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

Aripiprazole in the Treatment of Patients With Psychosis Associated With Dementia of Alzheimer's Type

Sponsors

Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Collaborator: Otsuka America Pharmaceutical

Source Otsuka Pharmaceutical Development & Commercialization, Inc.
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.

Overall Status Completed
Start Date August 2000
Completion Date July 2010
Primary Completion Date July 2010
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Change From Baseline in Neuropsychiatric Inventory (NPI) Psychosis Subscale Score at Week 10 in Acute Phase Baseline (Day 0), Week 10
Secondary Outcome
Measure Time Frame
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
Enrollment 232
Condition
Intervention

Intervention type: Drug

Intervention name: Aripiprazole (BMS-337039)

Description: Acute Phase: Oral, Tablets (1 and 5 mg), Week 1-2: 2 mg, Week 3-4: 2 - 5 mg, Week 5-6: 2 - 10 mg, Weeks 7-10: 2 - 15 mg, Once daily, 10 weeks Extension Phase: Oral, Tablets (1 and 5 mg), Week 11: 2 mg, Weeks 12-13: 2 - 5 mg, Weeks 14-15: 2 - 10 mg, Weeks 16-140: 2 - 15 mg, Once daily, 130 weeks

Arm group label: Aripiprazole (BMS-337039)

Intervention type: Drug

Intervention name: Placebo

Description: Acute Phase: Oral, Tablets, 0 mg, Once daily, 10 Weeks

Arm group label: Placebo

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:

- delirium

- 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

- Patients with substance-induced persistent dementia

- Patients with dementia due to vascular causes, multi-infarct, head trauma, Pick's disease, Parkinson's disease, frontal or temporal dementia, Lewy body dementia, or any specific non-Alzheimer's type dementia

- Patients with seizure disorders

- Patients who have been refractory to neuroleptics used to treat psychotic symptoms in the past when treated for an adequate period with a therapeutic dose, unless permission is obtained from Bristol-Myers Squibb

- Patients who have met DSM-IV criteria for any significant substance use disorder within the 6 months prior to the start of screening

Gender: All

Minimum age: 55 Years

Maximum age: 95 Years

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Bristol-Myers Squibb Study Director Bristol-Myers Squibb
Verification Date

November 2013

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Aripiprazole (BMS-337039)

Arm group type: Experimental

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

Arm group label: Placebo

Arm group type: Placebo Comparator

Description: Double blind Acute Phase (Week 1 to Week 10)

Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov