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

NCT04408755 | Terminated Phase 3 Results FDA Drug

• 3 other identifiers: 20-AVP-786-3062020-000798-262023-504990-19-00
• Study Type: interventional
• Target: 184
• Locations: 11 countries
• Sites: 95

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 (95)

Clinical Research Site #840-081

Fort Smith, Arkansas, 72901, United States

Location

Clinical Research Site #840-035

La Jolla, California, 92093, United States

Location

Clinical Research Site #840-084

Los Angeles, California, 70072, United States

Location

Clinical Research Site #840-050

Oceanside, California, 92056, United States

Location

Clinical Research Site #840-064

Pasadena, California, 91105, United States

Location

Clinical Research Site #840-098

Santa Ana, California, 92705, United States

Location

Clinical Research Site #840-090

Basalt, Colorado, 81621, United States

Location

Clinical Research Site #840-009

Atlantis, Florida, 33462, United States

Location

Clinical Research Site #840-056

Brandon, Florida, 33511, United States

Location

Clinical Research Site #840-020

Coral Gables, Florida, 33134, United States

Location

Clinical Research Site #840-059

Doral, Florida, 33166, United States

Location

Clinical Research Site #840-131

Hialeah, Florida, 33012, United States

Location

Clinical Research Site #840-039

Jacksonville, Florida, 32256, United States

Location

Clinical Research Site #840-012

Kissimmee, Florida, 34744, United States

Location

Clinical Research Site #840-069

Maitland, Florida, 32751, United States

Location

Clinical Research Site #840-083

Maitland, Florida, 32751, United States

Location

Clinical Research Site #840-118

Miami, Florida, 33032, United States

Location

Clinical Research Site #840-004

Miami, Florida, 33126, United States

Location

Clinical Research Site #840-125

Miami, Florida, 33126, United States

Location

Clinical Research Site #840-104

Miami, Florida, 33144, United States

Location

Clinical Research Site #840-133

Miami, Florida, 33165, United States

Location

Clinical Research Site #840-042

Miami, Florida, 33175, United States

Location

Clinical Research Site #840-003

Miami, Florida, 33467, United States

Location

Clinical Research Site #840-036

Orlando, Florida, 32819, United States

Location

Clinical Research Site 840-111

Pembroke Pines, Florida, 33024, United States

Location

Clinical Research Site #840-096

Pensacola, Florida, 32503, United States

Location

Clinical Research Site

Pompano Beach, Florida, 33064, United States

Location

Clinical Research Site #840-079

Tampa, Florida, 33614, United States

Location

Clinical Research Site #840-112

Tampa, Florida, 33615, United States

Location

Clinical Research Site #840-046

Tampa, Florida, 33634, United States

Location

Clinical Research Site #840-107

West Palm Beach, Florida, 33407, United States

Location

Clinical Research Site #840-049

Glen Burnie, Maryland, 21061, United States

Location

Clinical Research Site #840-093

Rochester Hills, Michigan, 48307, United States

Location

Clinical Research Site #840-015

Hattiesburg, Mississippi, 39401, United States

Location

Clinical Research Site #840-029

West Long Branch, New Jersey, 07764, United States

Location

Clinical Research Site #840-072

New Windsor, New York, 12553, United States

Location

Clinical Research Site #840-097

The Bronx, New York, 10466, United States

Location

Clinical Research Site #840-095

Monroe, North Carolina, 28112, United States

Location

Clinical Research Site #840-060

Canton, Ohio, 44718, United States

Location

Clinical Research Site #840-028

Columbus, Ohio, 43210, United States

Location

Clinical Research Site #840-061

Edmond, Oklahoma, 73012, United States

Location

Clinical Research Site #840-099

Tulsa, Oklahoma, 74136, United States

Location

Clinical Research Site #840-115

McKinney, Texas, 75069, United States

Location

Clinical Research Site

The Woodlands, Texas, 77381, United States

Location

Clinical Research Site #840-025

Richmond, Virginia, 23236, United States

Location

Clinical Research Site #100-115

Pernik, 2300, Bulgaria

Location

Clinical Research Site #100-112

Pleven, 5800, Bulgaria

Location

Clinical Research Site #100-106

Plovdiv, 4002, Bulgaria

Location

Clinical Research Site #100-102

Sofia, 1408, Bulgaria

Location

Clinical Research Site #100-111

Sofia, 1408, Bulgaria

Location

Clinical Research Site #100-105

Varna, 9020, Bulgaria

Location

Clinical Research Site #100-108

Varna, 9020, Bulgaria

Location

Clinical Research Site #100-113

Veliko Tarnovo, 5006, Bulgaria

Location

Clinical Research Site # 208-001

Aalborg, North Denmark, 9000, Denmark

Location

Clinical Research Site #208-002

Aalborg, 9000, Denmark

Location

Clinical Research Site #1 Site #233-002

Tallinn, 11315, Estonia

Location

Clinical Research Site #2 Site #233-004

Tallinn, 11315, Estonia

Location

Clinical Research Site #233-001

Tartu, 50406, Estonia

Location

Clinical Research Site #276-017

Böblingen, Baden-Wurttemberg, 71034, Germany

Location

Clinical Research Site #276-005

Bad Homburg, Hesse, 61348, Germany

Location

Clinical Research Site #276-012

Gera, Thuringia, 935, Germany

Location

Clinical Research Site 276-014

Berlin, 13187, Germany

Location

Clinical Research Site# 300-005

Athens, 15125, Greece

Location

Clinical Research Site #300-006

Ioannina, 45500, Greece

Location

Clinical Research Site #300-003

Thessaloniki, 54645, Greece

Location

Clinical Research Site #616-018

Zabrze, Katowice, 41-807, Poland

Location

Clinical Research Site #616-009

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-023, Poland

Location

Clinical Research Site #616-006

Lublin, Lublin Voivodeship, 20-093, Poland

Location

Clinical Research Site #616-015

Sochaczew, Masovian Voivodeship, 96-500, Poland

Location

Clinical Research Site #616-013

Bydgoszcz, 85-163, Poland

Location

Clinical Research Site #616-004

Kielce, 25-411, Poland

Location

Clinical Research Site #616-008

Lublin, 20-064, Poland

Location

Clinical Research Site #616-010

Lublin, 20-080, Poland

Location

Clinical Research Site #616-012

Poznan, 60-369, Poland

Location

Clinical Research Site #616-005

Poznan, 61-853, Poland

Location

Clinical Research Site #616-001

Pruszcz Gdański, 83-000, Poland

Location

Clinical Research Site #616-007

Warsaw, 01-737, Poland

Location

Clinical Research Site #620-007

Guimarães, Braga District, 4835-044, Portugal

Location

Clinical Research Site #620-004

Braga, 4710-243, Portugal

Location

Clinical Research Site #620-005

Coimbra, 3000-075, Portugal

Location

Clinical Research Site #620-002

Torres Vedras, 2560-280, Portugal

Location

Clinical Research Site #630-001

Bayamón, 00961, Puerto Rico

Location

Clinical Research Site #630-003

Rio Piedras, 00935, Puerto Rico

Location

Clinical Research Site #630-002

San Juan, 00918, Puerto Rico

Location

Clinical Research Site #630-005

San Juan, 926, Puerto Rico

Location

Clinical Research Site #804-006

Dnipro, 49005, Ukraine

Location

Clinical Research Site #804-003

Kharkiv, 61068, Ukraine

Location

Clinical Research Site #804-004

Kiev, 8631, Ukraine

Location

Clinical Research Site #804-005

Kyiv, 04080, Ukraine

Location

Clinical Research Site #804-007

Lviv, 79021, Ukraine

Location

Clinical Research Site #826-003

Blandford Forum, DT11 7DD, United Kingdom

Location

Clinical Research Site #826-004

Crowborough, TN61NY, United Kingdom

Location

Clinical Research Site #826-001

Fulwood, PR2 9HT, United Kingdom

Location

Clinical Research Site# 826-006

Manchester, M25 3BL, United Kingdom

Location

Clinical Research Site #826-002

Motherwell, ML1 4UF, United Kingdom

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: May 26, 2020
• First Posted: May 29, 2020
• Study Start: July 13, 2020
• Primary Completion: June 27, 2024
• Study Completion: June 27, 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

PT (4); GR (3); BU (8); PL (12); PR (4); ES (3); DE (4); US (45); UA (5); GB (5); DK (2)