Clinical trial NCT04464564: 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
Official title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety, and Tolerability of AVP-786 (Deudextromethorphan 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: TERMINATED
Phase: PHASE3
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
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
First posted: 2020-07-09
Enrollment: 241
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: 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.

241 participants were enrolled into the study.

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

Eligibility criteria: 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

Primary outcomes:
measure: Change From the End of Period A (Week 1) to Week 10 in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score
timeFrame: Week 1 to Week 10
measure: Number of Participants With Treatment Emergent Adverse Events (TEAE) and Serious TEAE
timeFrame: From randomization (Week 2) up to 30 days after last dose of study drug (Up to Week 16)
Secondary outcomes:
measure: 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
timeFrame: Week 1 to Week 10
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Clinical Research Site #840-020
state: Arizona
city: Anaheim
country: United States
facility: Clinical Research Site #840-047
state: California
city: Costa Mesa
country: United States
facility: Clinical Research Site #840-090
state: California
city: Lafayette
country: United States
facility: Clinical Research Site #840-059
state: California
city: Lomita
country: United States
facility: Clinical Research Site #840-048
state: California
city: Long Beach
country: United States
facility: Clinical Research Site #840-095
state: California
city: Los Angeles
country: United States
facility: Clinical Research Site #840-004
state: California
city: Panorama City
country: United States
facility: Clinical Research Site #840-006
state: California
city: San Diego
country: United States
facility: Clinical Research Site
state: California
city: Apopka
country: United States
facility: Clinical Research Site #840-070
state: Florida
city: Bradenton
country: United States
facility: Clinical Research Site #840-055
state: Florida
city: Cape Coral
country: United States
facility: Clinical Research Site #840-096
state: Florida
city: Clermont
country: United States
facility: Clinical Research Site #840-077
state: Florida
city: Coral Springs
country: United States
facility: Clinical Research Site #840-066
state: Florida
city: Hallandale Beach
country: United States
facility: Clinical Research Site #840-039
state: Florida
city: Kissimmee
country: United States
facility: Clinical Research Site #840-089
state: Florida
city: Lady Lake
country: United States
facility: Clinical Research Site #840-034
state: Florida
city: Miami
country: United States
facility: Clinical Research Site #840-037
state: Florida
city: Miami
country: United States
facility: Clinical Research Site #840-092
state: Florida
city: Miami
country: United States
facility: Clinical Research Site #840-041
state: Florida
city: Miami
country: United States
facility: Clinical Research Site #840-007
state: Florida
city: Miami
country: United States
facility: Clinical Research Site #840-103
state: Florida
city: Miami
country: United States
facility: Clinical Research Site #840-042
state: Florida
city: Naples
country: United States
facility: Clinical Research Site #840-051
state: Florida
city: Orlando
country: United States
facility: Clinical Research Site #840-087
state: Florida
city: Pensacola
country: United States
facility: Clinical Research Site 840-028
state: Florida
city: Tampa
country: United States
facility: Clinical Research Site # 840-105
state: Florida
city: Tampa
country: United States
facility: Clinical Research Site #840-104
state: Florida
city: West Palm Beach
country: United States
facility: Clinical Research Site #840-049
state: Florida
city: Winter Park
country: United States
facility: Clinical Research Site #840-036
state: Florida
city: Atlanta
country: United States
facility: Clinical Research Site #840-065
state: Georgia
city: Chicago
country: United States
facility: Clinical Research Site #840-030
state: Illinois
city: Boston
country: United States
facility: Clinical Research Site #840-073
state: Massachusetts
city: Bloomfield Township
country: United States
facility: Clinical Research Site #840-014
state: Michigan
city: Detroit
country: United States
facility: Clinical Research Site #840-022
state: Michigan
city: O'Fallon
country: United States
facility: Clinical Research Site #840-024
state: Missouri
city: Buffalo
country: United States
facility: Clinical Research Site #840-031
state: New York
city: Manhasset
country: United States
facility: Clinical Research Site #840-021
state: New York
city: New Hyde Park
country: United States
facility: Clinical Research Site #840-058
state: New York
city: Cypress
country: United States
facility: Clinical Research Site #840-035
state: Texas
city: Dallas
country: United States
facility: Clinical Research Site #840-053
state: Texas
city: El Paso
country: United States
facility: Clinical Research Site #840-093
state: Texas
city: Houston
country: United States
facility: Clinical Research Site #840-072
state: Texas
city: Houston
country: United States
facility: Clinical Research Site #840-057
state: Texas
city: Mesquite
country: United States
facility: Clinical Research Site #840-086
state: Texas
city: Fairfax
country: United States
facility: Clinical Research Site #840-044
state: Virginia
city: Alken
country: Belgium
facility: Clinical Research Site #056-005
state: Limburg
city: Brussel
country: Belgium
facility: Clinical Research Site #056-004
city: Leuven
country: Belgium
facility: Clinical Research Site #056-003
city: Liège
country: Belgium
facility: Clinical Research Site # 056-002
city: Kelowna
country: Canada
facility: Clinical Research Site #124-003
state: British Columbia
city: Quebec City
country: Canada
facility: Clinical Research Site #124-008
state: Quebec
city: Viña Del Mar
country: Chile
facility: Clinical Research Site #152-007
state: Region Metropolitana De Santiago
city: Antofagasta
country: Chile
facility: Clinical Research Site #152-002
city: Independencia
country: Chile
facility: Clinical Research Site #152-005
city: Santiago de Chile
country: Chile
facility: Clinical Research Site #152-001
city: Santiago de Chile
country: Chile
facility: Clinical Research Site #152-006
city: Santiago
country: Chile
facility: Clinical Research Site #152-003
city: Bogota
country: Colombia
facility: Clinical Research Site #170-003
state: Columbia
city: Pereira
country: Colombia
facility: Clinical Research Site #170-002
state: Columbia
city: Florida Blanca
country: Colombia
facility: Clinical Research Site #170-007
state: Santander
city: Bello
country: Colombia
facility: Clinical Research Site #170-006
city: Bogota
country: Colombia
facility: Clinical Research Site #170-001
city: Bogotá
country: Colombia
facility: Clinical Research Site #170-004
city: Pula
country: Croatia
facility: Clinical Research Site #191-008
state: Istarska Županija
city: Rijeka
country: Croatia
facility: Clinical Research Site# 191-006
city: Zagreb
country: Croatia
facility: Clinical Research Site# 191-001
city: Zagreb
country: Croatia
facility: Clinical Research Site #191-003
city: Zagreb
country: Croatia
facility: Clinical Research Site #191-005
city: Zagreb
country: Croatia
facility: Clinical Research Site #191-002
city: Gyöngyös
country: Hungary
facility: Clinical Research Site #348-002
state: Heves
city: Budapest
country: Hungary
facility: Clinical Research Site #384-001
city: Budapest
country: Hungary
facility: Clinical Research Site #384-003
city: Zalaegerszeg
country: Hungary
facility: Clinical Research Site #348-004
city: Cork
country: Ireland
facility: Clinical Research Site #372-002
city: Cork
country: Ireland
facility: Clinical Research Site #372-003
city: Dublin
country: Ireland
facility: Clinical Research Site #372-004
city: Dublin
country: Ireland
facility: Clinical Research Site #372-001
city: Merida
country: Mexico
facility: Clinical Research Site #484-008
city: Mexico City
country: Mexico
facility: Clinical Research Site # 484-004
city: Monterrey
country: Mexico
facility: Clinical Research Site #484-006
city: Monterrey
country: Mexico
facility: Clinical Research Site #484-005
city: Monterrey
country: Mexico
facility: Clinical Research Site # 484-003
city: Saltillo
country: Mexico
facility: Clinical Research Site #484-010
city: Sinaloa
country: Mexico
facility: Clinical Research Site # 484-002
city: Tlalnepantla
country: Mexico
facility: Clinical Research Site #484-009
city: Amsterdam
country: Netherlands
facility: Clinical Trial Site #528-001
city: Dubnica Nad Váhom
country: Slovakia
facility: Clinical Research Site #703-009
state: Bratislavský Kraj
city: Rimavska Sobota
country: Slovakia
facility: Clinical Research Site #703-104
state: Sobota
city: Banská Bystrica
country: Slovakia
facility: Clinical Research Site #703-006
city: Bardejov
country: Slovakia
facility: Clinical Research Site #703-002
city: Košice
country: Slovakia
facility: Clinical Research Site #703-005
city: Trencin
country: Slovakia
facility: Clinical Research Site #703-003
city: Vranov Nad Topľou
country: Slovakia
facility: Clinical Research Site #703-001
city: Murska Sobota
country: Slovenia
facility: Clinical Research Site #705-006
state: Brezovica
city: Begunje na Gorenjskem
country: Slovenia
facility: Clinical Research Site #705-004
city: Ljubljana
country: Slovenia
facility: Clinical Research Site #705-003
city: Ljubljana
country: Slovenia
facility: Clinical Research Site #705-002
city: Maribor
country: Slovenia
facility: Clinical Research Site #705-005
city: Nova Gorica
country: Slovenia
facility: Clinical Research Site #705-001
city: Seville
country: Spain
facility: Clinical Research Site #724-013
state: Andalucía
city: Palma De Mallorca
country: Spain
facility: Clinical Research Site #724-011
state: Baleares
city: Alicante
country: Spain
facility: Clinical Research Site #724-012
state: Valenciana, Comunitat
city: Coslada
country: Spain
facility: Clinical Research Site # 724-007
city: Madrid
country: Spain
facility: Clinical Research Site #724-009
city: Madrid
country: Spain
facility: Clinical Research Site #724-006
Study officials:
References: