Clinical trial NCT04408755: Assessment of 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: 2020-05-29
Enrollment: 184
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 a 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.

184 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: Fort Smith
country: United States
facility: Clinical Research Site #840-081
state: Arkansas
city: La Jolla
country: United States
facility: Clinical Research Site #840-035
state: California
city: Los Angeles
country: United States
facility: Clinical Research Site #840-084
state: California
city: Oceanside
country: United States
facility: Clinical Research Site #840-050
state: California
city: Pasadena
country: United States
facility: Clinical Research Site #840-064
state: California
city: Santa Ana
country: United States
facility: Clinical Research Site #840-098
state: California
city: Basalt
country: United States
facility: Clinical Research Site #840-090
state: Colorado
city: Atlantis
country: United States
facility: Clinical Research Site #840-009
state: Florida
city: Brandon
country: United States
facility: Clinical Research Site #840-056
state: Florida
city: Coral Gables
country: United States
facility: Clinical Research Site #840-020
state: Florida
city: Doral
country: United States
facility: Clinical Research Site #840-059
state: Florida
city: Hialeah
country: United States
facility: Clinical Research Site #840-131
state: Florida
city: Jacksonville
country: United States
facility: Clinical Research Site #840-039
state: Florida
city: Kissimmee
country: United States
facility: Clinical Research Site #840-012
state: Florida
city: Maitland
country: United States
facility: Clinical Research Site #840-069
state: Florida
city: Maitland
country: United States
facility: Clinical Research Site #840-083
state: Florida
city: Miami
country: United States
facility: Clinical Research Site #840-118
state: Florida
city: Miami
country: United States
facility: Clinical Research Site #840-004
state: Florida
city: Miami
country: United States
facility: Clinical Research Site #840-125
state: Florida
city: Miami
country: United States
facility: Clinical Research Site #840-104
state: Florida
city: Miami
country: United States
facility: Clinical Research Site #840-133
state: Florida
city: Miami
country: United States
facility: Clinical Research Site #840-042
state: Florida
city: Miami
country: United States
facility: Clinical Research Site #840-003
state: Florida
city: Orlando
country: United States
facility: Clinical Research Site #840-036
state: Florida
city: Pembroke Pines
country: United States
facility: Clinical Research Site 840-111
state: Florida
city: Pensacola
country: United States
facility: Clinical Research Site #840-096
state: Florida
city: Pompano Beach
country: United States
facility: Clinical Research Site
state: Florida
city: Tampa
country: United States
facility: Clinical Research Site #840-079
state: Florida
city: Tampa
country: United States
facility: Clinical Research Site #840-112
state: Florida
city: Tampa
country: United States
facility: Clinical Research Site #840-046
state: Florida
city: West Palm Beach
country: United States
facility: Clinical Research Site #840-107
state: Florida
city: Glen Burnie
country: United States
facility: Clinical Research Site #840-049
state: Maryland
city: Rochester Hills
country: United States
facility: Clinical Research Site #840-093
state: Michigan
city: Hattiesburg
country: United States
facility: Clinical Research Site #840-015
state: Mississippi
city: West Long Branch
country: United States
facility: Clinical Research Site #840-029
state: New Jersey
city: Bronx
country: United States
facility: Clinical Research Site #840-097
state: New York
city: New Windsor
country: United States
facility: Clinical Research Site #840-072
state: New York
city: Monroe
country: United States
facility: Clinical Research Site #840-095
state: North Carolina
city: Canton
country: United States
facility: Clinical Research Site #840-060
state: Ohio
city: Columbus
country: United States
facility: Clinical Research Site #840-028
state: Ohio
city: Edmond
country: United States
facility: Clinical Research Site #840-061
state: Oklahoma
city: Tulsa
country: United States
facility: Clinical Research Site #840-099
state: Oklahoma
city: McKinney
country: United States
facility: Clinical Research Site #840-115
state: Texas
city: The Woodlands
country: United States
facility: Clinical Research Site
state: Texas
city: Richmond
country: United States
facility: Clinical Research Site #840-025
state: Virginia
city: Pernik
country: Bulgaria
facility: Clinical Research Site #100-115
city: Pleven
country: Bulgaria
facility: Clinical Research Site #100-112
city: Plovdiv
country: Bulgaria
facility: Clinical Research Site #100-106
city: Sofia
country: Bulgaria
facility: Clinical Research Site #100-102
city: Sofia
country: Bulgaria
facility: Clinical Research Site #100-111
city: Varna
country: Bulgaria
facility: Clinical Research Site #100-105
city: Varna
country: Bulgaria
facility: Clinical Research Site #100-108
city: Veliko Tarnovo
country: Bulgaria
facility: Clinical Research Site #100-113
city: Aalborg
country: Denmark
facility: Clinical Research Site # 208-001
state: Region Nordjylland
city: Aalborg
country: Denmark
facility: Clinical Research Site #208-002
city: Tallinn
country: Estonia
facility: Clinical Research Site #1 Site #233-002
city: Tallinn
country: Estonia
facility: Clinical Research Site #2 Site #233-004
city: Tartu
country: Estonia
facility: Clinical Research Site #233-001
city: Böblingen
country: Germany
facility: Clinical Research Site #276-017
state: Baden-Württemberg
city: Bad Homburg Vor Der Höhe
country: Germany
facility: Clinical Research Site #276-005
state: Hessen
city: Gera
country: Germany
facility: Clinical Research Site #276-012
state: Thüringen
city: Berlin
country: Germany
facility: Clinical Research Site 276-014
city: Athens
country: Greece
facility: Clinical Research Site# 300-005
city: Ioannina
country: Greece
facility: Clinical Research Site #300-006
city: Thessaloníki
country: Greece
facility: Clinical Research Site #300-003
city: Zabrze
country: Poland
facility: Clinical Research Site #616-018
state: Katowice
city: Bydgoszcz
country: Poland
facility: Clinical Research Site #616-009
state: Kujawsko-Pomorskie
city: Lublin
country: Poland
facility: Clinical Research Site #616-006
state: Lubelskie
city: Sochaczew
country: Poland
facility: Clinical Research Site #616-015
state: Mazowieckie
city: Bydgoszcz
country: Poland
facility: Clinical Research Site #616-013
city: Kielce
country: Poland
facility: Clinical Research Site #616-004
city: Lublin
country: Poland
facility: Clinical Research Site #616-008
city: Lublin
country: Poland
facility: Clinical Research Site #616-010
city: Poznan
country: Poland
facility: Clinical Research Site #616-012
city: Poznan
country: Poland
facility: Clinical Research Site #616-005
city: Pruszcz Gdanski
country: Poland
facility: Clinical Research Site #616-001
city: Warszawa
country: Poland
facility: Clinical Research Site #616-007
city: Guimarães
country: Portugal
facility: Clinical Research Site #620-007
state: Braga
city: Braga
country: Portugal
facility: Clinical Research Site #620-004
city: Coimbra
country: Portugal
facility: Clinical Research Site #620-005
city: Torres Vedras
country: Portugal
facility: Clinical Research Site #620-002
city: Bayamon
country: Puerto Rico
facility: Clinical Research Site #630-001
city: Rio Piedras
country: Puerto Rico
facility: Clinical Research Site #630-003
city: San Juan
country: Puerto Rico
facility: Clinical Research Site #630-002
city: San Juan
country: Puerto Rico
facility: Clinical Research Site #630-005
city: Dnipro
country: Ukraine
facility: Clinical Research Site #804-006
city: Kharkiv
country: Ukraine
facility: Clinical Research Site #804-003
city: Kiev
country: Ukraine
facility: Clinical Research Site #804-004
city: Kyiv
country: Ukraine
facility: Clinical Research Site #804-005
city: Lviv
country: Ukraine
facility: Clinical Research Site #804-007
city: Blandford Forum
country: United Kingdom
facility: Clinical Research Site #826-003
city: Crowborough
country: United Kingdom
facility: Clinical Research Site #826-004
city: Fulwood
country: United Kingdom
facility: Clinical Research Site #826-001
city: Manchester
country: United Kingdom
facility: Clinical Research Site# 826-006
city: Motherwell
country: United Kingdom
facility: Clinical Research Site #826-002
Study officials:
References: