Clinical trial NCT02442778: Efficacy, Safety, and Tolerability of AVP-786 for the Treatment of Agitation in Participants 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 Participants With Dementia of the Alzheimer's Type
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
First posted: 2015-05-13
Enrollment: 522
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Participants with agitation secondary to dementia of the Alzheimer's type. The diagnosis of probable Alzheimer's disease (AD) will 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 a diagnosis of probable AD and must have clinically meaningful agitation secondary to AD.

This is a multicenter, randomized, placebo-controlled study, consisting of 12 weeks of treatment.

Approximately 470 participants will be enrolled at approximately 75 centers in North America.

Study medication will be administered orally twice-daily from Day 1 through Week 12 (Day 85). Screening will occur within approximately 4 weeks prior to randomization. Following screening procedures for assessment of inclusion and exclusion criteria, eligible participants will be randomized into the study.

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 participants 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: Change From Baseline to Week 12 in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Relative Change From Baseline to Week 12 in the Modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC)-Agitation Score
timeFrame: Baseline, Week 12
measure: Change From Baseline to Week 12 in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score
timeFrame: Baseline, Week 12
measure: Change From Baseline to Week 12 in the NPI Agitation/Aggression Caregiver Distress Score
timeFrame: Baseline, Week 12
measure: Change From Baseline to Week 12 in the NPI Aberrant Motor Behavior Domain Score
timeFrame: Baseline, Week 12
measure: Change From Baseline to Week 12 in the Zarit Burden Interview (ZBI) Score
timeFrame: Baseline, Week 12
measure: Change From Baseline to Week 12 in the NPI Irritability/Lability Domain Score
timeFrame: Baseline, Week 12
measure: Change From Baseline to Week 12 in the NPI Total Score
timeFrame: Baseline, Week 12
measure: Change From Baseline to Week 12 in the Clinical Global Impression of Severity of Illness (CGIS)-Agitation Domain Score
timeFrame: Baseline, Week 12
measure: Change From Baseline to Week 12 in the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Overall Rating
timeFrame: Baseline, Week 12
measure: Change From Baseline to Week 12 in the Patient Global Impression of Change (PGIC) Score
timeFrame: Baseline, Week 12
measure: Change From Baseline to Week 12 in the Dementia Quality of Life (DEMQOL) Score
timeFrame: Baseline, Week 12
measure: Change From Baseline in the Cornell Scale for Depression in Dementia (CSDD) Score
timeFrame: Baseline, Week 12
measure: Number of Participants With the Change From Baseline in the General Medical Health Rating (GMHR) Score at Week 12
timeFrame: Week 12
measure: Change From Baseline to Week 12 in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score
timeFrame: Baseline, Week 12
measure: Resource Utilization in Dementia (RUD) Score: Number of Hours Per Day the Caregiver Spent Assisting the Participant
timeFrame: Week 12
measure: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant
timeFrame: Week 12
measure: Resource Utilization in Dementia (RUD) Score: Number of Visits to Hospital, Emergency, and Healthcare Professional
timeFrame: Week 12
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Brain and Spine Center
state: Arizona
city: Tucson
country: United States
facility: Territory Neurology & Research Institute
state: Arizona
city: Fayetteville
country: United States
facility: Health Initiatives Research
state: Arkansas
city: Glendale
country: United States
facility: Behavioral Research Specialists, LLC
state: California
city: Irvine
country: United States
facility: Irvine Center for Clinical Research
state: California
city: Panorama City
country: United States
facility: California Neurological Services
state: California
city: Pasadena
country: United States
facility: Havana Research Institute
state: California
city: San Diego
country: United States
facility: Pacific Research Network, Inc
state: California
city: Santa Ana
country: United States
facility: Syrentis Clinical Research
state: California
city: Temecula
country: United States
facility: Viking Clinical Research
state: California
city: Denver
country: United States
facility: Denver Neurological Research, LLC
state: Colorado
city: Atlantis
country: United States
facility: JEM Research Institute
state: Florida
city: Brandon
country: United States
facility: Clinical Research Of Brandon, LLC
state: Florida
city: Brooksville
country: United States
facility: Meridien Research
state: Florida
city: Doral
country: United States
facility: Moonshine Research Center, Inc
state: Florida
city: Doral
country: United States
facility: Science Connections, LLC
state: Florida
city: Greenacres City
country: United States
facility: Finlay Medical Research Corp
state: Florida
city: Hialeah
country: United States
facility: Indago Research & Health Center, Inc.
state: Florida
city: Hialeah
country: United States
facility: New Life Medical Research Center, Inc.
state: Florida
city: Hialeah
country: United States
facility: Reliable Clinical Research,LLC
state: Florida
city: Hialeah
country: United States
facility: Research in Miami, Inc
state: Florida
city: Hialeah
country: United States
facility: The Research Center, Inc
state: Florida
city: Hialeah
country: United States
facility: Maxblue Institute
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Lake Worth
country: United States
facility: Alzheimer's Research and Treatment Center
state: Florida
city: Miami
country: United States
facility: Premier Clinical Research Institute, Inc.
state: Florida
city: Miami
country: United States
facility: Project 4 Research
state: Florida
city: Miami
country: United States
facility: BioMed Research Institute
state: Florida
city: Miami
country: United States
facility: CCM Clinical Research Group
state: Florida
city: Miami
country: United States
facility: DADE Research Center, LLC
state: Florida
city: Miami
country: United States
facility: AMB Research Center, Inc.
state: Florida
city: Miami
country: United States
facility: United Health Research Corp
state: Florida
city: Miami
country: United States
facility: Advance Medical Research Center
state: Florida
city: Miami
country: United States
facility: Coral Research Clinic Corp
state: Florida
city: Miami
country: United States
facility: P&S Reasearch
state: Florida
city: Miami
country: United States
facility: The Neurology Research Group, LLC
state: Florida
city: Miami
country: United States
facility: Kendall Research Institute
state: Florida
city: Miami
country: United States
facility: Nuovida Research Center Corp.
state: Florida
city: Naples
country: United States
facility: Collier Neurologic Specialists, LLC
state: Florida
city: North Palm Beach
country: United States
facility: Lazlo J. Mate, MD, PA
state: Florida
city: Orlando
country: United States
facility: Compass Research, LLC
state: Florida
city: Palmetto Bay
country: United States
facility: IMIC Inc.
state: Florida
city: Pensacola
country: United States
facility: University of West Florida
state: Florida
city: West Palm Beach
country: United States
facility: Neurology Research Institute Palm Beach, LLC
state: Florida
city: Atlanta
country: United States
facility: Emory Brain Health Center
state: Georgia
city: Columbus
country: United States
facility: Columbus Research & Wellness Institute, INC
state: Georgia
city: Indianapolis
country: United States
facility: Josephson Wallack Munshower Neurology, PC
state: Indiana
city: Richmond
country: United States
facility: Baptist Health Medical Group
state: Kentucky
city: Easton
country: United States
facility: The Samuel & Alexia Bratton Memory Clinic
state: Maryland
city: Hagerstown
country: United States
facility: Mir Neurology
state: Maryland
city: Newton
country: United States
facility: Boston Center for Memory
state: Massachusetts
city: North Dartmouth
country: United States
facility: AMAC Research Institute
state: Massachusetts
city: East Lansing
country: United States
facility: Michigan State University
state: Michigan
city: Cherry Hill
country: United States
facility: Center for Emotional Fitness
state: New Jersey
city: Mount Arlington
country: United States
facility: The NeuroCognitive Institute
state: New Jersey
city: Brooklyn
country: United States
facility: Brooklyn Medical Institute
state: New York
city: Brooklyn
country: United States
facility: Integrative Clinical Trials, LLC
state: New York
city: New York
country: United States
facility: Eastside Comprehensive Medical Center, LLC
state: New York
city: White Plains
country: United States
facility: Burke Rehabilitation Hospital
state: New York
city: Chapel Hill
country: United States
facility: Herbert Harris, MD, PhD, PA
state: North Carolina
city: Charlotte
country: United States
facility: ANI Neurology PLLC dba Alzheimer's Memory Center
state: North Carolina
city: Akron
country: United States
facility: Daystar Clinical Research Inc
state: Ohio
city: Centerville
country: United States
facility: Valley Medical Research
state: Ohio
city: Cincinnati
country: United States
facility: CTI Clinical Research Center
state: Ohio
city: Lakewood
country: United States
facility: Cleveland Clinic Lou Ruvo Center for Brain Health at Lakewood Hospital
state: Ohio
city: Beaver
country: United States
facility: Heritage Valley Medical Group, Inc.
state: Pennsylvania
city: Levittown
country: United States
facility: The Birches at Newton / Family Medical Associates
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Charleston
country: United States
facility: RH Johnson VA Medical Center
state: South Carolina
city: Spartanburg
country: United States
facility: BG Neurology
state: South Carolina
city: Dallas
country: United States
facility: Texas Neurology, P.A.
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Houston Methodist Neurological Institute
state: Texas
city: Houston
country: United States
facility: Clinical Trial Network
state: Texas
city: San Antonio
country: United States
facility: Texas Medical Research Associates, L.L.C.
state: Texas
city: Salt Lake City
country: United States
facility: Pharmaceuticals Research Associates, Inc.
state: Utah
city: Bennington
country: United States
facility: Clinical Neuroscience Research Associates, Inc. dba The Memory Clinic
state: Vermont
city: Salem
country: United States
facility: Veteran Affairs Medical Center, Salem Virginia
state: Virginia
city: Waukesha
country: United States
facility: IPC Research
state: Wisconsin
city: Calgary
country: Canada
facility: Dr. Alexander McIntyre Inc.
state: Alberta
city: Kelowna
country: Canada
facility: The Medical Art Health Research Group
state: Bristish Columbia
city: Penticton
country: Canada
facility: The Medical Art Health Research Group
state: Bristish Columbia
city: West Vancouver
country: Canada
facility: The Medical Art Health Research Group
state: Bristish Columbia
Study officials:
References: