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

Sponsor

Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01438060

Collaborator

Otsuka America Pharmaceutical (Industry)

232

Enrollment

Arms

119

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Dementia, Alzheimer Type	Drug: Aripiprazole (BMS-337039) Drug: Placebo	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

232 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

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

Primary Purpose:

Treatment

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 Start Date :

Aug 1, 2000

Actual Primary Completion Date :

Jul 1, 2010

Actual Study Completion Date :

Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aripiprazole (BMS-337039) Double blind Acute Phase (Week 1 to Week 10), Open label Extension Phase (Week 11 to Week 140)	Drug: Aripiprazole (BMS-337039) 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
Placebo Comparator: Placebo Double blind Acute Phase (Week 1 to Week 10)	Drug: Placebo Acute Phase: Oral, Tablets, 0 mg, Once daily, 10 Weeks

Arm

Intervention/Treatment

Experimental: Aripiprazole (BMS-337039)

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

Drug: Aripiprazole (BMS-337039)

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

Placebo Comparator: Placebo

Double blind Acute Phase (Week 1 to Week 10)

Drug: Placebo

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

Outcome Measures

Primary Outcome Measures

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

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]
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.
Change From Baseline in NPI Total Score in Acute Phase [Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 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 Total Score is calculated by adding the Individual Item Scores for all 12 domains, to yield a possible NPI Total Score of 0 to 144. Lower score=less severity. A negative change score from baseline indicates improvement.
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]
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.
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]
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 Total Score is calculated by adding the Individual Item Scores for all 12 domains, to yield a possible NPI Total Score of 0 to 144. Lower score=less severity. A negative change score from baseline indicates improvement.
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]
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 Caregiver Distress Score is calculated by adding Individual Item Scores for the domains of Delusions and Hallucinations, to yield a possible total score of 0 to 10. Lower score=less severity. A negative change score from baseline=improvement.
Change From Baseline in NPI Total Caregiver Distress Score in Acute Phase [Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 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 total NPI Caregiver Distress Score is calculated by adding the 12 Caregiver Distress Individual Item Scores, to yield a possible total score of 0 to 60. Lower score=less severity. A negative change score from baseline indicates improvement.
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]
The CGI rating scale, which measures symptom severity, treatment response and the efficacy of treatments, is used in clinical studies on mental disorders. CGI Severity scale is a 7-point scale that requires the clinician to rate the severity of the illness at the time of assessment, relative to the clinician's past experience with participants who have the same diagnosis. The assessment is based on severity of mental illness at the time of rating, 0=not assessed, 1=normal, 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; or 7=extremely ill.
CGI Improvement Score in Acute Phase [Weeks 1, 2, 3, 4, 6, 8, and 10]
The CGI rating scale, which measures symptom severity, treatment response and the efficacy of treatments, is used in clinical studies on mental disorders. CGI Improvement scale is a 7 point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse.
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]
The BPRS is designed to measure clinical change in participants and is used as a global measure of psychopathology. The BPRS includes 18 items with items devoted to hallucinatory behavior, suspiciousness, unusual thought content, etc. BPRS is an 18-item clinician rated scale with 11 general symptom items, 5 positive-symptom items, and 2 negative symptom items scored on a 7-point scale (1=not present and 7=extremely severe), with higher score indicating greater severity of symptom. Total possible score range=18 to 126. A negative change score signifies improvement.
Change From Baseline in Mini Mental State Examination (MMSE) Total Score in Acute Phase [Baseline (Day 0), Week 10]
The MMSE is a screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language). It is a 19 item scale, the total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement from baseline.
Change From Baseline in NPI Individual Item Scores in Acute Phase: Delusions [Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10]
The 12 individual items in NPI that quantify behavioral changes in dementia are delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, euphoria, aberrant motor behavior, nighttime behaviors, and appetite. For each behavioral domain there are 4 scores (refer to outcome 1 for the scoring for frequency, severity, total, caregiver distress). Presence of symptoms (0=no, 1=yes) x ratings for frequency and severity yield a total possible score of 0 to 12 for each item. Lower score=less severity. A negative change score from baseline indicates improvement.
