A Multicenter, Randomized, Double-Blind, Placebo Controlled Flexible Dose Study of Aripiprazole in the Treatment of Patients With Psychosis Associated With Dementia of Alzheimer's Type

Otsuka Pharmaceutical Development & Commercialization, Inc.0 sites232 target enrollmentAugust 2000

ConditionsDementia, Alzheimer Type

InterventionsAripiprazole (BMS-337039)Placebo

DrugsAripiprazole (BMS-337039)Placebo

Overview

Phase: Phase 3
Intervention: Aripiprazole (BMS-337039)
Conditions: Dementia, Alzheimer Type
Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Enrollment: 232
Primary Endpoint: Change From Baseline in Neuropsychiatric Inventory (NPI) Psychosis Subscale Score at Week 10 in Acute Phase
Status: Completed
Last Updated: 12 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

The primary objective of the study is to compare the efficacy of aripiprazole with placebo in patients with psychosis associated with Alzheimer's dementia.

Detailed Description

Open label Extension Phase: The 130-week Extension Phase was conducted to provide information regarding long-term safety and efficacy of aripiprazole in participants who were diagnosed at the onset of the Acute Phase with psychotic symptoms associated with dementia of the Alzheimer's type who responded to treatment in the 10-week Acute Phase of this study. Treatment beyond 140 week: A country-specific amendment for France, allowed participants treated with aripiprazole who, according to the investigator's opinion, showed improvement at the Week 140 visit to continue treatment beyond 140 weeks. The termination was to be determined by clinical benefit to he participant. Study design: Acute Phase: Randomized, double-blind, placebo-controlled, flexible-dose, parallel-group study. Extension Phase: Open label; flexible-dose.

Registry

clinicaltrials.gov

Start Date

August 2000

End Date

July 2010

Last Updated

12 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Otsuka Pharmaceutical Development & Commercialization, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Non-institutionalized patients with a diagnosis of Alzheimer's disease as defined by Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition (DSM-IV) criteria with symptoms of delusions or hallucinations, which have been present, at least intermittently for one month or longer
•Mini Mental State Examination (MMSE) score of 6 to 24 points
•Patients capable of self locomotion or locomotion with the aid of an assistive device
•Patients with an identified caregiver or proxy
•For Extension Phase:
•Eligible patients were males and females who had completed the 10-week Acute Phase in either treatment group; had a Week 10 Total Score of ≥ 6 on the NPI; and were, in the judgment of the investigator, deemed suitable for participation in the long-term trial.
•Treatment beyond 140 weeks:
•All subjects who completed the extension phase of CN138-006 in any French Investigational Site may be considered eligible for entry until they are no longer receiving clinical benefit, per the investigator's judgment

Exclusion Criteria

•Patients with an Axis I (DSM IV) diagnosis of:
•amnestic disorders
•bipolar disorder
•schizophrenia or schizoaffective disorder
•mood disorder with psychotic features
•Patients with reversible causes of dementia
•Patients with psychotic symptoms continuously present since prior to the onset of the symptoms of dementia
•Patients with psychotic symptoms that are better accounted for by another general medical condition or by direct physiological effects of a substance
•Patients with a current major depressive episode with psychotic symptoms of hallucinations or delusions
•Patients with a diagnosis of dementia related to infection with the human immunodeficiency virus

Arms & Interventions

Aripiprazole (BMS-337039)

Double blind Acute Phase (Week 1 to Week 10), Open label Extension Phase (Week 11 to Week 140)

Intervention: Aripiprazole (BMS-337039)

Placebo

Double blind Acute Phase (Week 1 to Week 10)

Intervention: Placebo

Outcomes

Primary Outcomes

Change From Baseline in Neuropsychiatric Inventory (NPI) Psychosis Subscale Score at Week 10 in Acute Phase

Time Frame: Baseline (Day 0), Week 10

The NPI is a questionnaire that quantifies behavioral changes in dementia. For each of 12 behavioral domains there are 4 scores: Frequency (scale:1=occasionally to 4=very frequently), Severity (scale:1=Mild to 3=Severe), Total (frequency x severity), Caregiver distress (scale: 0=not at all distressing to 5=extremely distressing).The NPI Psychosis Subscale consists of the two domains of Delusions and Hallucinations, calculated by adding the Individual Item Scores, to yield a possible total score of 0 to 24. Lower score=less severity. A negative change score from baseline indicates improvement.

Secondary Outcomes

Change From Baseline in NPI Psychosis Subscale Score Through Week 8 in Acute Phase(Baseline (Day 0), Weeks 1, 2, 3, 4, 6, and 8)
Change From Baseline in NPI Total Score in Acute Phase(Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10)
Participants Who Demonstrated a ≥ 50% Decrease From Baseline to Endpoint in the NPI Psychosis Subscale Score in Acute Phase(Weeks 1, 2, 3, 4, 6, 8, and 10)
Participants Who Demonstrated a ≥ 50% Decrease From Baseline in the Total NPI Score in Acute Phase(Weeks 1, 2, 3, 4, 6, 8, and 10)
Change From Baseline in NPI Psychosis Subscale Caregiver Distress Score in Acute Phase(Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10)
Change From Baseline in NPI Total Caregiver Distress Score in Acute Phase(Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10)
Change From Baseline in Clinical Global Impression (CGI) Severity of Illness Score in Acute Phase(Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10)
CGI Improvement Score in Acute Phase(Weeks 1, 2, 3, 4, 6, 8, and 10)
Change From Baseline in Brief Psychiatric Rating Scale (BPRS) Total Score in Acute Phase(Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10)
Change From Baseline in Mini Mental State Examination (MMSE) Total Score in Acute Phase(Baseline (Day 0), Week 10)
Change From Baseline in NPI Individual Item Scores in Acute Phase: Delusions(Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10)
Change From Baseline in NPI Individual Item Scores in Acute Phase: Hallucinations(Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10)
Change From Baseline in NPI Individual Item Scores in Acute Phase: Agitation/Aggression(Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10)
Change From Baseline in NPI Individual Item Scores in Acute Phase: Depression/Dysphoria(Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10)
Change From Baseline in NPI Individual Item Scores in Acute Phase: Anxiety(Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10)
Change From Baseline in NPI Individual Item Scores in Acute Phase: Apathy/Indifference(Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10)
Change From Baseline in NPI Individual Item Scores in Acute Phase: Elation/Euphoria(Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10)
Change From Baseline in NPI Individual Item Scores in Acute Phase: Disinhibition(Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10)
Change From Baseline in NPI Individual Item Scores in Acute Phase: Irritability/Lability(Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10)
Change From Baseline in NPI Individual Item Scores in Acute Phase: Aberrant Motor Behavior(Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10)
Change From Baseline in NPI Individual Item Scores in Acute Phase: Appetite/Eating Behaviors(Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10)
Change From Baseline in NPI Individual Item Scores in Acute Phase: Sleep(Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10)
Change From Baseline in Simpson-Angus Scale (SAS) Total Score in Acute Phase(Baseline (Day 0), Weeks 2, 4, and 10)
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score in Acute Phase(Baseline (Day 0), Weeks 2, 4, 8, and 10)
Change From Baseline in Barnes Global Clinical Assessment of Akathisia in Acute Phase(Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10)
Participants With Extrapyramidal Symptoms (EPS) Related Adverse Events in Acute Phase(Week 1 to week 10)
Participants Who Died, Experienced Serious Adverse Events (SAEs), Adverse Events (AEs) or Discontinuations Due to AEs in Acute Phase(Week 1 to week 10)
Participants With Potentially Clinically Significant Laboratory Abnormalities in Acute Phase(Week 1 to Week 10)
Participants With Potentially Clinically Significant (PCS) Vital Sign Abnormalities in Acute Phase(Week 1 to week 10)
Participants With Potentially Clinically Significant Electrocardiogram Abnormalities in Acute Phase(Week 1 to Week 10)
Change in Neuropsychiatric Inventory (NPI) Psychosis Subscale Score From Baseline During Extension Phase(Baseline (Day 0), Weeks 18,26,40,52,68,84,100,116,132,140)
Clinical Global Impression (CGI) Improvement Score During Extension Phase(Weeks 12, 14, 18, 22, 26, 30, 34, 40, 46, 52, 68, 84, 100, 116, 132, 140)
Change in Abnormal Involuntary Movement Scale (AIMS) Total Score During Extension Phase(End of Acute Phase (Week 10), Weeks 14, 18, 22, 26, 30, 34, 40, 46, 52, 68, 84, 100, 116, 140)
Change in Simpson-Angus Scale (SAS) Total Score During Extension Phase(End of Acute Phase (Week 10), Weeks 18,26, 40, 52)
Change in Barnes Global Clinical Assessment of Akathisia Score During Extension Phase(End of Acute Phase (Week 10), Weeks 18,26, 40, 52)
Participants With Extrapyramidal Symptoms (EPS) Related Adverse Events During Extension Phase(Week 11 to Week 140)
Participants Who Died, Experienced Serious Adverse Events (SAEs), Adverse Events (AEs) or Discontinuations Due to AE During Extension Phase(Week 11 to Week 140)
Participants With a Potentially Clinically Significant Vital Sign Abnormality During Extension Phase(Week 11 to Week 140)
Participants With a Potentially Clinically Significant Electrocardiogram Abnormalities During Extension Phase(Week 11 to Week 140)
Participants With Potentially Clinically Significant Laboratory Abnormalities During Extension Phase(Week 11 to Week 140)
Participants Who Died, Experienced Serious Adverse Events (SAEs), Adverse Events (AEs) or Discontinuations Due to AE During Treatment Beyond 140 Weeks(Week 140 to Week 328)