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Participants with agitation secondary to dementia of the Alzheimer's type. The diagnosis of probable Alzheimer's disease (AD) was to be based on the "2011 Diagnostic Guidelines for Alzheimer's Disease" issued by the National Institute on Aging (NIA)-Alzheimer's Association (AA) workgroups.
Eligible participants for this study must have had a diagnosis of probable AD and must have had clinically meaningful agitation secondary to AD.
This was to be a multicenter, randomized, placebo-controlled study, consisting of 12 weeks of treatment.
Approximately 380 participants were to be enrolled at approximately 60 centers in North America.
Study medication was to be administered orally twice-daily from Day 1 through Day 85. Screening was to occur within approximately 4 weeks prior to randomization. Following screening procedures for assessment of inclusion and exclusion criteria, eligible participants were to be randomized into the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Stage 1: Placebo | Placebo Comparator | Participants received matching placebo orally twice daily (BID) for 6 weeks (Days 1-42) in Stage 1. Participants who completed Stage 1 were eligible to Participate in Stage 2. |
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| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Experimental | Participants received AVP-786-18 mg orally once daily (QD) in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 8-42). Participants who completed Stage 1 were eligible to participate in Stage 2. |
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| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Experimental | Participants received AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for 2 weeks (Days 8-21). From Day 22, participants received AVP-786-28 mg orally BID for the remaining 3 weeks. Participants who completed Stage 1 were eligible to participate in Stage 2. |
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| Stage 2: Placebo | Placebo Comparator | Participants who received matching placebo orally BID for 6 consecutive weeks in Stage 1 were re-randomized in Stage 2 to receive the study drug or placebo from Day 43 to Day 85. |
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| Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) to: Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AVP-786 | Drug |
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| Measure | Description | Time Frame |
|---|---|---|
| Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | The CMAI score is used to assess the frequency of manifestations of agitated behaviors in participants. The CMAI consists of 29 agitated behaviors that are rated on a 7-point scale of frequency: 1, never; 2, less than once a week; 3, once or twice a week; 4, several times a week; 5, once or twice a day; 6, several times a day; 7, several times an hour. The CMAI total score ranges from 29 to 203. Higher scores indicate worsening of the condition. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Least Squares Mean Modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC)-Agitation Score at Week 6 and Week 12 | The intent of the ADCS version of the CGIC is to provide a means to reliably assess the global impression of change from Baseline in a clinical trial. The mADCS-CGIC is a modification of the ADCS-CGIC instrument that focuses specifically on agitation. The participants are asked to rate their impression of change from Baseline as: 1, marked improvement; 2, moderate improvement; 3, minimal improvement; 4, no change; 5, minimal worsening; 6, moderate worsening; 7, marked worsening. Baseline was defined as the last non-missing assessment prior to Stage 1 randomization. Treatment effects were estimated at each stage by analysis of covariance (ANCOVA) with fixed effects for treatment, Baseline CMAI Total score, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus [vs] > 6), risk assessments for falls (normal/mild vs moderate/severe), Baseline concomitant use of antipsychotic medications (yes vs no). Missing values were imputed by last observation carried forward (LOCF) within each stage. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Research Site | Phoenix | Arizona | 85032 | United States | ||
| Clinical Research Site |
This study was conducted in 2 stages. 387 participants were randomized to treatment in Stage 1 and all the participants completed Stage 1 and were re-randomized into Stage 2 to compare AVP-786 28 mg, AVP-786 18 mg and placebo in parallel group (PG) design. In Stage 2, participants randomized to active treatment in Stage 1 (AVP-786-18 or AVP-786-28) continued to receive the same treatment and those randomized to placebo in Stage 1 were re-randomized to AVP-786-18, AVP-786-28, or placebo.
Total of 695 participants were screened of these, 308 participants failed screening, 387 participants were randomized out of which 382 participants had at least 1 post baseline efficacy assessment. (Modified Intent-to-Treat { mITT} population).
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| ID | Title | Description |
|---|---|---|
| FG000 | Stage 1: Placebo | Participants received matching placebo orally twice daily (BID) for 6 weeks (Days 1-42) in Stage 1. Participants who completed Stage 1 were eligible to Participate in Stage 2. |
| FG001 | Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Stage 1- (Days 1 to 42) |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 16, 2016 | Dec 13, 2021 |
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Sequential parallel comparison design
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| Experimental |
Participants who received AVP-786-18 mg in Stage 1 continued to receive AVP-786-18 mg orally BID for the 6 weeks (Days 43-85) in Stage 2.. |
|
| Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Experimental | Participants who received AVP-786-28 mg in Stage 1 continued to receive AVP-786-28 mg orally BID for 6 weeks (Days 43-85) in Stage 2 |
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| Experimental: Stage 1: Placebo to: Stage 2: AVP-786-18 d6-DM 18 mg/Q 4.9 mg | Experimental | Participants who were placebo responders or non-responders in Stage 1 received AVP-786-18 for 1 week, orally, QD, followed by AVP-786-18 BID for 2 weeks; followed by AVP-786-28 BID for the last 3 weeks. |
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| Stage 1: Placebo to: Stage 2: AVP-786-28 d6 DM 28 mg/Q 4.9 mg | Experimental | Participants who were placebo responders or non-responders in Stage 1 received AVP-786-28 for 1 week, orally, QD, followed by AVP-786-28 BID for 2 weeks; followed by AVP-786-28 BID for the last 3 weeks. |
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| Placebo | Drug |
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| Stage 1 Week 6; Stage 2 Week 12 |
| Stage 1 and Stage 2: Change From Baseline in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score to Week 6 and Week 12 | The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. The Agitation/Aggression domain is designed to collect information on the behavioral aspects of agitation/aggression in participants with probable Alzheimer's Disease (AD) and clinically meaningful agitation secondary to AD. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, severe. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. Higher scores indicate worsening symptoms. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 |
| Stage 1 and Stage 2: Change From Baseline in the NPI Caregiver Distress Score to Week 6 and Week 12 | The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate caregiver distress. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, marked severe. The total caregiver distress score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. Higher scores indicate worsening symptoms. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 |
| Stage 1 and Stage 2: Change From Baseline in the NPI Aberrant Motor Behavior Domain Score to Week 6 and Week 12 | The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate aberrant motor behavior. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, severe. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. Higher scores indicate worsening of the symptoms. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 |
| Stage 1 and Stage 2: Change From Baseline in the Zarit Burden Interview (ZBI) Score to Week 6 and Week 12 | The ZBI is a 22-item scale used to assess the impact of a participant with dementia and also other illnesses on the caregiver's burden. For each item of the scale, the caregiver indicates how often they feel the burden (never, rarely, sometimes, quite frequently, or nearly always). The score ranges from 0 to 88 and is determined by adding the numbered responses of the individual items. Higher scores indicate greater caregiver distress. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus > 6), risk assessments for falls (normal/mild versus moderate/severe), Baseline concomitant use of antipsychotic medications (yes versus no). Missing values were imputed by LOCF within each stage. | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 |
| Stage 1 and Stage 2: Change From Baseline in the NPI Irritability/Lability Domain Score to Week 6 and Week 12 | The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains, including the irritability/lability domain score. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, severe. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. Higher scores indicate worsening of the symptoms. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 |
| Stage 1 and Stage 2: Change From Baseline in the NPI Total Score to Week 6 and Week 12 | NPI evaluates both frequency and severity of 12 neuropsychiatric disturbances including delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, nighttime behaviors, as well as appetite/eating. Total domain score= frequency x severity and thus ranges from 1 to 12. NPI domain is rated by caregiver for symptom frequency and severity. Frequency is rated as: 1=occasionally, 2=often, 3= frequently, and 4=very frequently. Severity is rated as: 1=mild; 2= moderate, and 3=severe. Frequency and severity rating scales has defined anchor points to enhance reliability of caregiver responses. Caregiver distress is rated for each positive neuropsychiatric symptom using following anchored scores. It is rated as 0=not at all, 1=minimal, 3=moderate, 4=severe, 5=very severe. Total score is calculated by adding the individual Item scores, to yield a possible total scores of 0 to 144. | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 |
| Stage 1 and Stage 2: Change From Baseline in the Clinical Global Impression of Severity of Illness (CGIS)-Agitation Domain Score to Week 6 and Week 12 | The CGIS-Agitation is an observer-rated scale that measures illness severity. CGIS is used to assess the severity of agitation. The CGIS score is rated on a 7-point scale (1 = normal, not at all ill; 7 = among the most extremely ill participants). Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus > 6), risk assessments for falls (normal/mild versus moderate/severe), Baseline concomitant use of antipsychotic medications (yes versus no). Missing values were imputed by LOCF within each stage. | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 |
| Stage 1 and Stage 2: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Rating at Week 6 and Week 12 | The ADCS-CGIC rating scale provides a reliable means to assess change from a Baseline level of global function within the time frame of the trial. ADCS-CGIC-Overall focuses on the clinician's observations of change in the participant's cognitive, functional, and behavioral performance. The ADCS-CGIC-Overall responses (1-7) are rated as: 1 = marked improvement, 2 = moderate improvement, 3 = minimal improvement, 4 = no change, 5 = minimal worsening, 6 = moderate worsening, or 7 = marked worsening. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline CMAI Total score, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus > 6), risk assessments for falls (normal/mild versus moderate/severe), Baseline concomitant use of antipsychotic medications (yes versus no). Missing values were imputed by LOCF within each stage. | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 |
| Stage 1 and Stage 2: Patient Global Impression of Change (PGIC) Score at Week 6 and Week 12 | The PGIC is a 7-point (1-7) scale used to assess treatment response: 1 = very much improved, = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, or 7 = very much worse. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline CMAI Total score, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus > 6), risk assessments for falls (normal/mild versus moderate/severe), Baseline concomitant use of antipsychotic medications (yes vs no). Missing values were imputed by LOCF within each stage. | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 |
| Stage 1 and Stage 2: Change From Baseline in the Dementia Quality of Life (DEMQOL) Score to Week 6 and Week 12 | The DEMQOL scale is used to evaluate health-related QOL in participants with dementia and their caregivers. There are 2 versions of the DEMQOL: a 28-item version (rated by the participant); and a 31-item version (DEMQOL-proxy, rated by the caregiver). Both versions are recommended for evaluating participants (and their caregivers) with mild to moderate dementia. The DEMQOL total score ranges from 28 to 112. The DEMQOL-proxy is used for participants with severe dementia; the total score ranges from 31 to 124. For both versions, higher scores indicate greater QOL. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline, and in the Stage 1 model, Baseline NPI AA (≤ 6 vs > 6), risk assessments for falls (normal/mild vs moderate/severe), Baseline concomitant use of antipsychotic medications (yes vs no). Missing values were imputed by LOCF within each stage. | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 |
| Stage 1 and Stage 2: Change From Baseline in the Cornell Scale for Depression in Dementia (CSDD) Score to Week 6 and Week 12 | The CSDD scale is used to assess signs/symptoms of major depression in participants with dementia. CSDD has 19 items, and each item is rated for severity on the following scale of 0 to 2 (0 =absent, 1= mild/intermittent 2=severe). CSDD score is calculated by summing non-missing scores from each item score. The scale ranges from 0-no depression to 38 maximum depressions. Scores above 10 indicate a probable major depression, above 18 indicate a definite major depression, and below 6 as a rule are associated with the absence of significant depressive symptoms. Higher score indicated maximum depression. | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 |
| Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | The GMHR is a global clinical rating for medical health, designed to quantify in a single number (1 to 4) the severity of general comorbidity in a participant with dementia. The ratings are: 1 = poor; 2 = fair; 3 = good; 4 = excellent to very good. Data was collected for the treatment arm groups as pre-specified in the protocol for this outcome measure. | Baseline; Week 12 |
| Stage 1 and Stage 2: Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score to Week 6 and Week 12 | The ADAS is designed to evaluate the cognitive and non-cognitive behavioral dysfunction characteristics of participants with AD. The cognitive subscale (ADAS-cog) consists of 11 subsets related to memory, praxis, and language. ADAS-cog scores range from 0 to 70. Higher scores indicate greater cognitive impairment. The ADAS-cog is assessed for participants with an Mini-Mental State Examination (MMSE) score of ≥10 at the Baseline Visit. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus > 6), risk assessments for falls (normal/mild versus moderate/severe), Baseline concomitant use of antipsychotic medications (yes vs no). Missing values were imputed by LOCF within each stage. | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 |
| Stage 1: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals | RUD evaluates dementia participants utilization of formal and informal healthcare resources, including hospitalizations and doctor visits, living assistance, and time spent by nonprofessional caregivers. The RUD is administered as a semi-structured interview with the participant's primary caregiver and contains 2 sections; one focusing on caregiver impact (loss of work and leisure time incurred by caregiver) and the other focusing on the participant's use of healthcare resources. Information of caregivers who reported their responsibilities affected their work and who visited healthcare professionals from the interviews during Stage 1 is reported for this outcome measure. Data was collected for the treatment arm groups as pre-specified in the protocol for this outcome measure. | Stage 1: Week 6 |
| Stage 2: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals | RUD evaluates dementia participants utilization of formal and informal healthcare resources, including hospitalizations and doctor visits, living assistance, and time spent by nonprofessional caregivers. The RUD is administered as a semi-structured interview with the participant's primary caregiver and contains 2 sections; one focusing on caregiver impact (loss of work and leisure time incurred by caregiver) and the other focusing on the participant's use of healthcare resources. Information of caregivers who reported their responsibilities affected their work and who visited healthcare professionals from the interviews during Stage 2 is reported for this outcome measure. Data was collected for the treatment arm groups as pre-specified in the protocol for this outcome measure. | Stage 2: Week 12 |
| Stage 1: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | RUD evaluates dementia participants utilization of formal, informal healthcare resources, including hospitalizations, doctor visits, living assistance, time spent by nonprofessional caregivers. Information on hours per day caregiver spent assisting participant from interviews during Stage 1 is reported for this outcome measure, where the following questions (Q), Q1= On typical care day during last 30 days, how much time per day did you assist participant with tasks such as toilet visits, eating, dressing, grooming, walking, bathing? Q2= On typical care day during the last 30 days, how much time per day did you assist participant with tasks as (shopping, food preparation, housekeeping, laundry, transportation, taking medication, managing financial matters?; Q3= On typical care day during last 30 days, how much time per day did you spend supervising (preventing dangerous events)?(Q3). Data is collected for treatment arm groups as pre-specified in protocol for this outcome measure. | Stage 1: Week 6 |
| Stage 2: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | RUD evaluates dementia participants utilization of formal, informal healthcare resources, including hospitalizations, doctor visits, living assistance, time spent by nonprofessional caregivers. Information on hours per day caregiver spent assisting participant from interviews during Stage 1 is reported for this outcome measure, where the following questions (Q), Q1= On typical care day during last 30 days, how much time per day did you assist participant with tasks such as toilet visits, eating, dressing, grooming, walking, bathing? Q2= On typical care day during the last 30 days, how much time per day did you assist participant with tasks as (shopping, food preparation, housekeeping, laundry, transportation, taking medication, managing financial matters?; Q3= On typical care day during last 30 days, how much time per day did you spend supervising (preventing dangerous events)?(Q3). Data is collected for treatment arm groups as pre-specified in protocol for this outcome measure. | Stage 2: Week 12 |
| Stage 1: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant | RUD evaluates dementia participants utilization of formal, informal healthcare resources, including hospitalizations, doctor visits, living assistance, time spent by nonprofessional caregivers. Information on days caregiver spent assisting participant from interviews during Stage 1 is reported for outcome measure, where following questions (Q), Q1= During last 30 days, how many days did you spend providing these (toilet visits, eating, dressing, grooming, walking, bathing) services to participant?; Q2= On typical care day during last 30 days, how much time per day did you assist participant with tasks such as shopping, food preparation, housekeeping, laundry, transportation, taking medication, managing financial matters?; Q3= During last 30 days, how many days did you spend providing these services (supervising) to the participant?. Data is collected for the treatment arm groups as pre-specified in the protocol for this outcome measure. | Stage 1: Week 6 |
| 12-Week Parallel Group: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant | RUD evaluates dementia participants utilization of formal, informal healthcare resources, including hospitalizations, doctor visits, living assistance, time spent by nonprofessional caregivers. Information on days caregiver spent assisting participant from interviews during Stage 1 is reported for outcome measure, where following questions (Q), Q1= During last 30 days, how many days did you spend providing these (toilet visits, eating, dressing, grooming, walking, bathing) services to participant?; Q2= On typical care day during last 30 days, how much time per day did you assist participant with tasks such as shopping, food preparation, housekeeping, laundry, transportation, taking medication, managing financial matters?; Q3= During last 30 days, how many days did you spend providing these services (supervising) to the participant?. Data is collected for the treatment arm groups as pre-specified in the protocol for this outcome measure. | 12-Week Parallel Group: Week 12 |
| Scottsdale |
| Arizona |
| 85254 |
| United States |
| Clinical Research Site | Little Rock | Arkansas | 72209 | United States |
| Clinical Research Site#1 | Irvine | California | 92697 | United States |
| Clinical Research Site#2 | Irvine | California | 92697 | United States |
| Clinical Research Site | Long Beach | California | 90806 | United States |
| Clinical Research Site | Oceanside | California | 92056 | United States |
| Clinical Research Site | Orange | California | 92868 | United States |
| Clinical Research Site#1 | San Diego | California | 92103 | United States |
| Clinical Research Site#2 | San Diego | California | 92103 | United States |
| Clinical Research Site | Santa Ana | California | 92704 | United States |
| Clinical Research Site | Tustin | California | 92780 | United States |
| Clinical Research Site | Denver | Colorado | 80209 | United States |
| Clinical Research Site | Cromwell | Connecticut | 06416 | United States |
| Clinical Research Site | New London | Connecticut | 06320 | United States |
| Clinical Research Site | Norwalk | Connecticut | 06851 | United States |
| Clinical Research Site | Atlantis | Florida | 33462 | United States |
| Clinical Research Site | Boca Raton | Florida | 33428 | United States |
| Clinical Research Site | Brandon | Florida | 33511 | United States |
| Clinical Research Site#1 | Coral Gables | Florida | 33134 | United States |
| Clinical Research Site#2 | Coral Gables | Florida | 33134 | United States |
| Clinical Research Site#3 | Coral Gables | Florida | 33134 | United States |
| Clinical Research Site#1 | Deerfield Beach | Florida | 33064 | United States |
| Clinical Research Site | Doral | Florida | 33166 | United States |
| Clinical Research Site | Hialeah | Florida | 33012 | United States |
| Clinical Research Site#1 | Hialeah | Florida | 33016 | United States |
| Clinical Research Site#2 | Hialeah | Florida | 33016 | United States |
| Clinical Research Site | Jacksonville | Florida | 32256 | United States |
| Clinical Research Site | Kendall | Florida | 33175 | United States |
| Clinical Research Site | Kissimmee | Florida | 34741 | United States |
| Clinical Research Site | Kissimmee | Florida | 34744 | United States |
| Clinical Research Site | Lake Worth | Florida | 33449 | United States |
| Clinical Research Site | Miami | Florida | 33122 | United States |
| Clinical Research Site#1 | Miami | Florida | 33125 | United States |
| Clinical Research Site#2 | Miami | Florida | 33125 | United States |
| Clinical Research Site | Miami | Florida | 33126 | United States |
| Clinical Research Site | Miami | Florida | 33133 | United States |
| Clinical Research Site#1 | Miami | Florida | 33135 | United States |
| Clinical Research Site#2 | Miami | Florida | 33135 | United States |
| Clinical Research Site | Miami | Florida | 33136 | United States |
| Clinical Research Site | Miami | Florida | 33137 | United States |
| Clinical Research Site | Miami | Florida | 33144 | United States |
| Clinical Research Site | Miami | Florida | 33145 | United States |
| Clinical Research Site | Miami | Florida | 33165 | United States |
| Clinical Research Site | Miami | Florida | 33175 | United States |
| Clinical Research Site#2 | Miami | Florida | 33176 | United States |
| Clinical Research Site | Miami | Florida | 33183 | United States |
| Clinical Research Site | Miami | Florida | 33467 | United States |
| Clinical Research Site | Naples | Florida | 34102 | United States |
| Clinical Research Site | Oakland Park | Florida | 33334 | United States |
| Clinical Research Site | Orlando | Florida | 32819 | United States |
| Clinical Research Site | Ormond Beach | Florida | 32174 | United States |
| Clinical Research Site | Palm Beach Gardens | Florida | 33410 | United States |
| Clinical Research Site | Palmetto Bay | Florida | 33157 | United States |
| Clinical Research Site#2 | Pompano Beach | Florida | 33064 | United States |
| Clinical Research Site | Sarasota | Florida | 34243 | United States |
| Clinical Research Site | St. Petersburg | Florida | 33713 | United States |
| Clinical Research Site#1 | Tampa | Florida | 33609 | United States |
| Clinical Research Site#2 | Tampa | Florida | 33609 | United States |
| Clinical Research Site#2 | Tampa | Florida | 33613 | United States |
| Clinical Research Site | Tampa | Florida | 33634 | United States |
| Clinical Research Site | The Villages | Florida | 32162 | United States |
| Clinical Research Site | West Palm Beach | Florida | 33407 | United States |
| Clinical Research Site | Winter Park | Florida | 32789 | United States |
| Clinical Research Site | Atlanta | Georgia | 30342 | United States |
| Clinical Research Site | Newnan | Georgia | 30265 | United States |
| Clinical Research Site | Honolulu | Hawaii | 96817 | United States |
| Clinical Research Site | Schaumburg | Illinois | 60194 | United States |
| Clinical Research Site | Indianapolis | Indiana | 46202 | United States |
| Clinical Research Site | Lenexa | Kansas | 66214 | United States |
| Clinical Research Site | Paducah | Kentucky | 42003 | United States |
| Clinical Research Site | Bedford | Massachusetts | 01730 | United States |
| Clinical Research Site | Quincy | Massachusetts | 02169 | United States |
| Clinical Research Site | Ann Arbor | Michigan | 48105 | United States |
| Clinical Research Site | Paw Paw | Michigan | 49079 | United States |
| Clinical Research Site | Hattiesburg | Mississippi | 39401 | United States |
| Clinical Research Site | Creve Coeur | Missouri | 63141 | United States |
| Clinical Research Site | St Louis | Missouri | 63128 | United States |
| Clinical Research Site | Mount Arlington | New Jersey | 07856 | United States |
| Clinical Research Site | Toms River | New Jersey | 08755 | United States |
| Clinical Research Site | West Long Branch | New Jersey | 07764 | United States |
| Clinical Research Site | Amherst | New York | 14226 | United States |
| Clinical Research Site | Brooklyn | New York | 11229 | United States |
| Clinical Research Site | New York | New York | 10032 | United States |
| Clinical Research Site | New York | New York | 10036 | United States |
| Clinical Research Site | Orangeburg | New York | 10962 | United States |
| Clinical Research Site | Rochester | New York | 14620 | United States |
| Clinical Research Site | Staten Island | New York | 10312 | United States |
| Clinical Research Site | Durham | North Carolina | 27710 | United States |
| Clinical Research Site | Winston-Salem | North Carolina | 27157 | United States |
| Clinical Research Site | Akron | Ohio | 44320 | United States |
| Clinical Research Site | Cincinnati | Ohio | 45219 | United States |
| Clinical Research Site#1 | Columbus | Ohio | 43210 | United States |
| Clinical Research Site#2 | Columbus | Ohio | 43210 | United States |
| Clinical Research Site | Dayton | Ohio | 45459 | United States |
| Clinical Research Site | Westerville | Ohio | 43082 | United States |
| Clinical Research Site | Edmond | Oklahoma | 73012 | United States |
| Clinical Research Site | Oklahoma City | Oklahoma | 73103 | United States |
| Clinical Research Site | Oklahoma City | Oklahoma | 73106 | United States |
| Clinical Research Site | Oklahoma City | Oklahoma | 73112 | United States |
| Clinical Research Site | Moosic | Pennsylvania | 18507 | United States |
| Clinical Research Site | Willow Grove | Pennsylvania | 19090 | United States |
| Clinical Research Site | East Providence | Rhode Island | 02914 | United States |
| Clinical Research Site | Charleston | South Carolina | 29401 | United States |
| Clinical Research Site#2 | Cordova | Tennessee | 38018 | United States |
| Clinical Research Site | Dallas | Texas | 75231 | United States |
| Clinical Research Site | Dallas | Texas | 75390-8898 | United States |
| Clinical Research Site | Irving | Texas | 75062 | United States |
| Clinical Research Site | Mansfield | Texas | 76063 | United States |
| Clinical Research Site | Clinton | Utah | 84015 | United States |
| Clinical Research Site | Woodstock | Vermont | 05091 | United States |
| Clinical Research Site#1 | Tallinn | 11315 | Estonia |
| Clinical Research Site#2 | Tallinn | 11315 | Estonia |
| Clinical Research Site | Tartu | 50406 | Estonia |
| Clinical Research Site | Mittweida | 9648 | Germany |
| Clinical Research Site | Lublin | Lublin Voivodeship | 20-093 | Poland |
| Clinical Research Site | Bydgoszcz | 85-163 | Poland |
| Clinical Research Site | Kielce | 25-411 | Poland |
| Clinical Research Site | Lublin | 20-064 | Poland |
| Clinical Research Site | Poznan | 60-369 | Poland |
| Clinical Research Site | Poznan | 61-853 | Poland |
| Clinical Research Site | Pruszcz Gdański | 83-000 | Poland |
| Clinical Research Site | Siemianowice Śląskie | 41-100 | Poland |
| Clinical Research Site | Torres Vedras | 2560-280 | Portugal |
| Clinical Research Site | Bayamón | 961 | Puerto Rico |
| Clinical Research Site | San Juan | 918 | Puerto Rico |
Participants received AVP-786-18 mg orally once daily (QD) in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 8-42). Participants who completed Stage 1 were eligible to participate in Stage 2. |
| FG002 | Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Participants received AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for 2 weeks (Days 8-21). From Day 22, participants received AVP-786-28 mg orally BID for the remaining 3 weeks. Participants who completed Stage 1 were eligible to participate in Stage 2. |
| FG003 | Stage 2: Placebo | Participants who received matching placebo orally BID for 6 consecutive weeks in Stage 1 were re-randomized in Stage 2 to receive the study drug or placebo from Day 43 to Day 85. |
| FG004 | Stage 1: Placebo to: Stage 2: AVP-786-28 d6-DM 18 mg/Q 4.9 mg | Participants who were placebo responders or non-responders in Stage 1 received AVP-786-18 for 1 week, orally, QD, followed by AVP-786-18 BID for 2 weeks; followed by AVP-786-28 BID for the last 3 weeks.. |
| FG005 | Stage 1: Placebo to: Stage 2: AVP-786-28 d6 DM 28 mg/Q 4.9 mg | Participants who were placebo responders or non-responders in Stage 1 received AVP-786-28 for 1 week, orally, QD, followed by AVP-786-28 BID for 2 weeks; followed by AVP-786-28 BID for the last 3 weeks. |
| FG006 | Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) to: Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Participants who received AVP-786-18 mg in Stage 1 continued to receive AVP-786-18 mg orally BID for the 6 weeks (Days 43-85) in Stage 2. |
| FG007 | Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Participants who received AVP-786-28 mg in Stage 1 continued to receive AVP-786-28 mg orally BID for 6 weeks (Days 43-85) in Stage 2. |
| COMPLETED |
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| NOT COMPLETED |
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| Stage 2- (Days 43 to 85) |
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Baseline data were collected in members of the Stage 1 Modified Intent-to-Treat (mITT) Population, comprised of all participants randomized in the study who had at least one post-Baseline efficacy assessment.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | In Stage 1, participants received matching placebo orally twice daily (BID). |
| BG001 | AVP-786-18 | In Stage 1, participants received AVP-786-18 orally once daily (OD) in the morning and placebo orally OD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for the remaining 5 weeks. In Stage 2, participants continued to receive AVP-786-18 mg orally BID for 6 consecutive weeks. |
| BG002 | AVP-786-28 | In Stage 1, participants received AVP-786-18 mg orally OD in the morning and placebo orally OD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for 2 weeks. From Day 22, participants received AVP-786-28 orally BID for the remaining 3 weeks. In Stage 2, participants continued to receive AVP-786-28 mg orally BID for 6 consecutive weeks. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | The CMAI score is used to assess the frequency of manifestations of agitated behaviors in participants. The CMAI consists of 29 agitated behaviors that are rated on a 7-point scale of frequency: 1, never; 2, less than once a week; 3, once or twice a week; 4, several times a week; 5, once or twice a day; 6, several times a day; 7, several times an hour. The CMAI total score ranges from 29 to 203. Higher scores indicate worsening of the condition. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. | Stage 1 Modified Intent-to-Treat (mITT) Population: all participants randomized in Stage 1 who had at least 1 post-Baseline efficacy assessment. Stage 2 mITT Population: all participants randomized in Stage 2 who had at least 1 efficacy assessment in Stage 2. Data were reported for only those participants contributing data to the analysis. | Posted | Mean | Standard Deviation | units on a scale | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 |
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| Secondary | Least Squares Mean Modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC)-Agitation Score at Week 6 and Week 12 | The intent of the ADCS version of the CGIC is to provide a means to reliably assess the global impression of change from Baseline in a clinical trial. The mADCS-CGIC is a modification of the ADCS-CGIC instrument that focuses specifically on agitation. The participants are asked to rate their impression of change from Baseline as: 1, marked improvement; 2, moderate improvement; 3, minimal improvement; 4, no change; 5, minimal worsening; 6, moderate worsening; 7, marked worsening. Baseline was defined as the last non-missing assessment prior to Stage 1 randomization. Treatment effects were estimated at each stage by analysis of covariance (ANCOVA) with fixed effects for treatment, Baseline CMAI Total score, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus [vs] > 6), risk assessments for falls (normal/mild vs moderate/severe), Baseline concomitant use of antipsychotic medications (yes vs no). Missing values were imputed by last observation carried forward (LOCF) within each stage. | Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis. | Posted | Least Squares Mean | Standard Error | score on a scale | Stage 1 Week 6; Stage 2 Week 12 |
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| Secondary | Stage 1 and Stage 2: Change From Baseline in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score to Week 6 and Week 12 | The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. The Agitation/Aggression domain is designed to collect information on the behavioral aspects of agitation/aggression in participants with probable Alzheimer's Disease (AD) and clinically meaningful agitation secondary to AD. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, severe. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. Higher scores indicate worsening symptoms. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. | Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis. | Posted | Mean | Standard Deviation | units on a scale | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 |
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| Secondary | Stage 1 and Stage 2: Change From Baseline in the NPI Caregiver Distress Score to Week 6 and Week 12 | The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate caregiver distress. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, marked severe. The total caregiver distress score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. Higher scores indicate worsening symptoms. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. | Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis. | Posted | Mean | Standard Deviation | units on a scale | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 |
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| Secondary | Stage 1 and Stage 2: Change From Baseline in the NPI Aberrant Motor Behavior Domain Score to Week 6 and Week 12 | The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate aberrant motor behavior. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, severe. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. Higher scores indicate worsening of the symptoms. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. | Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis. | Posted | Mean | Standard Deviation | units on a scale | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 |
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| Secondary | Stage 1 and Stage 2: Change From Baseline in the Zarit Burden Interview (ZBI) Score to Week 6 and Week 12 | The ZBI is a 22-item scale used to assess the impact of a participant with dementia and also other illnesses on the caregiver's burden. For each item of the scale, the caregiver indicates how often they feel the burden (never, rarely, sometimes, quite frequently, or nearly always). The score ranges from 0 to 88 and is determined by adding the numbered responses of the individual items. Higher scores indicate greater caregiver distress. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus > 6), risk assessments for falls (normal/mild versus moderate/severe), Baseline concomitant use of antipsychotic medications (yes versus no). Missing values were imputed by LOCF within each stage. | Stage 1 and Stage 2 mITT Populations. Overall number of participants analyzed are the number of participants with data available for analysis at given time point. | Posted | Mean | Standard Deviation | units on a scale | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 |
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| Secondary | Stage 1 and Stage 2: Change From Baseline in the NPI Irritability/Lability Domain Score to Week 6 and Week 12 | The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains, including the irritability/lability domain score. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, severe. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. Higher scores indicate worsening of the symptoms. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. | Stage 1 and Stage 2: mITT Populations. Data were reported for only those participants contributing data to the analysis. | Posted | Mean | Standard Deviation | units on a scale | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 |
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| Secondary | Stage 1 and Stage 2: Change From Baseline in the NPI Total Score to Week 6 and Week 12 | NPI evaluates both frequency and severity of 12 neuropsychiatric disturbances including delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, nighttime behaviors, as well as appetite/eating. Total domain score= frequency x severity and thus ranges from 1 to 12. NPI domain is rated by caregiver for symptom frequency and severity. Frequency is rated as: 1=occasionally, 2=often, 3= frequently, and 4=very frequently. Severity is rated as: 1=mild; 2= moderate, and 3=severe. Frequency and severity rating scales has defined anchor points to enhance reliability of caregiver responses. Caregiver distress is rated for each positive neuropsychiatric symptom using following anchored scores. It is rated as 0=not at all, 1=minimal, 3=moderate, 4=severe, 5=very severe. Total score is calculated by adding the individual Item scores, to yield a possible total scores of 0 to 144. | Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis. | Posted | Mean | Standard Deviation | units on a scale | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 |
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| Secondary | Stage 1 and Stage 2: Change From Baseline in the Clinical Global Impression of Severity of Illness (CGIS)-Agitation Domain Score to Week 6 and Week 12 | The CGIS-Agitation is an observer-rated scale that measures illness severity. CGIS is used to assess the severity of agitation. The CGIS score is rated on a 7-point scale (1 = normal, not at all ill; 7 = among the most extremely ill participants). Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus > 6), risk assessments for falls (normal/mild versus moderate/severe), Baseline concomitant use of antipsychotic medications (yes versus no). Missing values were imputed by LOCF within each stage. | Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis. | Posted | Mean | Standard Deviation | units on a scale | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 |
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| Secondary | Stage 1 and Stage 2: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Rating at Week 6 and Week 12 | The ADCS-CGIC rating scale provides a reliable means to assess change from a Baseline level of global function within the time frame of the trial. ADCS-CGIC-Overall focuses on the clinician's observations of change in the participant's cognitive, functional, and behavioral performance. The ADCS-CGIC-Overall responses (1-7) are rated as: 1 = marked improvement, 2 = moderate improvement, 3 = minimal improvement, 4 = no change, 5 = minimal worsening, 6 = moderate worsening, or 7 = marked worsening. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline CMAI Total score, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus > 6), risk assessments for falls (normal/mild versus moderate/severe), Baseline concomitant use of antipsychotic medications (yes versus no). Missing values were imputed by LOCF within each stage. | Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis. | Posted | Least Squares Mean | Standard Error | units on a scale | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 |
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| Secondary | Stage 1 and Stage 2: Patient Global Impression of Change (PGIC) Score at Week 6 and Week 12 | The PGIC is a 7-point (1-7) scale used to assess treatment response: 1 = very much improved, = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, or 7 = very much worse. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline CMAI Total score, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus > 6), risk assessments for falls (normal/mild versus moderate/severe), Baseline concomitant use of antipsychotic medications (yes vs no). Missing values were imputed by LOCF within each stage. | Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis. | Posted | Least Squares Mean | Standard Error | units on a scale | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 |
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| Secondary | Stage 1 and Stage 2: Change From Baseline in the Dementia Quality of Life (DEMQOL) Score to Week 6 and Week 12 | The DEMQOL scale is used to evaluate health-related QOL in participants with dementia and their caregivers. There are 2 versions of the DEMQOL: a 28-item version (rated by the participant); and a 31-item version (DEMQOL-proxy, rated by the caregiver). Both versions are recommended for evaluating participants (and their caregivers) with mild to moderate dementia. The DEMQOL total score ranges from 28 to 112. The DEMQOL-proxy is used for participants with severe dementia; the total score ranges from 31 to 124. For both versions, higher scores indicate greater QOL. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline, and in the Stage 1 model, Baseline NPI AA (≤ 6 vs > 6), risk assessments for falls (normal/mild vs moderate/severe), Baseline concomitant use of antipsychotic medications (yes vs no). Missing values were imputed by LOCF within each stage. | Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis. | Posted | Mean | Standard Deviation | units on a scale | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 |
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| Secondary | Stage 1 and Stage 2: Change From Baseline in the Cornell Scale for Depression in Dementia (CSDD) Score to Week 6 and Week 12 | The CSDD scale is used to assess signs/symptoms of major depression in participants with dementia. CSDD has 19 items, and each item is rated for severity on the following scale of 0 to 2 (0 =absent, 1= mild/intermittent 2=severe). CSDD score is calculated by summing non-missing scores from each item score. The scale ranges from 0-no depression to 38 maximum depressions. Scores above 10 indicate a probable major depression, above 18 indicate a definite major depression, and below 6 as a rule are associated with the absence of significant depressive symptoms. Higher score indicated maximum depression. | Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis. | Posted | Mean | Standard Deviation | units on a scale | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 |
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| Secondary | Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score | The GMHR is a global clinical rating for medical health, designed to quantify in a single number (1 to 4) the severity of general comorbidity in a participant with dementia. The ratings are: 1 = poor; 2 = fair; 3 = good; 4 = excellent to very good. Data was collected for the treatment arm groups as pre-specified in the protocol for this outcome measure. | Stage 2 mITT population included all participants who were rerandomized in Stage 2 and had at least 1 efficacy assessment in Stage 2 (after Week 6). The data is reported for stage 2 only. Overall number analyzed are the number of participants with data available for analyses. The percentages are rounded off to the nearest whole number. | Posted | Number | percentage of participants | Baseline; Week 12 |
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| Secondary | Stage 1 and Stage 2: Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score to Week 6 and Week 12 | The ADAS is designed to evaluate the cognitive and non-cognitive behavioral dysfunction characteristics of participants with AD. The cognitive subscale (ADAS-cog) consists of 11 subsets related to memory, praxis, and language. ADAS-cog scores range from 0 to 70. Higher scores indicate greater cognitive impairment. The ADAS-cog is assessed for participants with an Mini-Mental State Examination (MMSE) score of ≥10 at the Baseline Visit. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus > 6), risk assessments for falls (normal/mild versus moderate/severe), Baseline concomitant use of antipsychotic medications (yes vs no). Missing values were imputed by LOCF within each stage. | Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis. | Posted | Mean | Standard Deviation | units on a scale | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 |
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| Secondary | Stage 1: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals | RUD evaluates dementia participants utilization of formal and informal healthcare resources, including hospitalizations and doctor visits, living assistance, and time spent by nonprofessional caregivers. The RUD is administered as a semi-structured interview with the participant's primary caregiver and contains 2 sections; one focusing on caregiver impact (loss of work and leisure time incurred by caregiver) and the other focusing on the participant's use of healthcare resources. Information of caregivers who reported their responsibilities affected their work and who visited healthcare professionals from the interviews during Stage 1 is reported for this outcome measure. Data was collected for the treatment arm groups as pre-specified in the protocol for this outcome measure. | Stage 1 mITT Populations. Data were reported for only those participants contributing data to the analysis. Number analyzed are the number of participants available at the given timepoint. | Posted | Number | percentage of participants | Stage 1: Week 6 |
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| Secondary | Stage 2: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals | RUD evaluates dementia participants utilization of formal and informal healthcare resources, including hospitalizations and doctor visits, living assistance, and time spent by nonprofessional caregivers. The RUD is administered as a semi-structured interview with the participant's primary caregiver and contains 2 sections; one focusing on caregiver impact (loss of work and leisure time incurred by caregiver) and the other focusing on the participant's use of healthcare resources. Information of caregivers who reported their responsibilities affected their work and who visited healthcare professionals from the interviews during Stage 2 is reported for this outcome measure. Data was collected for the treatment arm groups as pre-specified in the protocol for this outcome measure. | Stage 2 mITT Population. Data were reported for only those participants contributing data to the analysis. Number analyzed are the number of participants available at the given timepoint. | Posted | Number | percentage of participants | Stage 2: Week 12 |
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| Secondary | Stage 1: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | RUD evaluates dementia participants utilization of formal, informal healthcare resources, including hospitalizations, doctor visits, living assistance, time spent by nonprofessional caregivers. Information on hours per day caregiver spent assisting participant from interviews during Stage 1 is reported for this outcome measure, where the following questions (Q), Q1= On typical care day during last 30 days, how much time per day did you assist participant with tasks such as toilet visits, eating, dressing, grooming, walking, bathing? Q2= On typical care day during the last 30 days, how much time per day did you assist participant with tasks as (shopping, food preparation, housekeeping, laundry, transportation, taking medication, managing financial matters?; Q3= On typical care day during last 30 days, how much time per day did you spend supervising (preventing dangerous events)?(Q3). Data is collected for treatment arm groups as pre-specified in protocol for this outcome measure. | Stage 1 mITT Populations. Data were reported for only those participants contributing data to the analysis. | Posted | Median | Full Range | hours | Stage 1: Week 6 |
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| Secondary | Stage 2: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant | RUD evaluates dementia participants utilization of formal, informal healthcare resources, including hospitalizations, doctor visits, living assistance, time spent by nonprofessional caregivers. Information on hours per day caregiver spent assisting participant from interviews during Stage 1 is reported for this outcome measure, where the following questions (Q), Q1= On typical care day during last 30 days, how much time per day did you assist participant with tasks such as toilet visits, eating, dressing, grooming, walking, bathing? Q2= On typical care day during the last 30 days, how much time per day did you assist participant with tasks as (shopping, food preparation, housekeeping, laundry, transportation, taking medication, managing financial matters?; Q3= On typical care day during last 30 days, how much time per day did you spend supervising (preventing dangerous events)?(Q3). Data is collected for treatment arm groups as pre-specified in protocol for this outcome measure. | Stage 2 mITT Population. The data is reported for stage 2 only. Data were reported for only those participants contributing data to the analysis | Posted | Median | Full Range | hours | Stage 2: Week 12 |
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| Secondary | Stage 1: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant | RUD evaluates dementia participants utilization of formal, informal healthcare resources, including hospitalizations, doctor visits, living assistance, time spent by nonprofessional caregivers. Information on days caregiver spent assisting participant from interviews during Stage 1 is reported for outcome measure, where following questions (Q), Q1= During last 30 days, how many days did you spend providing these (toilet visits, eating, dressing, grooming, walking, bathing) services to participant?; Q2= On typical care day during last 30 days, how much time per day did you assist participant with tasks such as shopping, food preparation, housekeeping, laundry, transportation, taking medication, managing financial matters?; Q3= During last 30 days, how many days did you spend providing these services (supervising) to the participant?. Data is collected for the treatment arm groups as pre-specified in the protocol for this outcome measure. | Stage 1 mITT Populations. Data were reported for only those participants contributing data to the analysis. | Posted | Median | Full Range | days | Stage 1: Week 6 |
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| Secondary | 12-Week Parallel Group: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant | RUD evaluates dementia participants utilization of formal, informal healthcare resources, including hospitalizations, doctor visits, living assistance, time spent by nonprofessional caregivers. Information on days caregiver spent assisting participant from interviews during Stage 1 is reported for outcome measure, where following questions (Q), Q1= During last 30 days, how many days did you spend providing these (toilet visits, eating, dressing, grooming, walking, bathing) services to participant?; Q2= On typical care day during last 30 days, how much time per day did you assist participant with tasks such as shopping, food preparation, housekeeping, laundry, transportation, taking medication, managing financial matters?; Q3= During last 30 days, how many days did you spend providing these services (supervising) to the participant?. Data is collected for the treatment arm groups as pre-specified in the protocol for this outcome measure. | mITT 12-Week Parallel-Group Population included all participants in the 12-Week Parallel Group who have at least one post-baseline efficacy assessment | Posted | Median | Full Range | days | 12-Week Parallel Group: Week 12 |
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Start of treatment up to Week 16 (End of treatment plus 30 days)
Treatment-emergent adverse events (TEAEs), defined as those adverse events that began or worsened on or after the first dose date and before the last dose date + 30 days, are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.Safety data were summarized based on the treatment the participants received at any time during the study.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
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| EG000 | Placebo | Participants received a matching placebo orally twice daily (BID) for 6 weeks (Days 1-42) in Stage 1. Participants who completed Stage 1 were eligible to participate in Stage 2. | 1 | 194 | 6 | 194 | 84 | 194 |
| EG001 | AVP-786-18 | Participants received AVP-786-18 mg orally once daily (QD) in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 8-42). Participants who completed Stage 1 were eligible to participate in Stage 2. | 3 | 156 | 17 | 156 | 78 | 156 |
| EG002 | AVP-786-28 | Participants received AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for 2 weeks (Days 8-21). From Day 22, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 22-42). Participants who completed Stage 1 were eligible to participate in Stage 2. | 1 | 159 | 7 | 159 | 71 | 159 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bradycardia | Cardiac disorders | MedDra 18.1 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDra 18.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDra 18.1 | Systematic Assessment |
| |
| Injury associated with device | General disorders | MedDra 18.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Epididymitis | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDra 18.1 | Systematic Assessment |
| |
| Foot fracture | Injury, poisoning and procedural complications | MedDra 18.1 | Systematic Assessment |
| |
| Alcohol poisoning | Injury, poisoning and procedural complications | MedDra 18.1 | Systematic Assessment |
| |
| Femoral neck fracture | Injury, poisoning and procedural complications | MedDra 18.1 | Systematic Assessment |
| |
| Hip fracture | Injury, poisoning and procedural complications | MedDra 18.1 | Systematic Assessment |
| |
| Rib fracture | Injury, poisoning and procedural complications | MedDra 18.1 | Systematic Assessment |
| |
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDra 18.1 | Systematic Assessment |
| |
| Lipase increased | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| White blood cell count increased | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Malnutrition | Metabolism and nutrition disorders | MedDra 18.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDra 18.1 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDra 18.1 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDra 18.1 | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Ischaemic stroke | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Agitation | Psychiatric disorders | MedDra 18.1 | Systematic Assessment |
| |
| Delirium | Psychiatric disorders | MedDra 18.1 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDra 18.1 | Systematic Assessment |
| |
| Hydroureter | Renal and urinary disorders | MedDra 18.1 | Systematic Assessment |
| |
| Nephrotic syndrome | Renal and urinary disorders | MedDra 18.1 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Haemothorax | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Pneumothorax spontaneous | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDra 18.1 | Systematic Assessment |
| |
| Hypertensive crisis | Vascular disorders | MedDra 18.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukocytosis | Blood and lymphatic system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Sinus bradycardia | Cardiac disorders | MedDra 18.1 | Systematic Assessment |
| |
| Ventricular extrasystoles | Cardiac disorders | MedDra 18.1 | Systematic Assessment |
| |
| Bundle branch block left | Cardiac disorders | MedDra 18.1 | Systematic Assessment |
| |
| Bradycardia | Cardiac disorders | MedDra 18.1 | Systematic Assessment |
| |
| Coronary artery disease | Cardiac disorders | MedDra 18.1 | Systematic Assessment |
| |
| Sinus arrhythmia | Cardiac disorders | MedDra 18.1 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDra 18.1 | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDra 18.1 | Systematic Assessment |
| |
| Atrioventricular block first degree | Cardiac disorders | MedDra 18.1 | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDra 18.1 | Systematic Assessment |
| |
| Type V hyperlipidaemia | Congenital, familial and genetic disorders | MedDra 18.1 | Systematic Assessment |
| |
| Tinnitus | Ear and labyrinth disorders | MedDra 18.1 | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDra 18.1 | Systematic Assessment |
| |
| Meniere's disease | Ear and labyrinth disorders | MedDra 18.1 | Systematic Assessment |
| |
| Diplopia | Eye disorders | MedDra 18.1 | Systematic Assessment |
| |
| Eye allergy | Eye disorders | MedDra 18.1 | Systematic Assessment |
| |
| Conjunctival hyperaemia | Eye disorders | MedDra 18.1 | Systematic Assessment |
| |
| Conjunctivitis allergic | Eye disorders | MedDra 18.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Anal fissure | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Diverticulum | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Poor dental condition | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Faecal incontinence | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Abdominal hernia | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Abdominal pain lower | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Inguinal hernia | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDra 18.1 | Systematic Assessment |
| |
| Feeling cold | General disorders | MedDra 18.1 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDra 18.1 | Systematic Assessment |
| |
| Malaise | General disorders | MedDra 18.1 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDra 18.1 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDra 18.1 | Systematic Assessment |
| |
| Gait disturbance | General disorders | MedDra 18.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDra 18.1 | Systematic Assessment |
| |
| Pain | General disorders | MedDra 18.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDra 18.1 | Systematic Assessment |
| |
| Seasonal allergy | Immune system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Fungal infection | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Acute sinusitis | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Arthritis infective | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Vaginal infection | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Ear infection | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Helicobacter infection | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Kidney infection | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Tooth abscess | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Tooth infection | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDra 18.1 | Systematic Assessment |
| |
| Skin abrasion | Injury, poisoning and procedural complications | MedDra 18.1 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDra 18.1 | Systematic Assessment |
| |
| Laceration | Injury, poisoning and procedural complications | MedDra 18.1 | Systematic Assessment |
| |
| Animal scratch | Injury, poisoning and procedural complications | MedDra 18.1 | Systematic Assessment |
| |
| Arthropod bite | Injury, poisoning and procedural complications | MedDra 18.1 | Systematic Assessment |
| |
| Ligament sprain | Injury, poisoning and procedural complications | MedDra 18.1 | Systematic Assessment |
| |
| Muscle rupture | Injury, poisoning and procedural complications | MedDra 18.1 | Systematic Assessment |
| |
| Muscle strain | Injury, poisoning and procedural complications | MedDra 18.1 | Systematic Assessment |
| |
| Rib fracture | Injury, poisoning and procedural complications | MedDra 18.1 | Systematic Assessment |
| |
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDra 18.1 | Systematic Assessment |
| |
| Craniocerebral injury | Injury, poisoning and procedural complications | MedDra 18.1 | Systematic Assessment |
| |
| Hand fracture | Injury, poisoning and procedural complications | MedDra 18.1 | Systematic Assessment |
| |
| Conjunctival laceration | Injury, poisoning and procedural complications | MedDra 18.1 | Systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Neutrophil count increased | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| White blood cell count increased | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Blood pressure increased | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Glycosylated haemoglobin increased | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| White blood cells urine positive | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Blood urea increased | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Electrocardiogram ST segment depression | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Weight increased | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Blood glucose increased | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Crystal urine | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Electrocardiogram abnormal | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Fungal test positive | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Glucose urine present | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Lymphocyte count increased | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDra 18.1 | Systematic Assessment |
| |
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDra 18.1 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDra 18.1 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDra 18.1 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDra 18.1 | Systematic Assessment |
| |
| Hyperlipasaemia | Metabolism and nutrition disorders | MedDra 18.1 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDra 18.1 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDra 18.1 | Systematic Assessment |
| |
| Malnutrition | Metabolism and nutrition disorders | MedDra 18.1 | Systematic Assessment |
| |
| Increased appetite | Metabolism and nutrition disorders | MedDra 18.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Synovitis | Musculoskeletal and connective tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Tendonitis | Musculoskeletal and connective tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Bursitis | Musculoskeletal and connective tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Fracture pain | Musculoskeletal and connective tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Arthropathy | Musculoskeletal and connective tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Skin cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDra 18.1 | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDra 18.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Lethargy | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Decreased vibratory sense | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Hyperreflexia | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Balance disorder | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Dyskinesia | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Metabolic encephalopathy | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Agitation | Psychiatric disorders | MedDra 18.1 | Systematic Assessment |
| |
| Hallucination | Psychiatric disorders | MedDra 18.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDra 18.1 | Systematic Assessment |
| |
| Abnormal behaviour | Psychiatric disorders | MedDra 18.1 | Systematic Assessment |
| |
| Abnormal dreams | Psychiatric disorders | MedDra 18.1 | Systematic Assessment |
| |
| Aggression | Psychiatric disorders | MedDra 18.1 | Systematic Assessment |
| |
| Hypnopompic hallucination | Psychiatric disorders | MedDra 18.1 | Systematic Assessment |
| |
| Delirium | Psychiatric disorders | MedDra 18.1 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDra 18.1 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDra 18.1 | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDra 18.1 | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDra 18.1 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDra 18.1 | Systematic Assessment |
| |
| Glycosuria | Renal and urinary disorders | MedDra 18.1 | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDra 18.1 | Systematic Assessment |
| |
| Spontaneous penile erection | Reproductive system and breast disorders | MedDra 18.1 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Pulmonary mass | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Acne | Skin and subcutaneous tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Pemphigus | Skin and subcutaneous tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Pruritus generalised | Skin and subcutaneous tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDra 18.1 | Systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDra 18.1 | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDra 18.1 | Systematic Assessment |
| |
| Orthostatic hypotension | Vascular disorders | MedDra 18.1 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDra 18.1 | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Clinical Development | Otsuka Pharmaceutical Development & Commercialization, Inc. | 1-609-524-6788 | clinicaltransparency@otsuka-us.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 16, 2018 | Dec 14, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D011595 | Psychomotor Agitation |
| D003704 | Dementia |
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D020820 | Dyskinesias |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D011596 | Psychomotor Disorders |
| D019954 | Neurobehavioral Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000096762 | Aberrant Motor Behavior in Dementia |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
Not provided
Not provided
| Death |
|
| Lack of Efficacy |
|
| Protocol Deviation |
|
| Study Participant Withdrawal by Parent or Guardian |
|
| Lost to Follow-up |
|
| Withdrawal by Subject |
|
