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Safety and Tolerability Study of Two Fixed-doses of Brexpiprazole in the Treatment of Subjects With Agitation Associated With Dementia of the Alzheimer's Type

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ClinicalTrials.gov Identifier: NCT01862640
Recruitment Status : Completed
First Posted : May 24, 2013
Last Update Posted : March 14, 2019
Sponsor:
Collaborator:
H. Lundbeck A/S
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

Tracking Information
First Submitted Date  ICMJE May 22, 2013
First Posted Date  ICMJE May 24, 2013
Last Update Posted Date March 14, 2019
Study Start Date  ICMJE July 2013
Actual Primary Completion Date March 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 23, 2013)
The primary outcome is the change in the Cohen-Mansfield Agitation Inventory (CMAI) total score [ Time Frame: Baseline to Week 12/Early Termination ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 22, 2013)
The primary outcome is the change in the Cohen-Mansfield Agitation Inventory (CMAI) [ Time Frame: Randomization Visit to End of Double-Blind Treatment (12 Weeks) ]
Change History Complete list of historical versions of study NCT01862640 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 23, 2013)
The secondary outcome is the change in the Clinical Global Impression-Severity of Illness (CGI-S) score, as related to symptoms of agitation [ Time Frame: Baseline to Week 12/Early Termination ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 22, 2013)
The secondary outcome is the change in the Clinical Global Impression of Severity (CGI-S) score, as related to symptoms of agitation [ Time Frame: Randomization Visit to End of Double-Blind Treatment (12 Weeks) ]
Current Other Pre-specified Outcome Measures
 (submitted: February 9, 2016)
  • Change in the CMAI subscale scores (aggressive behavior, physically nonaggressive behavior, verbally agitated behavior) [ Time Frame: Baseline to Week 12/Early Termination ]
  • Change in the NPI-NH total score, psychosis subscale score (delusions and hallucinations), individual item scores (eg, agitation/aggression, anxiety, irritability/lability), and occupational disruptiveness scores (individual item and total scores) [ Time Frame: Baseline to Week 12/Early Termination ]
    For institutionalized subjects. NPI-NH is an acronym for the Neuropsychiatric Inventory-Nursing Home Rating Scale.
  • Change in the NPI-NH total score, psychosis subscale score (delusions and hallucinations), individual item scores (eg, agitation/aggression, anxiety, irritability/lability), and in NPI distress scores (individual item and total scores) [ Time Frame: Baseline to Week 12/Early Termination ]
    For non-institutionalized subjects.
  • Clinical Global Impression-Improvement (CGI-I) score, as related to agitation [ Time Frame: Week 2 to Week 12/Early Termination ]
  • Clinical Global Impression-Efficacy Index (CGI-E) score, which is defined as the ratio of current therapeutic effect (as related to agitation) and severity of side effects [ Time Frame: Week 2 to Week 12/Early Termination ]
  • Change in the Modified Nursing Care Assessment Scale (M-NCAS) score (institutionalized subjects only) [ Time Frame: Baseline to Week 12/Early Termination ]
  • Change in the Quality of Life in Alzheimer's Disease (QoL-AD) score [ Time Frame: Baseline to Week 12/Early Termination ]
  • Change in the Nurses' Observation Scale for Geriatric Patients (NOSGER) score (institutionalized subjects only) [ Time Frame: Baseline to Week 12/Early Termination ]
  • Resource Utilization in Dementia (RUD) score [ Time Frame: Baseline to Week 12/Early Termination ]
  • Safety Variables [ Time Frame: Baseline to Week 12/Early Termination ]
    Safety variables to be examined will include: adverse events, physical examinations, neurological examinations, vital signs, body weight, waist circumference, clinical laboratory tests (hematology, serum chemistry, and urinalysis), electrocardiograms (ECGs), MMSE score, assessments of suicidality (Sheehan-STS), extrapyramidal symptoms (the Simpson Angus Scale [SAS], the Abnormal Involuntary Movement Scale [AIMS], the Barnes Akathisia Rating Scale [BARS]), adverse events of interest (eg, falls, sedation, diabetes, weight changes, QTc prolongation, or deaths), and change from baseline in body mass index (BMI).
Original Other Pre-specified Outcome Measures
 (submitted: May 22, 2013)
  • Change in the CMAI subscale scores (aggressive behavior, physically nonaggressive behavior, verbally agitated behavior) [ Time Frame: Baseline to End of Double-Blind Treatment (12 Weeks/Early Termination) ]
  • Change in the NPI-NH total score, psychosis subscale score (delusions and hallucinations), individual item scores (eg, agitation/aggression, anxiety, irritability/lability), and occupational disruptiveness scores (individual item and total scores) [ Time Frame: Baseline Visit to End of Double-Blind Treatment (12 Weeks/Early Termination) ]
  • Clinical Global Impression-Improvement (CGI-I) score, as related to agitation [ Time Frame: At Week 12/Early Termination ]
  • Clinical Global Impression-Efficacy Index (CGI-E) score, which is defined as the ratio of current therapeutic effect (as related to agitation) and severity of side effects [ Time Frame: At Week 12/Early Termination ]
 
Descriptive Information
Brief Title  ICMJE Safety and Tolerability Study of Two Fixed-doses of Brexpiprazole in the Treatment of Subjects With Agitation Associated With Dementia of the Alzheimer's Type
Official Title  ICMJE 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
Brief Summary To compare the efficacy of 2 fixed doses of brexpiprazole with placebo in subjects with agitation associated with dementia of the Alzheimer's type.
Detailed Description

Behavioral symptoms, such as agitation, are core features in subjects with Alzheimer's disease and related dementias and develop in the majority of dementia subjects. The presence of agitation in subjects with Alzheimer's disease places a significant burden not only on subjects 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 subjects 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 subjects 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 subject is not living alone.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Agitation Associated With
  • Alzheimer's Disease
  • Alzheimer's Type
  • Mental Disorder
  • Nervous System Diseases
Intervention  ICMJE
  • Drug: Brexpiprazole, OPC-34712
    Once-daily, tablets
  • Drug: Placebo Oral Tablet
    Once-daily, tablets
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Matching Placebo Once-Daily
    Intervention: Drug: Placebo Oral Tablet
  • Experimental: brexpiprazole 1mg
    titrate up from 0.25 mg/day brexpiprazole to 1 mg/day brexpiprazole
    Intervention: Drug: Brexpiprazole, OPC-34712
  • Experimental: brexpiprazole 2mg
    titrate up from 0.25 mg/day brexpiprazole to 2 mg/day brexpiprazole
    Intervention: Drug: Brexpiprazole, OPC-34712
Publications * 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. 2019 Oct 1. pii: S1064-7481(19)30521-4. doi: 10.1016/j.jagp.2019.09.009. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 6, 2017)
433
Original Estimated Enrollment  ICMJE
 (submitted: May 22, 2013)
560
Actual Study Completion Date  ICMJE March 2017
Actual Primary Completion Date March 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male and female subjects 55 to 90 years of age, inclusive, at the time of informed consent.
  • Subjects 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.
  • Subjects with a diagnosis of probable Alzheimer's disease according to NINCDS-ADRDA.
  • Subjects with a MMSE score of 5 to 22, inclusive, at screening and baseline visits.
  • Subjects with onset of symptoms of agitation at least 2 weeks prior to the screening visit.
  • Subjects with a score of ≥ 4 on the agitation/aggression item of the NPI-NH at the screening and baseline visits.
  • Subjects who require pharmacotherapy for treatment of agitation per the investigator's judgment, after an evaluation for reversible factors (eg, pain, infection, polypharmacy) and a trial of nonpharmacological intervention.
  • Subjects must have a previous MRI or CT scan 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:

  • Subjects with dementia or other memory impairment not due to Alzheimer's disease
  • Subjects with a history of stroke, well-documented transient ischemic attack, pulmonary or cerebral embolism.
  • Subjects who currently have clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, gastrointestinal, or psychiatric disorders.
  • Subjects who have been diagnosed with an Axis I disorder (DSM-IV-TR criteria)
  • Subjects with uncontrolled hypertension
  • Subjects with uncontrolled insulin-dependent diabetes mellitus (IDDM)
  • Subjects with epilepsy or a history of seizures
  • Subjects considered in poor general health based on the investigator's judgment.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 55 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Croatia,   Germany,   Russian Federation,   Serbia,   Spain,   Ukraine,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01862640
Other Study ID Numbers  ICMJE 331-12-283
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Otsuka Pharmaceutical Development & Commercialization, Inc.
Study Sponsor  ICMJE Otsuka Pharmaceutical Development & Commercialization, Inc.
Collaborators  ICMJE H. Lundbeck A/S
Investigators  ICMJE
Study Director: Eva Kohegyi, MD Otsuka Pharmaceutical Development & Commercialization, Inc.
PRS Account Otsuka Pharmaceutical Development & Commercialization, Inc.
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP