Clinical trial NCT03393520: Assessment of 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
Official title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-design 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: COMPLETED
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: 2018-01-08
Enrollment: 601
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 will be conducted to evaluate the efficacy, safety, and tolerability of AVP-786 compared to placebo, for the treatment of agitation in participants with dementia of the Alzheimer's type.

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

This is a multicenter, randomized, double-blind, placebo-controlled, parallel-design study, consisting of 12 weeks of treatment.

Approximately 550 participants will be enrolled at approximately 90 centers worldwide.

Study medication will be administered orally twice-daily from Day 1 through Day 85. Screening will occur within approximately 4 weeks prior to randomization. Following screening procedures for assessment of inclusion and exclusion criteria, eligible participants will be randomized into the study.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of probable Alzheimer's Disease (AD) according to the 2011 National Institute on Aging-Alzheimer's Association (NIA-AA) working groups criteria
* Participants with clinically significant, moderate/severe agitation at the time of screening and for at least 2 weeks prior to baseline that interferes with their daily routine and for which a prescription medication has been indicated, in the opinion of the investigator
* The diagnosis of agitation must meet the provisional consensus definition of agitation in participants with cognitive disorders developed by the International Psychogeriatric Association (IPA) Agitation Definition Work Group.
* A Clinical Global Impression of Severity of Illness scale for Agitation (CGIS-Agitation) score of ≥ 4 (moderately ill) at screening and baseline
* Participants must have a reliable caregiver who is able and willing to comply with study procedures, including not administering any prohibited medications during the course of the study.
* Caregiver who is able and willing to comply with all required study procedures. In order to qualify as a reliable informant (i.e., caregiver) capable of assessing changes in participant's condition during the study, the individual must spend 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 AD (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, 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 Baseline to Week 12 in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score
timeFrame: Baseline; Week 12
Secondary outcomes:
measure: Change from Baseline to Week 12 in the Clinical Global Impression of Severity (CGIS)-Agitation Domain Score
timeFrame: Baseline; Week 12
Other outcomes:
Locations:
city: Chandler
country: United States
facility: MD First Research #767
state: Arizona
city: Gilbert
country: United States
facility: Liv Generations of Agritopia / CCT #573
state: Arizona
city: Phoenix
country: United States
facility: Liv Generations of Ahwatukee / CCT #784
state: Arizona
city: Scottsdale
country: United States
facility: Perseverance Research Center
state: Arizona
city: Tempe
country: United States
facility: Medical Advancement Center of Arizona #820
state: Arizona
city: Little Rock
country: United States
facility: Clinical Trials Inc.
state: Arkansas
city: Anaheim
country: United States
facility: Advanced Research Center, Inc #835
state: California
city: Costa Mesa
country: United States
facility: ATP Clinical Research, Inc #763
state: California
city: La Mesa
country: United States
facility: Paradigm Clinical Research Centers, Inc.
state: California
city: Lafayette
country: United States
facility: Sunwise Clinical Research #831
state: California
city: Lomita
country: United States
facility: Torrance Clinical Research Institute, Inc. #826
state: California
city: Long Beach
country: United States
facility: Rohun Medical Corporation Site #770
state: California
city: Long Beach
country: United States
facility: Alliance for Wellness, Inc dba Alliance for Research #789
state: California
city: Pasadena
country: United States
facility: Havana Research Institute
state: California
city: Altamonte Springs
country: United States
facility: Neurology of Central Florida Rsch Ctr # 803
state: Florida
city: Aventura
country: United States
facility: Negron Research Services / Humanity Clinical Research #766
state: Florida
city: Boca Raton
country: United States
facility: SFM Clinical Research, LLC #563
state: Florida
city: Boynton Beach
country: United States
facility: Helix Biomedics LLC
state: Florida
city: Bradenton
country: United States
facility: Bradenton Research Center #834
state: Florida
city: Brandon
country: United States
facility: Clinical Research of Brandon #838
state: Florida
city: Brooksville
country: United States
facility: ASCLEPES Research Center #806
state: Florida
city: Cutler Bay
country: United States
facility: Beautiful Minds Clinical Research Center #808
state: Florida
city: Doral
country: United States
facility: Science Connections, LLC #814
state: Florida
city: Hialeah
country: United States
facility: ConSalud Medical Research #773
state: Florida
city: Hialeah
country: United States
facility: Direct Helpers Research Center # 801
state: Florida
city: Hollywood
country: United States
facility: New Med Research Inc #812
state: Florida
city: Jupiter
country: United States
facility: Alphab Global Research #793
state: Florida
city: Lake Worth
country: United States
facility: Alzheimer's Research and Treatment Center
state: Florida
city: Lakeland
country: United States
facility: Meridien Research - Lakeland Site Site #558
state: Florida
city: Lauderdale Lakes
country: United States
facility: Zynak Clinical Services
state: Florida
city: Lauderhill
country: United States
facility: Adaptive Clinical Research, Inc. Site# 815
state: Florida
city: Lauderhill
country: United States
facility: Innovative Clinical Research, Inc Site #819
state: Florida
city: Miami Lakes
country: United States
facility: Crystal Biomedical Research, LLC
state: Florida
city: Miami Lakes
country: United States
facility: Agility Medical Research, Inc Site #816
state: Florida
city: Miami
country: United States
facility: Homestead Associates in Research #797
state: Florida
city: Miami
country: United States
facility: Premier Clinical Research Institute, Inc. #817
state: Florida
city: Miami
country: United States
facility: Central Miami Medical Institute # 798
state: Florida
city: Miami
country: United States
facility: Project4Research #774
state: Florida
city: Miami
country: United States
facility: City Medical Group RC
state: Florida
city: Miami
country: United States
facility: Finlay Medical Research Corp #552
state: Florida
city: Miami
country: United States
facility: First Class Medical Services #807
state: Florida
city: Miami
country: United States
facility: Miami Jewish Health Systems, Inc. #786
state: Florida
city: Miami
country: United States
facility: New Horizon Research Center Site #795
state: Florida
city: Miami
country: United States
facility: Reliant Medical Research, LLC #811
state: Florida
city: Miami
country: United States
facility: Clinical Research Associates of South Florida
state: Florida
city: Miami
country: United States
facility: P&S Research, LLC #805
state: Florida
city: Miami
country: United States
facility: Pharmax Research of South Florida
state: Florida
city: Miami
country: United States
facility: Research Institute of West Kendall
state: Florida
city: New Port Richey
country: United States
facility: Bayside Clinical Research
state: Florida
city: Orlando
country: United States
facility: Combined Research Orlando #799
state: Florida
city: Palmetto
country: United States
facility: Innovation Medical Research Center #802
state: Florida
city: Pompano Beach
country: United States
facility: Quantum Laboratories Site #768
state: Florida
city: Port Charlotte
country: United States
facility: Neurostudies Inc. Site# 796
state: Florida
city: Tampa
country: United States
facility: VICIS Clinical Research Inc. #777
state: Florida
city: Tampa
country: United States
facility: Academic Alliance in Dermatology
state: Florida
city: Tampa
country: United States
facility: JSV Clinical Research Study, Inc. #829
state: Florida
city: Decatur
country: United States
facility: NeuroStudies. Net, LLC
state: Georgia
city: Honolulu
country: United States
facility: Hawaii Pacific Neuroscience #833
state: Hawaii
city: Covington
country: United States
facility: DelRicht Research #776
state: Louisiana
city: Braintree
country: United States
facility: Alzheimer Disease Center #804
state: Massachusetts
city: Bloomfield
country: United States
facility: Neurobehavioral Medicine Group #828
state: Michigan
city: Caro
country: United States
facility: Onyx Clinical Research, LLC
state: Michigan
city: Troy
country: United States
facility: Oakland Medical Research #762
state: Michigan
city: Flowood
country: United States
facility: Precise Research Centers Site #765
state: Mississippi
city: Chesterfield
country: United States
facility: Galen Research Site #550
state: Missouri
city: O'Fallon
country: United States
facility: Psychiatric Care and Research Center #827
state: Missouri
city: Toms River
country: United States
facility: Bio Behavioral Health
state: New Jersey
city: New Windsor
country: United States
facility: Mid Hudson Medical Research, PLLC #836
state: New York
city: Orangeburg
country: United States
facility: Nathan S. Kline Institute for Psychiatric Research
state: New York
city: Woodmere
country: United States
facility: Five Towns Neurology PC/Village Site #764
state: New York
city: Charlotte
country: United States
facility: The Neurological Institute #843
state: North Carolina
city: Charlotte
country: United States
facility: New Hope Clinical Research
state: North Carolina
city: Beachwood
country: United States
facility: Insight Clinical Trials LLC #570
state: Ohio
city: Centerville
country: United States
facility: Valley Medical Research Site#788
state: Ohio
city: Columbus
country: United States
facility: Osumc #837
state: Ohio
city: Middleburg Heights
country: United States
facility: NorthStar Medical Research #778
state: Ohio
city: Youngstown
country: United States
facility: Onyx Clinical Research, LLC
state: Ohio
city: Oklahoma City
country: United States
facility: Newton Clinical Research
state: Oklahoma
city: Oklahoma City
country: United States
facility: Orenda Research & Consulting LLC #840
state: Oklahoma
city: Norristown
country: United States
facility: Keystone Clinical Studies, LLC
state: Pennsylvania
city: Carrollton
country: United States
facility: Trinity Universal Research Associates Site #821
state: Texas
city: Dallas
country: United States
facility: Texas Neurology #832
state: Texas
city: DeSoto
country: United States
facility: InSite Clinical Research
state: Texas
city: Houston
country: United States
facility: Bio Pharma Informatic LLC Site #822
state: Texas
city: Houston
country: United States
facility: Bio Pharma Informatic Inc Site #769
state: Texas
city: Katy
country: United States
facility: Katy Neurology #823
state: Texas
city: Lewisville
country: United States
facility: Northpointe Psychiatry #761
state: Texas
city: McKinney
country: United States
facility: Wellness Clinical Research #824
state: Texas
city: Mesquite
country: United States
facility: PRX Research Site #825
state: Texas
city: Salt Lake City
country: United States
facility: Wasatch Clinical Research, LLC Site #771
state: Utah
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Everett
country: United States
facility: Core Clinical Research # 772
state: Washington
city: Waukesha
country: United States
facility: IPC Research
state: Wisconsin
city: Nedlands
country: Australia
facility: Australian Alzheimer's Research Foundation
city: Noble Park
country: Australia
facility: Neuro Trials Victoria Pty Ltd
city: Parkville
country: Australia
facility: The Alfred Hospital
city: Pleven
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Dr. Georgi Stranski
city: Plovdiv
country: Bulgaria
facility: Medical Center Hipokrat-N EOOD
city: Ruse
country: Bulgaria
facility: Center for Mental Health - Ruse
city: Sofia
country: Bulgaria
facility: Mental Health Centre Prof.Nikola Shipkovenski #713
city: Sofia
country: Bulgaria
facility: DCC "Sv. Vrach and Sv. Sv. Kuzma and Damian" OOD #710
city: Sofia
country: Bulgaria
facility: First Multiprofile Hospital for Active Treatment Sofia
city: Sofia
country: Bulgaria
facility: Medical Center Stimul
city: Sofia
country: Bulgaria
facility: Medical Center Sveti Naum #707
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Alexandrovska
city: Varna
country: Bulgaria
facility: Diagnostic-consultative center Mladost-М Varna OOD #711
city: Veliko Tarnovo
country: Bulgaria
facility: Medica Plus Medical Center #705
city: Vratsa
country: Bulgaria
facility: Mental Health Center Site #712
city: Brno
country: Czechia
facility: MUDr. Marta Holanová Site# 733
city: Brno
country: Czechia
facility: Fakultni Nemocnice u sv. Anny v Brne #722
city: Hostivice
country: Czechia
facility: Clinline Services s.r.0 Psychiatricka ambulance #732
city: Hradec Kralové
country: Czechia
facility: Fakultní Nemocnice Hradec Králové #724
city: Hradec Králové
country: Czechia
facility: NeuropsychiatrieHK #729
city: Kladno
country: Czechia
facility: Brain-Soultherapy #728
city: Kutná Hora
country: Czechia
facility: Supervize #723
city: Plzen
country: Czechia
facility: A-Shine s.r.o.
city: Praha
country: Czechia
facility: Ad71 #727
city: Praha
country: Czechia
facility: Clintrial #720
city: Praha
country: Czechia
facility: INEP Medical s.r.o. Institut Neuropsychiatricke Pece #730
city: Praha
country: Czechia
facility: Neurologicka Ambulance - Forbeli #721
city: Praha
country: Czechia
facility: Neuropsychiatrie #726
city: Rychnov nad Kněžnou
country: Czechia
facility: Vestra Clinics #725
city: Caen cedex 9
country: France
facility: Centre Hospitalier Universitaire de Caen - Hôpital Côte de Nacre
city: Calais
country: France
facility: Centre Hospitalier de Calais
city: Dijon Cedex
country: France
facility: Centre Hospitalier Universitaire Dijon Bourgogn #536
city: Nantes Cedex
country: France
facility: Centre Hospitalier Universitaire de Nantes - Hôpital Nord Laennec #537
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire de Poitiers
city: Saint-Etienne
country: France
facility: Centre Hospitalier Universitaire de Saint-Étienne - Hôpital Nord #535
city: Toulouse
country: France
facility: Centre Hospitalier Universitaire Toulouse - Casselardit Ancely #533
city: Vandoeuvre les Nancy
country: France
facility: Centre Hospitalier Universitaire de Nancy - Hôpital de Brabois
city: Balassagyarmat
country: Hungary
facility: Dr. Kenessey Albert Kórház-Rendelőintézet
city: Budapest
country: Hungary
facility: Semmelweis Egyetem Site #595
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Budapest
country: Hungary
facility: Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak #586
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Kenezy Gyula Egyetemi Korhaz
city: Esztergom
country: Hungary
facility: Valeomed Egeszsegugyi es Szolgaltato Kft
city: Győr
country: Hungary
facility: Petz Aladár Egyetemi Oktató Kórház Site# 594
city: Kalocsa
country: Hungary
facility: Dr. Mathe es Tarsa Beteti Tarsasa Site #593
city: Miskolc
country: Hungary
facility: CRU Hungary Egészségügyi és Szolgáltató Korlátolt Felelősségű Társaság
city: Nyiregyhaza
country: Hungary
facility: Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz
city: Pecs
country: Hungary
facility: PsychoTech #580
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
city: Székesfehérvár
country: Hungary
facility: Fejér Megyei Szent György Egyetemi Oktató Kórház
city: Brescia
country: Italy
facility: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
city: Brescia
country: Italy
facility: Centro San Giovanni di Dio - Fatebenefratelli
city: Chieti
country: Italy
facility: Università degli studi G.D'Annunzio Chieti Pescara
city: Firenze
country: Italy
facility: Azienda Ospedaliero - Universitaria Careggi #610
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Monza
country: Italy
facility: Azienda Ospedaliera San Gerardo di Monza
city: Ponderano
country: Italy
facility: Azienda Sanitaria Locale di Biella - Nuovo Ospedale degli Infermi
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant'Andrea #606
city: Roma
country: Italy
facility: Fondazione Policlinico Tor Vergata #609
city: Roma
country: Italy
facility: Fondazione Santa Lucia - Istituto di Ricovero e Cura a Carattere Scientifico
city: Bydgoszcz
country: Poland
facility: Śródmieście Przychodnia - Bydgoszcz
city: Chorzów
country: Poland
facility: Centrum Medyczne Sensemed
city: Katowice
country: Poland
facility: Care Clinic #750
city: Katowice
country: Poland
facility: Wielospecjalistyczna Poradnia Lekarska Synapsis #741
city: Kraków
country: Poland
facility: Krakowska Akademia Neurologii #740
city: Kraków
country: Poland
facility: Pratia MCM Kraków #747
city: Lodz
country: Poland
facility: Medycyna Milorzab #743
city: Nowa Sól
country: Poland
facility: Twoja Przychodnia - Centrum Medyczne Nowa Sol #757
city: Plewiska
country: Poland
facility: Neurologiczny Niepubliczny Zakład Opieki Zdrowotnej
city: Poznań
country: Poland
facility: Centrum Medyczne HCP
city: Poznań
country: Poland
facility: Solumed Centrum Medyczne #753
city: Sochaczew
country: Poland
facility: RCMed Oddział Sochaczew #510
city: Suchy Las
country: Poland
facility: Amonaria Indywidualna Specjalistyczna Praktyka Lekarska Agnieszka Remlinger-Molenda #508
city: Szczecin
country: Poland
facility: Centrum Medyczne Euromedis
city: Warszawa
country: Poland
facility: Przychodnia Specjalistyczna Prosen Site#758
city: Warszawa
country: Poland
facility: Centrum Medyczne NeuroProtect
city: Warszawa
country: Poland
facility: Centrum Medyczne Pratia Warszawa
city: Zabrze
country: Poland
facility: ClinHouse Centrum Medyczne #755
city: Ścinawa
country: Poland
facility: Ośrodek Alzheimerowski #756
city: Cape Town
country: South Africa
facility: ACF Neurological Services
city: Cape Town
country: South Africa
facility: Cape Trial Centre #621
city: Cape Town
country: South Africa
facility: Flexivest Fourteen Research Centre #620
city: Johannesburg
country: South Africa
facility: Apollo Clinical Research #623
city: Rosebank
country: South Africa
facility: Medical and Dental Centre #625
city: Umhlanga
country: South Africa
facility: Dr. Chisto Carel Coetzee
city: Alcobendas
country: Spain
facility: Accellacare Alcobendas #659
state: Aocobendas
city: Barcelona
country: Spain
facility: Fundació ACE
city: Barcelona
country: Spain
facility: Fundació Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebrón
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia #647
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
city: Lleida
country: Spain
facility: Hospital Universitari de Santa Maria
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda #658
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca #656
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena #649
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico de La Fe
city: Zamora
country: Spain
facility: Complejo Asistencial de Zamora Hospital Virgen de la Concha #652
city: Zaragoza
country: Spain
facility: Hospital Viamed Montecanal #643
city: Barnsley
country: United Kingdom
facility: MAC Clinical Research - Barnsley Site #671
city: Bath
country: United Kingdom
facility: Research Institute for the Care of Older People
city: Belfast
country: United Kingdom
facility: Belfast Health and Social Care Trust
city: Blackpool
country: United Kingdom
facility: MAC Clinical Research - Blackpool
city: Cannock
country: United Kingdom
facility: MAC Clinical Research - Cannock #672
city: Leeds
country: United Kingdom
facility: MAC Clinical Research - Leeds
city: London
country: United Kingdom
facility: Re:Cognition Health - London
city: London
country: United Kingdom
facility: South London and Maudsley NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: MAC Clinical Research - Manchester
city: Northampton
country: United Kingdom
facility: Northamptonshire Healthcare NHS Foundation Trust #682
city: Prescot
country: United Kingdom
facility: MAC Clinical Research - Liverpool
city: Southampton
country: United Kingdom
facility: Southern Health NHS Foundation Trust #679
city: Swindon
country: United Kingdom
facility: Avon and Wiltshire Mental Health Partnership NHS Trust
city: Warrington
country: United Kingdom
facility: North West Boroughs Healthcare NHS Foundation Trust #685
Study officials:
References: