Agitation in Patients With Dementia of the Alzheimer's Type
Conditions
Keywords
Agitation, Dementia, Alzheimer's disease
Brief summary
Participants with agitation secondary to dementia of the Alzheimer's type. The diagnosis of probable Alzheimer's disease (AD) was to be based on the 2011 Diagnostic Guidelines for Alzheimer's Disease issued by the National Institute on Aging (NIA)-Alzheimer's Association (AA) workgroups.
Detailed description
Eligible participants for this study must have had a diagnosis of probable AD and must have had clinically meaningful agitation secondary to AD. This was to be a multicenter, randomized, placebo-controlled study, consisting of 12 weeks of treatment. Approximately 380 participants were to be enrolled at approximately 60 centers in North America. Study medication was to be administered orally twice-daily from Day 1 through Day 85. Screening was to occur within approximately 4 weeks prior to randomization. Following screening procedures for assessment of inclusion and exclusion criteria, eligible participants were to be randomized into the study.
Interventions
DRUGAVP-786
DRUGPlacebo
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Sequential parallel comparison design
Eligibility
Sex/Gender
ALL
Age
50 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of probable Alzheimer's Disease (AD) according to the 2011 National Institute on Aging-Alzheimer's Association (NIA-AA) working groups criteria * The participant has clinically significant, moderate/severe agitation at the time of screening and for at least 2 weeks prior to randomization * The diagnosis of agitation must meet the International Psychogeriatric Association (IPA) provisional definition of agitation * Either out patients or residents of an assisted-living facility or a skilled nursing home * Clinical Global Impression of Severity of Illness (CGIS) score assessing Agitation is \>= 4 (moderately ill) at screening and baseline * Mini-Mental State Examination (MMSE) score is between 6 and 26 (inclusive) at screening and baseline * Caregiver who is able and willing to comply with all required study procedures. In order to qualify as a reliable informant (i.e., caregiver) capable of assessing changes in participant's condition during the study, the individual must spend a minimum of 2 hours per day for 4 days per week with the participant.
Exclusion criteria
* Participant has dementia predominantly of non-Alzheimer's type (e.g., vascular dementia, frontotemporal dementia, Parkinson's disease, substance-induced dementia) * Participants with co-existent clinically significant or unstable systemic diseases that could confound the interpretation of the safety results of the study (e.g., malignancy, poorly controlled diabetes, poorly controlled hypertension, unstable pulmonary, renal or hepatic disease, unstable ischemic cardiac disease, dilated cardiomyopathy, or unstable valvular heart disease) * Participant with myasthenia gravis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | The CMAI score is used to assess the frequency of manifestations of agitated behaviors in participants. The CMAI consists of 29 agitated behaviors that are 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. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stage 1 and Stage 2: Change From Baseline in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score to Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. The Agitation/Aggression domain is designed to collect information on the behavioral aspects of agitation/aggression in participants with probable Alzheimer's Disease (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. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. |
| Stage 1 and Stage 2: Change From Baseline in the NPI Caregiver Distress Score to Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | 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. Higher scores indicate worsening symptoms. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. |
| Stage 1 and Stage 2: Change From Baseline in the NPI Aberrant Motor Behavior Domain Score to Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | 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, 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. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. |
| Stage 1 and Stage 2: Change From Baseline in the Zarit Burden Interview (ZBI) Score to Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | The ZBI is a 22-item scale used to assess the impact of a participant with dementia and also other illnesses on the caregiver's burden. For each item of the scale, the caregiver indicates how often they feel the burden (never, rarely, sometimes, quite frequently, or nearly always). The score ranges from 0 to 88 and is determined by adding the numbered responses of the individual items. Higher scores indicate greater caregiver distress. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus \> 6), risk assessments for falls (normal/mild versus moderate/severe), Baseline concomitant use of antipsychotic medications (yes versus no). Missing values were imputed by LOCF within each stage. |
| Stage 1 and Stage 2: Change From Baseline in the NPI Irritability/Lability Domain Score to Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | 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. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. |
| Stage 1 and Stage 2: Change From Baseline in the NPI Total Score to Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | 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, nighttime 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, and 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, 3=moderate, 4=severe, 5=very severe. Total score is calculated by adding the individual Item scores, to yield a possible total scores of 0 to 144. |
| Stage 1 and Stage 2: Change From Baseline in the Clinical Global Impression of Severity of Illness (CGIS)-Agitation Domain Score to Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | The CGIS-Agitation is an observer-rated scale that measures illness severity. CGIS is used to assess the severity of agitation. The CGIS score is rated on a 7-point scale (1 = normal, not at all ill; 7 = among the most extremely ill participants). Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus \> 6), risk assessments for falls (normal/mild versus moderate/severe), Baseline concomitant use of antipsychotic medications (yes versus no). Missing values were imputed by LOCF within each stage. |
| Stage 1 and Stage 2: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Rating at Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | 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. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline CMAI Total score, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus \> 6), risk assessments for falls (normal/mild versus moderate/severe), Baseline concomitant use of antipsychotic medications (yes versus no). Missing values were imputed by LOCF within each stage. |
| Stage 1 and Stage 2: Patient Global Impression of Change (PGIC) Score at Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | 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. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline CMAI Total score, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus \> 6), risk assessments for falls (normal/mild versus moderate/severe), Baseline concomitant use of antipsychotic medications (yes vs no). Missing values were imputed by LOCF within each stage. |
| Least Squares Mean Modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC)-Agitation Score at Week 6 and Week 12 | Stage 1 Week 6; Stage 2 Week 12 | The intent of the ADCS version of the CGIC is to provide a means to reliably assess the global impression of change from Baseline in a clinical trial. The mADCS-CGIC is a modification of the ADCS-CGIC instrument that focuses specifically on agitation. The participants are asked to rate their impression of change from Baseline as: 1, marked improvement; 2, moderate improvement; 3, minimal improvement; 4, no change; 5, minimal worsening; 6, moderate worsening; 7, marked worsening. Baseline was defined as the last non-missing assessment prior to Stage 1 randomization. Treatment effects were estimated at each stage by analysis of covariance (ANCOVA) with fixed effects for treatment, Baseline CMAI Total score, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus \[vs\] \> 6), risk assessments for falls (normal/mild vs moderate/severe), Baseline concomitant use of antipsychotic medications (yes vs no). Missing values were imputed by last observation carried forward (LOCF) within each stage. |
| Stage 1 and Stage 2: Change From Baseline in the Cornell Scale for Depression in Dementia (CSDD) Score to Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | 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 depressions. 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. |
| Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | Baseline; Week 12 | The GMHR is a global clinical rating for medical health, designed to quantify in a single number (1 to 4) the severity of general comorbidity in a participant with dementia. The ratings are: 1 = poor; 2 = fair; 3 = good; 4 = excellent to very good. Data was collected for the treatment arm groups as pre-specified in the protocol for this outcome measure. |
| Stage 1 and Stage 2: Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score to Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | 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. The ADAS-cog is assessed for participants with an Mini-Mental State Examination (MMSE) score of ≥10 at the Baseline Visit. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus \> 6), risk assessments for falls (normal/mild versus moderate/severe), Baseline concomitant use of antipsychotic medications (yes vs no). Missing values were imputed by LOCF within each stage. |
| Stage 1: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals | Stage 1: Week 6 | RUD evaluates dementia participants utilization of formal and informal healthcare resources, including hospitalizations and doctor visits, living assistance, and time spent by nonprofessional caregivers. The RUD is administered as a semi-structured interview with the participant's primary caregiver and contains 2 sections; one focusing on caregiver impact (loss of work and leisure time incurred by caregiver) and the other focusing on the participant's use of healthcare resources. Information of caregivers who reported their responsibilities affected their work and who visited healthcare professionals from the interviews during Stage 1 is reported for this outcome measure. Data was collected for the treatment arm groups as pre-specified in the protocol for this outcome measure. |
| Stage 2: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals | Stage 2: Week 12 | RUD evaluates dementia participants utilization of formal and informal healthcare resources, including hospitalizations and doctor visits, living assistance, and time spent by nonprofessional caregivers. The RUD is administered as a semi-structured interview with the participant's primary caregiver and contains 2 sections; one focusing on caregiver impact (loss of work and leisure time incurred by caregiver) and the other focusing on the participant's use of healthcare resources. Information of caregivers who reported their responsibilities affected their work and who visited healthcare professionals from the interviews during Stage 2 is reported for this outcome measure. Data was collected for the treatment arm groups as pre-specified in the protocol for this outcome measure. |
| Stage 1: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | Stage 1: Week 6 | RUD evaluates dementia participants utilization of formal, informal healthcare resources, including hospitalizations, doctor visits, living assistance, time spent by nonprofessional caregivers. Information on hours per day caregiver spent assisting participant from interviews during Stage 1 is reported for this outcome measure, where the following questions (Q), Q1= On typical care day during last 30 days, how much time per day did you assist participant with tasks such as toilet visits, eating, dressing, grooming, walking, bathing? Q2= On typical care day during the last 30 days, how much time per day did you assist participant with tasks as (shopping, food preparation, housekeeping, laundry, transportation, taking medication, managing financial matters?; Q3= On typical care day during last 30 days, how much time per day did you spend supervising (preventing dangerous events)?(Q3). Data is collected for treatment arm groups as pre-specified in protocol for this outcome measure. |
| Stage 2: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | Stage 2: Week 12 | RUD evaluates dementia participants utilization of formal, informal healthcare resources, including hospitalizations, doctor visits, living assistance, time spent by nonprofessional caregivers. Information on hours per day caregiver spent assisting participant from interviews during Stage 1 is reported for this outcome measure, where the following questions (Q), Q1= On typical care day during last 30 days, how much time per day did you assist participant with tasks such as toilet visits, eating, dressing, grooming, walking, bathing? Q2= On typical care day during the last 30 days, how much time per day did you assist participant with tasks as (shopping, food preparation, housekeeping, laundry, transportation, taking medication, managing financial matters?; Q3= On typical care day during last 30 days, how much time per day did you spend supervising (preventing dangerous events)?(Q3). Data is collected for treatment arm groups as pre-specified in protocol for this outcome measure. |
| Stage 1: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant | Stage 1: Week 6 | RUD evaluates dementia participants utilization of formal, informal healthcare resources, including hospitalizations, doctor visits, living assistance, time spent by nonprofessional caregivers. Information on days caregiver spent assisting participant from interviews during Stage 1 is reported for outcome measure, where following questions (Q), Q1= During last 30 days, how many days did you spend providing these (toilet visits, eating, dressing, grooming, walking, bathing) services to participant?; Q2= On typical care day during last 30 days, how much time per day did you assist participant with tasks such as shopping, food preparation, housekeeping, laundry, transportation, taking medication, managing financial matters?; Q3= During last 30 days, how many days did you spend providing these services (supervising) to the participant?. Data is collected for the treatment arm groups as pre-specified in the protocol for this outcome measure. |
| 12-Week Parallel Group: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant | 12-Week Parallel Group: Week 12 | RUD evaluates dementia participants utilization of formal, informal healthcare resources, including hospitalizations, doctor visits, living assistance, time spent by nonprofessional caregivers. Information on days caregiver spent assisting participant from interviews during Stage 1 is reported for outcome measure, where following questions (Q), Q1= During last 30 days, how many days did you spend providing these (toilet visits, eating, dressing, grooming, walking, bathing) services to participant?; Q2= On typical care day during last 30 days, how much time per day did you assist participant with tasks such as shopping, food preparation, housekeeping, laundry, transportation, taking medication, managing financial matters?; Q3= During last 30 days, how many days did you spend providing these services (supervising) to the participant?. Data is collected for the treatment arm groups as pre-specified in the protocol for this outcome measure. |
| Stage 1 and Stage 2: Change From Baseline in the Dementia Quality of Life (DEMQOL) Score to Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | 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. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline, and in the Stage 1 model, Baseline NPI AA (≤ 6 vs \> 6), risk assessments for falls (normal/mild vs moderate/severe), Baseline concomitant use of antipsychotic medications (yes vs no). Missing values were imputed by LOCF within each stage. |
Countries
Estonia, Germany, Poland, Portugal, Puerto Rico, United States
Participant flow
Recruitment details
Total of 695 participants were screened of these, 308 participants failed screening, 387 participants were randomized out of which 382 participants had at least 1 post baseline efficacy assessment. (Modified Intent-to-Treat { mITT} population).
Pre-assignment details
This study was conducted in 2 stages. 387 participants were randomized to treatment in Stage 1 and all the participants completed Stage 1 and were re-randomized into Stage 2 to compare AVP-786 28 mg, AVP-786 18 mg and placebo in parallel group (PG) design. In Stage 2, participants randomized to active treatment in Stage 1 (AVP-786-18 or AVP-786-28) continued to receive the same treatment and those randomized to placebo in Stage 1 were re-randomized to AVP-786-18, AVP-786-28, or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Placebo In Stage 1, participants received matching placebo orally twice daily (BID). | 191 |
| AVP-786-18 In Stage 1, participants received AVP-786-18 orally once daily (OD) in the morning and placebo orally OD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for the remaining 5 weeks. In Stage 2, participants continued to receive AVP-786-18 mg orally BID for 6 consecutive weeks. | 94 |
| AVP-786-28 In Stage 1, participants received AVP-786-18 mg orally OD in the morning and placebo orally OD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for 2 weeks. From Day 22, participants received AVP-786-28 orally BID for the remaining 3 weeks. In Stage 2, participants continued to receive AVP-786-28 mg orally BID for 6 consecutive weeks. | 97 |
| Total | 382 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Stage 2- (Days 43 to 85) | Adverse Event | 0 | 0 | 0 | 2 | 6 | 1 | 1 | 5 |
| Stage 2- (Days 43 to 85) | Death | 0 | 0 | 0 | 1 | 1 | 0 | 2 | 0 |
| Stage 2- (Days 43 to 85) | Lack of Efficacy | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Stage 2- (Days 43 to 85) | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 3 | 1 | 0 |
| Stage 2- (Days 43 to 85) | Protocol Deviation | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Stage 2- (Days 43 to 85) | Reason not specified | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
| Stage 2- (Days 43 to 85) | Study Participant Withdrawal by Parent or Guardian | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 4 |
| Stage 2- (Days 43 to 85) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 2 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Placebo | AVP-786-18 | AVP-786-28 | Total |
|---|---|---|---|---|
| Age, Continuous | 76.6 years STANDARD_DEVIATION 7.92 | 73.8 years STANDARD_DEVIATION 8.39 | 74.6 years STANDARD_DEVIATION 7.69 | 75.4 years STANDARD_DEVIATION 8.06 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 6 Participants | 6 Participants | 24 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 175 Participants | 87 Participants | 89 Participants | 351 Participants |
| Sex: Female, Male Female | 112 Participants | 47 Participants | 54 Participants | 213 Participants |
| Sex: Female, Male Male | 79 Participants | 47 Participants | 43 Participants | 169 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 194 | 3 / 156 | 1 / 159 |
| other Total, other adverse events | 84 / 194 | 78 / 156 | 71 / 159 |
| serious Total, serious adverse events | 6 / 194 | 17 / 156 | 7 / 159 |
Outcome results
Primary
Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12
The CMAI score is used to assess the frequency of manifestations of agitated behaviors in participants. The CMAI consists of 29 agitated behaviors that are 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. Change from Baseline was calculated as the post-Baseline score minus the Baseline score.
Time frame: Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12
Population: Stage 1 Modified Intent-to-Treat (mITT) Population: all participants randomized in Stage 1 who had at least 1 post-Baseline efficacy assessment. Stage 2 mITT Population: all participants randomized in Stage 2 who had at least 1 efficacy assessment in Stage 2. Data were reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: Placebo | Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | Stage 1 Baseline | 73.9 units on a scale | Standard Deviation 22.23 |
| Stage 1: Placebo | Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -10.7 units on a scale | Standard Deviation 15.29 |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | Stage 1 Baseline | 72.3 units on a scale | Standard Deviation 23.08 |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -13.9 units on a scale | Standard Deviation 16.7 |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | Stage 1 Baseline | 71.7 units on a scale | Standard Deviation 23.57 |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -10.3 units on a scale | Standard Deviation 13.54 |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | Stage 2 Baseline | 66.0 units on a scale | Standard Deviation 24.71 |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | Change from Baseline at Week 12 | -1.6 units on a scale | Standard Deviation 11.08 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | Change from Baseline at Week 12 | -5.6 units on a scale | Standard Deviation 11.78 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | Stage 2 Baseline | 68.9 units on a scale | Standard Deviation 20.79 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | Stage 2 Baseline | 65.3 units on a scale | Standard Deviation 19.36 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | Change from Baseline at Week 12 | -4.9 units on a scale | Standard Deviation 12.13 |
p-value: =0.02195% CI: [-7.4, -0.6]mixed model repeated measures (MMRM)
p-value: =0.73195% CI: [-3.9, 2.7]MMRM
p-value: =0.15795% CI: [-8.4, 1.4]MMRM
p-value: =0.1595% CI: [-8.4, 1.3]MMRM
p-value: =0.008MMRM
p-value: =0.208MMRM
Secondary
12-Week Parallel Group: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant
RUD evaluates dementia participants utilization of formal, informal healthcare resources, including hospitalizations, doctor visits, living assistance, time spent by nonprofessional caregivers. Information on days caregiver spent assisting participant from interviews during Stage 1 is reported for outcome measure, where following questions (Q), Q1= During last 30 days, how many days did you spend providing these (toilet visits, eating, dressing, grooming, walking, bathing) services to participant?; Q2= On typical care day during last 30 days, how much time per day did you assist participant with tasks such as shopping, food preparation, housekeeping, laundry, transportation, taking medication, managing financial matters?; Q3= During last 30 days, how many days did you spend providing these services (supervising) to the participant?. Data is collected for the treatment arm groups as pre-specified in the protocol for this outcome measure.
Time frame: 12-Week Parallel Group: Week 12
Population: mITT 12-Week Parallel-Group Population included all participants in the 12-Week Parallel Group who have at least one post-baseline efficacy assessment
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Stage 1: Placebo | 12-Week Parallel Group: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant | Week 12 (Q3) | 30.0 days |
| Stage 1: Placebo | 12-Week Parallel Group: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant | Week 12 (Q2) | 30.0 days |
| Stage 1: Placebo | 12-Week Parallel Group: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant | Week 12 (Q1) | 30.0 days |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | 12-Week Parallel Group: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant | Week 12 (Q2) | 30.0 days |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | 12-Week Parallel Group: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant | Week 12 (Q1) | 30.0 days |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | 12-Week Parallel Group: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant | Week 12 (Q3) | 30.0 days |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | 12-Week Parallel Group: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant | Week 12 (Q1) | 30.0 days |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | 12-Week Parallel Group: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant | Week 12 (Q3) | 30.0 days |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | 12-Week Parallel Group: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant | Week 12 (Q2) | 30.0 days |
Secondary
Least Squares Mean Modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC)-Agitation Score at Week 6 and Week 12
The intent of the ADCS version of the CGIC is to provide a means to reliably assess the global impression of change from Baseline in a clinical trial. The mADCS-CGIC is a modification of the ADCS-CGIC instrument that focuses specifically on agitation. The participants are asked to rate their impression of change from Baseline as: 1, marked improvement; 2, moderate improvement; 3, minimal improvement; 4, no change; 5, minimal worsening; 6, moderate worsening; 7, marked worsening. Baseline was defined as the last non-missing assessment prior to Stage 1 randomization. Treatment effects were estimated at each stage by analysis of covariance (ANCOVA) with fixed effects for treatment, Baseline CMAI Total score, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus \[vs\] \> 6), risk assessments for falls (normal/mild vs moderate/severe), Baseline concomitant use of antipsychotic medications (yes vs no). Missing values were imputed by last observation carried forward (LOCF) within each stage.
Time frame: Stage 1 Week 6; Stage 2 Week 12
Population: Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: Placebo | Least Squares Mean Modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC)-Agitation Score at Week 6 and Week 12 | Stage 1 Week 6 | 3.4 score on a scale | Standard Error 1.13 |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Least Squares Mean Modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC)-Agitation Score at Week 6 and Week 12 | Stage 1 Week 6 | 3.2 score on a scale | Standard Error 1.24 |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Least Squares Mean Modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC)-Agitation Score at Week 6 and Week 12 | Stage 1 Week 6 | 3.3 score on a scale | Standard Error 1.12 |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Least Squares Mean Modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC)-Agitation Score at Week 6 and Week 12 | Stage 2 Week 12 | 3.9 score on a scale | Standard Error 0.18 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Least Squares Mean Modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC)-Agitation Score at Week 6 and Week 12 | Stage 2 Week 12 | 3.3 score on a scale | Standard Error 0.18 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Least Squares Mean Modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC)-Agitation Score at Week 6 and Week 12 | Stage 2 Week 12 | 3.5 score on a scale | Standard Error 0.17 |
p-value: 0.33195% CI: [-0.4, 0.1]ANCOVA
p-value: 0.495% CI: [-0.4, 0.2]ANCOVA
p-value: 0.01495% CI: [-1.1, -0.1]ANCOVA
p-value: 0.14595% CI: [-0.9, 0.1]ANCOVA
p-value: 0.012ANCOVA
p-value: 0.097ANCOVA
Secondary
Stage 1 and Stage 2: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Rating at Week 6 and Week 12
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. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline CMAI Total score, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus \> 6), risk assessments for falls (normal/mild versus moderate/severe), Baseline concomitant use of antipsychotic medications (yes versus no). Missing values were imputed by LOCF within each stage.
Time frame: Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12
Population: Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: Placebo | Stage 1 and Stage 2: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Rating at Week 6 and Week 12 | Stage 1 Week 6 | 3.7 units on a scale | Standard Error 0.11 |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Rating at Week 6 and Week 12 | Stage 1 Week 6 | 3.5 units on a scale | Standard Error 0.14 |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Rating at Week 6 and Week 12 | Stage 1 Week 6 | 3.6 units on a scale | Standard Error 0.13 |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 1 and Stage 2: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Rating at Week 6 and Week 12 | Stage 2 Week 12 | 4.0 units on a scale | Standard Error 0.17 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Rating at Week 6 and Week 12 | Stage 2 Week 12 | 3.6 units on a scale | Standard Error 0.17 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Rating at Week 6 and Week 12 | Stage 2 Week 12 | 3.7 units on a scale | Standard Error 0.16 |
p-value: =0.36495% CI: [-0.4, 0.1]ANCOVA
p-value: =0.42795% CI: [-0.4, 0.2]ANCOVA
p-value: =0.09895% CI: [-0.9, 0.1]ANCOVA
p-value: =0.16895% CI: [-0.8, 0.1]ANCOVA
p-value: =0.063ANCOVA
p-value: =0.115ANCOVA
Secondary
Stage 1 and Stage 2: Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score to Week 6 and Week 12
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. The ADAS-cog is assessed for participants with an Mini-Mental State Examination (MMSE) score of ≥10 at the Baseline Visit. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus \> 6), risk assessments for falls (normal/mild versus moderate/severe), Baseline concomitant use of antipsychotic medications (yes vs no). Missing values were imputed by LOCF within each stage.
Time frame: Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12
Population: Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: Placebo | Stage 1 and Stage 2: Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score to Week 6 and Week 12 | Stage 1 Baseline | 25.8 units on a scale | Standard Deviation 10.1 |
| Stage 1: Placebo | Stage 1 and Stage 2: Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -0.5 units on a scale | Standard Deviation 4.46 |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score to Week 6 and Week 12 | Stage 1 Baseline | 26.2 units on a scale | Standard Deviation 8.99 |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -2.0 units on a scale | Standard Deviation 4.28 |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score to Week 6 and Week 12 | Stage 1 Baseline | 25.3 units on a scale | Standard Deviation 8.88 |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -0.5 units on a scale | Standard Deviation 4.72 |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 1 and Stage 2: Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score to Week 6 and Week 12 | Stage 2 Baseline | 26.9 units on a scale | Standard Deviation 9.56 |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 1 and Stage 2: Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score to Week 6 and Week 12 | Change from Baseline at Week 12 | -0.8 units on a scale | Standard Deviation 5.05 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score to Week 6 and Week 12 | Change from Baseline at Week 12 | 0.3 units on a scale | Standard Deviation 4.95 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score to Week 6 and Week 12 | Stage 2 Baseline | 27.0 units on a scale | Standard Deviation 9.27 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score to Week 6 and Week 12 | Stage 2 Baseline | 25.3 units on a scale | Standard Deviation 10.91 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score to Week 6 and Week 12 | Change from Baseline at Week 12 | 0.1 units on a scale | Standard Deviation 5.47 |
p-value: =0.01895% CI: [-2.9, -0.3]ANCOVA
p-value: =0.95695% CI: [-1.3, 1.3]ANCOVA
p-value: =0.45195% CI: [-1.8, 4]ANCOVA
p-value: =0.51995% CI: [-1.9, 3.7]ANCOVA
p-value: =0.471ANCOVA
p-value: =0.618ANCOVA
Secondary
Stage 1 and Stage 2: Change From Baseline in the Clinical Global Impression of Severity of Illness (CGIS)-Agitation Domain Score to Week 6 and Week 12
The CGIS-Agitation is an observer-rated scale that measures illness severity. CGIS is used to assess the severity of agitation. The CGIS score is rated on a 7-point scale (1 = normal, not at all ill; 7 = among the most extremely ill participants). Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus \> 6), risk assessments for falls (normal/mild versus moderate/severe), Baseline concomitant use of antipsychotic medications (yes versus no). Missing values were imputed by LOCF within each stage.
Time frame: Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12
Population: Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: Placebo | Stage 1 and Stage 2: Change From Baseline in the Clinical Global Impression of Severity of Illness (CGIS)-Agitation Domain Score to Week 6 and Week 12 | Stage 1 Baseline | 4.5 units on a scale | Standard Deviation 0.64 |
| Stage 1: Placebo | Stage 1 and Stage 2: Change From Baseline in the Clinical Global Impression of Severity of Illness (CGIS)-Agitation Domain Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -0.5 units on a scale | Standard Deviation 0.78 |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Clinical Global Impression of Severity of Illness (CGIS)-Agitation Domain Score to Week 6 and Week 12 | Stage 1 Baseline | 4.3 units on a scale | Standard Deviation 0.49 |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Clinical Global Impression of Severity of Illness (CGIS)-Agitation Domain Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -0.7 units on a scale | Standard Deviation 0.97 |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Clinical Global Impression of Severity of Illness (CGIS)-Agitation Domain Score to Week 6 and Week 12 | Stage 1 Baseline | 4.4 units on a scale | Standard Deviation 0.7 |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Clinical Global Impression of Severity of Illness (CGIS)-Agitation Domain Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -0.7 units on a scale | Standard Deviation 1.04 |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 1 and Stage 2: Change From Baseline in the Clinical Global Impression of Severity of Illness (CGIS)-Agitation Domain Score to Week 6 and Week 12 | Stage 2 Baseline | 4.4 units on a scale | Standard Deviation 0.87 |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 1 and Stage 2: Change From Baseline in the Clinical Global Impression of Severity of Illness (CGIS)-Agitation Domain Score to Week 6 and Week 12 | Change from Baseline at Week 12 | -0.2 units on a scale | Standard Deviation 0.58 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Clinical Global Impression of Severity of Illness (CGIS)-Agitation Domain Score to Week 6 and Week 12 | Change from Baseline at Week 12 | -0.4 units on a scale | Standard Deviation 0.7 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Clinical Global Impression of Severity of Illness (CGIS)-Agitation Domain Score to Week 6 and Week 12 | Stage 2 Baseline | 4.2 units on a scale | Standard Deviation 0.77 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Clinical Global Impression of Severity of Illness (CGIS)-Agitation Domain Score to Week 6 and Week 12 | Stage 2 Baseline | 4.1 units on a scale | Standard Deviation 0.77 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Clinical Global Impression of Severity of Illness (CGIS)-Agitation Domain Score to Week 6 and Week 12 | Change from Baseline at Week 12 | -0.3 units on a scale | Standard Deviation 1.01 |
p-value: =0.11895% CI: [-0.4, 0]ANCOVA
p-value: =0.19195% CI: [-0.4, 0.1]ANCOVA
p-value: =0.22595% CI: [-0.5, 0.1]ANCOVA
p-value: =0.22795% CI: [-0.5, 0.1]ANCOVA
p-value: =0.049ANCOVA
p-value: =0.075ANCOVA
Secondary
Stage 1 and Stage 2: Change From Baseline in the Cornell Scale for Depression in Dementia (CSDD) Score to Week 6 and Week 12
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 depressions. 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.
Time frame: Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12
Population: Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: Placebo | Stage 1 and Stage 2: Change From Baseline in the Cornell Scale for Depression in Dementia (CSDD) Score to Week 6 and Week 12 | Stage 1 Baseline | 6.2 units on a scale | Standard Deviation 2.24 |
| Stage 1: Placebo | Stage 1 and Stage 2: Change From Baseline in the Cornell Scale for Depression in Dementia (CSDD) Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -0.3 units on a scale | Standard Deviation 3.01 |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Cornell Scale for Depression in Dementia (CSDD) Score to Week 6 and Week 12 | Stage 1 Baseline | 6.3 units on a scale | Standard Deviation 2.11 |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Cornell Scale for Depression in Dementia (CSDD) Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -0.7 units on a scale | Standard Deviation 3.09 |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Cornell Scale for Depression in Dementia (CSDD) Score to Week 6 and Week 12 | Stage 1 Baseline | 6.4 units on a scale | Standard Deviation 2.19 |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Cornell Scale for Depression in Dementia (CSDD) Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -0.5 units on a scale | Standard Deviation 2.93 |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 1 and Stage 2: Change From Baseline in the Cornell Scale for Depression in Dementia (CSDD) Score to Week 6 and Week 12 | Stage 2 Baseline | 6.6 units on a scale | Standard Deviation 3.89 |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 1 and Stage 2: Change From Baseline in the Cornell Scale for Depression in Dementia (CSDD) Score to Week 6 and Week 12 | Change from Baseline at Week 12 | -0.4 units on a scale | Standard Deviation 2.56 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Cornell Scale for Depression in Dementia (CSDD) Score to Week 6 and Week 12 | Change from Baseline at Week 12 | -0.5 units on a scale | Standard Deviation 2.36 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Cornell Scale for Depression in Dementia (CSDD) Score to Week 6 and Week 12 | Stage 2 Baseline | 5.9 units on a scale | Standard Deviation 2.78 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Cornell Scale for Depression in Dementia (CSDD) Score to Week 6 and Week 12 | Stage 2 Baseline | 6.8 units on a scale | Standard Deviation 2.84 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Cornell Scale for Depression in Dementia (CSDD) Score to Week 6 and Week 12 | Change from Baseline at Week 12 | -0.3 units on a scale | Standard Deviation 3.09 |
p-value: =0.27895% CI: [-1.1, 0.3]ANCOVA
p-value: =0.81795% CI: [-0.8, 0.6]ANCOVA
p-value: =0.595% CI: [-1.4, 0.7]ANCOVA
p-value: =0.79595% CI: [-0.9, 1.2]ANCOVA
p-value: =0.213ANCOVA
p-value: =0.985ANCOVA
Secondary
Stage 1 and Stage 2: Change From Baseline in the Dementia Quality of Life (DEMQOL) Score to Week 6 and Week 12
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. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline, and in the Stage 1 model, Baseline NPI AA (≤ 6 vs \> 6), risk assessments for falls (normal/mild vs moderate/severe), Baseline concomitant use of antipsychotic medications (yes vs no). Missing values were imputed by LOCF within each stage.
Time frame: Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12
Population: Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: Placebo | Stage 1 and Stage 2: Change From Baseline in the Dementia Quality of Life (DEMQOL) Score to Week 6 and Week 12 | Stage 1 Baseline | 85.7 units on a scale | Standard Deviation 10.63 |
| Stage 1: Placebo | Stage 1 and Stage 2: Change From Baseline in the Dementia Quality of Life (DEMQOL) Score to Week 6 and Week 12 | Change from Baseline at Week 6 | 2.3 units on a scale | Standard Deviation 8.26 |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Dementia Quality of Life (DEMQOL) Score to Week 6 and Week 12 | Stage 1 Baseline | 82.9 units on a scale | Standard Deviation 10.22 |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Dementia Quality of Life (DEMQOL) Score to Week 6 and Week 12 | Change from Baseline at Week 6 | 3.5 units on a scale | Standard Deviation 8.57 |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Dementia Quality of Life (DEMQOL) Score to Week 6 and Week 12 | Stage 1 Baseline | 84.0 units on a scale | Standard Deviation 11.98 |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Dementia Quality of Life (DEMQOL) Score to Week 6 and Week 12 | Change from Baseline at Week 6 | 4.4 units on a scale | Standard Deviation 10.79 |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 1 and Stage 2: Change From Baseline in the Dementia Quality of Life (DEMQOL) Score to Week 6 and Week 12 | Stage 2 Baseline | 86.8 units on a scale | Standard Deviation 9.96 |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 1 and Stage 2: Change From Baseline in the Dementia Quality of Life (DEMQOL) Score to Week 6 and Week 12 | Change from Baseline at Week 12 | 2.5 units on a scale | Standard Deviation 5.4 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Dementia Quality of Life (DEMQOL) Score to Week 6 and Week 12 | Change from Baseline at Week 12 | 3.1 units on a scale | Standard Deviation 9.52 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Dementia Quality of Life (DEMQOL) Score to Week 6 and Week 12 | Stage 2 Baseline | 90.0 units on a scale | Standard Deviation 9.51 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Dementia Quality of Life (DEMQOL) Score to Week 6 and Week 12 | Stage 2 Baseline | 87.8 units on a scale | Standard Deviation 10.72 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Dementia Quality of Life (DEMQOL) Score to Week 6 and Week 12 | Change from Baseline at Week 12 | 1.1 units on a scale | Standard Deviation 13.06 |
p-value: =0.90995% CI: [-2.2, 2.5]ANCOVA
p-value: =0.22695% CI: [-0.9, 3.8]ANCOVA
p-value: =0.40595% CI: [-2.9, 7.1]ANCOVA
p-value: =0.71495% CI: [-5.8, 4]ANCOVA
p-value: =0.456ANCOVA
p-value: =0.678ANCOVA
Secondary
Stage 1 and Stage 2: Change From Baseline in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score to Week 6 and Week 12
The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. The Agitation/Aggression domain is designed to collect information on the behavioral aspects of agitation/aggression in participants with probable Alzheimer's Disease (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. Change from Baseline was calculated as the post-Baseline score minus the Baseline score.
Time frame: Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12
Population: Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: Placebo | Stage 1 and Stage 2: Change From Baseline in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score to Week 6 and Week 12 | Stage 1 Baseline | 7.1 units on a scale | Standard Deviation 2.39 |
| Stage 1: Placebo | Stage 1 and Stage 2: Change From Baseline in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -1.8 units on a scale | Standard Deviation 3.58 |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score to Week 6 and Week 12 | Stage 1 Baseline | 6.5 units on a scale | Standard Deviation 1.94 |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -2.0 units on a scale | Standard Deviation 3.03 |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score to Week 6 and Week 12 | Stage 1 Baseline | 7.2 units on a scale | Standard Deviation 2.42 |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -2.1 units on a scale | Standard Deviation 2.94 |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 1 and Stage 2: Change From Baseline in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score to Week 6 and Week 12 | Stage 2 Baseline | 6.9 units on a scale | Standard Deviation 2.84 |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 1 and Stage 2: Change From Baseline in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score to Week 6 and Week 12 | Change from Baseline at Week 12 | -1.7 units on a scale | Standard Deviation 3 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score to Week 6 and Week 12 | Change from Baseline at Week 12 | -0.8 units on a scale | Standard Deviation 3.15 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score to Week 6 and Week 12 | Stage 2 Baseline | 6.3 units on a scale | Standard Deviation 2.71 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score to Week 6 and Week 12 | Stage 2 Baseline | 6.3 units on a scale | Standard Deviation 2.81 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score to Week 6 and Week 12 | Change from Baseline at Week 12 | -0.9 units on a scale | Standard Deviation 3.35 |
p-value: =0.18295% CI: [-1.3, 0.2]MMRM
p-value: =0.3995% CI: [-1.1, 0.4]MMRM
p-value: =0.46295% CI: [-0.8, 1.7]MMRM
p-value: =0.52895% CI: [-0.8, 1.6]MMRM
p-value: =0.695ANCOVA
p-value: =0.904ANCOVA
Secondary
Stage 1 and Stage 2: Change From Baseline in the NPI Aberrant Motor Behavior Domain Score to Week 6 and Week 12
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, 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. Change from Baseline was calculated as the post-Baseline score minus the Baseline score.
Time frame: Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12
Population: Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: Placebo | Stage 1 and Stage 2: Change From Baseline in the NPI Aberrant Motor Behavior Domain Score to Week 6 and Week 12 | Change from Baseline at Week 6 Stage 2 Baseline | -0.9 units on a scale | Standard Deviation 3.62 |
| Stage 1: Placebo | Stage 1 and Stage 2: Change From Baseline in the NPI Aberrant Motor Behavior Domain Score to Week 6 and Week 12 | Stage 1 Baseline | 5.1 units on a scale | Standard Deviation 3.94 |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Aberrant Motor Behavior Domain Score to Week 6 and Week 12 | Stage 1 Baseline | 4.9 units on a scale | Standard Deviation 3.77 |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Aberrant Motor Behavior Domain Score to Week 6 and Week 12 | Change from Baseline at Week 6 Stage 2 Baseline | -1.6 units on a scale | Standard Deviation 3.74 |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Aberrant Motor Behavior Domain Score to Week 6 and Week 12 | Stage 1 Baseline | 5.1 units on a scale | Standard Deviation 4.07 |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Aberrant Motor Behavior Domain Score to Week 6 and Week 12 | Change from Baseline at Week 6 Stage 2 Baseline | -0.7 units on a scale | Standard Deviation 3.86 |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 1 and Stage 2: Change From Baseline in the NPI Aberrant Motor Behavior Domain Score to Week 6 and Week 12 | Stage 2 Baseline | 5.2 units on a scale | Standard Deviation 3.79 |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 1 and Stage 2: Change From Baseline in the NPI Aberrant Motor Behavior Domain Score to Week 6 and Week 12 | Change from Baseline at Week 12 | -0.4 units on a scale | Standard Deviation 2.16 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Aberrant Motor Behavior Domain Score to Week 6 and Week 12 | Change from Baseline at Week 12 | 0.6 units on a scale | Standard Deviation 3.24 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Aberrant Motor Behavior Domain Score to Week 6 and Week 12 | Stage 2 Baseline | 4.0 units on a scale | Standard Deviation 3.87 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Aberrant Motor Behavior Domain Score to Week 6 and Week 12 | Stage 2 Baseline | 4.3 units on a scale | Standard Deviation 4.32 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Aberrant Motor Behavior Domain Score to Week 6 and Week 12 | Change from Baseline at Week 12 | 1.1 units on a scale | Standard Deviation 3.54 |
p-value: =0.14695% CI: [-1.4, 0.2]MMRM
p-value: =0.39995% CI: [-0.4, 1.1]MMRM
p-value: =0.28395% CI: [-0.6, 2]MMRM
p-value: =0.06595% CI: [-0.1, 2.5]MMRM
p-value: =0.829ANCOVA
p-value: =0.052ANCOVA
Secondary
Stage 1 and Stage 2: Change From Baseline in the NPI Caregiver Distress Score to Week 6 and Week 12
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. Higher scores indicate worsening symptoms. Change from Baseline was calculated as the post-Baseline score minus the Baseline score.
