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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor:
Collaborator:
H. Lundbeck A/S
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT01922258
First received: August 12, 2013
Last updated: July 31, 2014
Last verified: July 2014
  Purpose

To compare the efficacy of flexible dosing of brexpiprazole with placebo in subjects with agitation associated with dementia of the Alzheimer's type


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

Primary Outcome Measures:
  • Change in the Cohen-Mansfield Agitation Inventory (CMAI) total score [ Time Frame: Baseline to Week 12/Early Termination ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Change in the CMAI subscale scores (aggressive behavior, physically nonaggressive behavior, verbally agitated behavior) [ Time Frame: Baseline to Week 12/Early Termination ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    For non-institutionalized subjects.

  • Clinical Global Impression-Improvement (CGI-I) score, as related to agitation [ Time Frame: Week 12/Early Termination ] [ Designated as safety issue: No ]
  • 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 12/Early Termination ] [ Designated as safety issue: No ]
  • Change in the Modified Nursing Care Assessment Scale (M-NCAS) score (institutionalized subjects only) [ Time Frame: Baseline to Week 12/Early Termination ] [ Designated as safety issue: No ]
  • Change in the Quality of Life in Alzheimer's Disease (QoL-AD) score [ Time Frame: Baseline to Week 12/Early Termination ] [ Designated as safety issue: No ]
  • Change in the Nurses' Observation Scale for Geriatric Patients (NOSGER) score (institutionalized subjects only) [ Time Frame: Baseline to Week 12/Early Termination ] [ Designated as safety issue: No ]
  • Resource Utilization in Dementia (RUD) score [ Time Frame: Baseline to Week 12/Early Termination ] [ Designated as safety issue: No ]
  • Safety Variables [ Time Frame: Baseline to Week 12/Early Termination ] [ Designated as safety issue: Yes ]
    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).


Estimated Enrollment: 230
Study Start Date: September 2013
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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 (e.g., dementia unit, nursing home, assisted living facility, or other residential care facility) or in a non-institutionalized setting where the subject is not living alone.

  Eligibility

Ages Eligible for Study:   55 Years to 90 Years
Genders Eligible for Study:   Both
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 either in an institutionalized setting (e.g., at a dementia unit, nursing home, assisted living facility, or other residential care facility) or in a non-institutionalized setting where the subject is not living alone. Subjects must have been at their current location for at least 14 days before screening and plan 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 score of greater than or equal to 4 on the agitation/aggression item of the 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 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 a history of stroke, transient ischemic attack, pulmonary or cerebral embolism, or traumatic brain injury.
  • Subjects with deep venous thrombosis within 5 years prior to the screening visit.
  • Subjects who have been diagnosed with an Axis I or Axis II disorder (DSM-IV-TR criteria).
  • Subjects with uncontrolled hypertension.
  • Subjects with uncontrolled insulin-dependent diabetes mellitus (IDDM) without current microalbuminuria.
  • Subjects with epilepsy or a history of seizures.
  • Subjects who are bedridden.
  • Subjects with clinically significant infection, with treatment of intravenous antibiotics or hospitalization, within two weeks of the screening visits.
  • Inability to swallow tablets or tolerate oral medication.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01922258

Contacts
Contact: Alison Hart 512-579-4737 Alison.Hart@incresearch.com
Contact: Rozina Jadoon, PMP 919-418-6218 Rozina.Jadoon@incresearch.com

Locations
United States, Hawaii
Recruiting
Honolulu, Hawaii, United States, 96817
United States, Massachusetts
Recruiting
Quincy, Massachusetts, United States, 02171
United States, New York
Recruiting
Buffalo, New York, United States, 14215
Recruiting
New Hyde Park, New York, United States, 11040
United States, North Carolina
Recruiting
Raleigh, North Carolina, United States, 27609
Canada, Nova Scotia
Recruiting
Kentville, Nova Scotia, Canada, B4N 4K9
Ukraine
Recruiting
Kharkiv, Ukraine, 61068
Recruiting
Kherson, Ukraine, 73488
Recruiting
Kiev, Ukraine, 04114
Recruiting
Kiev, Ukraine, 04080
Recruiting
Lviv, Ukraine, 79021
Recruiting
Poltava, Ukraine, 36013
Recruiting
Vinnytsia, Ukraine, 21005
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
H. Lundbeck A/S
Investigators
Study Director: Eva Koheygi, MD Otsuka Pharmaceutical Development and Commercialization, Inc.
  More Information

No publications provided

Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01922258     History of Changes
Other Study ID Numbers: 331-12-284
Study First Received: August 12, 2013
Last Updated: July 31, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Ukraine: State Administration of Medicinal Products
France: Ministry of Health

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
OPC-34712
brexpiprazole
Dementia
Alzheimer's Disease
Cognitive Disorders
Memory
Agitation

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Psychomotor Agitation
Mental Disorders
Psychotic Disorders
Nervous System Diseases
Brain Diseases
Central Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Dyskinesias
Neurologic Manifestations
Psychomotor Disorders
Neurobehavioral Manifestations
Signs and Symptoms
Schizophrenia and Disorders with Psychotic Features

ClinicalTrials.gov processed this record on September 22, 2014