Back to resultsA Phase 3, 12-week, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of 2 Fixed Doses of Brexpiprazole in the Treatment of Alzheimer's Agitation
Primary Purpose
Agitation Associated With, Alzheimer's Disease, Alzheimer's Type
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Brexpiprazole, OPC-34712
Placebo Oral Tablet
Sponsored by
About this trial
This is an interventional treatment trial for Agitation Associated With focused on measuring OPC-34712, brexpiprazole, Dementia, Alzheimer's Disease, Cognitive Disorders, Agitation
Eligibility Criteria
Inclusion Criteria:
- Male and female participants 55 to 90 years of age, inclusive, at the time of informed consent.
- Participants who are residing at their current location for at least 14 days before screening and are expected to remain at the same location for the duration of the trial.
- Participants with a diagnosis of probable Alzheimer's disease according to National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association.
- Participants with a Mini-Mental State Exam score of 5 to 22, inclusive, at screening and baseline visits.
- Participants with onset of symptoms of agitation at least 2 weeks prior to the screening visit.
- Participants with a score of ≥ 4 on the agitation/aggression item of the Neuropsychiatric Inventory-Nursing Home at the screening and baseline visits.
- Participants who require pharmacotherapy for treatment of agitation per the investigator's judgment, after an evaluation for reversible factors (for example, pain, infection, polypharmacy) and a trial of nonpharmacological intervention.
- Participants must have a previous magnetic resonance imaging or computed tomography of the brain, which was performed after the onset of symptoms of dementia, with findings consistent with the diagnosis of Alzheimer's disease.
Exclusion Criteria:
- Participants with dementia or other memory impairment not due to Alzheimer's disease
- Participants with a history of stroke, well-documented transient ischemic attack, pulmonary or cerebral embolism.
- Participants who currently have clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, gastrointestinal, or psychiatric disorders.
- Participants who have been diagnosed with an Axis I disorder (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision criteria)
- Participants with uncontrolled hypertension
- Participants with uncontrolled insulin-dependent diabetes mellitus
- Participants with epilepsy or a history of seizures
- Participants considered in poor general health based on the investigator's judgment.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Experimental
Experimental
Arm Label
Placebo
Brexpiprazole 1 mg
Brexpiprazole 2 mg
Arm Description
Matching placebo once daily
Titrate up from 0.25 milligrams (mg)/day brexpiprazole to 1 mg/day brexpiprazole
Titrate up from 0.25 mg/day brexpiprazole to 2 mg/day brexpiprazole
Outcomes
Primary Outcome Measures
Change From Baseline In The Cohen-Mansfield Agitation Inventory (CMAI) Total Score After 12 Weeks Of Brexpiprazole Treatment
To compare the efficacy of 2 fixed doses (1 mg/day and 2 mg/day) of brexpiprazole with placebo in participants with agitation associated with dementia of the Alzheimer's type, by the assessment of CMAI after 12 weeks of treatment. The CMAI assesses the frequency of agitated behaviors in elderly persons, such as hitting, cursing, and restlessness. It consists of 29 items all rated on a 1 to 7 scale with 1 being the "best" rating and 7 being the "worst" rating. The minimum possible CMAI total score is 29, and the maximum possible CMAI total score is 203. A decrease in score indicates improvement in symptoms. To control the overall type I error at 0.05 level when making 2 comparisons of brexpiprazole doses versus placebo, statistical testing was carried out using a hierarchical testing procedure in the order of: 1) comparison of 2 mg/day brexpiprazole versus placebo, and 2) comparison of 1 mg/day brexpiprazole versus placebo.
Secondary Outcome Measures
Change From Baseline In The Clinical Global Impression-Severity Of Illness (CGI-S) Score, As Related To Symptoms Of Agitation After 12 Weeks Of Brexpiprazole Treatment
To compare the efficacy of 2 fixed doses (1 mg/day and 2 mg/day) of brexpiprazole with placebo in participants with agitation associated with Alzheimer's dementia, by the assessment of CGI-S score after 12 weeks of treatment. The CGI-S was used to rate the severity of agitation. Scores were: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants. A decrease in score indicates improvement in symptoms.
Full Information
NCT ID
NCT01862640
First Posted
May 22, 2013
Last Updated
December 8, 2020
Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
Collaborators
H. Lundbeck A/S
1. Study Identification
Unique Protocol Identification Number
NCT01862640
Brief Title
A Phase 3, 12-week, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of 2 Fixed Doses of Brexpiprazole in the Treatment of Alzheimer's Agitation
Official Title
A Phase 3, 12-week, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of 2 Fixed Doses of Brexpiprazole (OPC-34712) in the Treatment of Subjects With Agitation Associated With Dementia of the Alzheimer's Type
Study Type
Interventional
2. Study Status
Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
July 11, 2013 (Actual)
Primary Completion Date
March 15, 2017 (Actual)
Study Completion Date
March 15, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
Collaborators
H. Lundbeck A/S
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To compare the efficacy of 2 fixed doses of brexpiprazole with placebo in participants with agitation associated with dementia of the Alzheimer's type.
Detailed Description
Behavioral symptoms, such as agitation, are core features in participants with Alzheimer's disease and related dementias and develop in the majority of dementia participants. The presence of agitation in participants with Alzheimer's disease places a significant burden not only on participants and their caregivers but also on the healthcare system.
This is a trial designed to assess the safety and efficacy of brexpiprazole in the treatment of participants with agitation associated with dementia of the Alzheimer's Type. The trial consists of a continuous 12-week double-blind treatment period with a 30-day follow-up. The trial population will include male and female participants between 55 and 90 years of age (inclusive) with a diagnosis of probable Alzheimer's disease, who are residing either in an institutionalized setting or in a non-institutionalized setting where the participant is not living alone.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Agitation Associated With, Alzheimer's Disease, Alzheimer's Type, Mental Disorder, Nervous System Diseases
Keywords
OPC-34712, brexpiprazole, Dementia, Alzheimer's Disease, Cognitive Disorders, Agitation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
433 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo once daily
Arm Title
Brexpiprazole 1 mg
Arm Type
Experimental
Arm Description
Titrate up from 0.25 milligrams (mg)/day brexpiprazole to 1 mg/day brexpiprazole
Arm Title
Brexpiprazole 2 mg
Arm Type
Experimental
Arm Description
Titrate up from 0.25 mg/day brexpiprazole to 2 mg/day brexpiprazole
Intervention Type
Drug
Intervention Name(s)
Brexpiprazole, OPC-34712
Intervention Description
Once-daily, tablets
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Tablet
Intervention Description
Once-daily, tablets
Primary Outcome Measure Information:
Title
Change From Baseline In The Cohen-Mansfield Agitation Inventory (CMAI) Total Score After 12 Weeks Of Brexpiprazole Treatment
Description
To compare the efficacy of 2 fixed doses (1 mg/day and 2 mg/day) of brexpiprazole with placebo in participants with agitation associated with dementia of the Alzheimer's type, by the assessment of CMAI after 12 weeks of treatment. The CMAI assesses the frequency of agitated behaviors in elderly persons, such as hitting, cursing, and restlessness. It consists of 29 items all rated on a 1 to 7 scale with 1 being the "best" rating and 7 being the "worst" rating. The minimum possible CMAI total score is 29, and the maximum possible CMAI total score is 203. A decrease in score indicates improvement in symptoms. To control the overall type I error at 0.05 level when making 2 comparisons of brexpiprazole doses versus placebo, statistical testing was carried out using a hierarchical testing procedure in the order of: 1) comparison of 2 mg/day brexpiprazole versus placebo, and 2) comparison of 1 mg/day brexpiprazole versus placebo.
Time Frame
Baseline, Week 12/Early Termination (ET)
Secondary Outcome Measure Information:
Title
Change From Baseline In The Clinical Global Impression-Severity Of Illness (CGI-S) Score, As Related To Symptoms Of Agitation After 12 Weeks Of Brexpiprazole Treatment
Description
To compare the efficacy of 2 fixed doses (1 mg/day and 2 mg/day) of brexpiprazole with placebo in participants with agitation associated with Alzheimer's dementia, by the assessment of CGI-S score after 12 weeks of treatment. The CGI-S was used to rate the severity of agitation. Scores were: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants. A decrease in score indicates improvement in symptoms.
