Long Term, Extension Study of the Safety and Efficacy of AVP-786 for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type

A Phase 3, Multicenter, Long Term, Extension Study of the Safety and Efficacy of AVP-786 (Deuterated [d6] Dextromethorphan Hydrobromide [d6-DM]/Quinidine Sulfate [Q]) for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type

This was an extension study of the Phase 3 Studies 15-AVP-786-301, 15-AVP-786-302, and 17-AVP-786-305.

Study Overview

• Status: Terminated
• Conditions: Agitation in Patients With Dementia of the Alzheimer's Type
• Intervention / Treatment: Drug: AVP-786

Detailed Description

Eligible participants for this study had successfully completed Studies 15-AVP-786-301, 15-AVP-786-302, 12-AVR-131, or 17-AVP-786-305.

Study medication was administered orally twice daily.

• Study Type: Interventional
• Enrollment (Actual): 1197
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Rousse, Bulgaria
    • Center for Mental Health - Ruse
  • Sofia, Bulgaria, 1000
    • Mental Health Centre Prof. Nikola Shipkovenski Site #713
  • Sofia, Bulgaria, 1113
    • Medical Center Sveti Naum Site #707
  • Sofia, Bulgaria, 1408
    • Vrach and Sv. Sv. Kuzma and Damian Site #710
  • Sofia, Bulgaria
    • University Multiprofile Hospital for Active Treatment Alexandrovska Site #704
  • Varna, Bulgaria, 9020
    • Medical Center Mladost-M
  • Veliko Tarnovo, Bulgaria
    • Medica Plus Medical Center
• Canada
  • Penticton, Canada
    • Dr. Alexander McIntyre Inc.
• Czechia
  • Brno, Czechia
    • Fakultni Nemocnice u sv. Anny v Brne Site #722
  • Hradec Kralové, Czechia
    • Fakultní Nemocnice Hradec Králové Site #724
  • Hradec Kralové, Czechia
    • NeuropsychiatrieHK Site #729
  • Kladno, Czechia
    • Brain-Soultherapy
  • Kutná Hora, Czechia
    • Námestí národního odboje 692 Site #723
  • Pilsen, Czechia
    • A-Shine s.r.o. Site #731
  • Prague, Czechia
    • AD71
  • Prague, Czechia
    • Clintrial
  • Prague, Czechia
    • Neurologická Ambulance - Forbeli
  • Prague, Czechia
    • Neuropsychiatrie Site #726
  • Rychnov nad Kněžnou, Czechia
    • Vestra Clinics
• France
  • Dijon, France
    • Centre Hospitalier Universitaire Dijon Bourgogn Site #536
  • Toulouse, France
    • Centre Hospitalier Universitaire Toulouse - Casselardit Ancely Site #533
  • Auvergne-Rhône-Alpes
    • Saint-Etienne, Auvergne-Rhône-Alpes, France
      • Centre Hospitalier Universitaire de Saint-Étienne - Hôpital Nord Site #535
• Hungary
  • Balassagyarmat, Hungary
    • Dr. Kenessey Albert Korhaz-Rendelointezet
  • Budapest, Hungary
    • Semmelweis Egyetem
  • Budapest, Hungary
    • Pszichiatriai es Pszichiatriai Rehabilitacios Osztaly Site #586
  • Debrecen, Hungary
    • Debreceni Egyetem Kenézy Gyula Egyetemi Kórház
  • Kalocsa, Hungary, 6300
    • Dr. Mathe es Tarsa Beteti Tarsasag Site #593
  • Pécs, Hungary
    • PsychoTech Clinical Research Site# 580
• Italy
  • Roma, Italy
    • Fondazione Santa Lucia - Istituto di Ricovero e Cura a Carattere Scientifico
  • Roma, Italy
    • Azienda Ospedaliera Sant'Andrea Site #606
  • Roma, Italy
    • Fondazione Policlinico Tor Vergata Site #609
• Poland
  • Bydgoszcz, Poland
    • Ksiedza Hugona Kollataja 9
  • Katowice, Poland
    • Care Clinic Clinical Research Site #750
  • Katowice, Poland
    • Wielospecjalistyczna Poradnia Lekarska Synapsis Site #741
  • Krakow, Poland
    • Krakowska Akademia Neurologii Site #740
  • Krakow, Poland
    • Malopolskie Centrum Medyczne Site #747
  • Lodz, Poland
    • Medycyna Milorzab Site #743
  • Poznan, Poland
    • Solumed Centrum Medyczne Site #753
  • Szczecin, Poland
    • Centrum Medyczne Euromedis
  • Warsaw, Poland
    • Centrum Medyczne NeuroProtect Site #742
  • Zabrze, Poland, 41-807
    • Clinhouse Centrum Medyczne
  • Lubusz Voivodeship
    • Nowa Sól, Lubusz Voivodeship, Poland, 67-100
      • Twoja Przychodnia - Centrum Medyczne Nowa Sol Site #757
  • Masovian Voivodeship
    • Sochaczew, Masovian Voivodeship, Poland, 96-500
      • RCMed Oddział Sochaczew Site #510
• South Africa
  • Cape Town, South Africa
    • Flexivest Fourteen Research Centre
  • Cape Town, South Africa
    • Cape Trial Centre
  • Cape Town, South Africa
    • ACF Neurological Services
  • Johannesburg, South Africa
    • Apollo Clinical Research Site #623
  • Rosebank, South Africa
    • Medical and Dental Centre
• Spain
  • Alcobendas, Spain, 28100
    • Accellacare Alcobendas
  • Barcelona, Spain
    • Hospital Clinic De Barcelona
  • Barcelona, Spain
    • Fundació ACE
  • Elche, Spain
    • Hospital General Universitario de Elche
  • Salamanca, Spain
    • Hospital Universitario de Salamanca
  • Seville, Spain
    • Hospital Universitario Virgen Macarena Site #649
  • Zamora, Spain
    • Complejo Asistencial de Zamora Hospital Virgen de la Concha
  • Zaragoza, Spain
    • Hospital Viamed Montecanal Site #643
• United States
  • Arizona
    • Chandler, Arizona, United States, 85286
      • MD First Research, LLC Site #767
    • Phoenix, Arizona, United States, 85032
      • NoesisPharma, LLC
    • Scottsdale, Arizona, United States, 85254
      • Perseverance Research Center, LLC
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Health Initiatives Research
  • California
    • Anaheim, California, United States, 92805
      • Advanced Research Center, Inc. Site #835
    • Costa Mesa, California, United States, 92626
      • ATP Clinical Research, Inc. Site #763
    • Glendale, California, United States, 91206
      • Behavioral Research Specialists, LLC
    • Irvine, California, United States, 92614
      • Irvine Center for Clinical Research
    • Lakewood, California, United States, 90805
      • Sheenath Clinical Service Site #770
    • Lomita, California, United States, 90717
      • Torrance Clinical Research Institute, Inc. Site #826
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Network, LLC.
    • Long Beach, California, United States, 90807
      • Alliance for Wellness, Inc dba Alliance for Research Site #789
    • Orange, California, United States, 92868
      • NRC Research Institute
    • Panorama City, California, United States, 91402
      • California Neurological Services
    • Pasadena, California, United States, 91105
      • Havana Research Institute
    • Pasadena, California, United States, 91105
      • Havana Research Institute Site 787
    • San Diego, California, United States, 92103
      • Pacific Research Network, Inc. #1
    • San Diego, California, United States, 92103
      • Pacific Research Network, Inc. #2
    • Santa Ana, California, United States, 92705
      • Syrentis Clinical Research
    • Santa Ana, California, United States, 92704
      • HB Clinical Trials Inc.
    • Temecula, California, United States, 92591
      • Viking Clinical Research
  • Colorado
    • Denver, Colorado, United States, 80209
      • Lytle and Weiss, PLLC dba Clinical Trials of the Rockies
  • Connecticut
    • New London, Connecticut, United States, 06320
      • Coastal Connecticut Research, LLC
    • Norwalk, Connecticut, United States, 06851
      • Research Center for Clinical Studies, Inc.
  • Florida
    • Altamonte Springs, Florida, United States, 32714
      • Neurology of Central Florida Rsch Ctr Site #803
    • Atlantis, Florida, United States, 33462
      • JEM Research Institute
    • Aventura, Florida, United States, 33180
      • Negron Research Services / Humanity Clinical Research Site# 766
    • Boca Raton, Florida, United States, 33487
      • SFM Clinical Research, LLC Site #563
    • Bradenton, Florida, United States, 34205
      • Bradenton Research Center Site #834
    • Brandon, Florida, United States, 33511
      • Clinical Research of Brandon
    • Brandon, Florida, United States, 33511
      • Clinical Research Of Brandon, LLC Site #838
    • Brooksville, Florida, United States, 34601
      • Meridien Research
    • Deerfield Beach, Florida, United States, 33064
      • Quantum Laboratories, Inc.
    • Doral, Florida, United States, 33166
      • Moonshine Research Center, Inc
    • Doral, Florida, United States, 33178
      • Science Connections, LLC Site #814
    • Greenacres City, Florida, United States, 33467
      • Finlay Medical Research Corp
    • Hialeah, Florida, United States, 33016
      • Galiz Research
    • Hialeah, Florida, United States, 33012
      • Indago Research & Health Center, Inc.
    • Hialeah, Florida, United States, 33016
      • Berma Research Group
    • Hialeah, Florida, United States, 33012
      • New Life Medical Research Center, Inc.
    • Hialeah, Florida, United States, 33018
      • Maxblue Institute
    • Hialeah, Florida, United States, 33012
      • Reliable Clinical Research,LLC
    • Hialeah, Florida, United States, 33013
      • Research in Miami, Inc
    • Hialeah, Florida, United States, 33013
      • The Research Center, Inc
    • Hialeah, Florida, United States, 33012
      • Direct Helpers Research Center #801
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions, Inc.
    • Jupiter, Florida, United States, 33458
      • Alphab Global Research #793
    • Kissimmee, Florida, United States, 34741
      • SIH Research, LLC
    • Lake Worth, Florida, United States, 33449
      • Alzheimer's Research and Treatment Center #1
    • Lake Worth, Florida, United States, 33449
      • Alzheimer's Research and Treatment Center #2
    • Lake Worth, Florida, United States, 33449
      • Alzheimer's Research and Treatment Center #3
    • Lakeland, Florida, United States, 33803
      • Meridien Research Site #558
    • Lauderhill, Florida, United States, 33319
      • Innovative Clinical Research, Inc. Site #819
    • Miami, Florida, United States, 33136
      • University of Miami
    • Miami, Florida, United States, 33126
      • BioMed Research Institute
    • Miami, Florida, United States, 33133
      • CCM Clinical Research Group
    • Miami, Florida, United States, 33175
      • Pharmax Research of South Florida
    • Miami, Florida, United States, 33165
      • Future Care Solution, LLC
    • Miami, Florida, United States, 33133
      • Innova Clinical Trials
    • Miami, Florida, United States, 33125
      • Optimus U Corp
    • Miami, Florida, United States, 33175
      • Coral Research Clinic Corp
    • Miami, Florida, United States, 33125
      • Global Medical Institutes, LLC
    • Miami, Florida, United States, 33135
      • Vitae Researrch Center LLC
    • Miami, Florida, United States, 33137
      • Miami Jewish Health Systems, Inc.
    • Miami, Florida, United States, 33145
      • Advanced Medical Center Group
    • Miami, Florida, United States, 33183
      • Kendall Research Institute
    • Miami, Florida, United States, 33186
      • Nuovida Research Center Corp.
    • Miami, Florida, United States, 33032
      • Homestead Associates in Research Site# 797
    • Miami, Florida, United States, 33122
      • Premier Clinical Research Institute, Inc. #1
    • Miami, Florida, United States, 33122
      • Premier Clinical Research Institute, Inc. #2
    • Miami, Florida, United States, 33125
      • Central Miami Medical Institute Site #798
    • Miami, Florida, United States, 33125
      • Project 4 Research #1
    • Miami, Florida, United States, 33125
      • Project 4 Research #2
    • Miami, Florida, United States, 33126
      • Finlay Medical Research Corp Site #552
    • Miami, Florida, United States, 33126
      • First Class Medical Services Site #807
    • Miami, Florida, United States, 33135
      • Advance Medical Research Center #1
    • Miami, Florida, United States, 33135
      • Advance Medical Research Center #2
    • Miami, Florida, United States, 33135
      • Dade Research Center Llc
    • Miami, Florida, United States, 33144
      • United Health Research Corp. #1
    • Miami, Florida, United States, 33144
      • United Health Research Corp. #2
    • Miami, Florida, United States, 33165
      • Reliant Medical Research LLC Site #811
    • Miami, Florida, United States, 33166
      • Hope Research Network LLC Site #773
    • Miami, Florida, United States, 33172
      • Clinical Research Associates of South Florida #1
    • Miami, Florida, United States, 33172
      • Clinical Research Associates of South Florida #2
    • Miami, Florida, United States, 33175
      • P&S RESEARCH, LLC. Site #805
    • Miami Gardens, Florida, United States, 33056
      • New Med Research, Inc Site #812
    • Naples, Florida, United States, 34102
      • Collier Neurologic Specialists, LLC
    • Naples, Florida, United States, 34102
      • Naples Research, Inc
    • New Port Richey, Florida, United States, 34655
      • Bayside Clinical Research Site #556
    • Oakland Park, Florida, United States, 33334
      • Research Centers of America, LLC
    • Orlando, Florida, United States, 32806
      • Compass Research, LLC
    • Orlando, Florida, United States, 32807
      • Combined Research Orlando Site #799
    • Ormond Beach, Florida, United States, 32174
      • Neurology Associates of Ormond Beach
    • Palmetto Bay, Florida, United States, 33157
      • IMIC Inc.
    • Palmetto Bay, Florida, United States, 03157
      • Innovation Medical Research Center
    • Palmetto Bay, Florida, United States, 33157
      • Innovation Medical Research Center Site #802
    • Pensacola, Florida, United States, 32514
      • University of West Florida
    • Port Charlotte, Florida, United States, 33952
      • Neurostudies Inc. Site#796
    • Sarasota, Florida, United States, 34243
      • Roskamp Institute
    • Tampa, Florida, United States, 33609
      • Olympian Clinical Research
    • Tampa, Florida, United States, 33615
      • VICIS Clinical Research Inc. Site #777
    • The Villages, Florida, United States, 32162
      • Compass Research North, LLC
    • West Palm Beach, Florida, United States, 33407
      • Neurology Research Institute Palm Beach, LLC #1
    • West Palm Beach, Florida, United States, 33407
      • Neurology Research Institute Palm Beach, LLC #2
    • Winter Park, Florida, United States, 32789
      • Florida Premier Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • NeuroTrials Research Inc
    • Columbus, Georgia, United States, 31909
      • Medical Research & Health Education Foundation, Inc.
    • Columbus, Georgia, United States, 31904
      • Columbus Research & Wellness Institute, INC
    • Decatur, Georgia, United States, 30033
      • NeuroStudies. Net, LLC
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine
    • Indianapolis, Indiana, United States, 46256
      • Josephson Wallack Munshower Neurology, PC
  • Kansas
    • Lenexa, Kansas, United States, 66214
      • MidAmerica Neuroscience Research Foundation
  • Kentucky
    • Paducah, Kentucky, United States, 42003
      • Four Rivers Clinical Research Inc.
  • Maryland
    • Easton, Maryland, United States, 21601
      • The Samuel & Alexia Bratton Memory Clinic
    • Hagerstown, Maryland, United States, 21742
      • Mir Neurology
  • Massachusetts
    • Braintree, Massachusetts, United States, 02184
      • Alzheimer Disease Center Site #804
    • Newton, Massachusetts, United States, 02459
      • Boston Center for Memory
    • Quincy, Massachusetts, United States, 02169
      • Alzheimer's Disease Center
  • Michigan
    • Caro, Michigan, United States, 48723
      • Onyx Clinical Research, LLC
    • East Lansing, Michigan, United States, 48824
      • Michigan State University Department of Neurology
    • Troy, Michigan, United States, 48085
      • Oakland Medical Research Site #762
  • Missouri
    • Chesterfield, Missouri, United States, 63005
      • Galen Research
    • Creve Coeur, Missouri, United States, 63141
      • Millennium Psychiatric Associates, LLC
