Clinical trial NCT02442765: Efficacy, Safety and Tolerability of AVP-786 for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type
Official title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety, and Tolerability of AVP-786 (Deuterated [d6]-Dextromethorphan Hydrobromide [d6-DM]/Quinidine Sulfate [Q]) for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Agitation in Patients With Dementia of the Alzheimer's Type
Keywords: Agitation
Dementia
Alzheimer's disease
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
First posted: 2015-05-13
Enrollment: 387
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Sequential parallel comparison design
Primary purpose: TREATMENT

Brief summary: Participants with agitation secondary to dementia of the Alzheimer's type. The diagnosis of probable Alzheimer's disease (AD) was to be based on the "2011 Diagnostic Guidelines for Alzheimer's Disease" issued by the National Institute on Aging (NIA)-Alzheimer's Association (AA) workgroups.

Detailed description: Eligible participants for this study must have had a diagnosis of probable AD and must have had clinically meaningful agitation secondary to AD.

This was to be a multicenter, randomized, placebo-controlled study, consisting of 12 weeks of treatment.

Approximately 380 participants were to be enrolled at approximately 60 centers in North America.

Study medication was to be administered orally twice-daily from Day 1 through Day 85. Screening was to occur within approximately 4 weeks prior to randomization. Following screening procedures for assessment of inclusion and exclusion criteria, eligible participants were to be randomized into the study.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of probable Alzheimer's Disease (AD) according to the 2011 National Institute on Aging-Alzheimer's Association (NIA-AA) working groups criteria
* The participant has clinically significant, moderate/severe agitation at the time of screening and for at least 2 weeks prior to randomization
* The diagnosis of agitation must meet the International Psychogeriatric Association (IPA) provisional definition of agitation
* Either out patients or residents of an assisted-living facility or a skilled nursing home
* Clinical Global Impression of Severity of Illness (CGIS) score assessing Agitation is \>= 4 (moderately ill) at screening and baseline
* Mini-Mental State Examination (MMSE) score is between 6 and 26 (inclusive) at screening and baseline
* Caregiver who is able and willing to comply with all required study procedures. In order to qualify as a reliable informant (i.e., caregiver) capable of assessing changes in participant's condition during the study, the individual must spend a minimum of 2 hours per day for 4 days per week with the participant.

Exclusion Criteria:

* Participant has dementia predominantly of non-Alzheimer's type (e.g., vascular dementia, frontotemporal dementia, Parkinson's disease, substance-induced dementia)
* Participants with co-existent clinically significant or unstable systemic diseases that could confound the interpretation of the safety results of the study (e.g., malignancy, poorly controlled diabetes, poorly controlled hypertension, unstable pulmonary, renal or hepatic disease, unstable ischemic cardiac disease, dilated cardiomyopathy, or unstable valvular heart disease)
* Participant with myasthenia gravis

Primary outcomes:
measure: Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12
timeFrame: Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12
Secondary outcomes:
measure: Least Squares Mean Modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC)-Agitation Score at Week 6 and Week 12
timeFrame: Stage 1 Week 6; Stage 2 Week 12
measure: Stage 1 and Stage 2: Change From Baseline in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score to Week 6 and Week 12
timeFrame: Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12
measure: Stage 1 and Stage 2: Change From Baseline in the NPI Caregiver Distress Score to Week 6 and Week 12
timeFrame: Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12
measure: Stage 1 and Stage 2: Change From Baseline in the NPI Aberrant Motor Behavior Domain Score to Week 6 and Week 12
timeFrame: Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12
measure: Stage 1 and Stage 2: Change From Baseline in the Zarit Burden Interview (ZBI) Score to Week 6 and Week 12
timeFrame: Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12
measure: Stage 1 and Stage 2: Change From Baseline in the NPI Irritability/Lability Domain Score to Week 6 and Week 12
timeFrame: Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12
measure: Stage 1 and Stage 2: Change From Baseline in the NPI Total Score to Week 6 and Week 12
timeFrame: Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12
measure: 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
timeFrame: Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12
measure: Stage 1 and Stage 2: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Rating at Week 6 and Week 12
timeFrame: Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12
measure: Stage 1 and Stage 2: Patient Global Impression of Change (PGIC) Score at Week 6 and Week 12
timeFrame: Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12
measure: Stage 1 and Stage 2: Change From Baseline in the Dementia Quality of Life (DEMQOL) Score to Week 6 and Week 12
timeFrame: Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12
measure: Stage 1 and Stage 2: Change From Baseline in the Cornell Scale for Depression in Dementia (CSDD) Score to Week 6 and Week 12
timeFrame: Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12
measure: Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score
timeFrame: Baseline; Week 12
measure: Stage 1 and Stage 2: Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score to Week 6 and Week 12
timeFrame: Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12
measure: Stage 1: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals
timeFrame: Stage 1: Week 6
measure: Stage 2: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals
timeFrame: Stage 2: Week 12
measure: Stage 1: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant
timeFrame: Stage 1: Week 6
measure: Stage 2: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant
timeFrame: Stage 2: Week 12
measure: Stage 1: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant
timeFrame: Stage 1: Week 6
measure: 12-Week Parallel Group: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant
timeFrame: 12-Week Parallel Group: Week 12
Other outcomes:
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city: Dallas
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state: Utah
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state: Vermont
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country: Estonia
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country: Estonia
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city: Tartu
country: Estonia
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city: Mittweida
country: Germany
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country: Poland
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state: Lubelskie
city: Bydgoszcz
country: Poland
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country: Poland
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city: Lublin
country: Poland
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city: Poznan
country: Poland
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city: Poznan
country: Poland
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city: Pruszcz Gdanski
country: Poland
facility: Clinical Research Site
city: Siemianowice Śląskie
country: Poland
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city: Torres Vedras
country: Portugal
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city: Bayamon
country: Puerto Rico
facility: Clinical Research Site
city: San Juan
country: Puerto Rico
facility: Clinical Research Site
Study officials:
References: