Trial · NCT02442765
Efficacy, Safety and Tolerability of AVP-786 for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type
NCT02442765, Phase 3, Completed, Otsuka Pharmaceutical Development & Commercialization, Inc.; results first posted 2023-02-13
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Efficacy, Safety and Tolerability of AVP-786 for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type. Trials, record NCT02442765. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT02442765
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Efficacy, Safety and Tolerability of AVP-786 for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type
- NCT number
- NCT02442765
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 387 participants, actual
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.
- Conditions
- Agitation in Patients With Dementia of the Alzheimer's Type
- Interventions
- AVP-786, Placebo
- First posted
- 2015-05-13
- Last updated
- 2023-02-13
- Results first posted
- 2023-02-13
Source ClinicalTrials.gov
Registered outcomes21
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | The CMAI score is used to assess the frequency of manifestations of agitated behaviors in participants. The CMAI consists of 29 agitated behaviors that are rated on a 7-point scale of frequency: 1, never; 2, less than once a week; 3, once or twice a week; 4, several times a week; 5, once or twice a day; 6, several times a day; 7, several times an hour. The CMAI total score ranges from 29 to 203. Higher scores indicate worsening of the condition. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. |
| Secondary | Least Squares Mean Modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC)-Agitation Score at Week 6 and Week 12 | Stage 1 Week 6; Stage 2 Week 12 | The intent of the ADCS version of the CGIC is to provide a means to reliably assess the global impression of change from Baseline in a clinical trial. The mADCS-CGIC is a modification of the ADCS-CGIC instrument that focuses specifically on agitation. The participants are asked to rate their impression of change from Baseline as: 1, marked improvement; 2, moderate improvement; 3, minimal improvement; 4, no change; 5, minimal worsening; 6, moderate worsening; 7, marked worsening. Baseline was defined as the last non-missing assessment prior to Stage 1 randomization. Treatment effects were estimated at each stage by analysis of covariance (ANCOVA) with fixed effects for treatment, Baseline CMAI Total score, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus \[vs\] \> 6), risk assessments for falls (normal/mild vs moderate/severe), Baseline concomitant use of antipsychotic medications (yes vs no). Missing values were imputed by last observation carried forward (LOCF) within each stage. |
| Secondary | Stage 1 and Stage 2: Change From Baseline in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score to Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. The Agitation/Aggression domain is designed to collect information on the behavioral aspects of agitation/aggression in participants with probable Alzheimer's Disease (AD) and clinically meaningful agitation secondary to AD. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, severe. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. Higher scores indicate worsening symptoms. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. |
| Secondary | Stage 1 and Stage 2: Change From Baseline in the NPI Caregiver Distress Score to Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate caregiver distress. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, marked severe. The total caregiver distress score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. Higher scores indicate worsening symptoms. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. |
| Secondary | Stage 1 and Stage 2: Change From Baseline in the NPI Aberrant Motor Behavior Domain Score to Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate aberrant motor behavior. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, severe. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. Higher scores indicate worsening of the symptoms. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. |
| Secondary | Stage 1 and Stage 2: Change From Baseline in the Zarit Burden Interview (ZBI) Score to Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | The ZBI is a 22-item scale used to assess the impact of a participant with dementia and also other illnesses on the caregiver's burden. For each item of the scale, the caregiver indicates how often they feel the burden (never, rarely, sometimes, quite frequently, or nearly always). The score ranges from 0 to 88 and is determined by adding the numbered responses of the individual items. Higher scores indicate greater caregiver distress. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus \> 6), risk assessments for falls (normal/mild versus moderate/severe), Baseline concomitant use of antipsychotic medications (yes versus no). Missing values were imputed by LOCF within each stage. |
| Secondary | Stage 1 and Stage 2: Change From Baseline in the NPI Irritability/Lability Domain Score to Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains, including the irritability/lability domain score. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, severe. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. Higher scores indicate worsening of the symptoms. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. |
| Secondary | Stage 1 and Stage 2: Change From Baseline in the NPI Total Score to Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | NPI evaluates both frequency and severity of 12 neuropsychiatric disturbances including delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, nighttime behaviors, as well as appetite/eating. Total domain score= frequency x severity and thus ranges from 1 to 12. NPI domain is rated by caregiver for symptom frequency and severity. Frequency is rated as: 1=occasionally, 2=often, 3= frequently, and 4=very frequently. Severity is rated as: 1=mild; 2= moderate, and 3=severe. Frequency and severity rating scales has defined anchor points to enhance reliability of caregiver responses. Caregiver distress is rated for each positive neuropsychiatric symptom using following anchored scores. It is rated as 0=not at all, 1=minimal, 3=moderate, 4=severe, 5=very severe. Total score is calculated by adding the individual Item scores, to yield a possible total scores of 0 to 144. |
| 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 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | The CGIS-Agitation is an observer-rated scale that measures illness severity. CGIS is used to assess the severity of agitation. The CGIS score is rated on a 7-point scale (1 = normal, not at all ill; 7 = among the most extremely ill participants). Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus \> 6), risk assessments for falls (normal/mild versus moderate/severe), Baseline concomitant use of antipsychotic medications (yes versus no). Missing values were imputed by LOCF within each stage. |
| 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 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | The ADCS-CGIC rating scale provides a reliable means to assess change from a Baseline level of global function within the time frame of the trial. ADCS-CGIC-Overall focuses on the clinician's observations of change in the participant's cognitive, functional, and behavioral performance. The ADCS-CGIC-Overall responses (1-7) are rated as: 1 = marked improvement, 2 = moderate improvement, 3 = minimal improvement, 4 = no change, 5 = minimal worsening, 6 = moderate worsening, or 7 = marked worsening. Treatment effects were estimated at each stage by ANCOVA with fixed effects for treatment, Baseline CMAI Total score, and in the Stage 1 model, Baseline NPI AA (≤ 6 versus \> 6), risk assessments for falls (normal/mild versus moderate/severe), Baseline concomitant use of antipsychotic medications (yes versus no). Missing values were imputed by LOCF within each stage. |
1 to 10 of 21Source ClinicalTrials.gov
See all 21 registered outcomesOutcomes21
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | 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. | units on a scale | MEAN |
| 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 | Stage 1 Week 6; Stage 2 Week 12 | Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis. | score on a scale | LEAST_SQUARES_MEAN |
| SECONDARY | Stage 1 and Stage 2: Change From Baseline in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score to Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis. | units on a scale | MEAN |
| SECONDARY | Stage 1 and Stage 2: Change From Baseline in the NPI Caregiver Distress Score to Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis. | units on a scale | MEAN |
| SECONDARY | Stage 1 and Stage 2: Change From Baseline in the NPI Aberrant Motor Behavior Domain Score to Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis. | units on a scale | MEAN |
| SECONDARY | Stage 1 and Stage 2: Change From Baseline in the Zarit Burden Interview (ZBI) Score to Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | 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. | units on a scale | MEAN |
| SECONDARY | Stage 1 and Stage 2: Change From Baseline in the NPI Irritability/Lability Domain Score to Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | Stage 1 and Stage 2: mITT Populations. Data were reported for only those participants contributing data to the analysis. | units on a scale | MEAN |
| SECONDARY | Stage 1 and Stage 2: Change From Baseline in the NPI Total Score to Week 6 and Week 12 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis. | units on a scale | MEAN |
| 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 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis. | units on a scale | MEAN |
| 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 | Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12 | Stage 1 and Stage 2 mITT Populations. Data were reported for only those participants contributing data to the analysis. | units on a scale | LEAST_SQUARES_MEAN |
1 to 10 of 21Source ClinicalTrials.gov
See all 21 outcomesResults by group233
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | Stage 1: Placebo | Stage 1 Baseline | 73.9 | Standard Deviation 22.23 | units on a scale |
| Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 1 Baseline | 72.3 | Standard Deviation 23.08 | units on a scale |
| Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 1 Baseline | 71.7 | Standard Deviation 23.57 | units on a scale |
| Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | Stage 1: Placebo | Change from Baseline at Week 6 | -10.7 | Standard Deviation 15.29 | units on a scale |
| Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Change from Baseline at Week 6 | -13.9 | Standard Deviation 16.70 | units on a scale |
| Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Change from Baseline at Week 6 | -10.3 | Standard Deviation 13.54 | units on a scale |
| Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | Stage 1: Placebo Non-responders to Stage 2: Placebo | Stage 2 Baseline | 66.0 | Standard Deviation 24.71 | units on a scale |
| Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | Stage 2 Baseline | 68.9 | Standard Deviation 20.79 | units on a scale |
| Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | Stage 2 Baseline | 65.3 | Standard Deviation 19.36 | units on a scale |
| Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12 | Stage 1: Placebo Non-responders to Stage 2: Placebo | Change from Baseline at Week 12 | -1.6 | Standard Deviation 11.08 | units on a scale |
1 to 10 of 233Source ClinicalTrials.gov
See all 233 results by groupParticipant flow48
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Stage 1- (Days 1 to 42) | STARTED | Stage 1: Placebo | 194 | |
| Stage 1- (Days 1 to 42) | STARTED | Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | 96 | |
| Stage 1- (Days 1 to 42) | STARTED | Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) | 97 | |
| Stage 1- (Days 1 to 42) | STARTED | Stage 2: Placebo | 0 | |
| Stage 1- (Days 1 to 42) | STARTED | Stage 1: Placebo to: Stage 2: AVP-786-28 d6-DM 18 mg/Q 4.9 mg | 0 | |
| Stage 1- (Days 1 to 42) | STARTED | Stage 1: Placebo to: Stage 2: AVP-786-28 d6 DM 28 mg/Q 4.9 mg | 0 | |
| Stage 1- (Days 1 to 42) | STARTED | 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) | 0 | |
| Stage 1- (Days 1 to 42) | STARTED | 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) | 0 | |
| Stage 1- (Days 1 to 42) | COMPLETED | Stage 1: Placebo | 194 | |
| Stage 1- (Days 1 to 42) | COMPLETED | Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) | 96 |
1 to 10 of 48Source ClinicalTrials.gov
See all 48 participant flowAdverse events666
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Leukocytosis | Blood and lymphatic system disorders | Placebo | 0 | 194 | |
| other | Leukocytosis | Blood and lymphatic system disorders | AVP-786-18 | 1 | 156 | |
| other | Leukocytosis | Blood and lymphatic system disorders | AVP-786-28 | 2 | 159 | |
| other | Iron deficiency anaemia | Blood and lymphatic system disorders | Placebo | 0 | 194 | |
| other | Iron deficiency anaemia | Blood and lymphatic system disorders | AVP-786-18 | 0 | 156 | |
| other | Iron deficiency anaemia | Blood and lymphatic system disorders | AVP-786-28 | 1 | 159 | |
| other | Anaemia | Blood and lymphatic system disorders | Placebo | 0 | 194 | |
| other | Anaemia | Blood and lymphatic system disorders | AVP-786-18 | 1 | 156 | |
| other | Anaemia | Blood and lymphatic system disorders | AVP-786-28 | 0 | 159 | |
| other | Thrombocytopenia | Blood and lymphatic system disorders | Placebo | 0 | 194 |
1 to 10 of 666Source ClinicalTrials.gov
See all 666 adverse eventsAdverse event totals9
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Placebo | 1 | 194 |
| Total, all-cause mortality | AVP-786-18 | 3 | 156 |
| Total, all-cause mortality | AVP-786-28 | 1 | 159 |
| Total, other adverse events | Placebo | 84 | 194 |
| Total, other adverse events | AVP-786-18 | 78 | 156 |
| Total, other adverse events | AVP-786-28 | 71 | 159 |
| Total, serious adverse events | Placebo | 6 | 194 |
| Total, serious adverse events | AVP-786-18 | 17 | 156 |
| Total, serious adverse events | AVP-786-28 | 7 | 159 |
Source ClinicalTrials.gov
Papers0
The papers the trial lists on ClinicalTrials.gov.
None in this release.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
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