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

Agitation in Patients With Dementia of the Alzheimer's Type Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03393520
• Other study ID #: 17-AVP-786-305
• Secondary ID: 2017-001339-38
• Status: Completed
• Phase: Phase 3
• Start date: October 13, 2017
• Est. completion date: December 14, 2023

Study information

• Verified date: August 2023
• Source: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 601
• Est. completion date: December 14, 2023
• Est. primary completion date: November 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Agitation in Patients With Dementia of the Alzheimer's Type
• Alzheimer Disease
• Dementia
• Psychomotor Agitation

Intervention

Drug:
• Placebo
oral capsules
• AVP-786
oral capsules

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Otsuka Pharmaceutical Development & Commercialization, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Czechia,  France,  Hungary,  Italy,  Poland,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline to Week 12 in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score		Baseline; Week 12
Secondary	Change from Baseline to Week 12 in the Clinical Global Impression of Severity (CGIS)-Agitation Domain Score		Baseline; Week 12