Agitation, Alzheimer's Disease
Conditions
Keywords
AVP-923-20, AVP-923-30, AVP-923, Dextromethorphan, Quinidine, Neuropsychiatric Inventory, Aggression, Efficacy, Safety
Brief summary
The objectives of the study are to evaluate the safety, tolerability and efficacy of AVP-923 compared to placebo, for the treatment of symptoms of agitation in participants with Alzheimer's Disease (AD).
Detailed description
Eligible participants for this study must have a diagnosis of probable AD and must have clinically meaningful agitation secondary to AD. This is a multicenter, randomized, double-dummy, double-blind, placebo-controlled study, consisting of 10 weeks of treatment. Up to 200 participants will be enrolled at approximately 30-40 centers in the US. Study medication will be administered orally twice-daily from Day 1 through Day 70. Screening must occur within within approximately 4 weeks prior to randomization. Following screening procedures for assessment of inclusion and exclusion criteria, eligible participants will be randomized into the study.
Interventions
DRUGAVP-923-20
AVP-923-20: 20 mg of dextromethorphan and 10 mg of quinidine
DRUGPlacebo
Placebo capsule
DRUGAVP-923-30
AVP-923-30: 30 mg of dextromethorphan and 10 mg of quinidine
Sponsors
Avanir Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: Diagnosis of probable Alzheimer's disease (AD). The participant has clinically significant symptoms of agitation secondary to AD, that interfere with daily routine and for which a prescription medication is deemed indicated, in the opinion of the investigator. Either out-patients or residents of an assisted-living facility or a skilled nursing home. CGI-S score is ≥ 4 (moderately ill) at screening and baseline. Mini Mental State Examination (MMSE) score at screening between 8 and 28 (inclusive). Caregiver who is able and willing to comply with all required study procedures, ensuring that the participant attends all study visits and takes the study medication as instructed. In order to qualify as a caregiver for this study, the individual should spend time with the participant for a minimum of 4 hours on 4 separate days per week. Key
Exclusion criteria
Participant has other type of dementia (e.g., vascular dementia, frontotemporal dementia, Parkinson's disease, substance-induced dementia). Participant with co-existent clinically significant or unstable systemic diseases that could confound the interpretation of the safety results of the study (e.g. malignancy, poorly controlled diabetes, poorly controlled hypertension, unstable pulmonary, renal or hepatic disease, unstable ischemic cardiac disease, dilated cardiomyopathy, certain cardiac conduction abnormalities including QTc prolongation, or unstable valvular heart disease). Participant with myasthenia gravis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70 | 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 was 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, marked. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. A higher score represents worsening symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score. Data are reported for only those participants contributing data to the analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Total NPI Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70 | The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and 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. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. The total score is calculated as a sum of all 12 domain scores and thus ranges from 12 to 144. A higher score represents worsening symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score. |
| Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70 | The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and 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. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. A higher score represents worsening symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score. Sleep/nighttime behavior disorders = S/NB disorders. |
| Change in the Sum of the Agitation/Aggression, Irritability/Lability, Disinhibition, and Aberrant Motor Behavior NPI Domain (NPI4D) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70 | The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and 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. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. The NPI4D score is the sum of the Agitation/Aggression, Irritability/Lability, Disinhibition, and Aberrant Motor Behavior domain scores, and thus ranges from 4 to 48. A higher score represents worsening symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score. |
| Change in the Sum of the Agitation/Aggression, Irritability/Lability, Anxiety, and Aberrant Motor Behavior NPI Domain (NPI4A) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70 | The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and 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. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. The NPI4A score is the sum of the Agitation/Aggression, Irritability/Lability, Anxiety, and Aberrant Motor Behavior domain scores, and thus ranges from 4 to 48. A higher score represents worsening symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score. |
| Change in the Total Neuropsychiatric Inventory-Caregiver Distress Score (NPI-CDS) From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70 | The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. For each domain, the caregiver is asked to rate how emotionally distressing they find the symptom behavior on the following scale: 0, not at all; 1, minimally; 2, mildly; 3, moderately; 4, severely; 5, very severely or extremely. The total NPI-CDS score is calculated as the sum of all 12 domain scores and thus ranges from 0 to 60. A higher score represents increased distress. Change from Baseline is calculated as the post-Baseline score minus the Baseline score. |
| Change in the NPI-CDS for the Agitation/Aggression Domain From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70 | The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. For the Agitation/Aggression domain, the caregiver is asked to rate how emotionally distressing they find the symptom behavior on the following scale: 0, not at all; 1, minimally; 2, mildly; 3, moderately; 4, severely; 5, very severely or extremely. A higher score represents increased distress. Change from Baseline is calculated as the post-Baseline score minus the Baseline score. |
| Change in the NPI-CDS NPI4D Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70 | The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. For the NPI4D NPI-CDS score, the caregiver is asked to rate how emotionally distressing they find the symptom behavior (for the Agitation/Aggression, Irritability/Lability, Disinhibition, and Aberrant Motor Behavior domains) on the following scale: 0, not at all; 1, minimally; 2, mildly; 3, moderately; 4, severely; 5, very severely or extremely. The NPI4D NPI-CDS score ranges from 0 to 20. A higher score represents increased distress. Change from Baseline is calculated as the post-Baseline score minus the Baseline score. |
| Change in the NPI-CDS NPI4A Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70 | The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. For the NPI4A NPI-CDS score, the caregiver is asked to rate how emotionally distressing they find the symptom behavior (for the Agitation/Aggression, Irritability/Lability, Anxiety, and Aberrant Motor Behavior domains) on the following scale: 0, not at all; 1, minimally; 2, mildly; 3, moderately; 4, severely; 5, very severely or extremely. The NPI4A NPI-CDS score ranges from 0 to 20. Change from Baseline is calculated as the post-Baseline score minus the Baseline score. |
| Change in the Caregiver Strain Index (CSI) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70 | The CSI is a 13-question tool that is used to measure strain related to care provision and to identify families with potential caregiving concerns. There is at least one item for each of the following major domains: Employment, Financial, Physical, Social, and Time. A 0 (No) to 1 (Yes) scale is used for each of the 13 questions; thus the total score ranges from 0 to 13. Higher scores signify higher stress levels. Positive responses to 7 or more items on the index indicate a greater level of strain. Change from Baseline is calculated as the post-Baseline score minus the Baseline score. |
| Change in the Cornell Scale for Depression in Dementia (CSDD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70 | The CSDD is a 19-item interview specifically developed to assess the signs and symptoms of major depression in participants with dementia. Each of the 19 items is rated for severity on a scale of 0 to 2 (0, absent; 1, mild or intermittent; 2, severe). The total score is calculated as the sum of the item scores and thus ranges from 0 to 38. Higher scores signify more severe depression. Scores above 10 indicate probable major depression. Scores above 18 indicate definite major depression. Scores below 6, as a rule, are associated with the absence of significant depressive symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score. |
| Number of Participants With the Indicated Type of Adverse Event | up to Week 10 | Treatment-emergent adverse events (TEAEs) are defined as AEs that first occurred, or worsened, after the first dose of study medication and within 30 days after the permanent discontinuation of the study medication (first dose date ≤ AE start date ≤ date of last dose + 30 days) |
| Change in the Quality of Life-Alzheimer's Disease (QoL-AD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70 | The QoL-AD is a brief, 13-item measure designed specifically to obtain a rating of the participant's quality of life (QoL) from both the participant and the caregiver. It uses simple and straightforward language and responses and includes assessments of the individual's relationships with friends and family, concerns about finances, physical condition, mood, and an overall assessment of life quality. Caregivers complete the measure as a questionnaire about the participants' QoL, whereas participants complete it in interview format about their own QoL. Each of the 13 items is rated on a 4-point scale, with 1 indicating a poor QoL and 4 indicating an excellent QoL. Total scores range from 13 to 52, with a higher score indicating a better QoL. Change from Baseline is calculated as the post-Baseline score minus the Baseline score. |
| Change in the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70 | The ADCS-ADL inventory measures basic activities of daily living such as dressing, conversation, eating, bathing, and grooming. The 19-item version, covering mainly basic ADL, is used to assess participants with more severe disabilities. The ADCS-ADL uses a scale from 0 to 54. Lower scores indicate declining ability. Change from Baseline is calculated as the post-Baseline value minus the Baseline value. |
| Number of Participants With the Indicated Categorical Response on the PGI-C for the Caregiver Domain at Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 1 (Stage 1 Baseline); Day 70 | The PGI-C uses a 7-point scale to assess treatment response and to rate the global impression of clinical change in a participant's agitation. The participant is asked to rate their impression of change from Baseline as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; 7, very much worse. For placebo non-responders re-randomized to AVP-923 or placebo at Stage 2, Baseline is defined as the last non-missing assessment prior to Stage 2 re-randomization. |
| Change in the NPI Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 8 and Day 22 and From Day 36 (Stage 2 Baseline) to Day 43 and Day 57 | Day 1 (Stage 1 Baseline); Days 8 and 22; Day 36 (Stage 2 Baseline); Days 43 and 57 | 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 was designed to collect information on the behavioral aspects of agitation/aggression in participants with probable AD and clinically meaningful agitation secondary to AD. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, marked. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. A higher score represents worsening symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score. |
| Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70 | 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 participant is 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 is defined as the last non-missing assessment prior to Stage 1 randomization. |
| Number of Participants With the Indicated Response on the mADCS-CGIC Scale Agitation Domain at Day 70 Compared to Their Response at Day 36 (Stage 2 Baseline) | Day 36 (Stage 2 Baseline); Day 70 | 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 participant is 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. For placebo non-responders re-randomized to AVP-923 or placebo at Stage 2, Baseline is defined as the last non-missing assessment prior to Stage 2 re-randomization. |
| Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70 | The PGI-C uses a 7-point scale to assess treatment response and to rate the global impression of clinical change in a participant's agitation. The participant is asked to rate their impression of change from Baseline as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; 7, very much worse. Baseline is defined as the last non-missing assessment prior to Stage 1 randomization. |
| Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use | up to Week 10 | Concomitant medications (CMs) are defined as non-study medications with a start date on or before the final study visit, and that were either ongoing at the end of the study or had a stop date on or after the date of first dose of study drug. Drugs for the treatment of AD (e.g., donepezil, rivastigmine, galantamine, memantine) were allowed when administered at stable dose for at least 2 months prior to randomization. Concomitant use of the following medications was allowed, provided the participant had been on a stable dose for at least 1 month prior to randomization and remained stable throughout the study: medications for agitation secondary to AD; medications for nighttime management of insomnia or behavioral disturbances that included short-acting benzodiazepines, a low dose of alprazolam up to 0.5 milligrams (mg)/day, and a low dose of trazodone up to 50 mg/day; hypnotics for the treatment of insomnia; and certain classes of antidepressants. |
| Number of Participants Using Rescue Medications | up to Week 10 | Participants were allowed to receive oral lorazepam as rescue medication for the short-term treatment of symptoms of agitation, if deemed necessary by the investigator. Lorazepam was to be administered at doses up to 1.5 mg/day, and dosing was not to exceed 3 days in any 7-day period. |
| Change in the Mini-Mental State Examination (MMSE) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline), as Analyzed by the Specified SPCD Methodology | Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70 | The MMSE is a brief test that is used to screen for cognitive impairment. The MMSE scale comprises 11 questions or simple tasks concerning orientation, memory, attention, and language to evaluate the participant's cognitive state. The anchor values are not consistent for each task. The MMSE total score is calculated by summing the item scores across all 11 tasks. A participant's total possible MMSE score ranges from 0 to 30 points. Higher scores indicate milder cognitive impairment. Change from Baseline is calculated as the post-Baseline score minus the Baseline score. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AVP-923 Participants received oral AVP-923 during Stage 1 for 5 consecutive weeks. Participants received AVP-923-20 once daily (QD) in the morning and placebo in the evening (to maintain the blind) during the first week of Stage 1 (Days 1 to 7), AVP-923-20 twice a day (BID) during the next 2 consecutive weeks (Days 8 to 21), and AVP-923-30 BID during the final 2 weeks of Stage 1 (Days 22 to 35). | 93 |
| Placebo Participants received matching oral placebo during Stage 1 for 5 consecutive weeks. | 125 |
| Total | 218 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Stage 1 (5 Weeks) | Adverse Event | 5 | 3 | 0 | 0 | 0 |
| Stage 1 (5 Weeks) | Advised Not to Take Study Medication | 1 | 0 | 0 | 0 | 0 |
| Stage 1 (5 Weeks) | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 |
| Stage 1 (5 Weeks) | Protocol Violation | 2 | 3 | 0 | 0 | 0 |
| Stage 1 (5 Weeks) | Withdrawal by Parent/Guardian | 0 | 2 | 0 | 0 | 0 |
| Stage 1 (5 Weeks) | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 |
| Stage 2 (5 Weeks) | Adverse Event | 0 | 0 | 1 | 2 | 1 |
| Stage 2 (5 Weeks) | Unable to Return to Site: Rehabilitation | 0 | 0 | 1 | 0 | 0 |
| Stage 2 (5 Weeks) | Withdrawal by Subject | 0 | 0 | 1 | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | AVP-923 |
|---|---|---|---|
| Age, Continuous | 77.6 years STANDARD_DEVIATION 7.19 | 77.7 years STANDARD_DEVIATION 7.53 | 77.8 years STANDARD_DEVIATION 8.01 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 11 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 116 Participants | 200 Participants | 84 Participants |
| Sex: Female, Male Female | 74 Participants | 126 Participants | 52 Participants |
| Sex: Female, Male Male | 51 Participants | 92 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 93 | 0 / 59 | 0 / 68 |
| other Total, other adverse events | 24 / 93 | 12 / 59 | 17 / 68 |
| serious Total, serious adverse events | 9 / 93 | 3 / 59 | 6 / 68 |
Outcome results
Primary
Change in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
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 was 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, marked. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. A higher score represents worsening symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score. Data are reported for only those participants contributing data to the analysis.
Time frame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
Population: Stage 1 modified Intent-to-Treat (mITT) Population: all participants randomized in Stage 1 who had at least one post-Baseline NPI agitation/aggression score in Stage 1. Stage 2 mITT Population: all placebo non-responders from Stage 1 who were re-randomized in Stage 2 and had at least one post-Week 4 NPI agitation/aggression score in Stage 2
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36 | -1.7 score on a scale | Standard Deviation 3.1 |
| Placebo | Change in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70 | -0.8 score on a scale | Standard Deviation 3.59 |
| AVP-923 | Change in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36 | -3.3 score on a scale | Standard Deviation 2.98 |
| AVP-923 | Change in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70 | -2.0 score on a scale | Standard Deviation 3.19 |
p-value: <=0.001ANCOVA
Secondary
Change in the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
The ADCS-ADL inventory measures basic activities of daily living such as dressing, conversation, eating, bathing, and grooming. The 19-item version, covering mainly basic ADL, is used to assess participants with more severe disabilities. The ADCS-ADL uses a scale from 0 to 54. Lower scores indicate declining ability. Change from Baseline is calculated as the post-Baseline value minus the Baseline value.
Time frame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
Population: Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36 | -0.8 score on a scale | Standard Deviation 3.89 |
| Placebo | Change in the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70 | -0.6 score on a scale | Standard Deviation 3.45 |
| AVP-923 | Change in the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36 | -0.9 score on a scale | Standard Deviation 4.27 |
| AVP-923 | Change in the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70 | -2.0 score on a scale | Standard Deviation 4.64 |
p-value: 0.163ANCOVA
Secondary
Change in the Caregiver Strain Index (CSI) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
The CSI is a 13-question tool that is used to measure strain related to care provision and to identify families with potential caregiving concerns. There is at least one item for each of the following major domains: Employment, Financial, Physical, Social, and Time. A 0 (No) to 1 (Yes) scale is used for each of the 13 questions; thus the total score ranges from 0 to 13. Higher scores signify higher stress levels. Positive responses to 7 or more items on the index indicate a greater level of strain. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.
Time frame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
Population: Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in the Caregiver Strain Index (CSI) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36 | -0.6 score on a scale | Standard Deviation 2.06 |
| Placebo | Change in the Caregiver Strain Index (CSI) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70 | 0.1 score on a scale | Standard Deviation 1.88 |
| AVP-923 | Change in the Caregiver Strain Index (CSI) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36 | -1.2 score on a scale | Standard Deviation 2.37 |
| AVP-923 | Change in the Caregiver Strain Index (CSI) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70 | -0.2 score on a scale | Standard Deviation 1.62 |
p-value: 0.05ANCOVA
Secondary
Change in the Cornell Scale for Depression in Dementia (CSDD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
The CSDD is a 19-item interview specifically developed to assess the signs and symptoms of major depression in participants with dementia. Each of the 19 items is rated for severity on a scale of 0 to 2 (0, absent; 1, mild or intermittent; 2, severe). The total score is calculated as the sum of the item scores and thus ranges from 0 to 38. Higher scores signify more severe depression. Scores above 10 indicate probable major depression. Scores above 18 indicate definite major depression. Scores below 6, as a rule, are associated with the absence of significant depressive symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.
Time frame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
Population: Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in the Cornell Scale for Depression in Dementia (CSDD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36 | 0.6 score on a scale | Standard Deviation 3.84 |
| Placebo | Change in the Cornell Scale for Depression in Dementia (CSDD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70 | -0.7 score on a scale | Standard Deviation 2.58 |
| AVP-923 | Change in the Cornell Scale for Depression in Dementia (CSDD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36 | -1.0 score on a scale | Standard Deviation 3.43 |
| AVP-923 | Change in the Cornell Scale for Depression in Dementia (CSDD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70 | -0.9 score on a scale | Standard Deviation 2.93 |
p-value: 0.02ANCOVA
Secondary
Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and 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. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. A higher score represents worsening symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score. Sleep/nighttime behavior disorders = S/NB disorders.
Time frame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
Population: Stage 1 and Stage 2 mITT Population. Data are reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70, Delusions | -0.7 score on a scale | Standard Deviation 3.09 |
| Placebo | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36, Apathy/indifference | -0.5 score on a scale | Standard Deviation 3.69 |
| Placebo | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70, Hallucinations | -0.4 score on a scale | Standard Deviation 1.6 |
| Placebo | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36, Hallucinations | -0.1 score on a scale | Standard Deviation 1.68 |
| Placebo | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70, Depression/dysphoria | 0.2 score on a scale | Standard Deviation 2.36 |
| Placebo | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36, Disinhibition | -0.7 score on a scale | Standard Deviation 3.04 |
| Placebo | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70, Anxiety | -0.3 score on a scale | Standard Deviation 2.89 |
| Placebo | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36, Anxiety | -1.2 score on a scale | Standard Deviation 3.69 |
| Placebo | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70, Euphoria/elation | -0.0 score on a scale | Standard Deviation 1.25 |
| Placebo | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36, Irritability/lability | -1.2 score on a scale | Standard Deviation 3.23 |
| Placebo | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70, Apathy/indifference | 0.4 score on a scale | Standard Deviation 1.96 |
| Placebo | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36, Delusions | -0.6 score on a scale | Standard Deviation 2.93 |
| Placebo | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70, Disinhibition | -0.8 score on a scale | Standard Deviation 2.51 |
| Placebo | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36, Aberrant motor behavior | -0.4 score on a scale | Standard Deviation 3.95 |
| Placebo | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70, Irritability/lability | -0.7 score on a scale | Standard Deviation 3.71 |
| Placebo | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36, Euphoria/elation | -0.1 score on a scale | Standard Deviation 1.27 |
| Placebo | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70, Aberrant motor behavior | 0.4 score on a scale | Standard Deviation 3.15 |
| Placebo | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36, S/NB disorders | -0.1 score on a scale | Standard Deviation 2.5 |
| Placebo | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70, S/NB disorders | -0.1 score on a scale | Standard Deviation 2.04 |
| Placebo | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36, Appetite/eating changes | -1.2 score on a scale | Standard Deviation 3.25 |
| Placebo | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70, Appetite/eating changes | 0.4 score on a scale | Standard Deviation 2.28 |
| Placebo | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36, Depression/dysphoria | -1.0 score on a scale | Standard Deviation 2.89 |
| AVP-923 | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70, Appetite/eating changes | 0.1 score on a scale | Standard Deviation 2.73 |
| AVP-923 | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36, Delusions | -0.8 score on a scale | Standard Deviation 2.89 |
| AVP-923 | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36, Hallucinations | 0.2 score on a scale | Standard Deviation 1.76 |
| AVP-923 | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36, Depression/dysphoria | -0.9 score on a scale | Standard Deviation 2.49 |
| AVP-923 | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36, Anxiety | -0.6 score on a scale | Standard Deviation 3.21 |
| AVP-923 | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36, Euphoria/elation | -0.3 score on a scale | Standard Deviation 1.85 |
| AVP-923 | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36, Apathy/indifference | -0.9 score on a scale | Standard Deviation 4.11 |
| AVP-923 | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36, Disinhibition | -0.9 score on a scale | Standard Deviation 3.46 |
| AVP-923 | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36, Irritability/lability | -2.2 score on a scale | Standard Deviation 4.08 |
| AVP-923 | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36, Aberrant motor behavior | -1.2 score on a scale | Standard Deviation 3.98 |
| AVP-923 | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36, Appetite/eating changes | -1.2 score on a scale | Standard Deviation 3.68 |
| AVP-923 | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70, Delusions | 0.1 score on a scale | Standard Deviation 3.17 |
| AVP-923 | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70, Hallucinations | -0.1 score on a scale | Standard Deviation 2.03 |
| AVP-923 | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70, Depression/dysphoria | 0.2 score on a scale | Standard Deviation 2.2 |
| AVP-923 | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70, Anxiety | -1.0 score on a scale | Standard Deviation 2.76 |
| AVP-923 | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70, Euphoria/elation | -0.2 score on a scale | Standard Deviation 0.95 |
| AVP-923 | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70, Apathy/indifference | -0.5 score on a scale | Standard Deviation 3.43 |
| AVP-923 | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70, Disinhibition | -0.8 score on a scale | Standard Deviation 2.67 |
| AVP-923 | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70, Irritability/lability | -1.0 score on a scale | Standard Deviation 3.4 |
| AVP-923 | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70, Aberrant motor behavior | -0.8 score on a scale | Standard Deviation 2.52 |
| AVP-923 | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70, S/NB disorders | 0.0 score on a scale | Standard Deviation 2.46 |
| AVP-923 | Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36, S/NB disorders | -1.0 score on a scale | Standard Deviation 3.82 |
p-value: 0.444ANCOVA
p-value: 0.861ANCOVA
p-value: 0.749ANCOVA
p-value: 0.416ANCOVA
p-value: 0.287ANCOVA
p-value: 0.191ANCOVA
p-value: 0.271ANCOVA
p-value: 0.029ANCOVA
p-value: 0.027ANCOVA
p-value: 0.274ANCOVA
p-value: 0.513ANCOVA
Secondary
Change in the Mini-Mental State Examination (MMSE) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline), as Analyzed by the Specified SPCD Methodology
The MMSE is a brief test that is used to screen for cognitive impairment. The MMSE scale comprises 11 questions or simple tasks concerning orientation, memory, attention, and language to evaluate the participant's cognitive state. The anchor values are not consistent for each task. The MMSE total score is calculated by summing the item scores across all 11 tasks. A participant's total possible MMSE score ranges from 0 to 30 points. Higher scores indicate milder cognitive impairment. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.
Time frame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
Population: Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in the Mini-Mental State Examination (MMSE) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline), as Analyzed by the Specified SPCD Methodology | Day 36 | -0.3 score on a scale | Standard Deviation 2.77 |
| Placebo | Change in the Mini-Mental State Examination (MMSE) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline), as Analyzed by the Specified SPCD Methodology | Day 70 | -0.5 score on a scale | Standard Deviation 2.53 |
| AVP-923 | Change in the Mini-Mental State Examination (MMSE) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline), as Analyzed by the Specified SPCD Methodology | Day 36 | 0.2 score on a scale | Standard Deviation 3.02 |
| AVP-923 | Change in the Mini-Mental State Examination (MMSE) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline), as Analyzed by the Specified SPCD Methodology | Day 70 | 0.3 score on a scale | Standard Deviation 2.76 |
p-value: 0.053ANCOVA
Secondary
Change in the NPI Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 8 and Day 22 and From Day 36 (Stage 2 Baseline) to Day 43 and Day 57
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 was designed to collect information on the behavioral aspects of agitation/aggression in participants with probable AD and clinically meaningful agitation secondary to AD. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, marked. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. A higher score represents worsening symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.
Time frame: Day 1 (Stage 1 Baseline); Days 8 and 22; Day 36 (Stage 2 Baseline); Days 43 and 57
Population: Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in the NPI Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 8 and Day 22 and From Day 36 (Stage 2 Baseline) to Day 43 and Day 57 | Day 8 | -1.4 score on a scale | Standard Deviation 2.73 |
| Placebo | Change in the NPI Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 8 and Day 22 and From Day 36 (Stage 2 Baseline) to Day 43 and Day 57 | Day 22 | -1.6 score on a scale | Standard Deviation 2.86 |
| Placebo | Change in the NPI Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 8 and Day 22 and From Day 36 (Stage 2 Baseline) to Day 43 and Day 57 | Day 43 | -1.3 score on a scale | Standard Deviation 2.92 |
| Placebo | Change in the NPI Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 8 and Day 22 and From Day 36 (Stage 2 Baseline) to Day 43 and Day 57 | Day 57 | -1.3 score on a scale | Standard Deviation 2.86 |
| AVP-923 | Change in the NPI Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 8 and Day 22 and From Day 36 (Stage 2 Baseline) to Day 43 and Day 57 | Day 57 | -1.2 score on a scale | Standard Deviation 3.12 |
| AVP-923 | Change in the NPI Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 8 and Day 22 and From Day 36 (Stage 2 Baseline) to Day 43 and Day 57 | Day 8 | -2.2 score on a scale | Standard Deviation 2.93 |
| AVP-923 | Change in the NPI Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 8 and Day 22 and From Day 36 (Stage 2 Baseline) to Day 43 and Day 57 | Day 43 | -0.5 score on a scale | Standard Deviation 2.31 |
| AVP-923 | Change in the NPI Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 8 and Day 22 and From Day 36 (Stage 2 Baseline) to Day 43 and Day 57 | Day 22 | -2.7 score on a scale | Standard Deviation 3.18 |
p-value: 0.279ANCOVA
Secondary
Change in the NPI-CDS for the Agitation/Aggression Domain From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. For the Agitation/Aggression domain, the caregiver is asked to rate how emotionally distressing they find the symptom behavior on the following scale: 0, not at all; 1, minimally; 2, mildly; 3, moderately; 4, severely; 5, very severely or extremely. A higher score represents increased distress. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.
Time frame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
Population: Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in the NPI-CDS for the Agitation/Aggression Domain From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36 | -0.6 score on a scale | Standard Deviation 1.32 |
| Placebo | Change in the NPI-CDS for the Agitation/Aggression Domain From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70 | -0.7 score on a scale | Standard Deviation 1.38 |
| AVP-923 | Change in the NPI-CDS for the Agitation/Aggression Domain From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36 | -1.4 score on a scale | Standard Deviation 1.54 |
| AVP-923 | Change in the NPI-CDS for the Agitation/Aggression Domain From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70 | -0.5 score on a scale | Standard Deviation 1.44 |
p-value: 0.01ANCOVA
Secondary
Change in the NPI-CDS NPI4A Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. For the NPI4A NPI-CDS score, the caregiver is asked to rate how emotionally distressing they find the symptom behavior (for the Agitation/Aggression, Irritability/Lability, Anxiety, and Aberrant Motor Behavior domains) on the following scale: 0, not at all; 1, minimally; 2, mildly; 3, moderately; 4, severely; 5, very severely or extremely. The NPI4A NPI-CDS score ranges from 0 to 20. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.
Time frame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
Population: Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in the NPI-CDS NPI4A Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36 | -1.7 score on a scale | Standard Deviation 3.34 |
| Placebo | Change in the NPI-CDS NPI4A Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70 | -1.0 score on a scale | Standard Deviation 3.51 |
| AVP-923 | Change in the NPI-CDS NPI4A Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36 | -3.3 score on a scale | Standard Deviation 3.84 |
| AVP-923 | Change in the NPI-CDS NPI4A Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70 | -1.5 score on a scale | Standard Deviation 2.7 |
p-value: 0.008ANCOVA
Secondary
Change in the NPI-CDS NPI4D Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. For the NPI4D NPI-CDS score, the caregiver is asked to rate how emotionally distressing they find the symptom behavior (for the Agitation/Aggression, Irritability/Lability, Disinhibition, and Aberrant Motor Behavior domains) on the following scale: 0, not at all; 1, minimally; 2, mildly; 3, moderately; 4, severely; 5, very severely or extremely. The NPI4D NPI-CDS score ranges from 0 to 20. A higher score represents increased distress. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.
Time frame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
Population: Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in the NPI-CDS NPI4D Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36 | -1.5 score on a scale | Standard Deviation 3.39 |
| Placebo | Change in the NPI-CDS NPI4D Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70 | -1.2 score on a scale | Standard Deviation 3.08 |
| AVP-923 | Change in the NPI-CDS NPI4D Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36 | -3.3 score on a scale | Standard Deviation 4.11 |
| AVP-923 | Change in the NPI-CDS NPI4D Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70 | -1.8 score on a scale | Standard Deviation 3.12 |
p-value: 0.002ANCOVA
Secondary
Change in the Quality of Life-Alzheimer's Disease (QoL-AD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
The QoL-AD is a brief, 13-item measure designed specifically to obtain a rating of the participant's quality of life (QoL) from both the participant and the caregiver. It uses simple and straightforward language and responses and includes assessments of the individual's relationships with friends and family, concerns about finances, physical condition, mood, and an overall assessment of life quality. Caregivers complete the measure as a questionnaire about the participants' QoL, whereas participants complete it in interview format about their own QoL. Each of the 13 items is rated on a 4-point scale, with 1 indicating a poor QoL and 4 indicating an excellent QoL. Total scores range from 13 to 52, with a higher score indicating a better QoL. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.
Time frame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
Population: Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in the Quality of Life-Alzheimer's Disease (QoL-AD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36, Cargiver | 0.3 score on a scale | Standard Deviation 4.66 |
| Placebo | Change in the Quality of Life-Alzheimer's Disease (QoL-AD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70, Caregiver | 0.9 score on a scale | Standard Deviation 4.27 |
| Placebo | Change in the Quality of Life-Alzheimer's Disease (QoL-AD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36, Participant | -0.0 score on a scale | Standard Deviation 5.18 |
| Placebo | Change in the Quality of Life-Alzheimer's Disease (QoL-AD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70, Participant | 0.7 score on a scale | Standard Deviation 4.26 |
| AVP-923 | Change in the Quality of Life-Alzheimer's Disease (QoL-AD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70, Participant | 1.5 score on a scale | Standard Deviation 5.06 |
| AVP-923 | Change in the Quality of Life-Alzheimer's Disease (QoL-AD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36, Cargiver | 0.4 score on a scale | Standard Deviation 4.28 |
| AVP-923 | Change in the Quality of Life-Alzheimer's Disease (QoL-AD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36, Participant | 1.3 score on a scale | Standard Deviation 6.12 |
| AVP-923 | Change in the Quality of Life-Alzheimer's Disease (QoL-AD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70, Caregiver | -0.3 score on a scale | Standard Deviation 3.93 |
p-value: 0.469ANCOVA
p-value: 0.159ANCOVA
Secondary
Change in the Sum of the Agitation/Aggression, Irritability/Lability, Anxiety, and Aberrant Motor Behavior NPI Domain (NPI4A) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and 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. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. The NPI4A score is the sum of the Agitation/Aggression, Irritability/Lability, Anxiety, and Aberrant Motor Behavior domain scores, and thus ranges from 4 to 48. A higher score represents worsening symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.
Time frame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
Population: Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in the Sum of the Agitation/Aggression, Irritability/Lability, Anxiety, and Aberrant Motor Behavior NPI Domain (NPI4A) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36 | -4.5 score on a scale | Standard Deviation 8.53 |
| Placebo | Change in the Sum of the Agitation/Aggression, Irritability/Lability, Anxiety, and Aberrant Motor Behavior NPI Domain (NPI4A) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70 | -1.4 score on a scale | Standard Deviation 7.94 |
| AVP-923 | Change in the Sum of the Agitation/Aggression, Irritability/Lability, Anxiety, and Aberrant Motor Behavior NPI Domain (NPI4A) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36 | -7.3 score on a scale | Standard Deviation 9.08 |
| AVP-923 | Change in the Sum of the Agitation/Aggression, Irritability/Lability, Anxiety, and Aberrant Motor Behavior NPI Domain (NPI4A) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70 | -4.8 score on a scale | Standard Deviation 7.05 |
p-value: 0.001ANCOVA
Secondary
Change in the Sum of the Agitation/Aggression, Irritability/Lability, Disinhibition, and Aberrant Motor Behavior NPI Domain (NPI4D) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and 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. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. The NPI4D score is the sum of the Agitation/Aggression, Irritability/Lability, Disinhibition, and Aberrant Motor Behavior domain scores, and thus ranges from 4 to 48. A higher score represents worsening symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.
Time frame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
Population: Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in the Sum of the Agitation/Aggression, Irritability/Lability, Disinhibition, and Aberrant Motor Behavior NPI Domain (NPI4D) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36 | -4.0 score on a scale | Standard Deviation 8.24 |
| Placebo | Change in the Sum of the Agitation/Aggression, Irritability/Lability, Disinhibition, and Aberrant Motor Behavior NPI Domain (NPI4D) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70 | -1.9 score on a scale | Standard Deviation 7.65 |
| AVP-923 | Change in the Sum of the Agitation/Aggression, Irritability/Lability, Disinhibition, and Aberrant Motor Behavior NPI Domain (NPI4D) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36 | -7.6 score on a scale | Standard Deviation 9.08 |
| AVP-923 | Change in the Sum of the Agitation/Aggression, Irritability/Lability, Disinhibition, and Aberrant Motor Behavior NPI Domain (NPI4D) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70 | -4.6 score on a scale | Standard Deviation 7.31 |
p-value: <=0.001ANCOVA
Secondary
Change in the Total Neuropsychiatric Inventory-Caregiver Distress Score (NPI-CDS) From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. For each domain, the caregiver is asked to rate how emotionally distressing they find the symptom behavior on the following scale: 0, not at all; 1, minimally; 2, mildly; 3, moderately; 4, severely; 5, very severely or extremely. The total NPI-CDS score is calculated as the sum of all 12 domain scores and thus ranges from 0 to 60. A higher score represents increased distress. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.
Time frame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
Population: Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in the Total Neuropsychiatric Inventory-Caregiver Distress Score (NPI-CDS) From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36 | -3.6 score on a scale | Standard Deviation 6.64 |
| Placebo | Change in the Total Neuropsychiatric Inventory-Caregiver Distress Score (NPI-CDS) From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70 | -2.0 score on a scale | Standard Deviation 5.74 |
| AVP-923 | Change in the Total Neuropsychiatric Inventory-Caregiver Distress Score (NPI-CDS) From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36 | -6.6 score on a scale | Standard Deviation 7.81 |
| AVP-923 | Change in the Total Neuropsychiatric Inventory-Caregiver Distress Score (NPI-CDS) From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70 | -2.6 score on a scale | Standard Deviation 5.52 |
p-value: 0.014ANCOVA
Secondary
Change in the Total NPI Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and 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. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. The total score is calculated as a sum of all 12 domain scores and thus ranges from 12 to 144. A higher score represents worsening symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.
Time frame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
Population: Stage 1 and Stage 2 mITT Population. Data are reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in the Total NPI Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36 | -8.5 score on a scale | Standard Deviation 14.35 |
| Placebo | Change in the Total NPI Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70 | -2.5 score on a scale | Standard Deviation 11.82 |
| AVP-923 | Change in the Total NPI Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 36 | -13.5 score on a scale | Standard Deviation 17.48 |
| AVP-923 | Change in the Total NPI Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 | Day 70 | -6.0 score on a scale | Standard Deviation 2.48 |
p-value: 0.014ANCOVA
Secondary
Number of Participants Using Rescue Medications
Participants were allowed to receive oral lorazepam as rescue medication for the short-term treatment of symptoms of agitation, if deemed necessary by the investigator. Lorazepam was to be administered at doses up to 1.5 mg/day, and dosing was not to exceed 3 days in any 7-day period.
Time frame: up to Week 10
Population: mITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants Using Rescue Medications | Day 43 (Visit 5) | 2 participants |
| Placebo | Number of Participants Using Rescue Medications | Day 57 (Visit 6) | 1 participants |
| Placebo | Number of Participants Using Rescue Medications | Day 70 (Visit 70) | 2 participants |
| Placebo | Number of Participants Using Rescue Medications | Day 22 (Visit 3) | 3 participants |
| Placebo | Number of Participants Using Rescue Medications | Overall | 5 participants |
| Placebo | Number of Participants Using Rescue Medications | Day 36 (Visit 4) | 5 participants |
| Placebo | Number of Participants Using Rescue Medications | Day 8 (Visit 2) | 0 participants |
| AVP-923 | Number of Participants Using Rescue Medications | Overall | 11 participants |
| AVP-923 | Number of Participants Using Rescue Medications | Day 43 (Visit 5) | 3 participants |
| AVP-923 | Number of Participants Using Rescue Medications | Day 8 (Visit 2) | 3 participants |
| AVP-923 | Number of Participants Using Rescue Medications | Day 36 (Visit 4) | 3 participants |
| AVP-923 | Number of Participants Using Rescue Medications | Day 57 (Visit 6) | 3 participants |
| AVP-923 | Number of Participants Using Rescue Medications | Day 22 (Visit 3) | 3 participants |
| AVP-923 | Number of Participants Using Rescue Medications | Day 70 (Visit 70) | 3 participants |
| Placebo in Stage 1/Placebo in Stage 2 | Number of Participants Using Rescue Medications | Day 22 (Visit 3) | 3 participants |
| Placebo in Stage 1/Placebo in Stage 2 | Number of Participants Using Rescue Medications | Day 57 (Visit 6) | 4 participants |
| Placebo in Stage 1/Placebo in Stage 2 | Number of Participants Using Rescue Medications | Overall | 7 participants |
| Placebo in Stage 1/Placebo in Stage 2 | Number of Participants Using Rescue Medications | Day 8 (Visit 2) | 1 participants |
| Placebo in Stage 1/Placebo in Stage 2 | Number of Participants Using Rescue Medications | Day 70 (Visit 70) | 3 participants |
| Placebo in Stage 1/Placebo in Stage 2 | Number of Participants Using Rescue Medications | Day 36 (Visit 4) | 3 participants |
| Placebo in Stage 1/Placebo in Stage 2 | Number of Participants Using Rescue Medications | Day 43 (Visit 5) | 5 participants |
Secondary
Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline)
The PGI-C uses a 7-point scale to assess treatment response and to rate the global impression of clinical change in a participant's agitation. The participant is asked to rate their impression of change from Baseline as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; 7, very much worse. Baseline is defined as the last non-missing assessment prior to Stage 1 randomization.
Time frame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
Population: Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, Very much improved | 2 participants |
| Placebo | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, Much improved | 23 participants |
| Placebo | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, Minimally improved | 30 participants |
| Placebo | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, No change | 40 participants |
| Placebo | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, Minimally worse | 23 participants |
| Placebo | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, Much worse | 4 participants |
| Placebo | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, Very much worse | 1 participants |
| Placebo | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, Very much improved | 3 participants |
| Placebo | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, Much improved | 4 participants |
| Placebo | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, Minimally improved | 11 participants |
| Placebo | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, No change | 13 participants |
| Placebo | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, Minimally worse | 9 participants |
| Placebo | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, Much worse | 4 participants |
| Placebo | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, Very much worse | 0 participants |
| AVP-923 | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, No change | 10 participants |
| AVP-923 | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, Very much improved | 10 participants |
| AVP-923 | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, Very much improved | 3 participants |
| AVP-923 | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, Much improved | 24 participants |
| AVP-923 | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, Much worse | 2 participants |
| AVP-923 | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, Minimally improved | 20 participants |
| AVP-923 | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, Much improved | 10 participants |
| AVP-923 | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, No change | 20 participants |
| AVP-923 | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, Minimally worse | 4 participants |
| AVP-923 | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, Minimally worse | 13 participants |
| AVP-923 | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, Minimally improved | 14 participants |
| AVP-923 | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, Much worse | 1 participants |
| AVP-923 | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, Very much worse | 0 participants |
| AVP-923 | Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, Very much worse | 0 participants |
p-value: 0.00295% CI: [1.31, 3.55]ANCOVA
p-value: 0.03195% CI: [1.08, 5]ANCOVA
Secondary
Number of Participants With the Indicated Categorical Response on the PGI-C for the Caregiver Domain at Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline)
The PGI-C uses a 7-point scale to assess treatment response and to rate the global impression of clinical change in a participant's agitation. The participant is asked to rate their impression of change from Baseline as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; 7, very much worse. For placebo non-responders re-randomized to AVP-923 or placebo at Stage 2, Baseline is defined as the last non-missing assessment prior to Stage 2 re-randomization.
Time frame: Day 1 (Stage 1 Baseline); Day 70
Population: Only AVP-923/only placebo ITT Subset
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With the Indicated Categorical Response on the PGI-C for the Caregiver Domain at Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Very much worse | 0 participants |
| Placebo | Number of Participants With the Indicated Categorical Response on the PGI-C for the Caregiver Domain at Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Very much improved | 5 participants |
| Placebo | Number of Participants With the Indicated Categorical Response on the PGI-C for the Caregiver Domain at Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Much improved | 9 participants |
| Placebo | Number of Participants With the Indicated Categorical Response on the PGI-C for the Caregiver Domain at Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Minimally improved | 17 participants |
| Placebo | Number of Participants With the Indicated Categorical Response on the PGI-C for the Caregiver Domain at Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | No change | 14 participants |
| Placebo | Number of Participants With the Indicated Categorical Response on the PGI-C for the Caregiver Domain at Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Minimally worse | 10 participants |
| Placebo | Number of Participants With the Indicated Categorical Response on the PGI-C for the Caregiver Domain at Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Much worse | 4 participants |
| AVP-923 | Number of Participants With the Indicated Categorical Response on the PGI-C for the Caregiver Domain at Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Very much worse | 0 participants |
| AVP-923 | Number of Participants With the Indicated Categorical Response on the PGI-C for the Caregiver Domain at Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | No change | 13 participants |
| AVP-923 | Number of Participants With the Indicated Categorical Response on the PGI-C for the Caregiver Domain at Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Very much improved | 9 participants |
| AVP-923 | Number of Participants With the Indicated Categorical Response on the PGI-C for the Caregiver Domain at Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Much worse | 3 participants |
| AVP-923 | Number of Participants With the Indicated Categorical Response on the PGI-C for the Caregiver Domain at Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Much improved | 26 participants |
| AVP-923 | Number of Participants With the Indicated Categorical Response on the PGI-C for the Caregiver Domain at Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Minimally worse | 5 participants |
| AVP-923 | Number of Participants With the Indicated Categorical Response on the PGI-C for the Caregiver Domain at Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Minimally improved | 25 participants |
p-value: 0.004895% CI: [1.31, 4.46]ANCOVA
Secondary
Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use
Concomitant medications (CMs) are defined as non-study medications with a start date on or before the final study visit, and that were either ongoing at the end of the study or had a stop date on or after the date of first dose of study drug. Drugs for the treatment of AD (e.g., donepezil, rivastigmine, galantamine, memantine) were allowed when administered at stable dose for at least 2 months prior to randomization. Concomitant use of the following medications was allowed, provided the participant had been on a stable dose for at least 1 month prior to randomization and remained stable throughout the study: medications for agitation secondary to AD; medications for nighttime management of insomnia or behavioral disturbances that included short-acting benzodiazepines, a low dose of alprazolam up to 0.5 milligrams (mg)/day, and a low dose of trazodone up to 50 mg/day; hypnotics for the treatment of insomnia; and certain classes of antidepressants.
Time frame: up to Week 10
Population: mITT Population: all participants randomized in Stage 1 who had at least one post-Baseline NPI Agitation/Aggression score in Stage 1, and all placebo non-responders from Stage 1 who are re-randomized in Stage 2 and had at least one post-Week 4 NPI Agitation/Aggression score in Stage 2. Only those participants who took CMs were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use | Any change | 9 participants |
| Placebo | Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use | Dose reduced | 1 participants |
| Placebo | Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use | Dose increased | 0 participants |
| Placebo | Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use | Change in frequency | 1 participants |
| Placebo | Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use | Use discontinued | 2 participants |
| Placebo | Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use | New usage | 7 participants |
| AVP-923 | Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use | New usage | 6 participants |
| AVP-923 | Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use | Any change | 8 participants |
| AVP-923 | Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use | Change in frequency | 1 participants |
| AVP-923 | Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use | Use discontinued | 2 participants |
| AVP-923 | Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use | Dose reduced | 0 participants |
| AVP-923 | Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use | Dose increased | 1 participants |
| Placebo in Stage 1/Placebo in Stage 2 | Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use | Dose reduced | 1 participants |
| Placebo in Stage 1/Placebo in Stage 2 | Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use | Dose increased | 1 participants |
| Placebo in Stage 1/Placebo in Stage 2 | Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use | New usage | 11 participants |
| Placebo in Stage 1/Placebo in Stage 2 | Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use | Change in frequency | 1 participants |
| Placebo in Stage 1/Placebo in Stage 2 | Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use | Any change | 13 participants |
| Placebo in Stage 1/Placebo in Stage 2 | Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use | Use discontinued | 2 participants |
Secondary
Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline)
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 participant is 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 is defined as the last non-missing assessment prior to Stage 1 randomization.
Time frame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
Population: Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, No change | 14 participants |
| Placebo | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, Marked improvement | 1 participants |
| Placebo | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, Moderate improvement | 13 participants |
| Placebo | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, Minimal improvement | 43 participants |
| Placebo | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, No change | 48 participants |
| Placebo | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, Minimal worsening | 12 participants |
| Placebo | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, Moderate worsening | 6 participants |
| Placebo | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, Marked worsening | 0 participants |
| Placebo | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, Marked improvement | 4 participants |
| Placebo | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, Moderate improvement | 5 participants |
| Placebo | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, Minimal improvement | 11 participants |
| Placebo | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, Marked worsening | 9 participants |
| Placebo | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, Moderate worsening | 0 participants |
| Placebo | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, Minimal worsening | 1 participants |
| AVP-923 | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, Minimal improvement | 10 participants |
| AVP-923 | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, No change | 12 participants |
| AVP-923 | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, Marked worsening | 0 participants |
| AVP-923 | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, Marked improvement | 8 participants |
| AVP-923 | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, Moderate worsening | 3 participants |
| AVP-923 | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, Moderate improvement | 22 participants |
| AVP-923 | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, Marked improvement | 4 participants |
| AVP-923 | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, Minimal improvement | 28 participants |
| AVP-923 | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, Marked worsening | 3 participants |
| AVP-923 | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, No change | 22 participants |
| AVP-923 | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, Moderate improvement | 10 participants |
| AVP-923 | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, Minimal worsening | 7 participants |
| AVP-923 | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 70, Minimal worsening | 0 participants |
| AVP-923 | Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) | Day 36, Moderate worsening | 1 participants |
p-value: 0.000195% CI: [1.62, 4.5]ANCOVA
p-value: 0.218495% CI: [0.75, 3.43]ANCOVA
Secondary
Number of Participants With the Indicated Response on the mADCS-CGIC Scale Agitation Domain at Day 70 Compared to Their Response at Day 36 (Stage 2 Baseline)
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 participant is 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. For placebo non-responders re-randomized to AVP-923 or placebo at Stage 2, Baseline is defined as the last non-missing assessment prior to Stage 2 re-randomization.
Time frame: Day 36 (Stage 2 Baseline); Day 70
Population: Stage 2 mITT Population. Data are reported for only those participants contributing data to the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With the Indicated Response on the mADCS-CGIC Scale Agitation Domain at Day 70 Compared to Their Response at Day 36 (Stage 2 Baseline) | Minimal improvement | 8 participants |
| Placebo | Number of Participants With the Indicated Response on the mADCS-CGIC Scale Agitation Domain at Day 70 Compared to Their Response at Day 36 (Stage 2 Baseline) | Marked worsening | 6 participants |
| Placebo | Number of Participants With the Indicated Response on the mADCS-CGIC Scale Agitation Domain at Day 70 Compared to Their Response at Day 36 (Stage 2 Baseline) | Moderate improvement | 2 participants |
| Placebo | Number of Participants With the Indicated Response on the mADCS-CGIC Scale Agitation Domain at Day 70 Compared to Their Response at Day 36 (Stage 2 Baseline) | Moderate worsening | 2 participants |
| Placebo | Number of Participants With the Indicated Response on the mADCS-CGIC Scale Agitation Domain at Day 70 Compared to Their Response at Day 36 (Stage 2 Baseline) | No change | 19 participants |
| Placebo | Number of Participants With the Indicated Response on the mADCS-CGIC Scale Agitation Domain at Day 70 Compared to Their Response at Day 36 (Stage 2 Baseline) | Minimal worsening | 1 participants |
| Placebo | Number of Participants With the Indicated Response on the mADCS-CGIC Scale Agitation Domain at Day 70 Compared to Their Response at Day 36 (Stage 2 Baseline) | Marked improvement | 4 participants |
| AVP-923 | Number of Participants With the Indicated Response on the mADCS-CGIC Scale Agitation Domain at Day 70 Compared to Their Response at Day 36 (Stage 2 Baseline) | Minimal worsening | 0 participants |
| AVP-923 | Number of Participants With the Indicated Response on the mADCS-CGIC Scale Agitation Domain at Day 70 Compared to Their Response at Day 36 (Stage 2 Baseline) | Marked improvement | 0 participants |
| AVP-923 | Number of Participants With the Indicated Response on the mADCS-CGIC Scale Agitation Domain at Day 70 Compared to Their Response at Day 36 (Stage 2 Baseline) | Moderate improvement | 11 participants |
| AVP-923 | Number of Participants With the Indicated Response on the mADCS-CGIC Scale Agitation Domain at Day 70 Compared to Their Response at Day 36 (Stage 2 Baseline) | Minimal improvement | 15 participants |
| AVP-923 | Number of Participants With the Indicated Response on the mADCS-CGIC Scale Agitation Domain at Day 70 Compared to Their Response at Day 36 (Stage 2 Baseline) | No change | 11 participants |
| AVP-923 | Number of Participants With the Indicated Response on the mADCS-CGIC Scale Agitation Domain at Day 70 Compared to Their Response at Day 36 (Stage 2 Baseline) | Marked worsening | 4 participants |
| AVP-923 | Number of Participants With the Indicated Response on the mADCS-CGIC Scale Agitation Domain at Day 70 Compared to Their Response at Day 36 (Stage 2 Baseline) | Moderate worsening | 1 participants |
p-value: 0.026695% CI: [1.11, 5.42]ANCOVA
Secondary
Number of Participants With the Indicated Type of Adverse Event
Treatment-emergent adverse events (TEAEs) are defined as AEs that first occurred, or worsened, after the first dose of study medication and within 30 days after the permanent discontinuation of the study medication (first dose date ≤ AE start date ≤ date of last dose + 30 days)
Time frame: up to Week 10
Population: Safety Population: all randomized participants who received at least one dose of study treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With the Indicated Type of Adverse Event | Participants with ≥ 1 TEAE | 93 Participants |
| Placebo | Number of Participants With the Indicated Type of Adverse Event | Participants with discontinuations due to a TEAE | 8 Participants |
| Placebo | Number of Participants With the Indicated Type of Adverse Event | Participants who died | 0 Participants |
| AVP-923 | Number of Participants With the Indicated Type of Adverse Event | Participants with ≥ 1 TEAE | 55 Participants |
| AVP-923 | Number of Participants With the Indicated Type of Adverse Event | Participants with discontinuations due to a TEAE | 4 Participants |
| AVP-923 | Number of Participants With the Indicated Type of Adverse Event | Participants who died | 0 Participants |