  • New Jersey
    • Mount Arlington, New Jersey, United States, 07856
      • The NeuroCognitive Institute
    • Toms River, New Jersey, United States, 08755
      • Bio Behavioral Health
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurologic Institute
    • Brooklyn, New York, United States, 11229
      • Integrative Clinical Trials LLC #1
    • Brooklyn, New York, United States, 11229
      • Integrative Clinical Trials LLC #2
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10036
      • Manhattan Behavioral Medicine, PLLC
    • New York, New York, United States, 10128
      • Eastside Comprehensive Medical Center, LLC
    • Orangeburg, New York, United States, 10962
      • Nathan S. Kline Institute for Psychiatric Research #1
    • Orangeburg, New York, United States, 10962
      • Nathan S. Kline Institute for Psychiatric Research #571
    • Rochester, New York, United States, 14620
      • University of Rochester Medical Center
    • Staten Island, New York, United States, 10312
      • Richmond Behavioral Associates
    • White Plains, New York, United States, 10605
      • Burke Rehabilitation Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27517
      • Herbert Harris, Md, Phd, Pa
    • Charlotte, North Carolina, United States, 28270
      • ANI Neurology PLLC dba Alzheimer's Memory Center
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Akron, Ohio, United States, 44320
      • Neurology and Neuroscience Associates, Inc.
    • Beachwood, Ohio, United States, 44122
      • Insight Clinical Trials, LLC Site #570
    • Centerville, Ohio, United States, 45459
      • Valley Medical Research
    • Centerville, Ohio, United States, 45459
      • Valley Medical Research Site #788
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
    • Lakewood, Ohio, United States, 44107
      • Cleveland Clinic Lou Ruvo Center for Brain Health at Lakewood Hospital
    • Middleburg Heights, Ohio, United States, 44130
      • NorthStar Medical Research Site #778
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • IPS Research Company
    • Oklahoma City, Oklahoma, United States, 73112
      • Oklahoma Clinical Research Center
  • Pennsylvania
    • Beaver, Pennsylvania, United States, 15009
      • Heritage Valley Medical Group, Inc.
    • Willow Grove, Pennsylvania, United States, 19090
      • Abington Neurological Associates, LTD
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Rhode Island Mood & Memory Research Institute
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Roper St. Francis Healthcare
    • Charleston, South Carolina, United States, 29401
      • RH Johnson VA Medical Center
    • Spartanburg, South Carolina, United States, 29307
      • BG Neurology
  • Texas
    • Dallas, Texas, United States, 75214
      • Texas Neurology, P.A.
    • Dallas, Texas, United States, 75231
      • Neurology Consultants of Dallas, PA
    • Dallas, Texas, United States, 75390
      • University Texas Southwestern Medical Center
    • DeSoto, Texas, United States, 75115
      • InSite Clinical Research Site #576
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • Houston Methodist Neurological Institute
    • Mesquite, Texas, United States, 75149
      • PRX Research Site #825
    • San Antonio, Texas, United States, 78238
      • Texas Medical Research Associates, L.L.C.
  • Utah
    • Clinton, Utah, United States, 84015
      • Ericksen Research and Development
    • Salt Lake City, Utah, United States, 84107
      • Pharmaceuticals Research Associates, Inc.
  • Vermont
    • Bennington, Vermont, United States, 05201
      • Clinical Neuroscience Research Associates, Inc. dba The Memory Clinic
    • Woodstock, Vermont, United States, 05091
      • Neuropsychiatric Associates
  • Virginia
    • Salem, Virginia, United States, 24153
      • Veteran Affairs Medical Center, Salem Virginia
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center
    • Everett, Washington, United States, 98201
      • Core Clinical Research Site #772
  • Wisconsin
    • Waukesha, Wisconsin, United States, 53188
      • IPC Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant has successfully completed Studies 15-AVP-786-301, 15-AVP-786-302, 12-AVR-131, or 17-AVP-786-305. (Note: A delay in enrollment may include delays associated with COVID-19 restrictions.)
• Participants with a diagnosis of probable Alzheimer's Disease (AD) according to the 2011 National Institute on Aging-Alzheimer's Association (NIA-AA) working group criteria
• Either out-patients or residents of an assisted-living facility or a skilled nursing home
• Participants who delay enrollment must have clinically significant, moderate/severe agitation at least 2 weeks prior to baseline
• Participants who delay enrollment must have a diagnosis of agitation that must meet the International Psychogeriatric Association (IPA) provisional definition of agitation
• Participants who delay enrollment must have a Clinical Global Impression of Severity of Illness (CGIS) score assessing Agitation of ≥ 4 (moderately ill) at screening and baseline
• Participants who delay enrollment must have a Mini-Mental State Examination (MMSE) score between 6 and 26 (inclusive) at screening and baseline

Exclusion Criteria:

• 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 determined to have a high imminent risk of falls during the study based on a clinical evaluation by the investigator
• Participants who are currently using or were on NUEDEXTA® in the 2 weeks preceding baseline

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AVP-786 18 milligrams (mg); Participants who received AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) capsules in the previous studies 15-AVP-786-301 (NCT02442765), 15-AVP-786-302 (NCT02442778), or 17-AVP-786-305 (NCT03393520) continued to receive AVP-786-18 (d6-DM 18 mg/Q 4.9 mg), capsules, twice a day for 52 weeks in the current study.	Drug: AVP-786
Experimental: AVP-786 28 mg; Participants who received AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) capsules in the previous studies 15-AVP-786-301 (NCT02442765), 15-AVP-786-302 (NCT02442778), or 17-AVP-786-305 (NCT03393520) continued to receive AVP-786-28 (d6-DM 28 mg/Q 4.9 mg), capsules, twice a day for 52 weeks in the current study.	Drug: AVP-786
Experimental: AVP-786 42.63 mg; Participants who received placebo in the previous studies 15-AVP-786-301 (NCT02442765), 15-AVP-786-302 (NCT02442778), or 17-AVP-786-305 (NCT03393520) and those who had delayed enrolment, started AVP-786-28/4.9 (d6-DM 28 mg/Q 4.9 mg) in the current study and were eventually titrated to receive AVP-786-42.63/4.9 (d6-DM 42.63 mg/Q 4.9 mg) capsules, twice a day for 52 weeks.	Drug: AVP-786

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE)is any untoward medical occurrence or unintended change (e.g. physical, psychological, or behavioral), including inter-current illness, whether considered related to treatment or not. An AE can therefore be any unfavorable and unintended sign (including any clinically significant abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A TEAE is defined as an AE that occurred or worsened after the first dose of study treatment up until 30 days after last dose.	From first dose of study drug (in current study) up to 3 months after last dose of study drug (up to Week 64)
Number of Participants With Serious TEAE	A serious adverse event (SAE) is any AE occurring at any dose that results in death, life-threatening experience, persistent or significant disability/incapacity, in-patient hospitalization or prolongation of hospitalization or congenital anomaly/birth defect. A serious TEAE is defined as AE that occurred or worsened after the first dose of study treatment up until 30 days after last dose.	From first dose of study drug (in current study) up to 3 months after last dose of study drug (up to Week 64)
Number of Participants With Potentially Clinically Significant Laboratory Test Abnormalities	Laboratory assessments included clinical chemistry (alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bilirubin, blood urea nitrogen, calcium, carbon dioxide, cholesterol, creatinine kinase, creatinine, gamma glutamyl transferase, glucose, lactate dehydrogenase, magnesium, protein, potassium, sodium, triglycerides and uric acid), hematology (basophils, eosinophils/leukocytes, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes/leukocytes, monocytes, monocytes/leukocytes, neutrophils/leukocytes, platelets). Number of participants with clinically significant laboratory test abnormalities were reported as per criteria defined in statistical analysis plan (SAP). The categories with at least one participant with potentially clinically significant laboratory values are reported.	Baseline (current study) up to 52 weeks
Number of Participants With Potentially Clinically Significant 12-lead Electrocardiogram (ECG) Abnormalities	A resting 12-lead ECG was performed for all the participants. ECG data included PR interval (milliseconds {msec}) and QTcF (msec) along with change from baseline in QTcF. Number of participants with potentially clinically significant ECG abnormalities was reported as per the criteria defined in SAP.	Baseline (current study) up to 52 weeks
Number of Participants With Any Abnormal, Clinically Significant Physical and Neurological Examination Finding	The physical examination included assessments of head, eyes, ears, nose, throat, lymph nodes, skin, extremities, respiratory, gastrointestinal, musculoskeletal, cardiovascular, and nervous systems. The neurological examination included assessments of mental status, cranial nerves, motor system, reflexes, coordination, gait and station, and sensory system.	Baseline (current study), Week 52
Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs	Vital signs measurements included systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR). Blood pressure (i.e., SBP, DBP) and heart rate were measured in the supine and standing positions after the participant had been in each position for at least 5 and 3 minutes, respectively. Number of participants with clinically significant vital sign abnormalities were reported as per criteria defined in SAP. The categories with at least one participant with clinically significant vital signs abnormalities are reported here.	Baseline (current study) up to 52 weeks
Change From Baseline in the Sheehan Suicidality Tracking Scale (S-STS) Total Score at Week 64	The S-STS is a prospective scale that assesses treatment-emergent suicidal thoughts and behaviors. This is a 20-item scale where each item (except item 17) of the S-STS is scored on a 5-point Likert scale as: 0 = Not at all, 1 = A little, 2 = Moderate, 3 = Very, 4 = Extremely. The S-STS total score is calculated by the sum of items 1a (if present), items 2-11, highest score of item 12 or 16, highest score of item 14 or 15, item 17 and 20. The total score ranges from 0 to 156 (If response to S-STS item 17 =yes, a score of 100 was added to the S-STS total score). Higher scores indicate greater severity of suicidal ideation and/or behavior. A negative change from baseline reflects a reduction in suicidal thoughts or behaviors over time.	Baseline (current study), Week 64
Change From Baseline in the Mini-Mental State Examination (MMSE) Score at Week 52	The MMSE is a brief questionnaire that is used to assess cognitive impairment and severity of cognitive impairment. The MMSE scale comprises 11 questions or simple tasks concerning orientation, memory, attention, and language to evaluate a participant's cognitive state and are scored as follows: Orientation to Time - 0 to 5; Orientation to Place - 0 to 5; Registration - 0 to 3; Attention and Calculation - 0 to 5; Recall - 0 to 3; Naming - 0 to 2; Repetition - 0 to 1; Comprehension - 0 to 3; Reading - 0 to 1; Writing - 0 to 1; Drawing - 0 to 1. The total score was calculated by summing all of the item scores and ranges from 0 to 30. Higher scores indicate milder cognitive impairment. Negative change from baseline indicates decline in cognitive performance.	Baseline (current study), Week 52