| Reason not specified |
|
| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| OG005 |
| Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) |
Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for 2 weeks (Days 50-63). From Day 64, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 64-85). |
|
| Change from Baseline at Week 6 |
|
|
| Stage 2 Baseline |
|
|
| Change from Baseline at Week 12 |
|
|
| MMRM |
| =0.731 |
MMRMs include fixed effects of treatment, visit, treatment-by-visit, BL, BL-by-visit, and in the Stage 1 model, BL NPI AA, risk assessment for falls, BL concomitant antipsychotic medication use. Unstructured variance-covariance was used. |
| Least Squares Mean Difference |
| -0.6 |
| 2-Sided |
| 95 |
| -3.9 |
| 2.7 |
| Superiority |
| MMRM | =0.157 | MMRMs include fixed effects of treatment, visit, treatment-by-visit, BL, BL-by-visit, and in the Stage 1 model, BL NPI AA, risk assessment for falls, BL concomitant antipsychotic medication use. Unstructured variance-covariance was used. | Least Squares Mean Difference | -3.5 | 2-Sided | 95 | -8.4 | 1.4 | Superiority |
| MMRM | =0.150 | MMRMs include fixed effects of treatment, visit, treatment-by-visit, BL, BL-by-visit, and in the Stage 1 model, BL NPI AA, risk assessment for falls, BL concomitant antipsychotic medication use. Unstructured variance-covariance was used. | Least Squares Mean Difference | -3.6 | 2-Sided | 95 | -8.4 | 1.3 | Superiority |
| MMRM | Sequential Parallel Comparison Design (SPCD) was used with weight = 0.6 for Stage 1 and 0.4 for Stage 2. | =0.008 | MMRMs include fixed effects of treatment, visit, treatment-by-visit, BL, BL-by-visit, and in the Stage 1 model, BL NPI AA, risk assessment for falls, BL concomitant antipsychotic medication use. Unstructured variance-covariance was used. | MMRM weighted z-statistic | -2.65 | 2-Sided | Superiority |
| MMRM | SPCD was used with weight = 0.6 for Stage 1 and 0.4 for Stage 2. | =0.208 | MMRMs include fixed effects of treatment, visit, treatment-by-visit, BL, BL-by-visit, and in the Stage 1 model, BL NPI AA, risk assessment for falls, BL concomitant antipsychotic medication use. Unstructured variance-covariance was used. | MMRM weighted z-statistic | -1.26 | 2-Sided | Superiority |
| Stage 1: AVP-786-18 d6-DM 18 mg/Q 4.9 mg |
Participants received AVP-786-18 mg orally once daily (QD) in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 8-42). Participants who completed Stage 1 were eligible to participate in Stage 2. |
| OG002 | Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mg | Participants received AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for 2 weeks (Days 8-21). From Day 22, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 22-42). Participants who completed Stage 1 were eligible to participate in Stage 2. |
| OG003 | Stage 1: Placebo Non-responders to Stage 2: Placebo | Participants who received matching placebo in Stage 1 and were classified as non-responders (participants randomized to placebo in Stage 1 whose Clinical Global Impression of Severity of Illness scale for Agitation (CGIS-Agitation) score was ≤ 3 at Visit 4 (Day 43) and NPI- Agitation/Aggression Domain score has decreased by ≥ 25% from Baseline) were re-randomized to placebo and continued to receive placebo BID from Day 43 to Day 85 in Stage 2. |
| OG004 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 50-85). |
| OG005 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for 2 weeks (Days 50-63). From Day 64, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 64-85). |
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Participants received AVP-786-18 mg orally once daily (QD) in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 8-42). Participants who completed Stage 1 were eligible to participate in Stage 2. |
| OG002 | Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mg | Participants received AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for 2 weeks (Days 8-21). From Day 22, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 22-42). Participants who completed Stage 1 were eligible to participate in Stage 2. |
| OG003 | Stage 1: Placebo Non-responders to Stage 2: Placebo | Participants who received matching placebo in Stage 1 and were classified as non-responders (participants randomized to placebo in Stage 1 whose Clinical Global Impression of Severity of Illness scale for Agitation (CGIS-Agitation) score was ≤ 3 at Visit 4 (Day 43) and NPI- Agitation/Aggression Domain score has decreased by ≥ 25% from Baseline) were re-randomized to placebo and continued to receive placebo BID from Day 43 to Day 85 in Stage 2. |
| OG004 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 50-85). |
| OG005 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for 2 weeks (Days 50-63). From Day 64, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 64-85). |
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| OG002 | Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mg | Participants received AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for 2 weeks (Days 8-21). From Day 22, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 22-42). Participants who completed Stage 1 were eligible to participate in Stage 2. |
| OG003 | Stage 1: Placebo Non-responders to Stage 2: Placebo | Participants who received matching placebo in Stage 1 and were classified as non-responders (participants randomized to placebo in Stage 1 whose Clinical Global Impression of Severity of Illness scale for Agitation (CGIS-Agitation) score was ≤ 3 at Visit 4 (Day 43) and NPI- Agitation/Aggression Domain score has decreased by ≥ 25% from Baseline) were re-randomized to placebo and continued to receive placebo BID from Day 43 to Day 85 in Stage 2. |
| OG004 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 50-85). |
| OG005 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for 2 weeks (Days 50-63). From Day 64, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 64-85). |
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| OG002 | Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mg | Participants received AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for 2 weeks (Days 8-21). From Day 22, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 22-42). Participants who completed Stage 1 were eligible to participate in Stage 2. |
| OG003 | Stage 1: Placebo Non-responders to Stage 2: Placebo | Participants who received matching placebo in Stage 1 and were classified as non-responders (participants randomized to placebo in Stage 1 whose Clinical Global Impression of Severity of Illness scale for Agitation (CGIS-Agitation) score was ≤ 3 at Visit 4 (Day 43) and NPI- Agitation/Aggression Domain score has decreased by ≥ 25% from Baseline) were re-randomized to placebo and continued to receive placebo BID from Day 43 to Day 85 in Stage 2. |
| OG004 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 50-85). |
| OG005 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for 2 weeks (Days 50-63). From Day 64, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 65-85). |
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Participants received AVP-786-18 mg orally once daily (QD) in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 8-42). Participants who completed Stage 1 were eligible to participate in Stage 2. |
| OG002 | Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mg | Participants received AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for 2 weeks (Days 8-21). From Day 22, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 22-42). Participants who completed Stage 1 were eligible to participate in Stage 2. |
| OG003 | Stage 1: Placebo Non-responders to Stage 2: Placebo | Participants who received matching placebo in Stage 1 and were classified as non-responders (participants randomized to placebo in Stage 1 whose Clinical Global Impression of Severity of Illness scale for Agitation (CGIS-Agitation) score was ≤ 3 at Visit 4 (Day 43) and NPI- Agitation/Aggression Domain score has decreased by ≥ 25% from Baseline) were re-randomized to placebo and continued to receive placebo BID from Day 43 to Day 85 in Stage 2. |
| OG004 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 50-85). |
| OG005 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for 2 weeks (Days 50-63). From Day 64, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 64-85). |
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| OG002 | Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mg | Participants received AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for 2 weeks (Days 8-21). From Day 22, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 22-42). Participants who completed Stage 1 were eligible to participate in Stage 2. |
| OG003 | Stage 1: Placebo Non-responders to Stage 2: Placebo | Participants who received matching placebo in Stage 1 and were classified as non-responders (participants randomized to placebo in Stage 1 whose Clinical Global Impression of Severity of Illness scale for Agitation (CGIS-Agitation) score was ≤ 3 at Visit 4 (Day 43) and NPI- Agitation/Aggression Domain score has decreased by ≥ 25% from Baseline) were re-randomized to placebo and continued to receive placebo BID from Day 43 to Day 85 in Stage 2. |
| OG004 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 50-85). |
| OG005 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for 2 weeks (Days 50-63). From Day 64, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 64-85). |
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Participants received AVP-786-18 mg orally once daily (QD) in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 8-42). Participants who completed Stage 1 were eligible to participate in Stage 2. |
| OG002 | Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mg | Participants received AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for 2 weeks (Days 8-21). From Day 22, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 22-42). Participants who completed Stage 1 were eligible to participate in Stage 2. |
| OG003 | Stage 1: Placebo Non-responders to Stage 2: Placebo | Participants who received matching placebo in Stage 1 and were classified as non-responders (participants randomized to placebo in Stage 1 whose Clinical Global Impression of Severity of Illness scale for Agitation (CGIS-Agitation) score was ≤ 3 at Visit 4 (Day 43) and NPI- Agitation/Aggression Domain score has decreased by ≥ 25% from Baseline) were re-randomized to placebo and continued to receive placebo BID from Day 43 to Day 85 in Stage 2. |
| OG004 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 50-85). |
| OG005 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for 2 weeks (Days 50-63). From Day 64, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 64-85). |
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| OG002 | Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mg | Participants received AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for 2 weeks (Days 8-21). From Day 22, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 22-42). Participants who completed Stage 1 were eligible to participate in Stage 2. |
| OG003 | Stage 1: Placebo Non-responders to Stage 2: Placebo | Participants who received matching placebo in Stage 1 and were classified as non-responders (participants randomized to placebo in Stage 1 whose Clinical Global Impression of Severity of Illness scale for Agitation (CGIS-Agitation) score was ≤ 3 at Visit 4 (Day 43) and NPI- Agitation/Aggression Domain score has decreased by ≥ 25% from Baseline) were re-randomized to placebo and continued to receive placebo BID from Day 43 to Day 85 in Stage 2. |
