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

Sponsor

Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03393520

Collaborator

(none)

550

Enrollment

159

Locations

Arms

69.6

Anticipated Duration (Months)

3.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Agitation in Patients With Dementia of the Alzheimer's Type	Drug: Placebo Drug: AVP-786	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

550 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 13, 2017

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Aug 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants will be assigned to treatment with placebo capsules administered twice a day over a 12-week period.	Drug: Placebo oral capsules
Experimental: AVP-786; Dose 1 Participants will receive AVP-786 (Dose 1) capsules administered twice a day over a 12-week period.	Drug: AVP-786 oral capsules
Experimental: AVP-786; Dose 2 Participants will receive AVP-786 (Dose 2) capsules administered twice a day over a 12-week period.	Drug: AVP-786 oral capsules

Arm

Intervention/Treatment

Placebo Comparator: Placebo

Participants will be assigned to treatment with placebo capsules administered twice a day over a 12-week period.

Drug: Placebo

oral capsules

Experimental: AVP-786; Dose 1

Participants will receive AVP-786 (Dose 1) capsules administered twice a day over a 12-week period.

Drug: AVP-786

oral capsules

Experimental: AVP-786; Dose 2

Participants will receive AVP-786 (Dose 2) capsules administered twice a day over a 12-week period.

Drug: AVP-786

oral capsules

Outcome Measures

Primary Outcome Measures

Change from Baseline to Week 12 in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score [Baseline; Week 12]

Secondary Outcome Measures

Change from Baseline to Week 12 in the Clinical Global Impression of Severity (CGIS)-Agitation Domain Score [Baseline; Week 12]

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MD First Research #767	Chandler	Arizona	United States	85286
2	Liv Generations of Agritopia / CCT	Gilbert	Arizona	United States	85296
3	Liv Generations of Ahwatukee / CCT	Phoenix	Arizona	United States	85048
4	Perseverance Research Center	Scottsdale	Arizona	United States	85254
5	Clinical Trials Inc.	Little Rock	Arkansas	United States	72205
6	ATP Clinical Research, Inc	Costa Mesa	California	United States	92626
7	Paradigm Clinical Research Centers, Inc.	La Mesa	California	United States	91942
8	Rohun Medical Corporation Site #770	Long Beach	California	United States	90805
9	Alliance for Wellness, Inc dba Alliance for Research	Long Beach	California	United States	90807
10	Havana Research Institute	Pasadena	California	United States	91105
11	SFM Clinical Research, LLC	Boca Raton	Florida	United States	33487
12	Helix Biomedics LLC	Boynton Beach	Florida	United States	33436
13	ConSalud Medical Research	Hialeah	Florida	United States	33012
14	Alphab Global Research	Jupiter	Florida	United States	33458
15	Alzheimer's Research and Treatment Center	Lake Worth	Florida	United States	33449
16	Meridien Research - Lakeland Site Site #558	Lakeland	Florida	United States	33805
17	Zynak Clinical Services	Lauderdale Lakes	Florida	United States	33313
18	Crystal Biomedical Research, LLC	Miami Lakes	Florida	United States	33014
19	Project4Research #774	Miami	Florida	United States	33125
20	City Medical Group RC	Miami	Florida	United States	33126
21	Finlay Medical Research Corp	Miami	Florida	United States	33126
22	Miami Jewish Health Systems, Inc.	Miami	Florida	United States	33137
23	Clinical Research Associates of South Florida	Miami	Florida	United States	33172
24	Pharmax Research of South Florida	Miami	Florida	United States	33175
25	Research Institute of West Kendall	Miami	Florida	United States	33186
26	Bayside Clinical Research	New Port Richey	Florida	United States	34655
27	Quantum Laboratories Site #768	Pompano Beach	Florida	United States	33064
28	VICIS Clinical Research Inc.	Tampa	Florida	United States	33615
29	Academic Alliance in Dermatology	Tampa	Florida	United States	33617
30	NeuroStudies. Net, LLC	Decatur	Georgia	United States	30033
31	DelRicht Research #776	Covington	Louisiana	United States	70443
32	Onyx Clinical Research, LLC	Caro	Michigan	United States	48723
33	Oakland Medical Research #762	Troy	Michigan	United States	48085
34	Precise Research Centers Site #765	Flowood	Mississippi	United States	39232
35	Galen Research	Chesterfield	Missouri	United States	63005
36	Bio Behavioral Health	Toms River	New Jersey	United States	08755
37	Nathan S. Kline Institute for Psychiatric Research	Orangeburg	New York	United States	10962
38	Five Towns Neurology PC/Village Site #764	Woodmere	New York	United States	11598
39	New Hope Clinical Research	Charlotte	North Carolina	United States	28211
40	Insight Clinical Trials LLC	Beachwood	Ohio	United States	44122
41	Valley Medical Research	Centerville	Ohio	United States	45459
42	NorthStar Medical Research	Middleburg Heights	Ohio	United States	44130
43	Onyx Clinical Research, LLC	Youngstown	Ohio	United States	44505
44	Newton Clinical Research	Oklahoma City	Oklahoma	United States	73102
45	Keystone Clinical Studies, LLC	Norristown	Pennsylvania	United States	19403
46	InSite Clinical Research	DeSoto	Texas	United States	75115
47	Bio Pharma Informatic Inc Site #769	Houston	Texas	United States	77084
48	Northpointe Psychiatry	Lewisville	Texas	United States	75057
49	Wasatch Clinical Research, LLC Site #771	Salt Lake City	Utah	United States	84107
50	Northwest Clinical Research Center	Bellevue	Washington	United States	98007
51	IPC Research	Waukesha	Wisconsin	United States	53188
52	Australian Alzheimer's Research Foundation	Nedlands		Australia
53	Neuro Trials Victoria Pty Ltd	Noble Park		Australia
54	The Alfred Hospital	Parkville		Australia
55	University Multiprofile Hospital for Active Treatment Dr. Georgi Stranski	Pleven		Bulgaria
56	Medical Center Hipokrat-N EOOD	Plovdiv		Bulgaria
57	Center for Mental Health - Ruse	Ruse		Bulgaria
58	DCC "Sv. Vrach and Sv. Sv. Kuzma and Damian" OOD	Sofia		Bulgaria	1408
59	First Multiprofile Hospital for Active Treatment Sofia	Sofia		Bulgaria
60	Medical Center Stimul	Sofia		Bulgaria
61	Medical Center Sveti Naum	Sofia		Bulgaria
62	University Multiprofile Hospital for Active Treatment Alexandrovska	Sofia		Bulgaria
63	Diagnostic-consultative center Mladost-М Varna OOD #711	Varna		Bulgaria	3020
64	Medica Plus Medical Center	Veliko Tarnovo		Bulgaria
65	Mental Health Center Site #712	Vratsa		Bulgaria	3000
66	Fakultni Nemocnice u sv. Anny v Brne	Brno		Czechia
67	Clinline Services s.r.0 Psychiatricka Ambulance	Hostivice		Czechia
68	Fakultní Nemocnice Hradec Králové	Hradec Kralové		Czechia
69	NeuropsychiatrieHK	Hradec Králové		Czechia
70	Brain-Soultherapy	Kladno		Czechia
71	Supervize	Kutná Hora		Czechia
72	A-Shine s.r.o.	Plzen		Czechia
73	AD71	Praha		Czechia
74	Clintrial	Praha		Czechia
75	INEP Medical s.r.o. Institut Neuropsychiatricke Pece	Praha		Czechia
76	Neurologicka Ambulance - Forbeli	Praha		Czechia
77	Neuropsychiatrie	Praha		Czechia
78	Vestra Clinics	Rychnov nad Kněžnou		Czechia
79	Centre Hospitalier Universitaire de Caen - Hôpital Côte de Nacre	Caen cedex 9		France
80	Centre Hospitalier de Calais	Calais		France
81	Centre Hospitalier Universitaire Dijon Bourgogn	Dijon Cedex		France
82	Centre Hospitalier Universitaire de Nantes - Hôpital Nord Laennec	Nantes Cedex		France	44093
83	Centre Hospitalier Universitaire de Poitiers	Poitiers		France
84	Centre Hospitalier Universitaire de Saint-Étienne - Hôpital Nord	Saint-Etienne		France
85	Centre Hospitalier Universitaire Toulouse - Casselardit Ancely	Toulouse		France
86	Centre Hospitalier Universitaire de Nancy - Hôpital de Brabois	Vandoeuvre les Nancy		France
87	Dr. Kenessey Albert Kórház-Rendelőintézet	Balassagyarmat		Hungary
88	Semmelweis Egyetem	Budapest		Hungary
89	Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak	Budapest		Hungary
90	Debreceni Egyetem Kenezy Gyula Egyetemi Korhaz	Debrecen		Hungary
91	Valeomed Egeszsegugyi es Szolgaltato Kft	Esztergom		Hungary
92	Dr. Mathe es Tarsa Beteti Tarsasa Site #593	Kalocsa		Hungary	6300
93	CRU Hungary Egészségügyi és Szolgáltató Korlátolt Felelősségű Társaság	Miskolc		Hungary
94	Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz	Nyiregyhaza		Hungary
95	PsychoTech	Pecs		Hungary
96	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont	Szeged		Hungary
97	Fejér Megyei Szent György Egyetemi Oktató Kórház	Székesfehérvár		Hungary
98	Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia	Brescia		Italy
99	Centro San Giovanni di Dio - Fatebenefratelli	Brescia		Italy
100	Università degli studi G.D'Annunzio Chieti Pescara	Chieti		Italy
101	Azienda Ospedaliero - Universitaria Careggi	Firenze		Italy
102	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano		Italy
103	Azienda Ospedaliera San Gerardo di Monza	Monza		Italy
104	Azienda Sanitaria Locale di Biella - Nuovo Ospedale degli Infermi	Ponderano		Italy
105	Azienda Ospedaliera Sant'Andrea	Roma		Italy
106	Fondazione Policlinico Tor Vergata	Roma		Italy
107	Fondazione Santa Lucia - Istituto di Ricovero e Cura a Carattere Scientifico	Roma		Italy
108	Śródmieście Przychodnia - Bydgoszcz	Bydgoszcz		Poland
109	Centrum Medyczne Sensemed	Chorzów		Poland
110	Care Clinic	Katowice		Poland
111	Wielospecjalistyczna Poradnia Lekarska Synapsis	Katowice		Poland
112	Krakowska Akademia Neurologii	Kraków		Poland
113	Pratia MCM Kraków	Kraków		Poland
114	Medycyna Milorzab	Lodz		Poland
115	Neurologiczny Niepubliczny Zakład Opieki Zdrowotnej	Plewiska		Poland
116	Centrum Medyczne HCP	Poznań		Poland
117	Solumed Centrum Medyczne	Poznań		Poland
118	Centrum Medyczne Euromedis	Szczecin		Poland
119	Centrum Medyczne NeuroProtect	Warszawa		Poland
120	Centrum Medyczne Pratia Warszawa	Warszawa		Poland
121	ClinHouse Centrum Medyczne	Zabrze		Poland	41-807
122	ACF Neurological Services	Cape Town		South Africa
123	Cape Trial Centre	Cape Town		South Africa
124	Flexivest Fourteen Research Centre	Cape Town		South Africa
125	Apollo Clinical Research	Johannesburg		South Africa
126	Medical and Dental Centre	Rosebank		South Africa
127	Dr. Chisto Carel Coetzee	Umhlanga		South Africa
128	Fundació ACE	Barcelona		Spain
129	Fundació Hospital de la Santa Creu i Sant Pau	Barcelona		Spain
130	Hospital Clinic de Barcelona	Barcelona		Spain
131	Hospital Universitari Vall d'Hebrón	Barcelona		Spain
132	Hospital Universitario Reina Sofia	Córdoba		Spain
133	Hospital General Universitario de Elche	Elche		Spain
134	Hospital Universitari de Santa Maria	Lleida		Spain
135	Hospital General Universitario Gregorio Marañón	Madrid		Spain
136	Hospital Universitario 12 de Octubre	Madrid		Spain
137	Hospital Universitario La Paz	Madrid		Spain
138	Hospital Universitario Puerta de Hierro - Majadahonda	Majadahonda		Spain	28222
139	Clínica Universidad de Navarra	Pamplona		Spain
140	Hospital Universitario de Salamanca	Salamanca		Spain
141	Hospital Universitario Marqués de Valdecilla	Santander		Spain
142	Hospital Universitario Virgen Macarena	Sevilla		Spain
143	Hospital Universitario y Politécnico de La Fe	Valencia		Spain
144	Complejo Asistencial de Zamora Hospital Virgen de la Concha	Zamora		Spain
145	Hospital Viamed Montecanal	Zaragoza		Spain
146	MAC Clinical Research - Barnsley	Barnsley		United Kingdom
147	Research Institute for the Care of Older People	Bath		United Kingdom
148	Belfast Health and Social Care Trust	Belfast		United Kingdom
149	MAC Clinical Research - Blackpool	Blackpool		United Kingdom
150	MAC Clinical Research - Cannock	Cannock		United Kingdom
151	MAC Clinical Research - Leeds	Leeds		United Kingdom
152	Re:Cognition Health - London	London		United Kingdom
153	South London and Maudsley NHS Foundation Trust	London		United Kingdom
154	MAC Clinical Research - Manchester	Manchester		United Kingdom
155	Northamptonshire Healthcare NHS Foundation Trust	Northampton		United Kingdom
156	MAC Clinical Research - Liverpool	Prescot		United Kingdom
157	Southern Health NHS Foundation Trust	Southampton		United Kingdom
158	Avon and Wiltshire Mental Health Partnership NHS Trust	Swindon		United Kingdom
159	North West Boroughs Healthcare NHS Foundation Trust	Warrington		United Kingdom