Efficacy, Safety, and Tolerability of AVP-786 for the Treatment of Agitation in Participants With Dementia of the Alzheimer's Type

NCT02442778 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 15-AVP-786-302
• Study Type: interventional
• Target: 522
• Locations: 2 countries
• Sites: 83

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.

Conditions

Agitation in Participants With Dementia of the Alzheimer's Type

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Week 12 in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score

  The CMAI was used to assess the frequency of manifestations of agitated behaviors in elderly participants. It consists of 29 agitated items 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. Negative change from baseline indicates improvement. Mixed Model Repeated Measures (MMRM) was used for the analysis.

  Baseline, Week 12

Secondary Outcomes (17)

• Relative Change From Baseline to Week 12 in the Modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC)-Agitation Score

  Baseline, Week 12

• Change From Baseline to Week 12 in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score

  Baseline, Week 12

• Change From Baseline to Week 12 in the NPI Agitation/Aggression Caregiver Distress Score

  Baseline, Week 12

• Change From Baseline to Week 12 in the NPI Aberrant Motor Behavior Domain Score

  Baseline, Week 12

• Change From Baseline to Week 12 in the Zarit Burden Interview (ZBI) Score

  Baseline, Week 12

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Participants were administered AVP-786 matching placebo capsules, orally, twice daily (BID) for up to 12 weeks.

Drug: Placebo

AVP-786-28

EXPERIMENTAL

Participants were administered AVP-786-18 capsule, orally, once daily (QD) along with AVP-786 matching placebo capsule, orally, QD during Week 1 followed by AVP-786-18 capsules, orally, BID during Weeks 2, 3 and AVP-786-28 capsules, orally, BID during Weeks 4 to 12.

Drug: AVP-786-18; Drug: AVP-786-28

AVP-786-42.63

EXPERIMENTAL

Participants were administered AVP-786-28 capsules, orally, QD along with AVP-786 matching placebo capsule, orally, QD during Week 1 followed by AVP-786-28 capsules, orally, BID during Weeks 2, 3, and AVP-786-42.63 capsules, orally, BID during Weeks 4 to 12.

Drug: AVP-786-28; Drug: AVP-786-42.63

Interventions

AVP-786-18 DRUG

18 mg of Deudextromethorphan hydrobromide (d6-DM) and 4.9 mg of Quinidine sulfate (Q)

AVP-786-28

Placebo DRUG

Administered as capsules.

Placebo

AVP-786-28 DRUG

28 mg of d6-DM and 4.9 mg of Q

AVP-786-28; AVP-786-42.63

AVP-786-42.63 DRUG

42.63 mg of d6-DM and 4.9 mg of Q

AVP-786-42.63

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (83)

Brain and Spine Center

Chandler, Arizona, 85226, United States

Location

Territory Neurology & Research Institute

Tucson, Arizona, 85704, United States

Location

Health Initiatives Research

Fayetteville, Arkansas, 72703, United States

Location

Behavioral Research Specialists, LLC

Glendale, California, 91206, United States

Location

Irvine Center for Clinical Research

Irvine, California, 92614, United States

Location

California Neurological Services

Panorama City, California, 91402, United States

Location

Havana Research Institute

Pasadena, California, 91105, United States

Location

Pacific Research Network, Inc

San Diego, California, 92103, United States

Location

Syrentis Clinical Research

Santa Ana, California, 92705, United States

Location

Viking Clinical Research

Temecula, California, 92591, United States

Location

Denver Neurological Research, LLC

Denver, Colorado, 80210, United States

Location

JEM Research Institute

Atlantis, Florida, 33462, United States

Location

Clinical Research Of Brandon, LLC

Brandon, Florida, 33511, United States

Location

Meridien Research

Brooksville, Florida, 34601, United States

Location

Moonshine Research Center, Inc

Doral, Florida, 33166, United States

Location

Science Connections, LLC

Doral, Florida, 33166, United States

Location

Finlay Medical Research Corp

Greenacres City, Florida, 33467, United States

Location

Indago Research & Health Center, Inc.

Hialeah, Florida, 33012, United States

Location

New Life Medical Research Center, Inc.

Hialeah, Florida, 33012, United States

Location

Reliable Clinical Research,LLC

Hialeah, Florida, 33012, United States

Location

Research in Miami, Inc

Hialeah, Florida, 33013, United States

Location

The Research Center, Inc

Hialeah, Florida, 33013, United States

Location

Maxblue Institute

Hialeah, Florida, 33018, United States

Location

Clinical Neuroscience Solutions, Inc.

Jacksonville, Florida, 32256, United States

Location

Alzheimer's Research and Treatment Center

Lake Worth, Florida, 33449, United States

Location

Premier Clinical Research Institute, Inc.

Miami, Florida, 33122, United States

Location

Project 4 Research

Miami, Florida, 33125, United States

Location

BioMed Research Institute

Miami, Florida, 33126, United States

Location

CCM Clinical Research Group

Miami, Florida, 33133, United States

Location

DADE Research Center, LLC

Miami, Florida, 33135, United States

Location

AMB Research Center, Inc.

Miami, Florida, 33144, United States

Location

United Health Research Corp

Miami, Florida, 33144, United States

Location

Advance Medical Research Center

Miami, Florida, 33165, United States

Location

Coral Research Clinic Corp

Miami, Florida, 33175, United States

Location

P&S Reasearch

Miami, Florida, 33175, United States

Location

The Neurology Research Group, LLC

Miami, Florida, 33176, United States

Location

Kendall Research Institute

Miami, Florida, 33183, United States

Location

Nuovida Research Center Corp.

Miami, Florida, 33186, United States

Location

Collier Neurologic Specialists, LLC

Naples, Florida, 34102, United States

Location

Lazlo J. Mate, MD, PA

North Palm Beach, Florida, 33408, United States

Location

Compass Research, LLC

Orlando, Florida, 32806, United States

Location

IMIC Inc.

Palmetto Bay, Florida, 33157, United States

Location

University of West Florida

Pensacola, Florida, 32514, United States

Location

Neurology Research Institute Palm Beach, LLC

West Palm Beach, Florida, 33407, United States

Location

Emory Brain Health Center

Atlanta, Georgia, 30329, United States

Location

Columbus Research & Wellness Institute, INC

Columbus, Georgia, 31904, United States

Location

Josephson Wallack Munshower Neurology, PC

Indianapolis, Indiana, 46256, United States

Location

Baptist Health Medical Group

Richmond, Kentucky, 40475, United States

Location

The Samuel & Alexia Bratton Memory Clinic

Easton, Maryland, 21601, United States

Location

Mir Neurology

Hagerstown, Maryland, 21742, United States

Location

Boston Center for Memory

Newton, Massachusetts, 02459, United States

Location

AMAC Research Institute

North Dartmouth, Massachusetts, 02747, United States

Location

Michigan State University

East Lansing, Michigan, 48824, United States

Location

Center for Emotional Fitness

Cherry Hill, New Jersey, 08002, United States

Location

The NeuroCognitive Institute

Mount Arlington, New Jersey, 07856, United States

Location

Brooklyn Medical Institute

Brooklyn, New York, 11214, United States

Location

Integrative Clinical Trials, LLC

Brooklyn, New York, 11229, United States

Location

Eastside Comprehensive Medical Center, LLC

New York, New York, 10128, United States

Location

Burke Rehabilitation Hospital

White Plains, New York, 10605, United States

Location

Herbert Harris, MD, PhD, PA

Chapel Hill, North Carolina, 27517, United States

Location

ANI Neurology PLLC dba Alzheimer's Memory Center

Charlotte, North Carolina, 28270, United States

Location

Daystar Clinical Research Inc

Akron, Ohio, 44313, United States

Location

Valley Medical Research

Centerville, Ohio, 45459, United States

Location

CTI Clinical Research Center

Cincinnati, Ohio, 45212, United States

Location

Cleveland Clinic Lou Ruvo Center for Brain Health at Lakewood Hospital

Lakewood, Ohio, 44107, United States

Location

Heritage Valley Medical Group, Inc.

Beaver, Pennsylvania, 15009, United States

Location

The Birches at Newton / Family Medical Associates

Levittown, Pennsylvania, 19056, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

RH Johnson VA Medical Center

Charleston, South Carolina, 29401, United States

Location

BG Neurology

Spartanburg, South Carolina, 29307, United States

Location

Texas Neurology, P.A.

Dallas, Texas, 75214, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Houston Methodist Neurological Institute

Houston, Texas, 77030, United States

Location

Clinical Trial Network

Houston, Texas, 77074, United States

Location

Texas Medical Research Associates, L.L.C.

San Antonio, Texas, 78238, United States

Location

Pharmaceuticals Research Associates, Inc.

Salt Lake City, Utah, 84107, United States

Location

Clinical Neuroscience Research Associates, Inc. dba The Memory Clinic

Bennington, Vermont, 05201, United States

Location

Veteran Affairs Medical Center, Salem Virginia

Salem, Virginia, 24153, United States

Location

IPC Research

Waukesha, Wisconsin, 53188, United States

Location

Dr. Alexander McIntyre Inc.

Calgary, Alberta, N7L 1C1, Canada

Location

The Medical Art Health Research Group

Kelowna, Bristish Columbia, Canada

Location

The Medical Art Health Research Group

Penticton, Bristish Columbia, Canada

Location

The Medical Art Health Research Group

West Vancouver, Bristish Columbia, Canada

Location

Results Point of Contact

• Title: Global Clinical Development
• Organization: Otsuka Pharmaceutical Development & Commercialization, Inc.

clinicaltransparency@otsuka-us.com

1-609-524-6788

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2015
• First Posted: May 13, 2015
• Study Start: November 11, 2015
• Primary Completion: August 14, 2019
• Study Completion: September 9, 2019
• Last Updated: September 9, 2022
• Results First Posted: September 9, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article publica data.
• Access Criteria: Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/O

Locations

US (79); CA (4)