| OG004 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 50-85). |
| OG005 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for 2 weeks (Days 50-63). From Day 64, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 64-85). |
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Participants received AVP-786-18 mg orally once daily (QD) in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 8-42). Participants who completed Stage 1 were eligible to participate in Stage 2. |
| OG002 | Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mg | Participants received AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for 2 weeks (Days 8-21). From Day 22, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 22-42). Participants who completed Stage 1 were eligible to participate in Stage 2. |
| OG003 | Stage 1: Placebo Non-responders to Stage 2: Placebo | Participants who received matching placebo in Stage 1 and were classified as non-responders (participants randomized to placebo in Stage 1 whose Clinical Global Impression of Severity of Illness scale for Agitation (CGIS-Agitation) score was ≤ 3 at Visit 4 (Day 43) and NPI- Agitation/Aggression Domain score has decreased by ≥ 25% from Baseline) were re-randomized to placebo and continued to receive placebo BID from Day 43 to Day 85 in Stage 2. |
| OG004 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 50-85). |
| OG005 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for 2 weeks (Days 50-63). From Day 64, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 64-85). |
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| OG002 | Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mg | Participants received AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for 2 weeks (Days 8-21). From Day 22, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 22-42). Participants who completed Stage 1 were eligible to participate in Stage 2. |
| OG003 | Stage 1: Placebo Non-responders to Stage 2: Placebo | Participants who received matching placebo in Stage 1 and were classified as non-responders (participants randomized to placebo in Stage 1 whose Clinical Global Impression of Severity of Illness scale for Agitation (CGIS-Agitation) score was ≤ 3 at Visit 4 (Day 43) and NPI- Agitation/Aggression Domain score has decreased by ≥ 25% from Baseline) were re-randomized to placebo and continued to receive placebo BID from Day 43 to Day 85 in Stage 2. |
| OG004 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 50-85). |
| OG005 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for 2 weeks (Days 50-63). From Day 64, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 64-85). |
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| Stage 1: AVP-786-18 d6-DM 18 mg/Q 4.9 mg |
Participants received AVP-786-18 mg orally once daily (QD) in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 8-42). Participants who completed Stage 1 were eligible to participate in Stage 2. |
| OG002 | Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mg | Participants received AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for 2 weeks (Days 8-21). From Day 22, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 22-42). Participants who completed Stage 1 were eligible to participate in Stage 2. |
| OG003 | Stage 1: Placebo Non-responders to Stage 2: Placebo | Participants who received matching placebo in Stage 1 and were classified as non-responders (participants randomized to placebo in Stage 1 whose Clinical Global Impression of Severity of Illness scale for Agitation (CGIS-Agitation) score was ≤ 3 at Visit 4 (Day 43) and NPI- Agitation/Aggression Domain score has decreased by ≥ 25% from Baseline) were re-randomized to placebo and continued to receive placebo BID from Day 43 to Day 85 in Stage 2. |
| OG004 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 50-85). |
| OG005 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for 2 weeks (Days 50-63). From Day 64, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 64-85). |
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| OG002 | Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mg | Participants received AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for 2 weeks (Days 8-21). From Day 22, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 22-42). Participants who completed Stage 1 were eligible to participate in Stage 2. |
| OG003 | Stage 1: Placebo Non-responders to Stage 2: Placebo | Participants who received matching placebo in Stage 1 and were classified as non-responders (participants randomized to placebo in Stage 1 whose Clinical Global Impression of Severity of Illness scale for Agitation (CGIS-Agitation) score was ≤ 3 at Visit 4 (Day 43) and NPI- Agitation/Aggression Domain score has decreased by ≥ 25% from Baseline) were re-randomized to placebo and continued to receive placebo BID from Day 43 to Day 85 in Stage 2. |
| OG004 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 50-85). |
| OG005 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for 2 weeks (Days 50-63). From Day 64, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 64-85). |
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| Stage 1: Placebo to: Stage 2: AVP-786-28 d6 DM 28 mg/Q 4.9 mg |
Participants who were placebo responders or non-responders in Stage 1 received AVP-786-28 for 1 week, orally, QD, followed by AVP-786-28 BID for 2 weeks; followed by AVP-786-28 BID for the last 3 weeks. |
| OG003 | Stage 1: AVP-786-18 d6-DM 18 mg/Q 4.9 mg to Stage 2: AVP-786-18 d6-DM 18 mg/Q 4.9 mg | Participants who received AVP-786-18 mg in Stage 1 continued to receive AVP-786-18 mg orally BID for the 6 weeks (Days 43-85) in Stage 2. |
| OG004 | Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Participants who received AVP-786-28 mg in Stage 1 continued to receive AVP-786-28 mg orally BID for 6 weeks (Days 43-85) in Stage 2. |
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Participants received AVP-786-18 mg orally once daily (QD) in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 8-42). Participants who completed Stage 1 were eligible to participate in Stage 2. |
| OG002 | Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mg | Participants received AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for 2 weeks (Days 8-21). From Day 22, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 22-42). Participants who completed Stage 1 were eligible to participate in Stage 2. |
| OG003 | Stage 1: Placebo Non-responders to Stage 2: Placebo | Participants who received matching placebo in Stage 1 and were classified as non-responders (participants randomized to placebo in Stage 1 whose Clinical Global Impression of Severity of Illness scale for Agitation (CGIS-Agitation) score was ≤ 3 at Visit 4 (Day 43) and NPI- Agitation/Aggression Domain score has decreased by ≥ 25% from Baseline) were re-randomized to placebo and continued to receive placebo BID from Day 43 to Day 85 in Stage 2. |
| OG004 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 50-85). |
| OG005 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Participants who received matching placebo in Stage 1 and were classified non-responders were re-randomized in Stage 2 to receive AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for 2 weeks (Days 50-63). From Day 64, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 64-85). |
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Participants received AVP-786-18 mg orally once daily (QD) in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 8-42). Participants who completed Stage 1 were eligible to participate in Stage 2.
| OG002 | Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Participants received AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for 2 weeks (Days 8-21). From Day 22, participants received AVP-786-28 mg orally BID for the remaining 3 weeks. Participants who completed Stage 1 were eligible to participate in Stage 2. |
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Participants who were placebo responders or non-responders in Stage 1 received AVP-786-18 for 1 week, orally, QD, followed by AVP-786-18 BID for 2 weeks; followed by AVP-786-28 BID for the last 3 weeks. |
| OG002 | Stage 1: Placebo to: Stage 2: AVP-786-28 d6 DM 28 mg/Q 4.9 mg | Participants who were placebo responders or non-responders in Stage 1 received AVP-786-28 for 1 week, orally, QD, followed by AVP-786-28 BID for 2 weeks; followed by AVP-786-28 BID for the last 3 weeks. |
| OG003 | Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) to: Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Participants who received AVP-786-18 mg in Stage 1 continued to receive AVP-786-18 mg orally BID for the 6 weeks (Days 43-85) in Stage 2 |
| OG004 | Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Participants who received AVP-786-28 mg in Stage 1 continued to receive AVP-786-28 mg orally BID for 6 weeks (Days 43-85) in Stage 2. |
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Participants received AVP-786-18 mg orally once daily (QD) in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 8-42). Participants who completed Stage 1 were eligible to participate in Stage 2. |
| OG002 | Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Participants received AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for 2 weeks (Days 8-21). From Day 22, participants received AVP-786-28 mg orally BID for the remaining 3 weeks. Participants who completed Stage 1 were eligible to participate in Stage 2. |
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Participants who received matching placebo in Stage 1 were re-randomized to AVP-786-18 mg and received AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 50-85). |
| OG002 | Stage 1: Placebo to Stage 2: AVP-786 28 mg | Participants who received matching placebo in Stage 1 were re-randomized to AVP-786-28 mg and received AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for 2 weeks (Days 50-63). From Day 64, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 64-85). |
| OG003 | Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) to: Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Participants who received AVP-786-18 mg in Stage 1 continued to receive AVP-786-18 mg orally BID for the 6 weeks (Days 43-85) in Stage 2. |
| OG004 | Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Participants who received AVP-786-28 mg in Stage 1 continued to receive AVP-786-28 mg orally BID for 6 weeks (Days 43-85) in Stage 2. |
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Participants received AVP-786-18 mg orally once daily (QD) in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 8-42). Participants who completed Stage 1 were eligible to participate in Stage 2.
| OG002 | Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mg | Participants received AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for 2 weeks (Days 8-21). From Day 22, participants received AVP-786-28 mg orally BID for the remaining 3 weeks. Participants who completed Stage 1 were eligible to participate in Stage 2. |
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Participants who received matching placebo in Stage 1 were re-randomized to AVP-786-18 mg and received AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 50-85) |
| OG002 | Stage 1: Placebo to Stage 2: AVP-786 28 mg | Participants who received matching placebo in Stage 1 were re-randomized to AVP-786-28 mg and received AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days of Stage 2 (Days 43-49), followed by AVP-786-18 mg orally BID for 2 weeks (Days 50-63). From Day 64, participants received AVP-786-28 mg orally BID for the remaining 3 weeks (Days 64-85). |
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