Clinical trial NCT01438060: Aripiprazole in the Treatment of Patients With Psychosis Associated With Dementia of Alzheimer's Type
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dementia, Alzheimer Type
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Otsuka America Pharmaceutical
First posted: 2011-09-21
Enrollment: 232
Sex: ALL
Minimum age (years): 55
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

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