitation must meet the International Psychogeriatric Association (IPA) provisional definition of agitation
  • Either out participants or residents of an assisted-living facility or a skilled nursing home
  • Clinical Global Impression of Severity of Illness (CGIS) score assessing Agitation is >=4 (moderately ill) at screening and baseline
  • Mini-Mental State Examination (MMSE) score is between 6 and 26 (inclusive) at screening and baseline
  • Caregiver who is able and willing to comply with all required study procedures. In order to qualify as a reliable informant (i.e., caregiver) capable of assessing changes in participant's condition during the study, the individual must spend a minimum of 2 hours per day for 4 days per week with the participant.

Exclusion Criteria:

  • Participant has dementia predominantly of non-Alzheimer's type (e.g., vascular dementia, frontotemporal dementia, Parkinson's disease, substance-induced dementia)
  • Participants with co-existent clinically significant or unstable systemic diseases that could confound the interpretation of the safety results of the study (e.g., malignancy, poorly controlled diabetes, poorly controlled hypertension, unstable pulmonary, renal or hepatic disease, unstable ischemic cardiac disease, dilated cardiomyopathy, or unstable valvular heart disease)
  • Participant with myasthenia gravis

Sites / Locations

  • Brain and Spine Center
  • Territory Neurology & Research Institute
  • Health Initiatives Research
  • Behavioral Research Specialists, LLC
  • Irvine Center for Clinical Research
  • California Neurological Services
  • Havana Research Institute
  • Pacific Research Network, Inc
  • Syrentis Clinical Research
  • Viking Clinical Research
  • Denver Neurological Research, LLC
  • JEM Research Institute
  • Clinical Research Of Brandon, LLC
  • Meridien Research
  • Moonshine Research Center, Inc
  • Science Connections, LLC
  • Finlay Medical Research Corp
  • Indago Research & Health Center, Inc.
  • New Life Medical Research Center, Inc.
  • Reliable Clinical Research,LLC
  • Research in Miami, Inc
  • The Research Center, Inc
  • Maxblue Institute
  • Clinical Neuroscience Solutions, Inc.
  • Alzheimer's Research and Treatment Center
  • Premier Clinical Research Institute, Inc.
  • Project 4 Research
  • BioMed Research Institute
  • CCM Clinical Research Group
  • DADE Research Center, LLC
  • AMB Research Center, Inc.
  • United Health Research Corp
  • Advance Medical Research Center
  • Coral Research Clinic Corp
  • P&S Reasearch
  • The Neurology Research Group, LLC
  • Kendall Research Institute
  • Nuovida Research Center Corp.
  • Collier Neurologic Specialists, LLC
  • Lazlo J. Mate, MD, PA
  • Compass Research, LLC
  • IMIC Inc.
  • University of West Florida
  • Neurology Research Institute Palm Beach, LLC
  • Emory Brain Health Center
  • Columbus Research & Wellness Institute, INC
  • Josephson Wallack Munshower Neurology, PC
  • Baptist Health Medical Group
  • The Samuel & Alexia Bratton Memory Clinic
  • Mir Neurology
  • Boston Center for Memory
  • AMAC Research Institute
  • Michigan State University
  • Center for Emotional Fitness
  • The NeuroCognitive Institute
  • Brooklyn Medical Institute
  • Integrative Clinical Trials, LLC
  • Eastside Comprehensive Medical Center, LLC
  • Burke Rehabilitation Hospital
  • Herbert Harris, MD, PhD, PA
  • ANI Neurology PLLC dba Alzheimer's Memory Center
  • Daystar Clinical Research Inc
  • Valley Medical Research
  • CTI Clinical Research Center
  • Cleveland Clinic Lou Ruvo Center for Brain Health at Lakewood Hospital
  • Heritage Valley Medical Group, Inc.
  • The Birches at Newton / Family Medical Associates
  • Thomas Jefferson University
  • RH Johnson VA Medical Center
  • BG Neurology
  • Texas Neurology, P.A.
  • Baylor College of Medicine
  • Houston Methodist Neurological Institute
  • Clinical Trial Network
  • Texas Medical Research Associates, L.L.C.
  • Pharmaceuticals Research Associates, Inc.
  • Clinical Neuroscience Research Associates, Inc. dba The Memory Clinic
  • Veteran Affairs Medical Center, Salem Virginia
  • IPC Research
  • Dr. Alexander McIntyre Inc.
  • The Medical Art Health Research Group
  • The Medical Art Health Research Group
  • The Medical Art Health Research Group

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Experimental

Arm Label

Placebo

AVP-786-28

AVP-786-42.63

Arm Description

Participants were administered AVP-786 matching placebo capsules, orally, twice daily (BID) for up to 12 weeks.

Participants were administered AVP-786-18 capsule, orally, once daily (QD) along with AVP-786 matching placebo capsule, orally, QD during Week 1 followed by AVP-786-18 capsules, orally, BID during Weeks 2, 3 and AVP-786-28 capsules, orally, BID during Weeks 4 to 12.

Participants were administered AVP-786-28 capsules, orally, QD along with AVP-786 matching placebo capsule, orally, QD during Week 1 followed by AVP-786-28 capsules, orally, BID during Weeks 2, 3, and AVP-786-42.63 capsules, orally, BID during Weeks 4 to 12.

Outcomes

Primary Outcome Measures

Change From Baseline to Week 12 in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score
The CMAI was used to assess the frequency of manifestations of agitated behaviors in elderly participants. It consists of 29 agitated items rated on a 7-point scale of frequency: 1, never; 2, less than once a week; 3, once or twice a week; 4, several times a week; 5, once or twice a day; 6, several times a day; 7, several times an hour. The CMAI total score ranges from 29 to 203. Higher scores indicate worsening of the condition. Negative change from baseline indicates improvement. Mixed Model Repeated Measures (MMRM) was used for the analysis.

Secondary Outcome Measures

Relative Change From Baseline to Week 12 in the Modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC)-Agitation Score
The mADCS-CGIC-Agitation is a modified version of the ADCS-CGIC containing additional questions related to agitation and an assessment of the Clinician's Impression of Change focused specifically on agitation. Participants are asked to rate their impression of change as: 1=Marked Improvement; 2=Moderate Improvement; 3=Minimal Improvement; 4=No Change; 5=Minimal Worsening; 6=Moderate Worsening; 7=Marked Worsening. Higher scores indicate worsening of agitation and positive change from baseline indicates worsening. MMRM was used for the analysis.
Change From Baseline to Week 12 in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score
The NPI is a retrospective caregiver-informant interview covering 12 neuropsychiatric symptom domains. The Agitation/Aggression domain is designed to collect information on the behavioral aspects of agitation/aggression in participants with probable AD and clinically meaningful agitation secondary to AD. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as:1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, severe. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. Higher scores indicate worsening symptoms. Negative change from baseline indicates improvement in symptoms. MMRM was used for the analysis.
Change From Baseline to Week 12 in the NPI Agitation/Aggression Caregiver Distress Score
The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate caregiver distress. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as:1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as:1, mild; 2, moderate; 3, marked severe. The total caregiver distress score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12 with a higher score indicating worsening of symptoms. Negative change from baseline indicates improvement in symptoms. MMRM was used for the analysis.
Change From Baseline to Week 12 in the NPI Aberrant Motor Behavior Domain Score
The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate aberrant motor behavior. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, marked severe. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12 with a higher score indicating worsening of symptoms. Negative change from baseline indicates improvement in symptoms. MMRM was used for the analysis.
Change From Baseline to Week 12 in the Zarit Burden Interview (ZBI) Score
The ZBI is a 22-item scale used to assess the impact of a participants' disabilities on the caregiver's life. It is designed to reflect the burden experienced by caregivers of dementia participants and can either be completed by the caregiver or administered as an interview. Each item of the scale is rated to reflect the burden using the 5-point scale: 0=Never; 1=Rarely; 2=Sometimes; 3=Quite Frequently; 4=Nearly Always. The ZBI is scored by summing the responses of the individual questions and ranges from 0 to 88. Higher scores indicate greater caregiver distress. Negative change from baseline indicates less distress. MMRM was used for the analysis.
Change From Baseline to Week 12 in the NPI Irritability/Lability Domain Score
The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains, including the irritability/lability domain score. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as:1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as:1, mild; 2, moderate; 3, severe. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. Higher scores indicate worsening of the symptoms. Negative change from baseline indicates improvement in symptoms. MMRM was used for the analysis.
Change From Baseline to Week 12 in the NPI Total Score
NPI evaluates both frequency and severity of 12 neuropsychiatric disturbances including delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, night time behaviors, as well as appetite/eating. Total domain score= frequency x severity and thus ranges from 1 to 12. NPI domain is rated by caregiver for symptom frequency and severity. Frequency is rated as:1=occasionally, 2=often, 3= frequently, and 4=very frequently. Severity is rated as:1=mild,2=moderate,3=severe. Frequency and severity rating scales has defined anchor points to enhance reliability of caregiver responses. Caregiver distress is rated for each positive neuropsychiatric symptom using following anchored scores. It is rated as 0=not at all,1=minimal,2=mild,3=moderate,4=severe,5=very severe. Individual Item scores are added to yield a possible total score of 0 to 144. MMRM was used for the analysis.
Change From Baseline to Week 12 in the Clinical Global Impression of Severity of Illness (CGIS)-Agitation Domain Score
The CGIS-Agitation is an observer-rated scale that measures illness severity. The CGIS-Agitation is a 7-point (1-7) scale (1=normal, not at all ill participants; 7=among the most extremely ill participants) and is assessed for severity of agitation. A value of 0 is given to participants who are not assessed. Higher scores indicate poor health of participants. MMRM was used for the analysis.
Change From Baseline to Week 12 in the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Overall Rating
The ADCS-CGIC rating scale provides a reliable means to assess change from a Baseline level of global function within the time frame of the trial. ADCS-CGIC-Overall focuses on the clinician's observations of change in the participant's cognitive, functional, and behavioral performance. The ADCS-CGIC-Overall responses (1-7) are rated as: 1 = marked improvement, 2 = moderate improvement, 3 = minimal improvement, 4 = no change, 5 = minimal worsening, 6 = moderate worsening, or 7 = marked worsening. MMRM was used for the analysis.
Change From Baseline to Week 12 in the Patient Global Impression of Change (PGIC) Score
The PGIC is a 7-point (1-7) scale used to assess treatment response: 1 = very much improved, = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, or 7 = very much worse. Higher scores indicate less response to treatment. MMRM was used for the analysis.
Change From Baseline to Week 12 in the Dementia Quality of Life (DEMQOL) Score
The DEMQOL scale is used to evaluate health-related QOL in participants with dementia and their caregivers. There are 2 versions of the DEMQOL: a 28-item version (rated by the participant); and a 31-item version (DEMQOL-proxy, rated by the caregiver). Both versions are recommended for evaluating participants (and their caregivers) with mild to moderate dementia. The DEMQOL total score ranges from 28 to 112. The DEMQOL-proxy is used for participants with severe dementia; the total score ranges from 31 to 124. For both versions, higher scores indicate greater QOL. MMRM was used for the analysis.
Change From Baseline in the Cornell Scale for Depression in Dementia (CSDD) Score
The CSDD scale is used to assess signs/symptoms of major depression in participants with dementia. CSDD has 19 items, and each item is rated for severity on the following scale of 0 to 2 (0 =absent, 1= mild/intermittent 2=severe). CSDD score is calculated by summing non-missing scores from each item score. The scale ranges from 0 (no depression) to 38 (maximum depression). Scores above 10 indicate a probable major depression, above 18 indicate a definite major depression, and below 6 as a rule are associated with the absence of significant depressive symptoms. Higher score indicated maximum depression. MMRM was used for the analysis.
Number of Participants With the Change From Baseline in the General Medical Health Rating (GMHR) Score at Week 12
The GMHR is a global clinical rating for medical health, designed to quantify in a single number (1 to 4) the severity of general comorbidity in a participant with dementia. The ratings are: 1 = poor; 2 = fair; 3 = good; 4 = excellent to very good. MMRM was used for the analysis.
Change From Baseline to Week 12 in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score
The ADAS is designed to evaluate the cognitive and non-cognitive behavioral dysfunction characteristics of participants with AD. The cognitive subscale (ADAS-cog) consists of 11 subsets related to memory, praxis, and language. ADAS-cog scores range from 0 to 70. Higher scores indicate greater cognitive impairment. Negative change from baseline indicates less cognitive impairment. MMRM method was used for analysis.
Resource Utilization in Dementia (RUD) Score: Number of Hours Per Day the Caregiver Spent Assisting the Participant
The RUD evaluates dementia participants' utilization of formal and informal healthcare resources, including hospitalizations and doctor visits, living assistance, and time spent by nonprofessional caregivers. Information on hours per day the caregiver spent assisting participant were reported in this outcome measure, using the following questions: Q1= On a typical care day during the last 30 days, how much time per day did you assist the participant with tasks such as toilet visits, eating, dressing, grooming, walking and bathing? Q2= On a typical care day during the last 30 days, how much time per day did you assist the participant with tasks such as shopping, food preparation, housekeeping, laundry, transportation, taking medication and managing financial matters? Q3= On a typical care day during the last 30 days, how much time per day did you spend supervising (that is, preventing dangerous events) the participant?
Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant
The RUD evaluates dementia participants' utilization of formal and informal healthcare resources, including hospitalizations, doctor visits, living assistance, and time spent by nonprofessional caregivers. Information on days the caregiver spent assisting participant were reported in this outcome measure, using the following questions: Q1= During the last 30 days, how many days did you spend providing these (toilet visits, eating, dressing, grooming, walking and bathing) services to the participant? Q2= During the last 30 days, how many days did you spend providing these (shopping, food preparation, housekeeping, laundry, transportation, taking medication and managing financial matters) services to the participant? Q3= During the last 30 days, how many days did you spend providing these services (supervising) to the participant?
Resource Utilization in Dementia (RUD) Score: Number of Visits to Hospital, Emergency, and Healthcare Professional
The RUD evaluates dementia participants' utilization of formal and informal healthcare resources, including hospitalizations, doctor visits, living assistance, and time spent by nonprofessional caregivers. Information on the number of hospital visits, emergency visits and visits to healthcare professional were reported in this outcome measure using the following questions: Q1= During the last 30 days, how many times did the participant receive care in a hospital emergency room (for less than 24 hours)? Q2= During the last 30 days, how many times did the caregiver receive care in a hospital emergency room (for less than 24 hours)? Q3= During the last 30 days total number of visits by participant to a health care professional? Q4= During the last 30 days, how many times (number of visits for each) the participant visited any other health care professional?

Full Information

First Posted
May 11, 2015
Last Updated
August 12, 2022
Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02442778
Brief Title
Efficacy, Safety, and Tolerability of AVP-786 for the Treatment of Agitation in Participants With Dementia of the Alzheimer's Type
Official Title
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety, and Tolerability of AVP-786 (Deuterated [d6]-Dextromethorphan Hydrobromide [d6-DM]/Quinidine Sulfate [Q]) for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
November 11, 2015 (Actual)
Primary Completion Date
August 14, 2019 (Actual)
Study Completion Date
September 9, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Participants with agitation secondary to dementia of the Alzheimer's type. The diagnosis of probable Alzheimer's disease (AD) will be based on the "2011 Diagnostic Guidelines for Alzheimer's Disease" issued by the National Institute on Aging (NIA)-Alzheimer's Association (AA) workgroups.
Detailed Description
Eligible participants for this study must have a diagnosis of probable AD and must have clinically meaningful agitation secondary to AD. This is a multicenter, randomized, placebo-controlled study, consisting of 12 weeks of treatment. Approximately 470 participants will be enrolled at approximately 75 centers in North America. Study medication will be administered orally twice-daily from Day 1 through Week 12 (Day 85). Screening will occur within approximately 4 weeks prior to randomization. Following screening procedures for assessment of inclusion and exclusion criteria, eligible participants will be randomized into the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Agitation in Participants With Dementia of the Alzheimer's Type

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
522 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants were administered AVP-786 matching placebo capsules, orally, twice daily (BID) for up to 12 weeks.
Arm Title
AVP-786-28
Arm Type
Experimental
Arm Description
Participants were administered AVP-786-18 capsule, orally, once daily (QD) along with AVP-786 matching placebo capsule, orally, QD during Week 1 followed by AVP-786-18 capsules, orally, BID during Weeks 2, 3 and AVP-786-28 capsules, orally, BID during Weeks 4 to 12.
Arm Title
AVP-786-42.63
Arm Type
Experimental
Arm Description
Participants were administered AVP-786-28 capsules, orally, QD along with AVP-786 matching placebo capsule, orally, QD during Week 1 followed by AVP-786-28 capsules, orally, BID during Weeks 2, 3, and AVP-786-42.63 capsules, orally, BID during Weeks 4 to 12.
Intervention Type
Drug
Intervention Name(s)
AVP-786-18
Intervention Description
18 mg of Deudextromethorphan hydrobromide (d6-DM) and 4.9 mg of Quinidine sulfate (Q)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered as capsules.
Intervention Type
Drug
Intervention Name(s)
AVP-786-28
Intervention Description
28 mg of d6-DM and 4.9 mg of Q
Intervention Type
Drug
Intervention Name(s)
AVP-786-42.63
Intervention Description
42.63 mg of d6-DM and 4.9 mg of Q
Primary Outcome Measure Information:
Title
Change From Baseline to Week 12 in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score
Description
The CMAI was used to assess the frequency of manifestations of agitated behaviors in elderly participants. It consists of 29 agitated items rated on a 7-point scale of frequency: 1, never; 2, less than once a week; 3, once or twice a week; 4, several times a week; 5, once or twice a day; 6, several times a day; 7, several times an hour. The CMAI total score ranges from 29 to 203. Higher scores indicate worsening of the condition. Negative change from baseline indicates improvement. Mixed Model Repeated Measures (MMRM) was used for the analysis.
Time Frame
Baseline, Week 12
Secondary Outcome Measure Information:
Title
Relative Change From Baseline to Week 12 in the Modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC)-Agitation Score
Description
The mADCS-CGIC-Agitation is a modified version of the ADCS-CGIC containing additional questions related to agitation and an assessment of the Clinician's Impression of Change focused specifically on agitation. Participants are asked to rate their impression of change as: 1=Marked Improvement; 2=Moderate Improvement; 3=Minimal Improvement; 4=No Change; 5=Minimal Worsening; 6=Moderate Worsening; 7=Marked Worsening. Higher scores indicate worsening of agitation and positive change from baseline indicates worsening. MMRM was used for the analysis.
Time Frame
Baseline, Week 12
Title
Change From Baseline to Week 12 in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score
Description
The NPI is a retrospective caregiver-informant interview covering 12 neuropsychiatric symptom domains. The Agitation/Aggression domain is designed to collect information on the behavioral aspects of agitation/aggression in participants with probable AD and clinically meaningful agitation secondary to AD. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as:1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, severe. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. Higher scores indicate worsening symptoms. Negative change from baseline indicates improvement in symptoms. MMRM was used for the analysis.
Time Frame
Baseline, Week 12
Title
Change From Baseline to Week 12 in the NPI Agitation/Aggression Caregiver Distress Score
Description
The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate caregiver distress. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as:1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as:1, mild; 2, moderate; 3, marked severe. The total caregiver distress score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12 with a higher score indicating worsening of symptoms. Negative change from baseline indicates improvement in symptoms. MMRM was used for the analysis.
Time Frame
Baseline, Week 12
Title
Change From Baseline to Week 12 in the NPI Aberrant Motor Behavior Domain Score
Description
The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate aberrant motor behavior. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, marked severe. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12 with a higher score indicating worsening of symptoms. Negative change from baseline indicates improvement in symptoms. MMRM was used for the analysis.
Time Frame
Baseline, Week 12
Title
Change From Baseline to Week 12 in the Zarit Burden Interview (ZBI) Score
Description
The ZBI is a 22-item scale used to assess the impact of a participants' disabilities on the caregiver's life. It is designed to reflect the burden experienced by caregivers of dementia participants and can either be completed by the caregiver or administered as an interview. Each item of the scale is rated to reflect the burden using the 5-point scale: 0=Never; 1=Rarely; 2=Sometimes; 3=Quite Frequently; 4=Nearly Always. The ZBI is scored by summing the responses of the individual questions and ranges from 0 to 88. Higher scores indicate greater caregiver distress. Negative change from baseline indicates less distress. MMRM was used for the analysis.
Time Frame
Baseline, Week 12
Title
Change From Baseline to Week 12 in the NPI Irritability/Lability Domain Score
Description
The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains, including the irritability/lability domain score. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as:1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as:1, mild; 2, moderate; 3, severe. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. Higher scores indicate worsening of the symptoms. Negative change from baseline indicates improvement in symptoms. MMRM was used for the analysis.
Time Frame
Baseline, Week 12
Title
Change From Baseline to Week 12 in the NPI Total Score
Description
NPI evaluates both frequency and severity of 12 neuropsychiatric disturbances including delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, night time behaviors, as well as appetite/eating. Total domain score= frequency x severity and thus ranges from 1 to 12. NPI domain is rated by caregiver for symptom frequency and severity. Frequency is rated as:1=occasionally, 2=often, 3= frequently, and 4=very frequently. Severity is rated as:1=mild,2=moderate,3=severe. Frequency and severity rating scales has defined anchor points to enhance reliability of caregiver responses. Caregiver distress is rated for each positive neuropsychiatric symptom using following anchored scores. It is rated as 0=not at all,1=minimal,2=mild,3=moderate,4=severe,5=very severe. Individual Item scores are added to yield a possible total score of 0 to 144. MMRM was used for the analysis.
Time Frame
Baseline, Week 12
Title
Change From Baseline to Week 12 in the Clinical Global Impression of Severity of Illness (CGIS)-Agitation Domain Score
Description
The CGIS-Agitation is an observer-rated scale that measures illness severity. The CGIS-Agitation is a 7-point (1-7) scale (1=normal, not at all ill participants; 7=among the most extremely ill participants) and is assessed for severity of agitation. A value of 0 is given to participants who are not assessed. Higher scores indicate poor health of participants. MMRM was used for the analysis.
Time Frame
Baseline, Week 12
Title
Change From Baseline to Week 12 in the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Overall Rating
Description
The ADCS-CGIC rating scale provides a reliable means to assess change from a Baseline level of global function within the time frame of the trial. ADCS-CGIC-Overall focuses on the clinician's observations of change in the participant's cognitive, functional, and behavioral performance. The ADCS-CGIC-Overall responses (1-7) are rated as: 1 = marked improvement, 2 = moderate improvement, 3 = minimal improvement, 4 = no change, 5 = minimal worsening, 6 = moderate worsening, or 7 = marked worsening. MMRM was used for the analysis.
Time Frame
Baseline, Week 12
Title
Change From Baseline to Week 12 in the Patient Global Impression of Change (PGIC) Score
Description
The PGIC is a 7-point (1-7) scale used to assess treatment response: 1 = very much improved, = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, or 7 = very much worse. Higher scores indicate less response to treatment. MMRM was used for the analysis.
Time Frame
Baseline, Week 12
Title
Change From Baseline to Week 12 in the Dementia Quality of Life (DEMQOL) Score
Description
The DEMQOL scale is used to evaluate health-related QOL in participants with dementia and their caregivers. There are 2 versions of the DEMQOL: a 28-item version (rated by the participant); and a 31-item version (DEMQOL-proxy, rated by the caregiver). Both versions are recommended for evaluating participants (and their caregivers) with mild to moderate dementia. The DEMQOL total score ranges from 28 to 112. The DEMQOL-proxy is used for participants with severe dementia; the total score ranges from 31 to 124. For both versions, higher scores indicate greater QOL. MMRM was used for the analysis.
Time Frame
Baseline, Week 12
Title
Change From Baseline in the Cornell Scale for Depression in Dementia (CSDD) Score
Description
The CSDD scale is used to assess signs/symptoms of major depression in participants with dementia. CSDD has 19 items, and each item is rated for severity on the following scale of 0 to 2 (0 =absent, 1= mild/intermittent 2=severe). CSDD score is calculated by summing non-missing scores from each item score. The scale ranges from 0 (no depression) to 38 (maximum depression). Scores above 10 indicate a probable major depression, above 18 indicate a definite major depression, and below 6 as a rule are associated with the absence of significant depressive symptoms. Higher score indicated maximum depression. MMRM was used for the analysis.
Time Frame
Baseline, Week 12
Title
Number of Participants With the Change From Baseline in the General Medical Health Rating (GMHR) Score at Week 12
Description
The GMHR is a global clinical rating for medical health, designed to quantify in a single number (1 to 4) the severity of general comorbidity in a participant with dementia. The ratings are: 1 = poor; 2 = fair; 3 = good; 4 = excellent to very good. MMRM was used for the analysis.
Time Frame
Week 12
Title
Change From Baseline to Week 12 in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score
Description
The ADAS is designed to evaluate the cognitive and non-cognitive behavioral dysfunction characteristics of participants with AD. The cognitive subscale (ADAS-cog) consists of 11 subsets related to memory, praxis, and language. ADAS-cog scores range from 0 to 70. Higher scores indicate greater cognitive impairment. Negative change from baseline indicates less cognitive impairment. MMRM method was used for analysis.
Time Frame
Baseline, Week 12
Title
Resource Utilization in Dementia (RUD) Score: Number of Hours Per Day the Caregiver Spent Assisting the Participant
Description
The RUD evaluates dementia participants' utilization of formal and informal healthcare resources, including hospitalizations and doctor visits, living assistance, and time spent by nonprofessional caregivers. Information on hours per day the caregiver spent assisting participant were reported in this outcome measure, using the following questions: Q1= On a typical care day during the last 30 days, how much time per day did you assist the participant with tasks such as toilet visits, eating, dressing, grooming, walking and bathing? Q2= On a typical care day during the last 30 days, how much time per day did you assist the participant with tasks such as shopping, food preparation, housekeeping, laundry, transportation, taking medication and managing financial matters? Q3= On a typical care day during the last 30 days, how much time per day did you spend supervising (that is, preventing dangerous events) the participant?
Time Frame
Week 12
Title
Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant
Description
The RUD evaluates dementia participants' utilization of formal and informal healthcare resources, including hospitalizations, doctor visits, living assistance, and time spent by nonprofessional caregivers. Information on days the caregiver spent assisting participant were reported in this outcome measure, using the following questions: Q1= During the last 30 days, how many days did you spend providing these (toilet visits, eating, dressing, grooming, walking and bathing) services to the participant? Q2= During the last 30 days, how many days did you spend providing these (shopping, food preparation, housekeeping, laundry, transportation, taking medication and managing financial matters) services to the participant? Q3= During the last 30 days, how many days did you spend providing these services (supervising) to the participant?
Time Frame
Week 12
Title
Resource Utilization in Dementia (RUD) Score: Number of Visits to Hospital, Emergency, and Healthcare Professional
Description
The RUD evaluates dementia participants' utilization of formal and informal healthcare resources, including hospitalizations, doctor visits, living assistance, and time spent by nonprofessional caregivers. Information on the number of hospital visits, emergency visits and visits to healthcare professional were reported in this outcome measure using the following questions: Q1= During the last 30 days, how many times did the participant receive care in a hospital emergency room (for less than 24 hours)? Q2= During the last 30 days, how many times did the caregiver receive care in a hospital emergency room (for less than 24 hours)? Q3= During the last 30 days total number of visits by participant to a health care professional? Q4= During the last 30 days, how many times (number of visits for each) the participant visited any other health care professional?
Time Frame
Week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of probable Alzheimer's Disease (AD) according to the 2011 National Institute on Aging-Alzheimer's Association (NIA-AA) working groups criteria The participant has clinically significant, moderate/severe agitation at the time of screening and for at least 2 weeks prior to randomization The diagnosis of agitation must meet the International Psychogeriatric Association (IPA) provisional definition of agitation Either out participants or residents of an assisted-living facility or a skilled nursing home Clinical Global Impression of Severity of Illness (CGIS) score assessing Agitation is >=4 (moderately ill) at screening and baseline Mini-Mental State Examination (MMSE) score is between 6 and 26 (inclusive) at screening and baseline Caregiver who is able and willing to comply with all required study procedures. In order to qualify as a reliable informant (i.e., caregiver) capable of assessing changes in participant's condition during the study, the individual must spend a minimum of 2 hours per day for 4 days per week with the participant. Exclusion Criteria: Participant has dementia predominantly of non-Alzheimer's type (e.g., vascular dementia, frontotemporal dementia, Parkinson's disease, substance-induced dementia) Participants with co-existent clinically significant or unstable systemic diseases that could confound the interpretation of the safety results of the study (e.g., malignancy, poorly controlled diabetes, poorly controlled hypertension, unstable pulmonary, renal or hepatic disease, unstable ischemic cardiac disease, dilated cardiomyopathy, or unstable valvular heart disease) Participant with myasthenia gravis
Facility Information:
Facility Name
Brain and Spine Center
City
Chandler
State/Province
Arizona
ZIP/Postal Code
85226
Country
United States
Facility Name
Territory Neurology & Research Institute
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85704
Country
United States
Facility Name
Health Initiatives Research
City
Fayetteville
State/Province
Arkansas
ZIP/Postal Code
72703
Country
United States
Facility Name
Behavioral Research Specialists, LLC
City
Glendale
State/Province
California
ZIP/Postal Code
91206
Country
United States
Facility Name
Irvine Center for Clinical Research
City
Irvine
State/Province
California
ZIP/Postal Code
92614
Country
United States
Facility Name
California Neurological Services
City
Panorama City
State/Province
California
ZIP/Postal Code
91402
Country
United States
Facility Name
Havana Research Institute
City
Pasadena
State/Province
California
ZIP/Postal Code
91105
Country
United States
Facility Name
Pacific Research Network, Inc
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Syrentis Clinical Research
City
Santa Ana
State/Province
California
ZIP/Postal Code
92705
Country
United States
Facility Name
Viking Clinical Research
City
Temecula
State/Province
California
ZIP/Postal Code
92591
Country
United States
Facility Name
Denver Neurological Research, LLC
City
Denver
State/Province
Colorado
ZIP/Postal Code
80210
Country
United States
Facility Name
JEM Research Institute
City
Atlantis
State/Province
Florida
ZIP/Postal Code
33462
Country
United States
Facility Name
Clinical Research Of Brandon, LLC
City
Brandon
State/Province
Florida
ZIP/Postal Code
33511
Country
United States
Facility Name
Meridien Research
City
Brooksville
State/Province
Florida
ZIP/Postal Code
34601
Country
United States
Facility Name
Moonshine Research Center, Inc
City
Doral
State/Province
Florida
ZIP/Postal Code
33166
Country
United States
Facility Name
Science Connections, LLC
City
Doral
State/Province
Florida
ZIP/Postal Code
33166
Country
United States
Facility Name
Finlay Medical Research Corp
City
Greenacres City
State/Province
Florida
ZIP/Postal Code
33467
Country
United States
Facility Name
Indago Research & Health Center, Inc.
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33012
Country
United States
Facility Name
New Life Medical Research Center, Inc.
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33012
Country
United States
Facility Name
Reliable Clinical Research,LLC
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33012
Country
United States
Facility Name
Research in Miami, Inc
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33013
Country
United States
Facility Name
The Research Center, Inc
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33013
Country
United States
Facility Name
Maxblue Institute
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33018
Country
United States
Facility Name
Clinical Neuroscience Solutions, Inc.
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32256
Country
United States
Facility Name
Alzheimer's Research and Treatment Center
City
Lake Worth
State/Province
Florida
ZIP/Postal Code
33449
Country
United States
Facility Name
Premier Clinical Research Institute, Inc.
City
Miami
State/Province
Florida
ZIP/Postal Code
33122
Country
United States
Facility Name
Project 4 Research
City
Miami
State/Province
Florida
ZIP/Postal Code
33125
Country
United States
Facility Name
BioMed Research Institute
City
Miami
State/Province
Florida
ZIP/Postal Code
33126
Country
United States
Facility Name
CCM Clinical Research Group
City
Miami
State/Province
Florida
ZIP/Postal Code
33133
Country
United States
Facility Name
DADE Research Center, LLC
City
Miami
State/Province
Florida
ZIP/Postal Code
33135
Country
United States
Facility Name
AMB Research Center, Inc.
City
Miami
State/Province
Florida
ZIP/Postal Code
33144
Country
United States
Facility Name
United Health Research Corp
City
Miami
State/Province
Florida
ZIP/Postal Code
33144
Country
United States
Facility Name
Advance Medical Research Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33165
Country
United States
Facility Name
Coral Research Clinic Corp
City
Miami
State/Province
Florida
ZIP/Postal Code
33175
Country
United States
Facility Name
P&S Reasearch
City
Miami
State/Province
Florida
ZIP/Postal Code
33175
Country
United States
Facility Name
The Neurology Research Group, LLC
City
Miami
State/Province
Florida
ZIP/Postal Code
33176
Country
United States
Facility Name
Kendall Research Institute
City
Miami
State/Province
Florida
ZIP/Postal Code
33183
Country
United States
Facility Name
Nuovida Research Center Corp.
City
Miami
State/Province
Florida
ZIP/Postal Code
33186
Country
United States
Facility Name
Collier Neurologic Specialists, LLC
City
Naples
State/Province
Florida
ZIP/Postal Code
34102
Country
United States
Facility Name
Lazlo J. Mate, MD, PA
City
North Palm Beach
State/Province
Florida
ZIP/Postal Code
33408
Country
United States
Facility Name
Compass Research, LLC
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
IMIC Inc.
City
Palmetto Bay
State/Province
Florida
ZIP/Postal Code
33157
Country
United States
Facility Name
University of West Florida
City
Pensacola
State/Province
Florida
ZIP/Postal Code
32514
Country
United States
Facility Name
Neurology Research Institute Palm Beach, LLC
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33407
Country
United States
Facility Name
Emory Brain Health Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30329
Country
United States
Facility Name
Columbus Research & Wellness Institute, INC
City
Columbus
State/Province
Georgia
ZIP/Postal Code
31904
Country
United States
Facility Name
Josephson Wallack Munshower Neurology, PC
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46256
Country
United States
Facility Name
Baptist Health Medical Group
City
Richmond
State/Province
Kentucky
ZIP/Postal Code
40475
Country
United States
Facility Name
The Samuel & Alexia Bratton Memory Clinic
City
Easton
State/Province
Maryland
ZIP/Postal Code
21601
Country
United States
Facility Name
Mir Neurology
City
Hagerstown
State/Province
Maryland
ZIP/Postal Code
21742
Country
United States
Facility Name
Boston Center for Memory
City
Newton
State/Province
Massachusetts
ZIP/Postal Code
02459
Country
United States
Facility Name
AMAC Research Institute
City
North Dartmouth
State/Province
Massachusetts
ZIP/Postal Code
02747
Country
United States
Facility Name
Michigan State University
City
East Lansing
State/Province
Michigan
ZIP/Postal Code
48824
Country
United States
Facility Name
Center for Emotional Fitness
City
Cherry Hill
State/Province
New Jersey
ZIP/Postal Code
08002
Country
United States
Facility Name
The NeuroCognitive Institute
City
Mount Arlington
State/Province
New Jersey
ZIP/Postal Code
07856
Country
United States
Facility Name
Brooklyn Medical Institute
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11214
Country
United States
Facility Name
Integrative Clinical Trials, LLC
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11229
Country
United States
Facility Name
Eastside Comprehensive Medical Center, LLC
City
New York
State/Province
New York
ZIP/Postal Code
10128
Country
United States
Facility Name
Burke Rehabilitation Hospital
City
White Plains
State/Province
New York
ZIP/Postal Code
10605
Country
United States
Facility Name
Herbert Harris, MD, PhD, PA
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27517
Country
United States
Facility Name
ANI Neurology PLLC dba Alzheimer's Memory Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28270
Country
United States
Facility Name
Daystar Clinical Research Inc
City
Akron
State/Province
Ohio
ZIP/Postal Code
44313
Country
United States
Facility Name
Valley Medical Research
City
Centerville
State/Province
Ohio
ZIP/Postal Code
45459
Country
United States
Facility Name
CTI Clinical Research Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45212
Country
United States
Facility Name
Cleveland Clinic Lou Ruvo Center for Brain Health at Lakewood Hospital
City
Lakewood
State/Province
Ohio
ZIP/Postal Code
44107
Country
United States
Facility Name
Heritage Valley Medical Group, Inc.
City
Beaver
State/Province
Pennsylvania
ZIP/Postal Code
15009
Country
United States
Facility Name
The Birches at Newton / Family Medical Associates
City
Levittown
State/Province
Pennsylvania
ZIP/Postal Code
19056
Country
United States
Facility Name
Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
RH Johnson VA Medical Center
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29401
Country
United States
Facility Name
BG Neurology
City
Spartanburg
State/Province
South Carolina
ZIP/Postal Code
29307
Country
United States
Facility Name
Texas Neurology, P.A.
City
Dallas
State/Province
Texas
ZIP/Postal Code
75214
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Houston Methodist Neurological Institute
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Clinical Trial Network
City
Houston
State/Province
Texas
ZIP/Postal Code
77074
Country
United States
Facility Name
Texas Medical Research Associates, L.L.C.
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78238
Country
United States
Facility Name
Pharmaceuticals Research Associates, Inc.
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
Facility Name
Clinical Neuroscience Research Associates, Inc. dba The Memory Clinic
City
Bennington
State/Province
Vermont
ZIP/Postal Code
05201
Country
United States
Facility Name
Veteran Affairs Medical Center, Salem Virginia
City
Salem
State/Province
Virginia
ZIP/Postal Code
24153
Country
United States
Facility Name
IPC Research
City
Waukesha
State/Province
Wisconsin
ZIP/Postal Code
53188
Country
United States
Facility Name
Dr. Alexander McIntyre Inc.
City
Calgary
State/Province
Alberta
ZIP/Postal Code
N7L 1C1
Country
Canada
Facility Name
The Medical Art Health Research Group
City
Kelowna
State/Province
Bristish Columbia
Country
Canada
Facility Name
The Medical Art Health Research Group
City
Penticton
State/Province
Bristish Columbia
Country
Canada
Facility Name
The Medical Art Health Research Group
City
West Vancouver
State/Province
Bristish Columbia
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researcher sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
IPD Sharing Time Frame
Data will be available after marketing approval in global markets, or beginning 1-3 years following article publica data.
IPD Sharing Access Criteria
Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/O
IPD Sharing URL
https://clinical-trials.otsuka.com

Learn more about this trial

Efficacy, Safety, and Tolerability of AVP-786 for the Treatment of Agitation in Participants With Dementia of the Alzheimer's Type

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