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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02442778
Recruitment Status : Completed
First Posted : May 13, 2015
Results First Posted : September 9, 2022
Last Update Posted : September 9, 2022
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Agitation in Participants With Dementia of the Alzheimer's Type
Interventions Drug: AVP-786-18
Drug: Placebo
Drug: AVP-786-28
Drug: AVP-786-42.63
Enrollment 522
Recruitment Details Participants took part in the study at 83 investigative sites in North America from 11 November 2015 to 09 September 2019.
Pre-assignment Details A total of 925 participants were screened of which 522 participants were enrolled and 521 participants were randomized to receive placebo or AVP-786-28 or AVP-786-42.63.
Arm/Group Title Placebo AVP-786-28 AVP-786-42.63
Hide Arm/Group 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 capsule, 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.
Period Title: Overall Study
Started 210 151 161
Safety Population [1] 210 151 160
Modified Intent-to-Treat (mITT) Population [2] 210 150 159
Completed 192 121 146
Not Completed 18 30 15
Reason Not Completed
Adverse Event             2             6             6
Death             0             2             0
Lack of Efficacy             1             0             0
Lost to Follow-up             1             1             1
Non-compliance with study drug             2             0             1
Physician Decision             1             1             1
Protocol Deviation             3             0             1
Study participant withdrawal by parent or guardian             3             12             2
Withdrawal by Subject             4             4             3
Reason not specified             1             4             0
[1]
Safety Population included all participants who received at least one dose of study medication. Participants were included in the treatment group based on the actual treatment received.
[2]
mITT Population included all randomized participants who had at least one post-baseline efficacy assessment. Participants were included in the treatment group to which they were randomized regardless of treatment received
Arm/Group Title Placebo AVP-786-28 AVP-786-42.63 Total
Hide Arm/Group Description Participants were administered AVP-786 matching placebo capsules, orally, BID for up to 12 weeks. Participants were administered AVP-786-18 capsule, orally, 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 capsule, 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. Total of all reporting groups
Overall Number of Baseline Participants 210 151 161 522
Hide Baseline Analysis Population Description
All Randomized Population included all the participants who were randomized in the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 210 participants 151 participants 161 participants 522 participants
76.7  (8.1) 74.6  (7.9) 74.8  (7.3) 75.5  (7.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 210 participants 151 participants 161 participants 522 participants
Female
117
  55.7%
84
  55.6%
96
  59.6%
297
  56.9%
Male
93
  44.3%
67
  44.4%
65
  40.4%
225
  43.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 210 participants 151 participants 161 participants 522 participants
White
196
  93.3%
129
  85.4%
155
  96.3%
480
  92.0%
Black or African American
13
   6.2%
14
   9.3%
6
   3.7%
33
   6.3%
Asian
0
   0.0%
2
   1.3%
0
   0.0%
2
   0.4%
American Indian or Alaska Native
1
   0.5%
0
   0.0%
0
   0.0%
1
   0.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   0.7%
0
   0.0%
1
   0.2%
Other
0
   0.0%
5
   3.3%
0
   0.0%
5
   1.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Ethnicity Number Analyzed 210 participants 151 participants 161 participants 522 participants
Hispanic or Latino
128
  61.0%
78
  51.7%
113
  70.2%
319
  61.1%
Not Hispanic or Latino
82
  39.0%
73
  48.3%
48
  29.8%
203
  38.9%
1.Primary Outcome
Title Change From Baseline to Week 12 in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population included all randomized participants who had at least one post-baseline efficacy assessment. Participants were included in the treatment group to which they were randomized regardless of treatment received. Number analysed signifies the number of participants with available data for analysis at a specific timepoint.
Arm/Group Title Placebo AVP-786-28 AVP-786-42.63
Hide Arm/Group Description:
Participants were administered AVP-786 matching placebo capsules, orally, BID for up to 12 weeks.
Participants were administered AVP-786-18 capsule, orally, 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 capsule, 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.
Overall Number of Participants Analyzed 210 150 159
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 210 participants 150 participants 159 participants
73.7  (21.13) 68.8  (19.39) 71.3  (20.87)
Change from Baseline at Week 12 Number Analyzed 188 participants 120 participants 141 participants
-16.2  (16.97) -12.7  (16.21) -17.0  (16.12)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-28
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.789
Comments MMRM included fixed effect treatment,visit,treatment-by-visit,baseline,baseline-by-visit,baseline Neuropsychiatric Inventory Agitation/Aggression(NPI AA)(≤6 vs. >6),falls risk assessment,baseline concomitant use of antipsychotic medications,cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares (LS) Mean Difference
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-2.7 to 3.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-42.63
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.200
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.0
Confidence Interval (2-Sided) 95%
-5.0 to 1.0
Estimation Comments [Not Specified]
2.Secondary Outcome
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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population included all randomized participants who had at least one post-baseline efficacy assessment. Participants were included in the treatment group to which they were randomized regardless of treatment received. Overall number of participants analysed signifies the number of participants with available data for analysis at specific timepoint.
Arm/Group Title Placebo AVP-786-28 AVP-786-42.63
Hide Arm/Group Description:
Participants were administered AVP-786 matching placebo capsules, orally, BID for up to 12 weeks.
Participants were administered AVP-786-18 capsule, orally, 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 capsule, 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.
Overall Number of Participants Analyzed 190 118 141
Mean (Standard Deviation)
Unit of Measure: score on a scale
2.9  (1.18) 3.1  (1.23) 2.8  (1.20)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-28
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.484
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.2 to 0.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-42.63
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.704
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.3 to 0.2
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline to Week 12 in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population included all randomized participants who had at least one post-baseline efficacy assessment. Participants were included in the treatment group to which they were randomized regardless of treatment received. Number analysed signifies the number of participants with available data for analysis at a specific timepoint.
Arm/Group Title Placebo AVP-786-28 AVP-786-42.63
Hide Arm/Group Description:
Participants were administered AVP-786 matching placebo capsules, orally, BID for up to 12 weeks.
Participants were administered AVP-786-18 capsule, orally, 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 capsule, 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.
Overall Number of Participants Analyzed 192 123 148
Mean (Standard Deviation)
Unit of Measure: score on a scale
-2.5  (3.17) -2.3  (3.32) -3.2  (3.32)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-28
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.416
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-0.9 to 0.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-42.63
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.066
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.3 to 0.0
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline to Week 12 in the NPI Agitation/Aggression Caregiver Distress Score
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population included all randomized participants who had at least one post-baseline efficacy assessment. Participants were included in the treatment group to which they were randomized regardless of treatment received. Overall number of participants analysed signifies the number of participants with available data for analysis at a specific timepoint.
Arm/Group Title Placebo AVP-786-28 AVP-786-42.63
Hide Arm/Group Description:
Participants were administered AVP-786 matching placebo capsules, orally, BID for up to 12 weeks.
Participants were administered AVP-786-18 capsule, orally, 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 capsule, 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.
Overall Number of Participants Analyzed 189 121 144
Mean (Standard Deviation)
Unit of Measure: score on a scale
-0.8  (1.44) -0.8  (1.61) -0.8  (1.47)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-28
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.249
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.5 to 0.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-42.63
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.199
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.5 to 0.1
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline to Week 12 in the NPI Aberrant Motor Behavior Domain Score
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population included all randomized participants who had at least one post-baseline efficacy assessment. Participants were included in the treatment group to which they were randomized regardless of treatment received. Number analysed signifies the number of participants with available data for analysis at a specific timepoint.
Arm/Group Title Placebo AVP-786-28 AVP-786-42.63
Hide Arm/Group Description:
Participants were administered AVP-786 matching placebo capsules, orally, BID for up to 12 weeks.
Participants were administered AVP-786-18 capsule, orally, 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 capsule, 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.
Overall Number of Participants Analyzed 192 123 148
Mean (Standard Deviation)
Unit of Measure: score on a scale
-1.2  (3.75) -1.2  (3.60) -1.8  (3.57)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-28
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.975
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.7 to 0.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-42.63
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.334
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-1.0 to 0.3
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline to Week 12 in the Zarit Burden Interview (ZBI) Score
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population included all randomized participants who had at least one post-baseline efficacy assessment. Participants were included in the treatment group to which they were randomized regardless of treatment received. Overall number of participants analysed signifies the number of participants with available data for analysis at a specific timepoint.
Arm/Group Title Placebo AVP-786-28 AVP-786-42.63
Hide Arm/Group Description:
Participants were administered AVP-786 matching placebo capsules, orally, BID for up to 12 weeks.
Participants were administered AVP-786-18 capsule, orally, 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 capsule, 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.
Overall Number of Participants Analyzed 190 118 141
Mean (Standard Deviation)
Unit of Measure: score on a scale
-1.77  (9.275) -1.03  (12.195) -0.23  (11.769)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-28
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.934
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-2.4 to 2.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-42.63
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.342
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.1
Confidence Interval (2-Sided) 95%
-1.2 to 3.4
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline to Week 12 in the NPI Irritability/Lability Domain Score
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population included all randomized participants who had at least one post-baseline efficacy assessment. Participants were included in the treatment group to which they were randomized regardless of treatment received. Overall number of participants analysed signifies the number of participants with available data for analysis at specific timepoint.
Arm/Group Title Placebo AVP-786-28 AVP-786-42.63
Hide Arm/Group Description:
Participants were administered AVP-786 matching placebo capsules, orally, BID for up to 12 weeks.
Participants were administered AVP-786-18 capsule, orally, 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 capsule, 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.
Overall Number of Participants Analyzed 192 123 148
Mean (Standard Deviation)
Unit of Measure: score on a scale
-1.8  (3.50) -1.2  (3.55) -2.2  (3.29)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-28
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.888
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.0
Confidence Interval (2-Sided) 95%
-0.7 to 0.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-42.63
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.019
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-1.3 to -0.1
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline to Week 12 in the NPI Total Score
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population included all randomized participants who had at least one post-baseline efficacy assessment. Participants were included in the treatment group to which they were randomized regardless of treatment received. Overall number of participants analysed signifies the number of participants with available data for analysis at a specific timepoint.
Arm/Group Title Placebo AVP-786-28 AVP-786-42.63
Hide Arm/Group Description:
Participants were administered AVP-786 matching placebo capsules, orally, BID for up to 12 weeks.
Participants were administered AVP-786-18 capsule, orally, 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 capsule, 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.
Overall Number of Participants Analyzed 192 123 148
Mean (Standard Deviation)
Unit of Measure: score on a scale
-12.3  (17.06) -9.5  (18.41) -16.9  (18.05)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-28
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.756
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.6
Confidence Interval (2-Sided) 95%
-2.9 to 4.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-42.63
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.038
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.6
Confidence Interval (2-Sided) 95%
-7.0 to -0.2
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline to Week 12 in the Clinical Global Impression of Severity of Illness (CGIS)-Agitation Domain Score
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population included all randomized participants who had at least one post-baseline efficacy assessment. Participants were included in the treatment group to which they were randomized regardless of treatment received. Overall number of participants analysed signifies the number of participants with available data for analysis at specific timepoint.
Arm/Group Title Placebo AVP-786-28 AVP-786-42.63
Hide Arm/Group Description:
Participants were administered AVP-786 matching placebo capsules, orally, BID for up to 12 weeks.
Participants were administered AVP-786-18 capsule, orally, 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 capsule, 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.
Overall Number of Participants Analyzed 190 118 141
Mean (Standard Deviation)
Unit of Measure: score on a scale
-0.7  (0.85) -0.7  (0.92) -0.8  (0.93)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-28
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.468
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.3 to 0.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-42.63
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.158
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.3 to 0.1
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline to Week 12 in the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Overall Rating
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population included all randomized participants who had at least one post-baseline efficacy assessment. Participants were included in the treatment group to which they were randomized regardless of treatment received. Overall number of participants analysed signifies the number of participants with available data for analysis at a specific timepoint.
Arm/Group Title Placebo AVP-786-28 AVP-786-42.63
Hide Arm/Group Description:
Participants were administered AVP-786 matching placebo capsules, orally, BID for up to 12 weeks.
Participants were administered AVP-786-18 capsule, orally, 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 capsule, 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.
Overall Number of Participants Analyzed 188 118 141
Mean (Standard Deviation)
Unit of Measure: score on a scale
3.2  (1.20) 3.4  (1.31) 3.1  (1.23)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-28
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.400
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.2 to 0.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-42.63
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.566
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.3 to 0.2
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline to Week 12 in the Patient Global Impression of Change (PGIC) Score
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population included all randomized participants who had at least one post-baseline efficacy assessment. Participants were included in the treatment group to which they were randomized regardless of treatment received. Overall number of participants analysed signifies the number of participants with available data for analysis at a specific timepoint.
Arm/Group Title Placebo AVP-786-28 AVP-786-42.63
Hide Arm/Group Description:
Participants were administered AVP-786 matching placebo capsules, orally, BID for up to 12 weeks.
Participants were administered AVP-786-18 capsule, orally, 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 capsule, 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.
Overall Number of Participants Analyzed 191 118 141
Mean (Standard Deviation)
Unit of Measure: score on a scale
3.1  (1.01) 3.1  (1.07) 2.9  (1.05)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-28
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.751
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.2 to 0.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-42.63
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.320
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.3 to 0.1
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline to Week 12 in the Dementia Quality of Life (DEMQOL) Score
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population included all randomized participants who had at least one post-baseline efficacy assessment. Participants were included in the treatment group to which they were randomized regardless of treatment received. Overall number of participants analysed signifies the number of participants with available data for analysis at specific timepoint.
Arm/Group Title Placebo AVP-786-28 AVP-786-42.63
Hide Arm/Group Description:
Participants were administered AVP-786 matching placebo capsules, orally, BID for up to 12 weeks.
Participants were administered AVP-786-18 capsule, orally, 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 capsule, 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.
Overall Number of Participants Analyzed 153 96 117
Mean (Standard Deviation)
Unit of Measure: score on a scale
2.9  (11.10) 3.8  (8.10) 3.2  (8.74)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-28
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.782
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-1.8 to 2.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-42.63
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.991
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.0
Confidence Interval (2-Sided) 95%
-2.1 to 2.0
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Change From Baseline in the Cornell Scale for Depression in Dementia (CSDD) Score
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population included all randomized participants who had at least one post-baseline efficacy assessment. Participants were included in the treatment group to which they were randomized regardless of treatment received. Overall number of participants analysed signifies the number of participants with available data for analysis at specific timepoint.
Arm/Group Title Placebo AVP-786-28 AVP-786-42.63
Hide Arm/Group Description:
Participants were administered AVP-786 matching placebo capsules, orally, BID for up to 12 weeks.
Participants were administered AVP-786-18 capsule, orally, 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 capsule, 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.
Overall Number of Participants Analyzed 189 118 141
Mean (Standard Deviation)
Unit of Measure: score on a scale
-1.1  (2.84) -0.5  (2.90) -1.5  (2.57)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-28
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.038
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.6
Confidence Interval (2-Sided) 95%
0.0 to 1.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-42.63
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.911
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.0
Confidence Interval (2-Sided) 95%
-0.6 to 0.5
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Number of Participants With the Change From Baseline in the General Medical Health Rating (GMHR) Score at Week 12
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population included all randomized participants who had at least one post-baseline efficacy assessment. Participants were included in the treatment group to which they were randomized regardless of treatment received. Overall number of participants analysed signifies the number of participants with available data for analysis at a specific timepoint.
Arm/Group Title Placebo AVP-786-28 AVP-786-42.63
Hide Arm/Group Description:
Participants were administered AVP-786 matching placebo capsules, orally, BID for up to 12 weeks.
Participants were administered AVP-786-18 capsule, orally, 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 capsule, 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.
Overall Number of Participants Analyzed 210 150 158
Measure Type: Count of Participants
Unit of Measure: Participants
Fair to Excellent to Very Good
6
   2.9%
6
   4.0%
3
   1.9%
Poor to Excellent to Very Good
22
  10.5%
7
   4.7%
10
   6.3%
Good to Good
17
   8.1%
9
   6.0%
10
   6.3%
Fair to Good
80
  38.1%
65
  43.3%
65
  41.1%
Poor to Good
6
   2.9%
6
   4.0%
4
   2.5%
Missing to Good
1
   0.5%
0
   0.0%
0
   0.0%
Good to Fair
53
  25.2%
31
  20.7%
43
  27.2%
Fair to Fair
11
   5.2%
6
   4.0%
11
   7.0%
Poor to Fair
0
   0.0%
3
   2.0%
1
   0.6%
Fair to Poor
1
   0.5%
0
   0.0%
0
   0.0%
Good to Missing
5
   2.4%
4
   2.7%
7
   4.4%
Fair to Missing
7
   3.3%
9
   6.0%
4
   2.5%
Poor to Missing
1
   0.5%
4
   2.7%
0
   0.0%
15.Secondary Outcome
Title Change From Baseline to Week 12 in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population included all randomized participants who had at least one post-baseline efficacy assessment. Participants were included in the treatment group to which they were randomized regardless of treatment received. Overall number analysed signifies the number of participants with available data for analysis at specific timepoint.
Arm/Group Title Placebo AVP-786-28 AVP-786-42.63
Hide Arm/Group Description:
Participants were administered AVP-786 matching placebo capsules, orally, BID for up to 12 weeks.
Participants were administered AVP-786-18 capsule, orally, 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 capsule, 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.
Overall Number of Participants Analyzed 143 91 97
Mean (Standard Deviation)
Unit of Measure: score on a scale
-2.0  (5.67) -1.0  (7.36) -1.5  (6.38)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-28
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.236
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.0
Confidence Interval (2-Sided) 95%
-0.6 to 2.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, AVP-786-42.63
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.684
Comments MMRM included fixed effect treatment, visit, treatment-by-visit, baseline, baseline-by-visit, baseline NPI AA (≤ 6 vs. > 6), risk assessment for falls, baseline concomitant use of antipsychotic medications and cohorts.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-1.3 to 1.9
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Resource Utilization in Dementia (RUD) Score: Number of Hours Per Day the Caregiver Spent Assisting the Participant
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population included all randomized participants who had at least one post-baseline efficacy assessment. Participants were included in the treatment group to which they were randomized regardless of treatment received. Number analysed signifies the number of participants with available data for analysis at a specific timepoint.
Arm/Group Title Placebo AVP-786-28 AVP-786-42.63
Hide Arm/Group Description:
Participants were administered AVP-786 matching placebo capsules, orally, BID for up to 12 weeks.
Participants were administered AVP-786-18 capsule, orally, 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 capsule, 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.
Overall Number of Participants Analyzed 210 150 159
Median (Full Range)
Unit of Measure: hours
Q1 Number Analyzed 173 participants 111 participants 136 participants
3.0
(0 to 24)
3.0
(0 to 18)
3.0
(0 to 24)
Q2 Number Analyzed 173 participants 111 participants 136 participants
4.5
(0 to 24)
5.0
(0 to 24)
5.0
(0 to 24)
Q3 Number Analyzed 173 participants 111 participants 136 participants
5.0
(0 to 24)
4.0
(0 to 24)
6.0
(0 to 24)
17.Secondary Outcome
Title Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant
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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
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Hide Analysis Population Description
mITT Population included all randomized participants who had at least one post-baseline efficacy assessment. Participants were included in the treatment group to which they were randomized regardless of treatment received. Number analysed signifies the number of participants with available data for analysis at a specific timepoint.
Arm/Group Title Placebo AVP-786-28 AVP-786-42.63
Hide Arm/Group Description:
Participants were administered AVP-786 matching placebo capsules, orally, BID for up to 12 weeks.
Participants were administered AVP-786-18 capsule, orally, 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 capsule, 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.
Overall Number of Participants Analyzed 210 150 159
Median (Full Range)
Unit of Measure: days
Q1 Number Analyzed 173 participants 111 participants 136 participants
30.0
(0 to 30)
30.0
(0 to 30)
30.0
(0 to 30)
Q2 Number Analyzed 173 participants 111 participants 136 participants
30.0
(0 to 30)
30.0
(0 to 30)
30.0
(0 to 30)
Q3 Number Analyzed 173 participants 111 participants 136 participants
30.0
(0 to 30)
30.0
(0 to 30)
30.0
(0 to 30)
18.Secondary Outcome
Title Resource Utilization in Dementia (RUD) Score: Number of Visits to Hospital, Emergency, and Healthcare Professional
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population included all randomized participants who had at least one post-baseline efficacy assessment. Participants were included in the treatment group to which they were randomized regardless of treatment received. Number analysed signifies the number of participants with available data for analysis at specific timepoint.
Arm/Group Title Placebo AVP-786-28 AVP-786-42.63
Hide Arm/Group Description:
Participants were administered AVP-786 matching placebo capsules, orally, BID for up to 12 weeks.
Participants were administered AVP-786-18 capsule, orally, 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 capsule, 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.
Overall Number of Participants Analyzed 210 150 159
Mean (Standard Deviation)
Unit of Measure: Number of visits
Q1 Number Analyzed 4 participants 3 participants 3 participants
1.0  (0.0) 1.3  (0.58) 1.3  (0.58)
Q2 Number Analyzed 1 participants 0 participants 2 participants
1.0 [1]   (NA) 1.0  (0.00)
Q3 Number Analyzed 173 participants 109 participants 130 participants
2.7  (1.35) 2.5  (1.28) 2.6  (1.45)
Q4 Number Analyzed 167 participants 101 participants 126 participants
2.2  (0.88) 2.1  (0.51) 2.0  (0.59)
[1]
SD cannot be calculated for 1 participant.
Time Frame From first dose up to 30 days after the last dose of study drug (up to 16 weeks)
Adverse Event Reporting Description

All-cause mortality: All Randomized Population included all the participants who were randomized in the study.

Adverse events: Safety Population included all participants who received at least one dose of study medication. Participants were included in the treatment group based on the actual treatment received.

 
Arm/Group Title Placebo AVP-786-28 AVP-786-42.63
Hide Arm/Group Description Participants were administered AVP-786 matching placebo capsules, orally, BID for up to 12 weeks. Participants were administered AVP-786-18 capsule, orally, 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 capsule, 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.
All-Cause Mortality
Placebo AVP-786-28 AVP-786-42.63
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/210 (0.00%)   3/151 (1.99%)   0/161 (0.00%) 
Hide Serious Adverse Events
Placebo AVP-786-28 AVP-786-42.63
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   10/210 (4.76%)   15/151 (9.93%)   8/160 (5.00%) 
Cardiac disorders       
Angina pectoris  1  0/210 (0.00%)  0/151 (0.00%)  1/160 (0.63%) 
Bradycardia  1  0/210 (0.00%)  1/151 (0.66%)  0/160 (0.00%) 
Myocardial infarction  1  1/210 (0.48%)  0/151 (0.00%)  0/160 (0.00%) 
Gastrointestinal disorders       
Intestinal mass  1  0/210 (0.00%)  1/151 (0.66%)  0/160 (0.00%) 
Upper gastrointestinal haemorrhage  1  0/210 (0.00%)  1/151 (0.66%)  0/160 (0.00%) 
Vomiting  1  0/210 (0.00%)  1/151 (0.66%)  0/160 (0.00%) 
Diarrhoea  1  1/210 (0.48%)  0/151 (0.00%)  0/160 (0.00%) 
Pancreatic insufficiency  1  1/210 (0.48%)  0/151 (0.00%)  0/160 (0.00%) 
Peptic ulcer  1  1/210 (0.48%)  0/151 (0.00%)  0/160 (0.00%) 
Small intestinal obstruction  1  1/210 (0.48%)  0/151 (0.00%)  0/160 (0.00%) 
General disorders       
Asthenia  1  1/210 (0.48%)  0/151 (0.00%)  0/160 (0.00%) 
Hepatobiliary disorders       
Hyperbilirubinaemia  1  0/210 (0.00%)  1/151 (0.66%)  0/160 (0.00%) 
Infections and infestations       
Pneumonia  1  1/210 (0.48%)  3/151 (1.99%)  1/160 (0.63%) 
Bronchitis  1  0/210 (0.00%)  1/151 (0.66%)  1/160 (0.63%) 
Administration site joint infection  1  0/210 (0.00%)  0/151 (0.00%)  1/160 (0.63%) 
Urinary tract infection  1  0/210 (0.00%)  0/151 (0.00%)  1/160 (0.63%) 
Gastroenteritis  1  0/210 (0.00%)  1/151 (0.66%)  0/160 (0.00%) 
Cellulitis  1  1/210 (0.48%)  0/151 (0.00%)  0/160 (0.00%) 
Gastroenteritis viral  1  1/210 (0.48%)  0/151 (0.00%)  0/160 (0.00%) 
Postoperative wound infection  1  1/210 (0.48%)  0/151 (0.00%)  0/160 (0.00%) 
Injury, poisoning and procedural complications       
Lumbar vertebral fracture  1  0/210 (0.00%)  0/151 (0.00%)  1/160 (0.63%) 
Fall  1  1/210 (0.48%)  3/151 (1.99%)  0/160 (0.00%) 
Hip Fracture  1  0/210 (0.00%)  1/151 (0.66%)  0/160 (0.00%) 
Subdural haematoma  1  0/210 (0.00%)  1/151 (0.66%)  0/160 (0.00%) 
Femur fracture  1  1/210 (0.48%)  0/151 (0.00%)  0/160 (0.00%) 
Investigations       
Electrocardiogram abnormal  1  1/210 (0.48%)  0/151 (0.00%)  0/160 (0.00%) 
Influenza A virus test positive  1  1/210 (0.48%)  0/151 (0.00%)  0/160 (0.00%) 
Metabolism and nutrition disorders       
Dehydration  1  0/210 (0.00%)  1/151 (0.66%)  0/160 (0.00%) 
Decreased appetite  1  1/210 (0.48%)  0/151 (0.00%)  0/160 (0.00%) 
Diabetic ketoacidosis  1  1/210 (0.48%)  0/151 (0.00%)  0/160 (0.00%) 
Musculoskeletal and connective tissue disorders       
Muscle spasms  1  0/210 (0.00%)  0/151 (0.00%)  1/160 (0.63%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Lung carcinoma cell type unspecified stage IV  1  0/210 (0.00%)  1/151 (0.66%)  0/160 (0.00%) 
Pancreatic carcinoma metastatic  1  0/210 (0.00%)  1/151 (0.66%)  0/160 (0.00%) 
Nervous system disorders       
Encephalopathy  1  0/210 (0.00%)  1/151 (0.66%)  1/160 (0.63%) 
Syncope  1  0/210 (0.00%)  3/151 (1.99%)  0/160 (0.00%) 
Normal pressure hydrocephalus  1  0/210 (0.00%)  1/151 (0.66%)  0/160 (0.00%) 
Subarachnoid haemorrhage  1  0/210 (0.00%)  1/151 (0.66%)  0/160 (0.00%) 
Psychiatric disorders       
Mental status changes  1  0/210 (0.00%)  1/151 (0.66%)  2/160 (1.25%) 
Agitation  1  0/210 (0.00%)  0/151 (0.00%)  1/160 (0.63%) 
Renal and urinary disorders       
Acute kidney injury  1  0/210 (0.00%)  1/151 (0.66%)  0/160 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Pulmonary mass  1  0/210 (0.00%)  1/151 (0.66%)  0/160 (0.00%) 
Respiratory failure  1  1/210 (0.48%)  1/151 (0.66%)  0/160 (0.00%) 
Acute respiratory failure  1  1/210 (0.48%)  0/151 (0.00%)  0/160 (0.00%) 
Chronic obstructive pulmonary disease  1  1/210 (0.48%)  0/151 (0.00%)  0/160 (0.00%) 
Vascular disorders       
Hypertension  1  0/210 (0.00%)  0/151 (0.00%)  1/160 (0.63%) 
Hypertensive crisis  1  0/210 (0.00%)  1/151 (0.66%)  0/160 (0.00%) 
Hypotension  1  0/210 (0.00%)  1/151 (0.66%)  0/160 (0.00%) 
Haematoma  1  1/210 (0.48%)  0/151 (0.00%)  0/160 (0.00%) 
1
Term from vocabulary, MedDRA 18.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo AVP-786-28 AVP-786-42.63
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   40/210 (19.05%)   31/151 (20.53%)   30/160 (18.75%) 
Gastrointestinal disorders       
Diarrhoea  1  14/210 (6.67%)  5/151 (3.31%)  5/160 (3.13%) 
Infections and infestations       
Urinary tract infection  1  11/210 (5.24%)  10/151 (6.62%)  3/160 (1.88%) 
Injury, poisoning and procedural complications       
Fall  1  8/210 (3.81%)  15/151 (9.93%)  10/160 (6.25%) 
Nervous system disorders       
Somnolence  1  2/210 (0.95%)  4/151 (2.65%)  11/160 (6.88%) 
Psychiatric disorders       
Agitation  1  12/210 (5.71%)  2/151 (1.32%)  4/160 (2.50%) 
1
Term from vocabulary, MedDRA 18.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
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Name/Title: Global Clinical Development
Organization: Otsuka Pharmaceutical Development & Commercialization, Inc.
Phone: 1-609-524-6788
EMail: clinicaltransparency@otsuka-us.com
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Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT02442778    
Other Study ID Numbers: 15-AVP-786-302
First Submitted: May 11, 2015
First Posted: May 13, 2015
Results First Submitted: August 12, 2022
Results First Posted: September 9, 2022
Last Update Posted: September 9, 2022