Time frame: Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12
Population: Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: Placebo | Stage 1 and Stage 2: Change From Baseline in the NPI Caregiver Distress Score to Week 6 and Week 12 | Stage 1 Baseline | 18.87 units on a scale | Standard Deviation 9.026 |
| Stage 1: Placebo | Stage 1 and Stage 2: Change From Baseline in the NPI Caregiver Distress Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -4.31 units on a scale | Standard Deviation 7.979 |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Caregiver Distress Score to Week 6 and Week 12 | Stage 1 Baseline | 18.90 units on a scale | Standard Deviation 9.266 |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Caregiver Distress Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -5.48 units on a scale | Standard Deviation 8.559 |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Caregiver Distress Score to Week 6 and Week 12 | Stage 1 Baseline | 18.88 units on a scale | Standard Deviation 10.015 |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Caregiver Distress Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -4.83 units on a scale | Standard Deviation 7.736 |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 1 and Stage 2: Change From Baseline in the NPI Caregiver Distress Score to Week 6 and Week 12 | Stage 2 Baseline | 17.33 units on a scale | Standard Deviation 9.01 |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 1 and Stage 2: Change From Baseline in the NPI Caregiver Distress Score to Week 6 and Week 12 | Change from Baseline at Week 12 | -0.73 units on a scale | Standard Deviation 6.533 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Caregiver Distress Score to Week 6 and Week 12 | Change from Baseline at Week 12 | -1.67 units on a scale | Standard Deviation 5.666 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Caregiver Distress Score to Week 6 and Week 12 | Stage 2 Baseline | 15.95 units on a scale | Standard Deviation 7.241 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Caregiver Distress Score to Week 6 and Week 12 | Stage 2 Baseline | 16.89 units on a scale | Standard Deviation 7.416 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Caregiver Distress Score to Week 6 and Week 12 | Change from Baseline at Week 12 | 0.44 units on a scale | Standard Deviation 7.265 |
p-value: =0.24795% CI: [-3.2, 0.8]MMRM
p-value: =0.72195% CI: [-2.3, 1.6]MMRM
p-value: =0.41995% CI: [-4.3, 1.8]MMRM
p-value: =0.53495% CI: [-2, 3.9]MMRM
p-value: =0.163ANCOVA
p-value: =0.851ANCOVA
Secondary
Stage 1 and Stage 2: Change From Baseline in the NPI Irritability/Lability Domain Score to Week 6 and Week 12
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. Change from Baseline was calculated as the post-Baseline score minus the Baseline score.
Time frame: Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12
Population: Stage 1 and Stage 2: mITT Populations. Data were reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: Placebo | Stage 1 and Stage 2: Change From Baseline in the NPI Irritability/Lability Domain Score to Week 6 and Week 12 | Stage 1 Baseline | 5.1 units on a scale | Standard Deviation 3.33 |
| Stage 1: Placebo | Stage 1 and Stage 2: Change From Baseline in the NPI Irritability/Lability Domain Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -1.1 units on a scale | Standard Deviation 3.84 |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Irritability/Lability Domain Score to Week 6 and Week 12 | Stage 1 Baseline | 5.1 units on a scale | Standard Deviation 3.62 |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Irritability/Lability Domain Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -1.9 units on a scale | Standard Deviation 3.71 |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Irritability/Lability Domain Score to Week 6 and Week 12 | Stage 1 Baseline | 5.2 units on a scale | Standard Deviation 3.39 |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Irritability/Lability Domain Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -1.4 units on a scale | Standard Deviation 3.62 |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 1 and Stage 2: Change From Baseline in the NPI Irritability/Lability Domain Score to Week 6 and Week 12 | Stage 2 Baseline | 4.5 units on a scale | Standard Deviation 3.99 |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 1 and Stage 2: Change From Baseline in the NPI Irritability/Lability Domain Score to Week 6 and Week 12 | Change from Baseline at Week 12 | 0.2 units on a scale | Standard Deviation 3.19 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Irritability/Lability Domain Score to Week 6 and Week 12 | Change from Baseline at Week 12 | -1.3 units on a scale | Standard Deviation 3.88 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Irritability/Lability Domain Score to Week 6 and Week 12 | Stage 2 Baseline | 5.3 units on a scale | Standard Deviation 3.54 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Irritability/Lability Domain Score to Week 6 and Week 12 | Stage 2 Baseline | 5.2 units on a scale | Standard Deviation 3.64 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Irritability/Lability Domain Score to Week 6 and Week 12 | Change from Baseline at Week 12 | -0.9 units on a scale | Standard Deviation 3.45 |
p-value: =0.06195% CI: [-1.6, 0]MMRM
p-value: =0.495% CI: [-1.1, 0.5]MMRM
p-value: =0.11595% CI: [-2.4, 0.3]MMRM
p-value: =0.26495% CI: [-2.1, 0.6]MMRM
p-value: =0.015ANCOVA
p-value: =0.163ANCOVA
Secondary
Stage 1 and Stage 2: Change From Baseline in the NPI Total Score to Week 6 and Week 12
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, nighttime 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, and 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, 3=moderate, 4=severe, 5=very severe. Total score is calculated by adding the individual Item scores, to yield a possible total scores of 0 to 144.
Time frame: Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12
Population: Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: Placebo | Stage 1 and Stage 2: Change From Baseline in the NPI Total Score to Week 6 and Week 12 | Stage 1 Baseline | 40.2 units on a scale | Standard Deviation 17.95 |
| Stage 1: Placebo | Stage 1 and Stage 2: Change From Baseline in the NPI Total Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -9.2 units on a scale | Standard Deviation 17.41 |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Total Score to Week 6 and Week 12 | Stage 1 Baseline | 39.4 units on a scale | Standard Deviation 18.93 |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Total Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -13.2 units on a scale | Standard Deviation 17.99 |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Total Score to Week 6 and Week 12 | Stage 1 Baseline | 40.1 units on a scale | Standard Deviation 19.98 |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Total Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -10.6 units on a scale | Standard Deviation 16.09 |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 1 and Stage 2: Change From Baseline in the NPI Total Score to Week 6 and Week 12 | Stage 2 Baseline | 39.2 units on a scale | Standard Deviation 22.47 |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 1 and Stage 2: Change From Baseline in the NPI Total Score to Week 6 and Week 12 | Change from Baseline at Week 12 | -5.1 units on a scale | Standard Deviation 14.03 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Total Score to Week 6 and Week 12 | Change from Baseline at Week 12 | -4.4 units on a scale | Standard Deviation 12.92 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Total Score to Week 6 and Week 12 | Stage 2 Baseline | 34.7 units on a scale | Standard Deviation 14.16 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Total Score to Week 6 and Week 12 | Stage 2 Baseline | 34.6 units on a scale | Standard Deviation 16.93 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the NPI Total Score to Week 6 and Week 12 | Change from Baseline at Week 12 | -0.1 units on a scale | Standard Deviation 18.82 |
p-value: =0.0595% CI: [-7.8, 0]MMRM
p-value: =0.41295% CI: [-5.4, 2.2]MMRM
p-value: =0.77595% CI: [-7.8, 5.8]MMRM
p-value: =0.33395% CI: [-3.5, 10.1]MMRM
p-value: =0.133ANCOVA
p-value: =0.829ANCOVA
Secondary
Stage 1 and Stage 2: Change From Baseline in the Zarit Burden Interview (ZBI) Score to Week 6 and Week 12
The ZBI is a 22-item scale used to assess the impact of a participant with dementia and also other illnesses on the caregiver's burden. For each item of the scale, the caregiver indicates how often they feel the burden (never, rarely, sometimes, quite frequently, or nearly always). The score ranges from 0 to 88 and is determined by adding the numbered responses of the individual items. Higher scores indicate greater caregiver distress. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus \> 6), risk assessments for falls (normal/mild versus moderate/severe), Baseline concomitant use of antipsychotic medications (yes versus no). Missing values were imputed by LOCF within each stage.
Time frame: Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12
Population: Stage 1 and Stage 2 mITT Populations. Overall number of participants analyzed are the number of participants with data available for analysis at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: Placebo | Stage 1 and Stage 2: Change From Baseline in the Zarit Burden Interview (ZBI) Score to Week 6 and Week 12 | Stage 1 Baseline | 30.9 units on a scale | Standard Deviation 16.19 |
| Stage 1: Placebo | Stage 1 and Stage 2: Change From Baseline in the Zarit Burden Interview (ZBI) Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -1.4 units on a scale | Standard Deviation 8.22 |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Zarit Burden Interview (ZBI) Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -2.0 units on a scale | Standard Deviation 8.44 |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Zarit Burden Interview (ZBI) Score to Week 6 and Week 12 | Stage 1 Baseline | 30.0 units on a scale | Standard Deviation 16.96 |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Zarit Burden Interview (ZBI) Score to Week 6 and Week 12 | Change from Baseline at Week 6 | -2.7 units on a scale | Standard Deviation 9.49 |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Zarit Burden Interview (ZBI) Score to Week 6 and Week 12 | Stage 1 Baseline | 33.0 units on a scale | Standard Deviation 16.68 |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 1 and Stage 2: Change From Baseline in the Zarit Burden Interview (ZBI) Score to Week 6 and Week 12 | Change from Baseline at Week 12 | -1.1 units on a scale | Standard Deviation 7.65 |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 1 and Stage 2: Change From Baseline in the Zarit Burden Interview (ZBI) Score to Week 6 and Week 12 | Stage 2 Baseline | 31.5 units on a scale | Standard Deviation 15.24 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Zarit Burden Interview (ZBI) Score to Week 6 and Week 12 | Stage 2 Baseline | 32.0 units on a scale | Standard Deviation 16.57 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Zarit Burden Interview (ZBI) Score to Week 6 and Week 12 | Change from Baseline at Week 12 | 1.4 units on a scale | Standard Deviation 8.71 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Zarit Burden Interview (ZBI) Score to Week 6 and Week 12 | Change from Baseline at Week 12 | -0.5 units on a scale | Standard Deviation 7.05 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Change From Baseline in the Zarit Burden Interview (ZBI) Score to Week 6 and Week 12 | Stage 2 Baseline | 28.6 units on a scale | Standard Deviation 16.76 |
p-value: =0.5395% CI: [-2.7, 1.4]ANCOVA
p-value: =0.32695% CI: [-3.1, 1]ANCOVA
p-value: =0.13595% CI: [-0.8, 5.9]ANCOVA
p-value: =0.89595% CI: [-3.1, 3.5]ANCOVA
p-value: =0.502ANCOVA
p-value: =0.564ANCOVA
Secondary
Stage 1 and Stage 2: Patient Global Impression of Change (PGIC) Score at Week 6 and Week 12
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. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline CMAI Total score, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus \> 6), risk assessments for falls (normal/mild versus moderate/severe), Baseline concomitant use of antipsychotic medications (yes vs no). Missing values were imputed by LOCF within each stage.
Time frame: Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12
Population: Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: Placebo | Stage 1 and Stage 2: Patient Global Impression of Change (PGIC) Score at Week 6 and Week 12 | Stage 1 Week 6 | 3.4 units on a scale | Standard Error 0.12 |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Patient Global Impression of Change (PGIC) Score at Week 6 and Week 12 | Stage 1 Week 6 | 3.0 units on a scale | Standard Error 0.15 |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Patient Global Impression of Change (PGIC) Score at Week 6 and Week 12 | Stage 1 Week 6 | 3.1 units on a scale | Standard Error 0.14 |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 1 and Stage 2: Patient Global Impression of Change (PGIC) Score at Week 6 and Week 12 | Stage 2 Week 12 | 3.6 units on a scale | Standard Error 0.2 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 and Stage 2: Patient Global Impression of Change (PGIC) Score at Week 6 and Week 12 | Stage 2 Week 12 | 3.1 units on a scale | Standard Error 0.2 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 and Stage 2: Patient Global Impression of Change (PGIC) Score at Week 6 and Week 12 | Stage 2 Week 12 | 3.3 units on a scale | Standard Error 0.19 |
p-value: =0.01495% CI: [-0.6, -0.1]ANCOVA
p-value: =0.11195% CI: [-0.5, 0.1]ANCOVA
p-value: =0.06295% CI: [-1.1, 0]ANCOVA
p-value: =0.30595% CI: [-0.8, 0.3]ANCOVA
p-value: =0.003ANCOVA
p-value: =0.073ANCOVA
Secondary
Stage 1: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant
RUD evaluates dementia participants utilization of formal, informal healthcare resources, including hospitalizations, doctor visits, living assistance, time spent by nonprofessional caregivers. Information on hours per day caregiver spent assisting participant from interviews during Stage 1 is reported for this outcome measure, where the following questions (Q), Q1= On typical care day during last 30 days, how much time per day did you assist participant with tasks such as toilet visits, eating, dressing, grooming, walking, bathing? Q2= On typical care day during the last 30 days, how much time per day did you assist participant with tasks as (shopping, food preparation, housekeeping, laundry, transportation, taking medication, managing financial matters?; Q3= On typical care day during last 30 days, how much time per day did you spend supervising (preventing dangerous events)?(Q3). Data is collected for treatment arm groups as pre-specified in protocol for this outcome measure.
Time frame: Stage 1: Week 6
Population: Stage 1 mITT Populations. Data were reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Stage 1: Placebo | Stage 1: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | Week 6 (Q2) | 4.0 hours |
| Stage 1: Placebo | Stage 1: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | Week 6 (Q1) | 2.0 hours |
| Stage 1: Placebo | Stage 1: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | Week 6 (Q3) | 3.0 hours |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | Week 6 (Q2) | 4.0 hours |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | Week 6 (Q1) | 2.0 hours |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | Week 6 (Q3) | 2.0 hours |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | Week 6 (Q1) | 2.0 hours |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | Week 6 (Q3) | 2.8 hours |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | Week 6 (Q2) | 4.0 hours |
Secondary
Stage 1: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals
RUD evaluates dementia participants utilization of formal and informal healthcare resources, including hospitalizations and doctor visits, living assistance, and time spent by nonprofessional caregivers. The RUD is administered as a semi-structured interview with the participant's primary caregiver and contains 2 sections; one focusing on caregiver impact (loss of work and leisure time incurred by caregiver) and the other focusing on the participant's use of healthcare resources. Information of caregivers who reported their responsibilities affected their work and who visited healthcare professionals from the interviews during Stage 1 is reported for this outcome measure. Data was collected for the treatment arm groups as pre-specified in the protocol for this outcome measure.
Time frame: Stage 1: Week 6
Population: Stage 1 mITT Populations. Data were reported for only those participants contributing data to the analysis. Number analyzed are the number of participants available at the given timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stage 1: Placebo | Stage 1: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals | Caregivers Who Reported that their Responsibilities Affected Their Work | 33.8 percentage of participants |
| Stage 1: Placebo | Stage 1: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals | Caregivers Who Visited Health Care Professionals | 42.2 percentage of participants |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals | Caregivers Who Reported that their Responsibilities Affected Their Work | 22.9 percentage of participants |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals | Caregivers Who Visited Health Care Professionals | 31.1 percentage of participants |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals | Caregivers Who Reported that their Responsibilities Affected Their Work | 34.2 percentage of participants |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals | Caregivers Who Visited Health Care Professionals | 44.8 percentage of participants |
Secondary
Stage 1: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant
RUD evaluates dementia participants utilization of formal, informal healthcare resources, including hospitalizations, doctor visits, living assistance, time spent by nonprofessional caregivers. Information on days caregiver spent assisting participant from interviews during Stage 1 is reported for outcome measure, where following questions (Q), Q1= During last 30 days, how many days did you spend providing these (toilet visits, eating, dressing, grooming, walking, bathing) services to participant?; Q2= On typical care day during last 30 days, how much time per day did you assist participant with tasks such as shopping, food preparation, housekeeping, laundry, transportation, taking medication, managing financial matters?; Q3= During last 30 days, how many days did you spend providing these services (supervising) to the participant?. Data is collected for the treatment arm groups as pre-specified in the protocol for this outcome measure.
Time frame: Stage 1: Week 6
Population: Stage 1 mITT Populations. Data were reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Stage 1: Placebo | Stage 1: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant | Week 6 (Q2) | 30.0 days |
| Stage 1: Placebo | Stage 1: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant | Week 6 (Q1) | 30.0 days |
| Stage 1: Placebo | Stage 1: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant | Week 6 (Q3) | 30.0 days |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant | Week 6 (Q2) | 30.0 days |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant | Week 6 (Q1) | 30.0 days |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant | Week 6 (Q3) | 30.0 days |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant | Week 6 (Q1) | 30.0 days |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant | Week 6 (Q3) | 30.0 days |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant | Week 6 (Q2) | 30.0 days |
Secondary
Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score
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. Data was collected for the treatment arm groups as pre-specified in the protocol for this outcome measure.
Time frame: Baseline; Week 12
Population: Stage 2 mITT population included all participants who were rerandomized in Stage 2 and had at least 1 efficacy assessment in Stage 2 (after Week 6). The data is reported for stage 2 only. Overall number analyzed are the number of participants with data available for analyses. The percentages are rounded off to the nearest whole number.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stage 1: Placebo | Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | Poor | 0 percentage of participants |
| Stage 1: Placebo | Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | Excellent to very good | 22.6 percentage of participants |
| Stage 1: Placebo | Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | Missing | 6.5 percentage of participants |
| Stage 1: Placebo | Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | Good | 59.7 percentage of participants |
| Stage 1: Placebo | Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | Fair | 11.3 percentage of participants |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | Poor | 0 percentage of participants |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | Fair | 7.8 percentage of participants |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | Good | 64.1 percentage of participants |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | Missing | 7.8 percentage of participants |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | Excellent to very good | 20.3 percentage of participants |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | Fair | 16.9 percentage of participants |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | Excellent to very good | 13.8 percentage of participants |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | Good | 58.5 percentage of participants |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | Poor | 0 percentage of participants |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | Missing | 10.8 percentage of participants |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | Missing | 7.4 percentage of participants |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | Excellent to very good | 20.2 percentage of participants |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | Poor | 0 percentage of participants |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | Fair | 13.8 percentage of participants |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | Good | 58.5 percentage of participants |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | Fair | 11.3 percentage of participants |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | Poor | 0 percentage of participants |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | Excellent to very good | 20.6 percentage of participants |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | Missing | 5.2 percentage of participants |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | Good | 62.9 percentage of participants |
Secondary
Stage 2: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant
RUD evaluates dementia participants utilization of formal, informal healthcare resources, including hospitalizations, doctor visits, living assistance, time spent by nonprofessional caregivers. Information on hours per day caregiver spent assisting participant from interviews during Stage 1 is reported for this outcome measure, where the following questions (Q), Q1= On typical care day during last 30 days, how much time per day did you assist participant with tasks such as toilet visits, eating, dressing, grooming, walking, bathing? Q2= On typical care day during the last 30 days, how much time per day did you assist participant with tasks as (shopping, food preparation, housekeeping, laundry, transportation, taking medication, managing financial matters?; Q3= On typical care day during last 30 days, how much time per day did you spend supervising (preventing dangerous events)?(Q3). Data is collected for treatment arm groups as pre-specified in protocol for this outcome measure.
Time frame: Stage 2: Week 12
Population: Stage 2 mITT Population. The data is reported for stage 2 only. Data were reported for only those participants contributing data to the analysis
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Stage 1: Placebo | Stage 2: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | Week 12 (Q1) | 1.5 hours |
| Stage 1: Placebo | Stage 2: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | Week 12 (Q3) | 1.0 hours |
| Stage 1: Placebo | Stage 2: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | Week 12 (Q2) | 4.0 hours |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 2: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | Week 12 (Q2) | 4.0 hours |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 2: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | Week 12 (Q1) | 2.0 hours |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 2: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | Week 12 (Q3) | 3.0 hours |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 2: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | Week 12 (Q2) | 4.0 hours |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 2: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | Week 12 (Q1) | 2.0 hours |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 2: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | Week 12 (Q3) | 3.0 hours |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 2: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | Week 12 (Q1) | 2.0 hours |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 2: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | Week 12 (Q3) | 2.0 hours |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 2: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | Week 12 (Q2) | 4.0 hours |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 2: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | Week 12 (Q2) | 4.0 hours |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 2: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | Week 12 (Q1) | 2.0 hours |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 2: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | Week 12 (Q3) | 2.0 hours |
Secondary
Stage 2: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals
RUD evaluates dementia participants utilization of formal and informal healthcare resources, including hospitalizations and doctor visits, living assistance, and time spent by nonprofessional caregivers. The RUD is administered as a semi-structured interview with the participant's primary caregiver and contains 2 sections; one focusing on caregiver impact (loss of work and leisure time incurred by caregiver) and the other focusing on the participant's use of healthcare resources. Information of caregivers who reported their responsibilities affected their work and who visited healthcare professionals from the interviews during Stage 2 is reported for this outcome measure. Data was collected for the treatment arm groups as pre-specified in the protocol for this outcome measure.
Time frame: Stage 2: Week 12
Population: Stage 2 mITT Population. Data were reported for only those participants contributing data to the analysis. Number analyzed are the number of participants available at the given timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stage 1: Placebo | Stage 2: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals | Caregivers Who Reported that their Responsibilities Affected Their Work | 44.0 percentage of participants |
| Stage 1: Placebo | Stage 2: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals | Caregivers Who Visited Health Care Professionals | 43.1 percentage of participants |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 2: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals | Caregivers Who Reported that their Responsibilities Affected Their Work | 28.6 percentage of participants |
| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 2: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals | Caregivers Who Visited Health Care Professionals | 30.5 percentage of participants |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 2: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals | Caregivers Who Reported that their Responsibilities Affected Their Work | 36.4 percentage of participants |
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 2: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals | Caregivers Who Visited Health Care Professionals | 29.3 percentage of participants |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 2: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals | Caregivers Who Visited Health Care Professionals | 26.7 percentage of participants |
| Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 2: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals | Caregivers Who Reported that their Responsibilities Affected Their Work | 24.2 percentage of participants |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 2: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals | Caregivers Who Reported that their Responsibilities Affected Their Work | 35.3 percentage of participants |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 2: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals | Caregivers Who Visited Health Care Professionals | 37.0 percentage of participants |