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Safety and Tolerability Study of Flexible Dosing of Brexpiprazole in the Treatment of Subjects With Agitation Associated With Dementia of the Alzheimer's Type

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01922258
Recruitment Status : Completed
First Posted : August 14, 2013
Results First Posted : July 7, 2020
Last Update Posted : November 20, 2020
Sponsor:
Collaborator:
H. Lundbeck A/S
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Description
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Brief Summary:
To compare the efficacy of flexible dosing of brexpiprazole with placebo in subjects with agitation associated with dementia of the Alzheimer's type

Condition or disease Intervention/treatment Phase
Agitation Associated With Alzheimer's Disease Alzheimer's Type Mental Disorder Nervous System Diseases Drug: Brexpiprazole, OPC-34712 Phase 3

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 flexible dosing of brexpiprazole in the treatment of subjects with agitation associated with dementia of the Alzheimer's type. The trial consists of a 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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 270 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, 12-week, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of Flexible Dosing of Brexpiprazole (OPC-34712) in the Treatment of Subjects With Agitation Associated With Dementia of the Alzheimer's Type
Actual Study Start Date : September 2013
Actual Primary Completion Date : March 2017
Actual Study Completion Date : March 2017

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Placebo Comparator: Placebo
Matching Placebo Once-Daily
 Drug: Brexpiprazole, OPC-34712
Flexible dose of 0.5 to 2 mg/day or placebo tablets for up to 12 weeks
Experimental: Brexpiprazole (flexible dose range 0.5 to 2 mg)
Titrate up from 0.25 mg/day brexpiprazole to 1 mg/day brexpiprazole. After achieving 1 mg/day target dose may be increased or decreased based on efficacy and tolerability. Allowable flexible doses will be 0.5 mg/day, 1 mg/day, or 2 mg/day.
 Drug: Brexpiprazole, OPC-34712
Flexible dose of 0.5 to 2 mg/day or placebo tablets for up to 12 weeks


Outcome Measures
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Primary Outcome Measures :
  1. Change From Baseline to Week 12/Early Termination in the Cohen-Mansfield Agitation Inventory (CMAI) Total Score [ Time Frame: From screening to week 12/early termination ]
    The CMAI is widely used in clinical research for evaluation of agitation associated with Alzheimer's dementia, with reliability and validity in both institutionalized and noninstitutionalized participants. It consists of 29 items, all rated on a 1 to 7 scale (1=Never and 7=Several times in an hour), with 1 being the "best" rating and 7 being the "worst" rating. The total score is the sum of ratings for all 29 items. The possible total scores range from 29 to 203. The total score will be unevaluable if less than 24 of the 29 items are recorded. If 24 to 28 of the 29 items are recorded, the total score will be the mean of the recorded items multiplied by 29 and rounded to the first decimal place. The mean change from baseline (Day 0) to week 12 in the CMAI total score is reported. Statistical comparison of interest was brexpiprazole flexible dose versus placebo, analyzed using a mixed-effect model repeated measure approach. A decrease in score indicates improvement in symptoms.


Secondary Outcome Measures :
  1. Change in the Clinical Global Impression Severity of Illness (CGI-S) Score, as Related to Symptoms of Agitation [ Time Frame: From screening to week 12/early termination ]
    The severity of agitation for each participant was rated using the CGI-S. The investigator (or designee) answered the following question: "Considering your total clinical experience with this particular population, how mentally ill (as related to agitation) was the participant at the observation period?" Response choices 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. The score 0 (= not assessed) was set to missing. The CGI-S was therefore a 7-point scale (1-7). The primary analysis used a mixed-effect model repeated measure approach.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   55 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 diagnosis of probable Alzheimer's disease according to NINCDS-ADRDA criteria.
  • 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 total score greater than or equal to 4 on the agitation aggression item of the NPI-NH or NPI/NPI-NH at the screening and baseline visits.
  • Subjects who require pharmacotherapy for the treatment of agitation per the investigator's judgement, after an evaluation of reversible factors (eg, pain, infection, polypharmacy) and a trial of nonpharmacological interventions.
  • 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 history of stroke, well-documented transient ischemic attack, or 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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01922258


Locations
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Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
H. Lundbeck A/S
Investigators
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Study Director: Eva Koheygi, MD Otsuka Pharmaceutical Development and Commercialization, Inc.
  Study Documents (Full-Text)

Documents provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
Study Protocol  [PDF] September 10, 2015
Statistical Analysis Plan  [PDF] March 22, 2017

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01922258    
Other Study ID Numbers: 331-12-284
First Posted: August 14, 2013    Key Record Dates
Results First Posted: July 7, 2020
Last Update Posted: November 20, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
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.
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
URL: https://clinical-trials.otsuka.com
Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
OPC-34712
brexpiprazole
Dementia
 Alzheimer's Disease
Cognitive Disorders
Agitation
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Psychomotor Agitation
Nervous System Diseases
Mental Disorders
Brain Diseases
Central Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Dyskinesias
 Neurologic Manifestations
Psychomotor Disorders
Neurobehavioral Manifestations
Brexpiprazole
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Dopamine Agonists
Dopamine Agents