Change From Baseline in the Epworth Sleepiness Scale (ESS) Score at Week 52	The ESS is an 8-item questionnaire that is used to measure sleepiness by rating the probability of falling asleep on 8 different situations that most people engage in during the day. The 8 questions are rated on a 4-point scale (0 to 3) where 0 = would never doze, 1 = slight chance of dozing, 2 = moderate chance of dozing, and 3 = high chance of dozing. The scores are summed to give an overall score of 0 to 24. A total score of 0 to 9 is considered to be normal. Higher score indicates greater daytime sleepiness. Negative change from baseline indicate improvement in daytime sleepiness.	Baseline (current study), Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score at Week 64	The CMAI is used to assess the frequency of manifestations of agitated behaviors in elderly persons. It consists of 29 agitated behaviors that are further categorized into distinct agitation syndromes, also known as CMAI factors of agitation. These distinct agitation syndromes include aggressive behavior, physically nonaggressive behavior, and verbally agitated behavior. Each of the 29 items is rated on a 7-point scale of frequency (1 = never, 2 = less than once a week but still occurring, 3 = once or twice a week, 4 = several times a week, 5 = once or twice a day, 6 = several times a day, 7 = several times an hour). The ratings are based on the 2 weeks preceding assessment of the CMAI. Higher scores indicate higher frequency of agitated behaviours while lower scores indicate lower frequency of agitated behaviours.	Baseline (current study), Week 64
Change From Baseline in the Agitation/Aggression, Irritability/Lability, and Aberrant Motor Behavior Domain Scores of the Neuropsychiatric Inventory (NPI) at Week 52	The NPI is a validated clinical instrument used to assess neuropsychiatric symptoms. It evaluates 12 neuropsychiatric symptom domains including delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, aberrant motor behavior, sleep and nighttime behavioral disorders, and appetite/eating disorders. Each symptom domain is rated by the caregiver based on the frequency (1 to 4) and severity (1 to 3) of symptoms, and a composite domain score is calculated by multiplying frequency and severity (range: 1-12). Additionally, caregiver distress for each positive symptom domain is rated on a 6-point scale (0 = not at all distressing, 5 = extremely distressing). In this study, the three NPI domains assessed were agitation/aggression, irritability/lability, and aberrant motor behavior. Higher scores indicate greater severity and frequency of neuropsychiatric symptoms.	Baseline (current study), Week 52
Change From Baseline in the Modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change-Agitation (mADCS-CGIC-Agitation) Score at Week 64	The mADCS-CGIC-Agitation is used to assess agitation in individuals with Alzheimer's disease. It includes questions focused on agitation and uses a semi-structured interview format involving both the participant and their caregiver. The clinician rates the participant's overall clinical status using a 7-point scale: 1 = marked improvement, 2 = moderate improvement, 3 = minimal improvement, 4 = no change, 5 = minimal worsening, 6 = moderate worsening, and 7 = marked worsening. Lower scores indicate improvement in agitation symptoms, while higher scores indicate worsening.	Baseline (current study), Week 64
Change From Baseline in the Clinical Global Impression of Severity of Illness (CGIS)-Agitation Domain Score at Week 52	The CGIS is an observer-rated scale that measures illness severity. The CGIS-Agitation is a 7-point (1-7) scale (1 = normal, not at all ill; 7 = extremely ill) that assessed the severity of agitation in this study. Higher scores indicate severe agitation, while the lower scores indicate little or no agitation.	Baseline (current study), Week 52
Change From Baseline in the Patient Global Impression of Change (PGIC) Score at Week 52	The PGIC is a 7-point scale used to assess perceived treatment response, as evaluated by the participant's caregiver. The caregiver rates the overall change in the participant's condition since the start of treatment. The PGIC score ranges from 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. Lower scores reflect greater improvement, while higher scores indicate worsening of the participant's condition.	Baseline (current study), Week 52
Change From Baseline in the Dementia Quality of Life (DEMQOL) Score at Week 52	The DEMQOL is a validated scale used to assess health-related quality of life in individuals with dementia and their caregivers. It includes two versions: a 28-item version completed by the participant (DEMQOL), and a 31-item proxy version completed by the caregiver (DEMQOL-proxy). Each item is rated using a 4-point scale to reflect the frequency or severity of health-related concerns: 1 = A lot, 2 = Quite a bit, 3 = A little, 4 = Not at all. Total score is derived by sum of all item scores, excluding item 29 of DEMQOL and item 32 of DEMQOL-proxy. Lower scores indicate better quality of life.	Baseline (current study), Week 52
Change From Baseline in the Resource Utilization in Dementia (RUD) Score at Week 52	The RUD is a standardized tool used to estimate healthcare costs associated with dementia. It assesses the use of both formal and informal (e.g., hospitalizations, doctor visits, living assistance, and unprofessional caregiver time) healthcare resources. The instrument is administered as a semi-structured interview with the participant's primary caregiver. It consists of two main sections: one evaluates the caregiver's burden, including lost work and leisure time, and the other documents the participant's use of healthcare services. Total healthcare costs are calculated by multiplying the quantity of resources used (e.g., number of doctor visits, hours of caregiver, nights in accommodation) by unit costs. Higher estimated totals reflect greater economic impact associated with dementia care.	Baseline (current study), Week 52
Change From Baseline in the EuroQol 5-Dimension 5-Level (EQ-5D-5L) for Participants From Study 17-AVP-786-305 at Week 52	The EQ-5D-5L is a standardized questionnaire used to assess health-related quality of life. It consists of two components: a descriptive system and the EuroQol Visual Analogue Scale (EQ VAS). The descriptive system covers five health dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated on a 5-level scale: 1 = No problems, 2 = Slight problems, 3 = Moderate problems, 4 = Severe problems, 5 = Extreme problems. The EQ VAS component allows participants or caregivers to rate the individual's overall health on a vertical scale from 0 (the worst imaginable health state) to 100 (the best imaginable health state). Only participants from Study 17-AVP-786-305 with a MMSE score of 10 or higher at the baseline visit were planned to complete the participant-rated version.	Baseline (current study), Week 52

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Using Concomitant Medications	Concomitant medications were defined as any medications taken on or after the date of first dose of study drug in Study 15-AVP-786-303 or that are ongoing concomitant medications from Studies 15-AVP-786-301, 15-AVP-786-302, 17-AVP-786-305, and 12-AVR-131.	Baseline (current study) up to 64 weeks

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2015
• Primary Completion (Actual): September 6, 2024
• Study Completion (Actual): September 6, 2024

Study Registration Dates

• First Submitted: May 11, 2015
• First Submitted That Met QC Criteria: May 14, 2015
• First Posted (Estimated): May 18, 2015

Study Record Updates

• Last Update Posted (Estimated): October 15, 2025
• Last Update Submitted That Met QC Criteria: September 30, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Aberrant Motor Behavior in Dementia; Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Behavioral Symptoms; Neurobehavioral Manifestations; Neurocognitive Disorders; Tauopathies; Neurodegenerative Diseases; Dyskinesias; Psychomotor Disorders; Alzheimer Disease; Dementia; Psychomotor Agitation
• Other Study ID Numbers: 15-AVP-786-303; 2017-002455-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
• IPD Sharing Time Frame: Data will be available after marketing approval in global markets or beginning 1-3 years following article publication. There is no end date to the availability of the data.
• IPD Sharing Access Criteria: Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No