Change From Baseline in NPI Individual Item Scores in Acute Phase: Hallucinations [Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10]
The 12 individual items in NPI that quantify behavioral changes in dementia are delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, euphoria, aberrant motor behavior, nighttime behaviors, and appetite. For each behavioral domain there are 4 scores (refer to outcome 1 for the scoring for frequency, severity, total, caregiver distress). Presence of symptoms (0=no, 1=yes) x ratings for frequency and severity yield a total possible score of 0 to 12 for each item. Lower score=less severity. A negative change score from baseline indicates improvement.
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]
The 12 individual items in NPI that quantify behavioral changes in dementia are delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, euphoria, aberrant motor behavior, nighttime behaviors, and appetite. For each behavioral domain there are 4 scores (refer to outcome 1 for the scoring for frequency, severity, total, caregiver distress). Presence of symptoms (0=no, 1=yes) x ratings for frequency and severity yield a total possible score of 0 to 12 for each item. Lower score=less severity. A negative change score from baseline indicates improvement.
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]
The 12 individual items in NPI that quantify behavioral changes in dementia are delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, euphoria, aberrant motor behavior, nighttime behaviors, and appetite. For each behavioral domain there are 4 scores (refer to outcome 1 for the scoring for frequency, severity, total, caregiver distress). Presence of symptoms (0=no, 1=yes) x ratings for frequency and severity yield a total possible score of 0 to 12 for each item. Lower score=less severity. A negative change score from baseline indicates improvement.
Change From Baseline in NPI Individual Item Scores in Acute Phase: Anxiety [Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10]
The 12 individual items in NPI that quantify behavioral changes in dementia are delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, euphoria, aberrant motor behavior, nighttime behaviors, and appetite. For each behavioral domain there are 4 scores (refer to outcome 1 for the scoring for frequency, severity, total, caregiver distress). Presence of symptoms (0=no, 1=yes) x ratings for frequency and severity yield a total possible score of 0 to 12 for each item. Lower score=less severity. A negative change score from baseline indicates improvement.
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]
The 12 individual items in NPI that quantify behavioral changes in dementia are delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, euphoria, aberrant motor behavior, nighttime behaviors, and appetite. For each behavioral domain there are 4 scores (refer to outcome 1 for the scoring for frequency, severity, total, caregiver distress). Presence of symptoms (0=no, 1=yes) x ratings for frequency and severity yield a total possible score of 0 to 12 for each item. Lower score=less severity. A negative change score from baseline indicates improvement.
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]
The 12 individual items in NPI that quantify behavioral changes in dementia are delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, euphoria, aberrant motor behavior, nighttime behaviors, and appetite. For each behavioral domain there are 4 scores (refer to outcome 1 for the scoring for frequency, severity, total, caregiver distress). Presence of symptoms (0=no, 1=yes) x ratings for frequency and severity yield a total possible score of 0 to 12 for each item. Lower score=less severity. A negative change score from baseline indicates improvement.
Change From Baseline in NPI Individual Item Scores in Acute Phase: Disinhibition [Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10]
The 12 individual items in NPI that quantify behavioral changes in dementia are delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, euphoria, aberrant motor behavior, nighttime behaviors, and appetite. For each behavioral domain there are 4 scores (refer to outcome 1 for the scoring for frequency, severity, total, caregiver distress). Presence of symptoms (0=no, 1=yes) x ratings for frequency and severity yield a total possible score of 0 to 12 for each item. Lower score=less severity. A negative change score from baseline indicates improvement.
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]
The 12 individual items in NPI that quantify behavioral changes in dementia are delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, euphoria, aberrant motor behavior, nighttime behaviors, and appetite. For each behavioral domain there are 4 scores (refer to outcome 1 for the scoring for frequency, severity, total, caregiver distress). Presence of symptoms (0=no, 1=yes) x ratings for frequency and severity yield a total possible score of 0 to 12 for each item. Lower score=less severity. A negative change score from baseline indicates improvement.
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]
The 12 individual items in NPI that quantify behavioral changes in dementia are delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, euphoria, aberrant motor behavior, nighttime behaviors, and appetite. For each behavioral domain there are 4 scores (refer to outcome 1 for the scoring for frequency, severity, total, caregiver distress). Presence of symptoms (0=no, 1=yes) x ratings for frequency and severity yield a total possible score of 0 to 12 for each item. Lower score=less severity. A negative change score from baseline indicates improvement.
