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

NCT04464564 | Terminated Phase 3 Results FDA Drug

• 3 other identifiers: 20-AVP-786-3072020-000799-392023-504991-31-00
• Study Type: interventional
• Target: 241
• Locations: 12 countries
• Sites: 100

Brief Summary

This study was conducted to evaluate the efficacy, safety, and tolerability of AVP-786 (deudextromethorphan hydrobromide \[d6-DM\]/quinidine sulfate \[Q\]) compared to placebo for the treatment of agitation in participants with dementia of the Alzheimer's type.

Conditions

Agitation in Patients With Dementia of the Alzheimer's Type

Keywords

Agitation; Dementia of the Alzheimer's type; Alzheimer's disease; AVP-786; Deudextromethorphan hydrobromide; Quinidine sulfate

Outcome Measures

Primary Outcomes (2)

• Change From the End of Period A (Week 1) to Week 10 in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score

  The CMAI is used to assess the frequency of manifestations of agitated behaviors in elderly persons. It consists of 29 agitated behaviors that are further categorized into distinct agitation syndromes, also known as CMAI factors of agitation. These distinct agitation syndromes include aggressive behavior, physically nonaggressive behavior, and verbally agitated behavior. Each of the 29 items is rated on a 7-point scale of frequency (1 = never, 2 = less than once a week but still occurring, 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 ratings are based on the 2 weeks preceding assessment of the CMAI. Higher scores indicate higher frequency of agitated behaviours while lower scores indicate lower frequency of agitated behaviours.

  Week 1 to Week 10

• Number of Participants With Treatment Emergent Adverse Events (TEAE) and Serious TEAE

  An adverse event (AE) is any untoward medical occurrence or unintended change (eg, physical, psychological, or behavioral), including inter-current illness, that does not necessarily have a causal relationship with the study treatment. A serious adverse event (SAE) is any AE occurring at any dose that results in death, life-threatening experience, persistent or significant disability/incapacity, in-patient hospitalization or prolongation of hospitalization or congenital anomaly/birth defect. TEAEs are all AEs (including serious and non-serious) which started after start of double-blind study drug treatment; or if the event was continuous from baseline and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy.

  From randomization (Week 2) up to 30 days after last dose of study drug (Up to Week 16)

Secondary Outcomes (1)

• Change From the End of Period A (Week 1) to Week 10 in the Clinical Global Impression of Severity of Illness (CGIS) Score, as Related to Agitation

  Week 1 to Week 10

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Participants who were enrolled in 1-week double-blind placebo lead-in Period A, were then randomized to receive AVP-786 matching placebo capsules, twice a day, for 11 weeks in Period B.

Drug: Placebo

AVP-786-18

EXPERIMENTAL

Participants who were enrolled in 1-week double-blind placebo lead-in Period A, were then randomized to receive AVP-786-18 (d6-DM 18 milligrams (mg)/Q 4.9 mg) capsules, twice a day, for 11 weeks in Period B.

Drug: AVP-786

AVP-786-42.63

EXPERIMENTAL

Participants who were enrolled in 1-week double-blind placebo lead-in Period A, were then randomized to receive AVP-786-42.63 (d6-DM 42.63 mg/Q 4.9 mg) capsules, twice a day, for 11 weeks in Period B.

Drug: AVP-786

Interventions

AVP-786 DRUG

oral capsules

AVP-786-18; AVP-786-42.63

Placebo DRUG

oral capsules

Placebo

Eligibility Criteria

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

You may qualify if:

• Participants with a diagnosis of probable Alzheimer's disease according to the 2011 Neuropsychiatric Inventory Agitation/Aggression (NPI-AA) working groups criteria
• Participants with clinically significant, moderate-to-severe agitation for at least 2 weeks prior to Screening that interferes with daily routine per the Investigator's judgment
• Participants who require pharmacotherapy for the treatment of agitation per the Investigator's judgment after an evaluation of reversible factors and a course of nonpharmacological interventions
• Diagnosis of agitation must meet the International Psychogeriatric Association (IPA) provisional definition of agitation.
• Participants meeting an additional predetermined blinded eligibility criterion, which will remain blinded to the clinical study site Investigators and staff
• Participants with a reliable caregiver who is able and willing to comply with all study procedures, including adherence to administering study drug and not administering any prohibited medications during the course of the study, and who spends a minimum of 2 hours per day for 4 days per week with the participant

You may not qualify if:

• Participants with dementia predominantly of the non-Alzheimer's type (e.g., vascular dementia, frontotemporal dementia, Parkinson's disease, substance-induced dementia)
• Participants with symptoms of agitation that are not secondary to Alzheimer's dementia (e.g., secondary to pain, other psychiatric disorder, or delirium)
• 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 \[except skin basal-cell carcinoma\], poorly controlled diabetes, poorly controlled hypertension, unstable pulmonary, renal or hepatic disease, unstable ischemic cardiac disease, dilated cardiomyopathy, or unstable valvular heart disease)
• Participants with myasthenia gravis

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (106)

Clinical Research Site #840-020

Phoenix, Arizona, 85004, United States

Location

Clinical Research Site #840-047

Anaheim, California, 92805, United States

Location

Clinical Research Site #840-090

Costa Mesa, California, 92626, United States

Location

Clinical Research Site #840-059

Lafayette, California, 94549, United States

Location

Clinical Research Site #840-048

Lomita, California, 90717, United States

Location

Clinical Research Site #840-095

Long Beach, California, 90807, United States

Location

Clinical Research Site #840-004

Los Angeles, California, 90024, United States

Location

Clinical Research Site #840-006

Panorama City, California, 91402, United States

Location

Clinical Research Site

San Diego, California, 92128, United States

Location

Clinical Research Site #840-070

Apopka, Florida, 32703, United States

Location

Clinical Research Site #840-055

Bradenton, Florida, 34205, United States

Location

Clinical Research Site #840-096

Cape Coral, Florida, 33904, United States

Location

Clinical Research Site #840-077

Clermont, Florida, 34771, United States

Location

Clinical Research Site #840-066

Coral Springs, Florida, 33067, United States

Location

Clinical Research Site #840-039

Hallandale, Florida, 33009, United States

Location

Clinical Research Site #840-089

Kissimmee, Florida, 34741, United States

Location

Clinical Research Site #840-034

Lady Lake, Florida, 32159, United States

Location

Clinical Research Site #840-037

Miami, Florida, 33122, United States

Location

Clinical Research Site #840-092

Miami, Florida, 33125, United States

Location

Clinical Research Site #840-041

Miami, Florida, 33126, United States

Location

Clinical Research Site #840-007

Miami, Florida, 33145, United States

Location

Clinical Research Site #840-103

Miami, Florida, 33175, United States

Location

Clinical Research Site #840-042

Miami, Florida, 33176, United States

Location

Clinical Research Site #840-051

Naples, Florida, 34105, United States

Location

Clinical Research Site #840-087

Orlando, Florida, 32807, United States

Location

Clinical Research Site 840-028

Pensacola, Florida, 32502, United States

Location

Clinical Research Site # 840-105

Tampa, Florida, 33614, United States

Location

Clinical Research Site #840-104

Tampa, Florida, 33614, United States

Location

Clinical Research Site #840-049

West Palm Beach, Florida, 33407, United States

Location

Clinical Research Site #840-036

Winter Park, Florida, 32789, United States

Location

Clinical Research Site #840-065

Atlanta, Georgia, 30318, United States

Location

Clinical Research Site #840-030

Chicago, Illinois, 60637, United States

Location

Clinical Research Site #840-073

Boston, Massachusetts, 02131, United States

Location

Clinical Research Site #840-014

Bloomfield Township, Michigan, 48302, United States

Location

Clinical Research Site #840-022

Detroit, Michigan, 48201, United States

Location

Clinical Research Site #840-024

O'Fallon, Missouri, 63368, United States

Location

Clinical Research Site #840-031

Buffalo, New York, 14030, United States

Location

Clinical Research Site #840-021

Manhasset, New York, 11030, United States

Location

Clinical Research Site #840-058

New Hyde Park, New York, 11040, United States

Location

Clinical Research Site #840-035

Cypress, Texas, 77429, United States

Location

Clinical Research Site #840-053

Dallas, Texas, 75206, United States

Location

Clinical Research Site #840-093

El Paso, Texas, 79902, United States

Location

Clinical Research Site #840-072

Houston, Texas, 77063, United States

Location

Clinical Research Site #840-057

Houston, Texas, 77077, United States

Location

Clinical Research Site #840-086

Mesquite, Texas, 75149, United States

Location

Clinical Research Site #840-044

Fairfax, Virginia, 22031, United States

Location

Clinical Research Site #056-005

Alken, Limburg, 3570, Belgium

Location

Clinical Research Site #056-004

Brussels, 1070, Belgium

Location

Clinical Research Site #056-003

Leuven, 3000, Belgium

Location

Clinical Research Site # 056-002

Liège, 4000, Belgium

Location

Clinical Research Site #124-003

Kelowna, British Columbia, V1Y 1Z9, Canada

Location

Clinical Research Site #124-008

Québec, Quebec, G3K 2P8, Canada

Location

Clinical Research Site #152-007

Viña Del Mar, Santiago Metropolitan, 2451029, Chile

Location

Clinical Research Site #152-002

Antofagasta, 1270244, Chile

Location

Clinical Research Site #152-005

Independencia, 8380456, Chile

Location

Clinical Research Site #152-001

Santiago, 7500710, Chile

Location

Clinical Research Site #152-003

Santiago, 7560356, Chile

Location

Clinical Research Site #152-006

Santiago, 9120000, Chile

Location

Clinical Research Site #170-003

Bogotá, Columbia, 111166, Colombia

Location

Clinical Research Site #170-002

Pereira, Columbia, 1111, Colombia

Location

Clinical Research Site #170-007

Floridablanca, Santander Department, 111511, Colombia

Location

Clinical Research Site #170-006

Bello, 051050, Colombia

Location

Clinical Research Site #170-001

Bogotá, 110231, Colombia

Location

Clinical Research Site #170-004

Bogotá, 110231, Colombia

Location

Clinical Research Site #191-008

Pula, Istria County, 52000, Croatia

Location

Clinical Research Site# 191-006

Rijeka, 51000, Croatia

Location

Clinical Research Site# 191-001

Zagreb, 10000, Croatia

Location

Clinical Research Site #191-003

Zagreb, 1000, Croatia

Location

Clinical Research Site #191-005

Zagreb, HR 10000, Croatia

Location

Clinical Research Site #191-002

Zagreb, HR-10090, Croatia

Location

Clinical Research Site #348-002

Gyöngyös, Heves County, 3200, Hungary

Location

Clinical Research Site #384-001

Budapest, 1036, Hungary

Location

Clinical Research Site #384-003

Budapest, 1036, Hungary

Location

Clinical Research Site #348-004

Zalaegerszeg, 8900, Hungary

Location

Clinical Research Site #372-002

Cork, T12 WE28, Ireland

Location

Clinical Research Site #372-003

Cork, T12 XH60, Ireland

Location

Clinical Research Site #372-004

Dublin, 24, Ireland

Location

Clinical Research Site #372-001

Dublin, D08 E191, Ireland

Location

Clinical Research Site # 484-004

Mexico City, 7000, Mexico

Location

Clinical Research Site #484-008

Mérida, 97070, Mexico

Location

Clinical Research Site #484-006

Monterrey, 64310, Mexico

Location

Clinical Research Site #484-005

Monterrey, 64460, Mexico

Location

Clinical Research Site # 484-003

Monterrey, 64710, Mexico

Location

Clinical Research Site #484-010

Saltillo, 25020, Mexico

Location

Clinical Research Site # 484-002

Sinaloa, 80020, Mexico

Location

Clinical Research Site #484-009

Tlalnepantla, 54055, Mexico

Location

Clinical Trial Site #528-001

Amsterdam, 1081GN, Netherlands

Location

Clinical Research Site #703-009

Dubnica Nad Váhom, Bratislava Region, 01851, Slovakia

Location

Clinical Research Site #703-104

Rimavská Sobota, Sobota, 97901, Slovakia

Location

Clinical Research Site #703-006

Banská Bystrica, 97404, Slovakia

Location

Clinical Research Site #703-002

Bardejov, 08501, Slovakia

Location

Clinical Research Site #703-005

Košice, 04001, Slovakia

Location

Clinical Research Site #703-003

Trenčín, 91108, Slovakia

Location

Clinical Research Site #703-001

Vranov nad Topľou, 09301, Slovakia

Location

Clinical Research Site #705-006

Murska Sobota, Brezovica, 9000, Slovenia

Location

Clinical Research Site #705-004

Begunje na Gorenjskem, 4275, Slovenia

Location

Clinical Research Site #705-003

Ljubljana, 1000, Slovenia

Location

Clinical Research Site #705-002

Ljubljana, 1260, Slovenia

Location

Clinical Research Site #705-005

Maribor, 2000, Slovenia

Location

Clinical Research Site #705-001

Nova Gorica, 52905000, Slovenia

Location

Clinical Research Site #724-013

Seville, Andalusia, 41013, Spain

Location

Clinical Research Site #724-011

Palma de Mallorca, Balearic Islands, 07120, Spain

Location

Clinical Research Site #724-012

Alicante, Valenciana, Comunitat, 03010, Spain

Location

Clinical Research Site # 724-007

Coslada, 28882, Spain

Location

Clinical Research Site #724-009

Madrid, 28006, Spain

Location

Clinical Research Site #724-006

Madrid, 28049, Spain

Location

MeSH Terms

Conditions

Psychomotor Agitation; Alzheimer Disease

Condition Hierarchy (Ancestors)

Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Psychomotor Disorders; Neurobehavioral Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Behavior; Dementia; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Limitations and Caveats

The study was prematurely terminated due to discontinuation of development of the AVP-786 compound.

Results Point of Contact

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

smb_clinicaltranspa@otsuka-us.com

08446878522

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: July 6, 2020
• First Posted: July 9, 2020
• Study Start: September 11, 2020
• Primary Completion: June 28, 2024
• Study Completion: June 28, 2024
• Last Updated: May 30, 2025
• Results First Posted: May 30, 2025

Record last verified: 2025-05

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 publication. There is no end date to the availability of the data.
• Access Criteria: Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/

Locations

CO (6); IE (4); CL (6); SL (7); US (46); CA (2); BE (4); CR (6); ME (8); NL (1); ES (6); HU (4)