Time Frame
Baseline, Week 12/ET
10. Eligibility
Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male and female participants 55 to 90 years of age, inclusive, at the time of informed consent.
Participants who are residing at their current location for at least 14 days before screening and are expected to remain at the same location for the duration of the trial.
Participants with a diagnosis of probable Alzheimer's disease according to National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association.
Participants with a Mini-Mental State Exam score of 5 to 22, inclusive, at screening and baseline visits.
Participants with onset of symptoms of agitation at least 2 weeks prior to the screening visit.
Participants with a score of ≥ 4 on the agitation/aggression item of the Neuropsychiatric Inventory-Nursing Home at the screening and baseline visits.
Participants who require pharmacotherapy for treatment of agitation per the investigator's judgment, after an evaluation for reversible factors (for example, pain, infection, polypharmacy) and a trial of nonpharmacological intervention.
Participants must have a previous magnetic resonance imaging or computed tomography of the brain, which was performed after the onset of symptoms of dementia, with findings consistent with the diagnosis of Alzheimer's disease.
Exclusion Criteria:
Participants with dementia or other memory impairment not due to Alzheimer's disease
Participants with a history of stroke, well-documented transient ischemic attack, pulmonary or cerebral embolism.
Participants who currently have clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, gastrointestinal, or psychiatric disorders.
Participants who have been diagnosed with an Axis I disorder (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision criteria)
Participants with uncontrolled hypertension
Participants with uncontrolled insulin-dependent diabetes mellitus
Participants with epilepsy or a history of seizures
Participants considered in poor general health based on the investigator's judgment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eva Kohegyi, MD
Organizational Affiliation
Otsuka Pharmaceutical Development & Commercialization, Inc.
Official's Role
Study Director
Facility Information:
City
Tuscaloosa
State/Province
Alabama
ZIP/Postal Code
35404
Country
United States
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
City
Bellflower
State/Province
California
ZIP/Postal Code
90706
Country
United States
City
Costa Mesa
State/Province
California
ZIP/Postal Code
92627
Country
United States
City
Downey
State/Province
California
ZIP/Postal Code
90706
Country
United States
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
City
Redlands
State/Province
California
ZIP/Postal Code
92373
Country
United States
City
Yorba Linda
State/Province
California
ZIP/Postal Code
92886
Country
United States
City
Norwalk
State/Province
Connecticut
ZIP/Postal Code
06851
Country
United States
City
Coconut Creek
State/Province
Florida
ZIP/Postal Code
33024
Country
United States
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33012
Country
United States
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33013
Country
United States
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33018
Country
United States
City
Lauderhill
State/Province
Florida
ZIP/Postal Code
33319
Country
United States
City
Miami Springs
State/Province
Florida
ZIP/Postal Code
33166
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33122
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33126
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33137
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33145
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33161
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33174
Country
United States
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34239
Country
United States
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
City
Suwanee
State/Province
Georgia
ZIP/Postal Code
30024
Country
United States
City
Weymouth
State/Province
Massachusetts
ZIP/Postal Code
02190
Country
United States
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63128
Country
United States
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89148
Country
United States
City
Manchester
State/Province
New Jersey
ZIP/Postal Code
08759
Country
United States
City
Mount Arlington
State/Province
New Jersey
ZIP/Postal Code
07856
Country
United States
City
Toms River
State/Province
New Jersey
ZIP/Postal Code
08755
Country
United States
City
Hickory
State/Province
North Carolina
ZIP/Postal Code
28601
Country
United States
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73118
Country
United States
City
Franklin
State/Province
Tennessee
ZIP/Postal Code
37064
Country
United States
City
Bedford
State/Province
Texas
ZIP/Postal Code
76022
Country
United States
City
Waukesha
State/Province
Wisconsin
ZIP/Postal Code
53188
Country
United States
City
Rijeka
ZIP/Postal Code
57000
Country
Croatia
City
Zadar
ZIP/Postal Code
23000
Country
Croatia
City
Zagreb
ZIP/Postal Code
10000
Country
Croatia
City
Zagreb
ZIP/Postal Code
10090
Country
Croatia
City
Mittweida
State/Province
Saxony
ZIP/Postal Code
09648
Country
Germany
City
Achim
ZIP/Postal Code
28832
Country
Germany
City
Berlin
ZIP/Postal Code
12209
Country
Germany
City
Bielefeld
ZIP/Postal Code
33647
Country
Germany
City
Bochum
ZIP/Postal Code
44791
Country
Germany
City
Hamburg
ZIP/Postal Code
22083
Country
Germany
City
Koln
ZIP/Postal Code
50935
Country
Germany
City
Ostfildern
ZIP/Postal Code
73760
Country
Germany
City
Westerstede
ZIP/Postal Code
26655
Country
Germany
City
Ekaterinburg
ZIP/Postal Code
620030
Country
Russian Federation
City
Samara
ZIP/Postal Code
443016
Country
Russian Federation
City
Saratov
ZIP/Postal Code
410060
Country
Russian Federation
City
St. Petersburg
ZIP/Postal Code
190000
Country
Russian Federation
City
St. Petersburg
ZIP/Postal Code
190005
Country
Russian Federation
City
St. Petersburg
ZIP/Postal Code
191119
Country
Russian Federation
City
St. Petersburg
ZIP/Postal Code
192019
Country
Russian Federation
City
St. Petersburg
ZIP/Postal Code
197341
Country
Russian Federation
City
St. Petersburg
ZIP/Postal Code
198510
Country
Russian Federation
City
Tonnel'nyy
ZIP/Postal Code
357034
Country
Russian Federation
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
City
Kovin
ZIP/Postal Code
26220
Country
Serbia
City
Kragujevac
ZIP/Postal Code
34000
Country
Serbia
City
Nis
ZIP/Postal Code
18000
Country
Serbia
City
Novi Knezevac
ZIP/Postal Code
23330
Country
Serbia
City
Novi Sad
ZIP/Postal Code
21000
Country
Serbia
City
Vrsac
ZIP/Postal Code
26300
Country
Serbia
City
Barcelona
ZIP/Postal Code
08028
Country
Spain
City
Getafe
ZIP/Postal Code
28905
Country
Spain
City
Girona
ZIP/Postal Code
17190
Country
Spain
City
Madrid
ZIP/Postal Code
28034
Country
Spain
City
Madrid
ZIP/Postal Code
28040
Country
Spain
City
Madrid
ZIP/Postal Code
28049
Country
Spain
City
Pamplona
ZIP/Postal Code
31014
Country
Spain
City
Salamanca
ZIP/Postal Code
37003
Country
Spain
City
Valencia
ZIP/Postal Code
46010
Country
Spain
City
Valencia
ZIP/Postal Code
46026
Country
Spain
City
Zamora
ZIP/Postal Code
49021
Country
Spain
City
Kharkiv
ZIP/Postal Code
61068
Country
Ukraine
City
Kherson
ZIP/Postal Code
73488
Country
Ukraine
City
Kiev
ZIP/Postal Code
04080
Country
Ukraine
City
Lviv
ZIP/Postal Code
79021
Country
Ukraine
City
Odessa
ZIP/Postal Code
65006
Country
Ukraine
City
Odessa
ZIP/Postal Code
67513
Country
Ukraine
City
Poltava
ZIP/Postal Code
36013
Country
Ukraine
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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 an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com
Citations:
PubMed Identifier
31708380
Citation
Grossberg GT, Kohegyi E, Mergel V, Josiassen MK, Meulien D, Hobart M, Slomkowski M, Baker RA, McQuade RD, Cummings JL. Efficacy and Safety of Brexpiprazole for the Treatment of Agitation in Alzheimer's Dementia: Two 12-Week, Randomized, Double-Blind, Placebo-Controlled Trials. Am J Geriatr Psychiatry. 2020 Apr;28(4):383-400. doi: 10.1016/j.jagp.2019.09.009. Epub 2019 Oct 1.
Results Reference
derived
Learn more about this trial
A Phase 3, 12-week, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of 2 Fixed Doses of Brexpiprazole in the Treatment of Alzheimer's Agitation
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