A Study of Three Fixed-doses of Brexpiprazole in the Treatment of Subjects With Agitation Associated With Dementia of the Alzheimer's Type

This study is currently recruiting participants.
Verified April 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:
NCT01862640
First received: May 22, 2013
Last updated: April 11, 2014
Last verified: April 2014
  Purpose

To compare the efficacy of 3 fixed doses 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 3 Fixed Doses 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:
  • The primary outcome is the 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:
  • 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 ] [ 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 ]
    NPI-NH is an acronym for the Neuropsychiatric Inventory-Nursing Home Rating Scale.

  • 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 [ 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 [ 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: 560
Study Start Date: July 2013
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Matching Placebo Once-Daily
Drug: Brexpiprazole, OPC-34712
Once-daily, tablets
Experimental: brexpiprazole 0.5mg
titrate up from 0.25mg/day brexpiprazole to 0.5mg/day brexpiprazole
Drug: Brexpiprazole, OPC-34712
Once-daily, tablets
Experimental: brexpiprazole 1mg
titrate up from 0.25 mg/day brexpiprazole to 1mg/day brexpiprazole
Drug: Brexpiprazole, OPC-34712
Once-daily, tablets
Experimental: brexpiprazole 2mg
titrate up from 0.25 mg/day brexpiprazole to 2mg/day brexpiprazole
Drug: Brexpiprazole, OPC-34712
Once-daily, tablets

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), who are residing in a dementia unit, nursing home, assisted living facility, or other residential care facility, with a diagnosis of probable Alzheimer's disease.

  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 in a dementia unit, nursing home, assisted living facility, or other residential care facility. Subjects must have been at their current residence for at least 1 month before screening and plan to remain at the same facility 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 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, transient ischemic attack, pulmonary or cerebral embolism or traumatic brain injury
  • Subjects with Deep Vein Thrombosis within 5 years prior to the screening visit
  • Subjects who have been diagnosed with an Axis I and Axis II disorder (DSM-IV-TR criteria)
  • Subjects with uncontrolled hypertension
  • Subjects with insulin-dependent diabetes mellitus (IDDM)
  • Subjects with epilepsy or a history of seizures
  • Subjects who are bedridden
  • Subjects with recent clinically significant infection, with treatment with intravenous antibiotics or hospitalization, within two weeks of the screening visit.
  • Inability to swallow tablets or tolerate oral medication.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01862640

Contacts
Contact: Rozina Jadoon, PMP 919-418-6218 rozina.jadoon@incresearch.com

Locations
United States, California
Recruiting
Costa Mesa, California, United States, 92627
Recruiting
Downey, California, United States, 90241
Recruiting
Redlands, California, United States, 92373
Recruiting
Yorba Linda, California, United States, 92886
United States, Connecticut
Recruiting
Norwalk, Connecticut, United States, 06851
United States, Florida
Recruiting
Miami, Florida, United States, 33137
Recruiting
Miami, Florida, United States, 33161
Recruiting
Miami, Florida, United States, 33174
Recruiting
Miami Springs, Florida, United States, 33166
United States, Georgia
Recruiting
Decatur, Georgia, United States, 30033
United States, New Jersey
Recruiting
Mt. Arlington, New Jersey, United States, 07856
Recruiting
Toms River, New Jersey, United States, 08755
United States, Wisconsin
Recruiting
Waukesha, Wisconsin, United States, 53188
Germany
Recruiting
Westerstede, Germany, 26655
Russian Federation
Recruiting
Ekaterinburg, Russian Federation, 620030
Recruiting
Samara, Russian Federation, 443016
Recruiting
Saratov, Russian Federation, 410060
Recruiting
St. Petersburg, Russian Federation, 192019
Recruiting
St. Petersburg, Russian Federation, 197341
Recruiting
St. Petersburg, Russian Federation, 190005
Recruiting
St. Petersburg, Russian Federation, 198510
Recruiting
Tonnelniy, Russian Federation, 357034
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
H. Lundbeck A/S
Investigators
Study Director: Eva Kohegyi, MD Otsuka Pharmaceutical Development & Commercialization, Inc.
  More Information

No publications provided

Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01862640     History of Changes
Other Study ID Numbers: 331-12-283
Study First Received: May 22, 2013
Last Updated: April 11, 2014
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Device
Russia: Ministry of Health of the Russian Federation

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

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

ClinicalTrials.gov processed this record on April 16, 2014