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

Phase 3

Terminated

• Conditions: Agitation in Patients With Dementia of the Alzheimer's Type
• Interventions: Drug: Placebo; Drug: AVP-786

• Registration Number: NCT04464564
• Lead Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

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.

Detailed Description

Eligible participants for this study had a diagnosis of probable Alzheimer's disease (AD) and had clinically significant, moderate/severe agitation secondary to AD.

This was multicenter, randomized, double-blind, placebo-controlled study, consisting of 12 weeks of treatment. Screening occurred within 4 weeks prior to randomization. Following screening procedures for assessment of inclusion and exclusion criteria, eligible participants were randomized into the study.

236 participants were randomized into the study.

Study medication was administered orally twice daily from Day 1 through Day 85.

Study Timeline

• Study First Submitted: 2020-07-06
• Study First Submitted QC: 2020-07-06
• Study First Posted: 2020-07-09
• Study Start: 2020-09-03
• Primary Completion: 2024-06-28
• Study Completion: 2024-06-28
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-17
• Last Update Posted: 2025-01-20

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 241

Inclusion Criteria

• 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

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants received AVP-786 matching placebo capsules, twice a day, over a 12-week treatment period.
AVP-786-18	AVP-786	Participants received AVP-786-18 (d6-DM 18 milligrams (mg)/Q 4.9 mg), twice a day, over a 12-week treatment period.
AVP-786-42.63	AVP-786	Participants received AVP-786-42.63 (d6-DM 42.63 mg/Q 4.9 mg) capsules, twice a day, over a 12-week treatment period.

Primary Outcome Measures

Name	Time	Method
Change from Baseline to Week 12 in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score	Baseline; Week 12

Secondary Outcome Measures

Name	Time	Method
Change from Baseline to Week 12 in the Clinical Global Impression of Severity of Illness (CGI-S) Score, as Related to Agitation	Baseline; Week 12

Trial Locations

Locations (106)

Clinical Research Site #840-020; 🇺🇸 Phoenix, Arizona, United States

Clinical Research Site #840-047; 🇺🇸 Anaheim, California, United States

Clinical Research Site #840-059; 🇺🇸 Lafayette, California, United States

Clinical Research Site #840-004; 🇺🇸 Los Angeles, California, United States

Clinical Research Site; 🇺🇸 San Diego, California, United States

Clinical Research Site #840-096; 🇺🇸 Cape Coral, Florida, United States

Clinical Research Site #840-090; 🇺🇸 Costa Mesa, California, United States

Clinical Research Site #840-095; 🇺🇸 Long Beach, California, United States

Clinical Research Site #840-066; 🇺🇸 Coral Springs, Florida, United States

Clinical Research Site #840-089; 🇺🇸 Kissimmee, Florida, United States

Clinical Research Site #840-037; 🇺🇸 Miami, Florida, United States

Clinical Research Site #840-051; 🇺🇸 Naples, Florida, United States

Clinical Research Site #840-104; 🇺🇸 Tampa, Florida, United States

Clinical Research Site #840-049; 🇺🇸 West Palm Beach, Florida, United States

Clinical Research Site #840-036; 🇺🇸 Winter Park, Florida, United States

Clinical Research Site #840-048; 🇺🇸 Lomita, California, United States

Clinical Research Site #840-006; 🇺🇸 Panorama City, California, United States

Clinical Research Site #840-070; 🇺🇸 Apopka, Florida, United States

Clinical Research Site #840-007; 🇺🇸 Miami, Florida, United States

Clinical Research Site #840-042; 🇺🇸 Miami, Florida, United States

Clinical Research Site #840-087; 🇺🇸 Orlando, Florida, United States

Clinical Research Site 840-028; 🇺🇸 Pensacola, Florida, United States

Clinical Research Site #840-055; 🇺🇸 Bradenton, Florida, United States

Clinical Research Site #840-077; 🇺🇸 Clermont, Florida, United States

Clinical Research Site #840-039; 🇺🇸 Hallandale Beach, Florida, United States

Clinical Research Site #840-034; 🇺🇸 Lady Lake, Florida, United States

Clinical Research Site #840-103; 🇺🇸 Miami, Florida, United States

Clinical Research Site #840-092; 🇺🇸 Miami, Florida, United States

Clinical Research Site #840-041; 🇺🇸 Miami, Florida, United States

Clinical Research Site # 840-105; 🇺🇸 Tampa, Florida, United States

Clinical Research Site #840-065; 🇺🇸 Atlanta, Georgia, United States

Clinical Research Site #840-030; 🇺🇸 Chicago, Illinois, United States

Clinical Research Site #840-073; 🇺🇸 Boston, Massachusetts, United States

Clinical Research Site #840-014; 🇺🇸 Bloomfield Township, Michigan, United States

Clinical Research Site #840-022; 🇺🇸 Detroit, Michigan, United States

Clinical Research Site #840-024; 🇺🇸 O'Fallon, Missouri, United States

Clinical Research Site #840-031; 🇺🇸 Buffalo, New York, United States

Clinical Research Site #840-021; 🇺🇸 Manhasset, New York, United States

Clinical Research Site #840-058; 🇺🇸 New Hyde Park, New York, United States

Clinical Research Site #840-035; 🇺🇸 Cypress, Texas, United States

Clinical Research Site #840-053; 🇺🇸 Dallas, Texas, United States

Clinical Research Site #840-093; 🇺🇸 El Paso, Texas, United States

Clinical Research Site #840-072; 🇺🇸 Houston, Texas, United States

Clinical Research Site #840-057; 🇺🇸 Houston, Texas, United States

Clinical Research Site #840-086; 🇺🇸 Mesquite, Texas, United States

Clinical Research Site #840-044; 🇺🇸 Fairfax, Virginia, United States

Clinical Research Site #056-005; 🇧🇪 Alken, Limburg, Belgium

Clinical Research Site #056-004; 🇧🇪 Brussel, Belgium

Clinical Research Site #056-003; 🇧🇪 Leuven, Belgium

Clinical Research Site # 056-002; 🇧🇪 Liège, Belgium

Clinical Research Site #124-003; 🇨🇦 Kelowna, British Columbia, Canada

Clinical Research Site #124-008; 🇨🇦 Quebec City, Quebec, Canada

Clinical Research Site #152-003; 🇨🇱 Santiago, Chile

Clinical Research Site #348-002; 🇭🇺 Gyöngyös, Heves, Hungary

Clinical Research Site #384-003; 🇭🇺 Budapest, Hungary

Clinical Research Site #484-008; 🇲🇽 Merida, Mexico

Clinical Research Site #152-007; 🇨🇱 Viña Del Mar, Region Metropolitana De Santiago, Chile

Clinical Research Site #170-002; 🇨🇴 Pereira, Columbia, Colombia

Clinical Research Site #152-002; 🇨🇱 Antofagasta, Chile

Clinical Research Site #152-001; 🇨🇱 Santiago de Chile, Chile

Clinical Research Site #170-001; 🇨🇴 Bogota, Colombia

Clinical Research Site #170-004; 🇨🇴 Bogotá, Colombia

Clinical Research Site #191-008; 🇭🇷 Pula, Istarska Županija, Croatia

Clinical Research Site# 191-001; 🇭🇷 Zagreb, Croatia

Clinical Research Site #191-003; 🇭🇷 Zagreb, Croatia

Clinical Research Site #372-003; 🇮🇪 Cork, Ireland

Clinical Research Site #484-005; 🇲🇽 Monterrey, Mexico

Clinical Research Site #484-009; 🇲🇽 Tlalnepantla, Mexico

Clinical Trial Site #528-001; 🇳🇱 Amsterdam, Netherlands

Clinical Research Site #703-009; 🇸🇰 Dubnica Nad Váhom, Bratislavský Kraj, Slovakia

Clinical Research Site #703-104; 🇸🇰 Rimavska Sobota, Sobota, Slovakia

Clinical Research Site #703-006; 🇸🇰 Banská Bystrica, Slovakia

Clinical Research Site #152-005; 🇨🇱 Independencia, Chile

Clinical Research Site #191-002; 🇭🇷 Zagreb, Croatia

Clinical Research Site #384-001; 🇭🇺 Budapest, Hungary

Clinical Research Site #372-002; 🇮🇪 Cork, Ireland

Clinical Research Site #372-001; 🇮🇪 Dublin, Ireland

Clinical Research Site # 484-003; 🇲🇽 Monterrey, Mexico

Clinical Research Site # 484-002; 🇲🇽 Sinaloa, Mexico

Clinical Research Site #152-006; 🇨🇱 Santiago de Chile, Chile

Clinical Research Site #170-003; 🇨🇴 Bogota, Columbia, Colombia

Clinical Research Site #170-007; 🇨🇴 Florida Blanca, Santander, Colombia

Clinical Research Site #170-006; 🇨🇴 Bello, Colombia

Clinical Research Site #372-004; 🇮🇪 Dublin, Ireland

Clinical Research Site #484-006; 🇲🇽 Monterrey, Mexico

Clinical Research Site# 191-006; 🇭🇷 Rijeka, Croatia

Clinical Research Site #191-005; 🇭🇷 Zagreb, Croatia

Clinical Research Site #348-004; 🇭🇺 Zalaegerszeg, Hungary

Clinical Research Site # 484-004; 🇲🇽 Mexico City, Mexico

Clinical Research Site #484-010; 🇲🇽 Saltillo, Mexico

Clinical Research Site #703-002; 🇸🇰 Bardejov, Slovakia

Clinical Research Site #703-005; 🇸🇰 Košice, Slovakia

Clinical Research Site #703-003; 🇸🇰 Trencin, Slovakia

Clinical Research Site #703-001; 🇸🇰 Vranov Nad Topľou, Slovakia

Clinical Research Site #705-006; 🇸🇮 Murska Sobota, Brezovica, Slovenia

Clinical Research Site #705-004; 🇸🇮 Begunje na Gorenjskem, Slovenia

Clinical Research Site #705-003; 🇸🇮 Ljubljana, Slovenia

Clinical Research Site #705-002; 🇸🇮 Ljubljana, Slovenia

Clinical Research Site #705-005; 🇸🇮 Maribor, Slovenia

Clinical Research Site #705-001; 🇸🇮 Nova Gorica, Slovenia

Clinical Research Site #724-013; 🇪🇸 Seville, Andalucía, Spain

Clinical Research Site #724-011; 🇪🇸 Palma De Mallorca, Baleares, Spain

Clinical Research Site #724-012; 🇪🇸 Alicante, Valenciana, Comunitat, Spain

Clinical Research Site # 724-007; 🇪🇸 Coslada, Spain

Clinical Research Site #724-009; 🇪🇸 Madrid, Spain

Clinical Research Site #724-006; 🇪🇸 Madrid, Spain