CompletedPhase 2Results posted

Efficacy, Safety and Tolerability Study of AVP-923 (Dextromethorphan/Quinidine) for Treatment of Symptoms of Agitation in Participants With Alzheimer's Disease

A Phase 2, Randomized, Double-dummy, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety and Tolerability of AVP-923 (Dextromethorphan/Quinidine) for the Treatment of Symptoms of Agitation in Patients With Alzheimer's Disease.

Lead sponsor

Avanir Pharmaceuticals

Asset

Nuedexta

Listed sites

Recruiting sites

Enrollment

220

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•MMSE 8-28•Study partner/caregiver required

Primary endpoint

•Neuropsychiatric Inventory (NPI)

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study ID12-AVR-131

NCT IDNCT01584440

Timeline

Milestones

Study first posted2012-04-25estimated

Study start2012-08-13actual

Primary completion2014-07-30actual

Study completion2014-07-30actual

Last update posted2021-11-26actual

Results first posted2021-11-26actual

Assets

Drug assets

Nuedexta

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years

Maximum age90 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

Key Inclusion Criteria:

Diagnosis of probable Alzheimer's disease (AD).

The participant has clinically significant symptoms of agitation secondary to AD, that interfere with daily routine and for which a prescription medication is deemed indicated, in the opinion of the investigator.

Either out-patients or residents of an assisted-living facility or a skilled nursing home.

CGI-S score is ≥ 4 (moderately ill) at screening and baseline.

Mini Mental State Examination (MMSE) score at screening between 8 and 28 (inclusive).

Caregiver who is able and willing to comply with all required study procedures, ensuring that the participant attends all study visits and takes the study medication as instructed. In order to qualify as a caregiver for this study, the individual should spend time with the participant for a minimum of 4 hours on 4 separate days per week

Exclusion criteria

Participant has other type of dementia (e.g., vascular dementia, frontotemporal dementia, Parkinson's disease, substance-induced dementia).

Participant 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, certain cardiac conduction abnormalities including QTc prolongation, or unstable valvular heart disease).

Participant with myasthenia gravis.

Endpoints (44)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Behavior / neuropsychiatric

Global cognition

Executive function / language

Function / daily living

Caregiver / quality of life

Safety / tolerability / PK

Global cognition

2 endpoints

Secondary/protocol endpoint

Change in the Mini-Mental State Examination (MMSE) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline), as Analyzed by the Specified SPCD Methodology

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/registry result

Change in the Mini-Mental State Examination (MMSE) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline), as Analyzed by the Specified SPCD Methodology

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
PlaceboDay 36n=125 Participants	-0.3	2.77
Day 70n=45 Participants	-0.5	2.53
AVP-923Day 36n=93 Participants	0.2	3.02
Day 70n=44 Participants	0.3	2.76

OLS Z-statistic1.94p0.053ANCOVA

ANCOVA Least Squares Mean Difference0.52

ANCOVA Least Squares Mean Difference0.84

Executive function / language

2 endpoints

Secondary/protocol endpoint

Change in the Quality of Life-Alzheimer's Disease (QoL-AD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

change from baseline, improvement

Secondary/registry result

Change in the Quality of Life-Alzheimer's Disease (QoL-AD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
PlaceboDay 36, Cargivern=125 Participants	0.3	4.66
Day 70, Caregivern=45 Participants	0.9	4.27
Day 36, Participantn=125 Participants	-0.0	5.18
Day 70, Participantn=45 Participants	0.7	4.26
AVP-923Day 36, Cargivern=93 Participants	0.4	4.28
Day 70, Caregivern=44 Participants	-0.3	3.93
Day 36, Participantn=93 Participants	1.3	6.12
Day 70, Participantn=44 Participants	1.5	5.06

OLS Z-statistic-0.72p0.469ANCOVA

ANCOVA Least Squares Mean Difference0.28

ANCOVA Least Squares Mean Difference-1.06

OLS Z-statistic1.41p0.159ANCOVA

ANCOVA Least Squares Mean Difference1.09

ANCOVA Least Squares Mean Difference0.70

Function / daily living

2 endpoints

Secondary/protocol endpoint

Change in the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Secondary/registry result

Change in the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
PlaceboDay 36n=125 Participants	-0.8	3.89
Day 70n=45 Participants	-0.6	3.45
AVP-923Day 36n=93 Participants	-0.9	4.27
Day 70n=44 Participants	-2.0	4.64

OLS Z-statistic-1.40p0.163ANCOVA

ANCOVA Least Squares Mean Difference-0.07

ANCOVA Least Squares Mean Difference-1.39

Behavior / neuropsychiatric

34 endpoints

Primary/protocol endpoint

Change in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Primary/registry result

Change in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
PlaceboDay 36n=125 Participants	-1.7	3.10
Day 70n=45 Participants	-0.8	3.59
AVP-923Day 36n=93 Participants	-3.3	2.98
Day 70n=44 Participants	-2.0	3.19

Ordinary Least Squares (OLS) Z-statistic-1.50p<=0.001ANCOVA

ANCOVA Least Squares Mean Difference-1.50

ANCOVA Least Squares Mean Difference-1.59

Secondary/protocol endpoint

Change in the Total NPI Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Change in the Sum of the Agitation/Aggression, Irritability/Lability, Disinhibition, and Aberrant Motor Behavior NPI Domain (NPI4D) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Change in the Sum of the Agitation/Aggression, Irritability/Lability, Anxiety, and Aberrant Motor Behavior NPI Domain (NPI4A) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Change in the Total Neuropsychiatric Inventory-Caregiver Distress Score (NPI-CDS) From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Change in the NPI-CDS for the Agitation/Aggression Domain From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Change in the NPI-CDS NPI4D Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Change in the NPI-CDS NPI4A Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Change in the Cornell Scale for Depression in Dementia (CSDD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

change from baseline, improvement

Secondary/protocol endpoint

Change in the NPI Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 8 and Day 22 and From Day 36 (Stage 2 Baseline) to Day 43 and Day 57

Time frame:Day 1 (Stage 1 Baseline); Days 8 and 22; Day 36 (Stage 2 Baseline); Days 43 and 57

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline)

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

change from baseline, improvement

Secondary/protocol endpoint

Number of Participants With the Indicated Response on the mADCS-CGIC Scale Agitation Domain at Day 70 Compared to Their Response at Day 36 (Stage 2 Baseline)

Time frame:Day 36 (Stage 2 Baseline); Day 70

change from baseline, improvement

Secondary/protocol endpoint

Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline)

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

change from baseline, improvement

Secondary/protocol endpoint

Number of Participants With the Indicated Categorical Response on the PGI-C for the Caregiver Domain at Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline)

Time frame:Day 1 (Stage 1 Baseline); Day 70

change from baseline, improvement

Secondary/protocol endpoint

Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use

Time frame:up to Week 10

change from baseline, improvement

Secondary/protocol endpoint

Number of Participants Using Rescue Medications

Time frame:up to Week 10

event count, event

Secondary/registry result

Change in the Total NPI Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
PlaceboDay 36n=125 Participants	-8.5	14.35
Day 70n=45 Participants	-2.5	11.82
AVP-923Day 36n=93 Participants	-13.5	17.48
Day 70n=44 Participants	-6.0	2.48

OLS Z-statistic-2.46p0.014ANCOVA

ANCOVA Least Squares Mean Difference-4.20

ANCOVA Least Squares Mean Difference-3.78

Secondary/registry result

Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
PlaceboDay 36, Delusionsn=125 Participants	-0.6	2.93
Day 36, Hallucinationsn=125 Participants	-0.1	1.68
Day 36, Depression/dysphorian=125 Participants	-1.0	2.89
Day 36, Anxietyn=125 Participants	-1.2	3.69
Day 36, Euphoria/elationn=125 Participants	-0.1	1.27
Day 36, Apathy/indifferencen=125 Participants	-0.5	3.69
Day 36, Disinhibitionn=125 Participants	-0.7	3.04
Day 36, Irritability/labilityn=125 Participants	-1.2	3.23
Day 36, Aberrant motor behaviorn=125 Participants	-0.4	3.95
Day 36, S/NB disordersn=125 Participants	-0.1	2.50
Day 36, Appetite/eating changesn=125 Participants	-1.2	3.25
Day 70, Delusionsn=45 Participants	-0.7	3.09
Day 70, Hallucinationsn=45 Participants	-0.4	1.60
Day 70, Depression/dysphorian=45 Participants	0.2	2.36
Day 70, Anxietyn=45 Participants	-0.3	2.89
Day 70, Euphoria/elationn=45 Participants	-0.0	1.25
Day 70, Apathy/indifferencen=45 Participants	0.4	1.96
Day 70, Disinhibitionn=45 Participants	-0.8	2.51
Day 70, Irritability/labilityn=45 Participants	-0.7	3.71
Day 70, Aberrant motor behaviorn=45 Participants	0.4	3.15
Day 70, S/NB disordersn=45 Participants	-0.1	2.04
Day 70, Appetite/eating changesn=45 Participants	0.4	2.28
AVP-923Day 36, Delusionsn=93 Participants	-0.8	2.89
Day 36, Hallucinationsn=93 Participants	0.2	1.76
Day 36, Depression/dysphorian=93 Participants	-0.9	2.49
Day 36, Anxietyn=93 Participants	-0.6	3.21
Day 36, Euphoria/elationn=93 Participants	-0.3	1.85
Day 36, Apathy/indifferencen=93 Participants	-0.9	4.11
Day 36, Disinhibitionn=93 Participants	-0.9	3.46
Day 36, Irritability/labilityn=93 Participants	-2.2	4.08
Day 36, Aberrant motor behaviorn=93 Participants	-1.2	3.98
Day 36, S/NB disordersn=93 Participants	-1.0	3.82
Day 36, Appetite/eating changesn=93 Participants	-1.2	3.68
Day 70, Delusionsn=44 Participants	0.1	3.17
Day 70, Hallucinationsn=44 Participants	-0.1	2.03
Day 70, Depression/dysphorian=44 Participants	0.2	2.20
Day 70, Anxietyn=44 Participants	-1.0	2.76
Day 70, Euphoria/elationn=93 Participants	-0.2	0.95
Day 70, Apathy/indifferencen=44 Participants	-0.5	3.43
Day 70, Disinhibitionn=44 Participants	-0.8	2.67
Day 70, Irritability/labilityn=44 Participants	-1.0	3.40
Day 70, Aberrant motor behaviorn=44 Participants	-0.8	2.52
Day 70, S/NB disordersn=44 Participants	0.0	2.46
Day 70, Appetite/eating changesn=44 Participants	0.1	2.73

OLS Z-statistic0.77p0.444ANCOVA

ANCOVA Least Squares Mean Difference-0.27

ANCOVA Least Squares Mean Difference0.78

OLS Z-statistic-0.18p0.861ANCOVA

ANCOVA Least Squares Mean Difference-0.29

ANCOVA Least Squares Mean Difference0.22

OLS Z-statistic-0.32p0.749ANCOVA

ANCOVA Least Squares Mean Difference-0.07

ANCOVA Least Squares Mean Difference-0.10

OLS Z-statistic-0.81p0.416ANCOVA

ANCOVA Least Squares Mean Difference0.28

ANCOVA Least Squares Mean Difference-0.81

OLS Z-statistic-1.07p0.287ANCOVA

ANCOVA Least Squares Mean Difference0.04

ANCOVA Least Squares Mean Difference-0.34

OLS Z-statistic-1.31p0.191ANCOVA

ANCOVA Least Squares Mean Difference-0.16

ANCOVA Least Squares Mean Difference-0.77

OLS Z-statistic-1.10p0.271ANCOVA

ANCOVA Least Squares Mean Difference-0.22

ANCOVA Least Squares Mean Difference-0.37

OLS Z-statistic-2.18p0.029ANCOVA

ANCOVA Least Squares Mean Difference-0.70

ANCOVA Least Squares Mean Difference-0.93

OLS Z-statistic-2.21p0.027ANCOVA

ANCOVA Least Squares Mean Difference-0.38

ANCOVA Least Squares Mean Difference-1.22

OLS Z-statistic-1.09p0.274ANCOVA

ANCOVA Least Squares Mean Difference-0.57

ANCOVA Least Squares Mean Difference-0.08

OLS Z-statistic-0.65p0.513ANCOVA

ANCOVA Least Squares Mean Difference-0.16

ANCOVA Least Squares Mean Difference-0.24

Secondary/registry result

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
PlaceboDay 36n=125 Participants	-4.0	8.24
Day 70n=45 Participants	-1.9	7.65
AVP-923Day 36n=93 Participants	-7.6	9.08
Day 70n=44 Participants	-4.6	7.31

OLS Z-statistic-3.53p<=0.001ANCOVA

ANCOVA Least Squares Mean Difference-3.01

ANCOVA Least Squares Mean Difference-3.49

Secondary/registry result

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
PlaceboDay 36n=125 Participants	-4.5	8.53
Day 70n=45 Participants	-1.4	7.94
AVP-923Day 36n=93 Participants	-7.3	9.08
Day 70n=44 Participants	-4.8	7.05

OLS Z-statistic-3.34p0.001ANCOVA

ANCOVA Least Squares Mean Difference-2.41

ANCOVA Least Squares Mean Difference-3.94

Secondary/registry result

Change in the Total Neuropsychiatric Inventory-Caregiver Distress Score (NPI-CDS) From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
PlaceboDay 36n=125 Participants	-3.6	6.64
Day 70n=45 Participants	-2.0	5.74
AVP-923Day 36n=93 Participants	-6.6	7.81
Day 70n=44 Participants	-2.6	5.52

OLS Z-statistic-2.46p0.014ANCOVA

ANCOVA Least Squares Mean Difference-2.65

ANCOVA Least Squares Mean Difference-1.01

Secondary/registry result

Change in the NPI-CDS for the Agitation/Aggression Domain From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
PlaceboDay 36n=125 Participants	-0.6	1.32
Day 70n=45 Participants	-0.7	1.38
AVP-923Day 36n=93 Participants	-1.4	1.54
Day 70n=44 Participants	-0.5	1.44

OLS Z-statistic-2.57p0.010ANCOVA

ANCOVA Least Squares Mean Difference-0.68

ANCOVA Least Squares Mean Difference-0.20

Secondary/registry result

Change in the NPI-CDS NPI4D Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
PlaceboDay 36n=125 Participants	-1.5	3.39
Day 70n=45 Participants	-1.2	3.08
AVP-923Day 36n=93 Participants	-3.3	4.11
Day 70n=44 Participants	-1.8	3.12

OLS Z-statistic-3.08p0.002ANCOVA

ANCOVA Least Squares Mean Difference-1.56

ANCOVA Least Squares Mean Difference-0.90

Secondary/registry result

Change in the NPI-CDS NPI4A Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
PlaceboDay 36n=125 Participants	-1.7	3.34
Day 70n=45 Participants	-1.0	3.51
AVP-923Day 36n=93 Participants	-3.3	3.84
Day 70n=44 Participants	-1.5	2.70

OLS Z-statistic-2.66p0.008ANCOVA

ANCOVA Least Squares Mean Difference-1.43

ANCOVA Least Squares Mean Difference-0.75

Secondary/registry result

Change in the Cornell Scale for Depression in Dementia (CSDD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
PlaceboDay 36n=125 Participants	0.6	3.84
Day 70n=45 Participants	-0.7	2.58
AVP-923Day 36n=93 Participants	-1.0	3.43
Day 70n=44 Participants	-0.9	2.93

OLS Z-statistic-2.33p0.020ANCOVA

ANCOVA Least Squares Mean Difference-1.57

ANCOVA Least Squares Mean Difference-0.18

Secondary/registry result

Change in the NPI Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 8 and Day 22 and From Day 36 (Stage 2 Baseline) to Day 43 and Day 57

Time frame:Day 1 (Stage 1 Baseline); Days 8 and 22; Day 36 (Stage 2 Baseline); Days 43 and 57

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
PlaceboDay 8n=124 Participants	-1.4	2.73
Day 22n=121 Participants	-1.6	2.86
Day 43n=45 Participants	-1.3	2.92
Day 57n=45 Participants	-1.3	2.86
AVP-923Day 8n=93 Participants	-2.2	2.93
Day 22n=90 Participants	-2.7	3.18
Day 43n=44 Participants	-0.5	2.31
Day 57n=44 Participants	-1.2	3.12

OLS Z-statistic-1.08p0.279ANCOVA

ANCOVA Least Squares Mean Difference-0.76

ANCOVA Least Squares Mean Difference-1.02

ANCOVA Least Squares Mean Difference0.74

ANCOVA Least Squares Mean Difference-0.05

Secondary/registry result

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

change from baseline, improvement

Posted result

Group	Value (number), participants	Reported bounds
PlaceboDay 36, Marked improvementn=123 Participants	1	-
Day 36, Moderate improvementn=123 Participants	13	-
Day 36, Minimal improvementn=123 Participants	43	-
Day 36, No changen=123 Participants	48	-
Day 36, Minimal worseningn=123 Participants	12	-
Day 36, Moderate worseningn=123 Participants	6	-
Day 36, Marked worseningn=123 Participants	0	-
Day 70, Marked improvementn=44 Participants	4	-
Day 70, Moderate improvementn=44 Participants	5	-
Day 70, Minimal improvementn=44 Participants	11	-
Day 70, No changen=44 Participants	14	-
Day 70, Marked worseningn=44 Participants	9	-
Day 70, Moderate worseningn=44 Participants	0	-
Day 70, Minimal worseningn=44 Participants	1	-
AVP-923Day 36, Marked improvementn=88 Participants	8	-
Day 36, Moderate improvementn=88 Participants	22	-
Day 36, Minimal improvementn=88 Participants	28	-
Day 36, No changen=88 Participants	22	-
Day 36, Minimal worseningn=88 Participants	7	-
Day 36, Moderate worseningn=88 Participants	1	-
Day 36, Marked worseningn=88 Participants	0	-
Day 70, Marked improvementn=42 Participants	4	-
Day 70, Moderate improvementn=42 Participants	10	-
Day 70, Minimal improvementn=42 Participants	10	-
Day 70, No changen=42 Participants	12	-
Day 70, Marked worseningn=42 Participants	3	-
Day 70, Moderate worseningn=42 Participants	3	-
Day 70, Minimal worseningn=42 Participants	0	-

Odds Ratio (OR)2.7095% CI1.62 - 4.50p0.0001ANCOVA

Odds Ratio (OR)1.6195% CI0.75 - 3.43p0.2184ANCOVA

Secondary/registry result

Number of Participants With the Indicated Response on the mADCS-CGIC Scale Agitation Domain at Day 70 Compared to Their Response at Day 36 (Stage 2 Baseline)

Time frame:Day 36 (Stage 2 Baseline); Day 70

change from baseline, improvement

Posted result

Group	Value (number), participants	Reported bounds
PlaceboMarked improvementn=42 Participants	4	-
Moderate improvementn=42 Participants	2	-
Minimal improvementn=42 Participants	8	-
No changen=42 Participants	19	-
Marked worseningn=42 Participants	6	-
Moderate worseningn=42 Participants	2	-
Minimal worseningn=42 Participants	1	-
AVP-923Marked improvementn=42 Participants	0	-
Moderate improvementn=42 Participants	11	-
Minimal improvementn=42 Participants	15	-
No changen=42 Participants	11	-
Marked worseningn=42 Participants	4	-
Moderate worseningn=42 Participants	1	-
Minimal worseningn=42 Participants	0	-

Odds Ratio (OR)2.4595% CI1.11 - 5.42p0.0266ANCOVA

Secondary/registry result

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

change from baseline, improvement

Posted result

Group	Value (number), participants	Reported bounds
PlaceboDay 36, Very much improvedn=123 Participants	2	-
Day 36, Much improvedn=123 Participants	23	-
Day 36, Minimally improvedn=123 Participants	30	-
Day 36, No changen=123 Participants	40	-
Day 36, Minimally worsen=123 Participants	23	-
Day 36, Much worsen=123 Participants	4	-
Day 36, Very much worsen=123 Participants	1	-
Day 70, Very much improvedn=44 Participants	3	-
Day 70, Much improvedn=44 Participants	4	-
Day 70, Minimally improvedn=44 Participants	11	-
Day 70, No changen=44 Participants	13	-
Day 70, Minimally worsen=44 Participants	9	-
Day 70, Much worsen=44 Participants	4	-
Day 70, Very much worsen=44 Participants	0	-
AVP-923Day 36, Very much improvedn=88 Participants	10	-
Day 36, Much improvedn=88 Participants	24	-
Day 36, Minimally improvedn=88 Participants	20	-
Day 36, No changen=88 Participants	20	-
Day 36, Minimally worsen=88 Participants	13	-
Day 36, Much worsen=88 Participants	1	-
Day 36, Very much worsen=88 Participants	0	-
Day 70, Very much improvedn=43 Participants	3	-
Day 70, Much improvedn=43 Participants	10	-
Day 70, Minimally improvedn=43 Participants	14	-
Day 70, No changen=43 Participants	10	-
Day 70, Minimally worsen=43 Participants	4	-
Day 70, Much worsen=43 Participants	2	-
Day 70, Very much worsen=43 Participants	0	-

Odds Ratio (OR)2.1695% CI1.31 - 3.55p0.002ANCOVA

Odds Ratio (OR)2.3295% CI1.08 - 5.00p0.031ANCOVA

Secondary/registry result

Number of Participants With the Indicated Categorical Response on the PGI-C for the Caregiver Domain at Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline)

Time frame:Day 1 (Stage 1 Baseline); Day 70

change from baseline, improvement

Posted result

Group	Value (number), participants	Reported bounds
PlaceboVery much improvedn=59 Participants	5	-
Much improvedn=59 Participants	9	-
Minimally improvedn=59 Participants	17	-
No changen=59 Participants	14	-
Minimally worsen=59 Participants	10	-
Much worsen=59 Participants	4	-
Very much worsen=59 Participants	0	-
AVP-923Very much improvedn=81 Participants	9	-
Much improvedn=81 Participants	26	-
Minimally improvedn=81 Participants	25	-
No changen=81 Participants	13	-
Minimally worsen=81 Participants	5	-
Much worsen=81 Participants	3	-
Very much worsen=81 Participants	0	-

Odds Ratio (OR)2.4195% CI1.31 - 4.46p0.0048ANCOVA

Secondary/registry result

Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use

Time frame:up to Week 10

change from baseline, improvement

Posted result

Group	Value (number), participants	Reported bounds
AVP-923 in Stage 1/AVP-923 in Stage 2Any changen=84 Participants	9	-
Dose reducedn=84 Participants	1	-
Dose increasedn=84 Participants	0	-
Change in frequencyn=84 Participants	1	-
Use discontinuedn=84 Participants	2	-
New usagen=84 Participants	7	-
Placebo in Stage 1/AVP-923 in Stage 2Any changen=53 Participants	8	-
Dose reducedn=53 Participants	0	-
Dose increasedn=53 Participants	1	-
Change in frequencyn=53 Participants	1	-
Use discontinuedn=53 Participants	2	-
New usagen=53 Participants	6	-
Placebo in Stage 1/Placebo in Stage 2Any changen=58 Participants	13	-
Dose reducedn=58 Participants	1	-
Dose increasedn=58 Participants	1	-
Change in frequencyn=58 Participants	1	-
Use discontinuedn=58 Participants	2	-
New usagen=58 Participants	11	-

Secondary/registry result

Number of Participants Using Rescue Medications

Time frame:up to Week 10

event count, event

Posted result

Group	Value (number), participants	Reported bounds
AVP-923 in Stage 1/AVP-923 in Stage 2Overalln=93 Participants	5	-
Day 8 (Visit 2)n=93 Participants	0	-
Day 22 (Visit 3)n=93 Participants	3	-
Day 36 (Visit 4)n=93 Participants	5	-
Day 43 (Visit 5)n=93 Participants	2	-
Day 57 (Visit 6)n=93 Participants	1	-
Day 70 (Visit 70)n=93 Participants	2	-
Placebo in Stage 1/AVP-923 in Stage 2Overalln=59 Participants	11	-
Day 8 (Visit 2)n=59 Participants	3	-
Day 22 (Visit 3)n=59 Participants	3	-
Day 36 (Visit 4)n=59 Participants	3	-
Day 43 (Visit 5)n=59 Participants	3	-
Day 57 (Visit 6)n=59 Participants	3	-
Day 70 (Visit 70)n=59 Participants	3	-
Placebo in Stage 1/Placebo in Stage 2Overalln=66 Participants	7	-
Day 8 (Visit 2)n=66 Participants	1	-
Day 22 (Visit 3)n=66 Participants	3	-
Day 36 (Visit 4)n=66 Participants	3	-
Day 43 (Visit 5)n=66 Participants	5	-
Day 57 (Visit 6)n=66 Participants	4	-
Day 70 (Visit 70)n=66 Participants	3	-

Caregiver / quality of life

2 endpoints

Secondary/protocol endpoint

Change in the Caregiver Strain Index (CSI) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

change from baseline, improvement

Secondary/registry result

Change in the Caregiver Strain Index (CSI) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70

Time frame:Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
PlaceboDay 36n=125 Participants	-0.6	2.06
Day 70n=45 Participants	0.1	1.88
AVP-923Day 36n=93 Participants	-1.2	2.37
Day 70n=44 Participants	-0.2	1.62

OLS Z-statistic-1.96p0.050ANCOVA

ANCOVA Least Squares Mean Difference-0.62

ANCOVA Least Squares Mean Difference-0.30

Safety / tolerability / PK

2 endpoints

Secondary/protocol endpoint

Number of Participants With the Indicated Type of Adverse Event

Time frame:up to Week 10

event count, event

Secondary/registry result

Number of Participants With the Indicated Type of Adverse Event

Time frame:up to Week 10

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
All AVP-923Participants with ≥ 1 TEAEn=152 Participants	93	-
Participants with discontinuations due to a TEAEn=152 Participants	8	-
Participants who diedn=152 Participants	0	-
PlaceboParticipants with ≥ 1 TEAEn=127 Participants	55	-
Participants with discontinuations due to a TEAEn=127 Participants	4	-
Participants who diedn=127 Participants	0	-

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Cummings JL, Lyketsos CG, Peskind ER, Porsteinsson AP, Mintzer JE, Scharre DW, De La Gandara JE, Agronin M, Davis CS, Nguyen U, Shin P, Tariot PN, Siffert J. Effect of Dextromethorphan-Quinidine on Agitation in Patients With Alzheimer Disease Dementia: A Randomized Clinical Trial. JAMA. 2015 Sep 22-29;314(12):1242-54. doi: 10.1001/jama.2015.10214.
PMID26393847via BACKGROUND

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.