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]
The 12 individual items in NPI that quantify behavioral changes in dementia are delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, euphoria, aberrant motor behavior, nighttime behaviors, and appetite. For each behavioral domain there are 4 scores (refer to outcome 1 for the scoring for frequency, severity, total, caregiver distress). Presence of symptoms (0=no, 1=yes) x ratings for frequency and severity yield a total possible score of 0 to 12 for each item. Lower score=less severity. A negative change score from baseline indicates improvement.
Change From Baseline in NPI Individual Item Scores in Acute Phase: Sleep [Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10]
The 12 individual items in NPI that quantify behavioral changes in dementia are delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, euphoria, aberrant motor behavior, nighttime behaviors, and appetite. For each behavioral domain there are 4 scores (refer to outcome 1 for the scoring for frequency, severity, total, caregiver distress). Presence of symptoms (0=no, 1=yes) x ratings for frequency and severity yield a total possible score of 0 to 12 for each item. Lower score=less severity. A negative change score from baseline indicates improvement.
Change From Baseline in Simpson-Angus Scale (SAS) Total Score in Acute Phase [Baseline (Day 0), Weeks 2, 4, and 10]
The SAS is a 10-item instrument used to evaluate the presence and severity of parkinsonian symptomatology. It is the most commonly used rating scale for Parkinsonism in clinical trials over the past 25 years. The ten items focus on rigidity rather than bradykinesia, and do not assess subjective rigidity or slowness. Items are rated for severity on a 0-4 scale, with definitions given for each anchor point. The total SAS Score has a possible range from 10 to 50.(lower score=less severe). Negative change scores indicate improvement.
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score in Acute Phase [Baseline (Day 0), Weeks 2, 4, 8, and 10]
The Abnormal Involuntary Movement Scale (AIMS) is a rating scale that was designed to measure involuntary movements (tardive dyskinesia). The AIMS test has a total of twelve items rating involuntary movements of various areas of the patient's body. These items are rated on a five-point scale of severity from 0-4. The scale is rated from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe). AIMS Total Score is from 0 to 28. A negative change score signifies improvement.
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]
The Barnes Akathisia Rating Scale is a 4-item scale to assess presence and severity of drug-induced akathisia, including both objective items and subjective items, together with a global clinical assessment of akathisia. Global assessment is made on a scale of 0 to 5 with comprehensive definitions provided for each anchor point on scale: 0=absent; 1=questionable; 2=mild akathisia; 3=moderate akathisia; 4=marked akathisia; 5=severe akathisia. Score has a possible range from 0 (absent) to 5 (severe akathisia). Negative change scores indicate improvement in akathisia.
Participants With Extrapyramidal Symptoms (EPS) Related Adverse Events in Acute Phase [Week 1 to week 10]
Extrapyramidal symptoms (EPS) are various movement disorders such as acute dystonic reactions, pseudoparkinsonism, or akathisia
Participants Who Died, Experienced Serious Adverse Events (SAEs), Adverse Events (AEs) or Discontinuations Due to AEs in Acute Phase [Week 1 to week 10]
AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
Participants With Potentially Clinically Significant Laboratory Abnormalities in Acute Phase [Week 1 to Week 10]
Criteria for identifying potentially clinically significant laboratory values were based on guidelines suggested by the FDA Division of Neuropharmacological Drug Products. Normal ranges are local lab data and vary according to the site. M=male, F=female. Criteria for hematocrit also includes a 3 point shift from baseline.
Participants With Potentially Clinically Significant (PCS) Vital Sign Abnormalities in Acute Phase [Week 1 to week 10]
Systolic BP: increase defined as ≥180 and a ≥20-mmHg increase from baseline (BL); decrease defined as ≤90 and a ≥20mmHg decrease from BL. Diastolic BP: increase defined as ≥105 and a ≥15mmHg decrease from BL, decrease defined as ≤50 and a ≥15mmHg decrease from BL. Heart rate: increase defined as ≥120 and ≥15bpm increase from BL, decrease defined as ≤50 and ≥15bpm decrease from BL; Weight: increase defined as ≥7% from BL, decrease defined as ≤7% decrease BL. Criteria for identifying PCS measurements are based on guidelines suggested by the FDA Division of Neuropharmacological Drug Products
Participants With Potentially Clinically Significant Electrocardiogram Abnormalities in Acute Phase [Week 1 to Week 10]
Bradycardia:Heart rate ≤50 bpm and ≥15 bpm decrease from baseline; Supraventricular premature beat: ≥2 per 10 seconds and any increase from baseline; 1st degree A-V Block: PR ≥0.20 seconds and increase of ≥0.05 second from baseline; Intraventricular conduction block:QRS ≥0.12 second and increase of ≥0.02 second from baseline; QTcB= ≥450 msec and ≥10% increase from baseline; QTcN =≥450 msec and ≥10% increase from baseline. All other events were not present at baseline but observed during the study. Inc=increase
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]
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.
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]
The CGI rating scale, which measures symptom severity, treatment response and the efficacy of treatments, is used in clinical studies on mental disorders. CGI Improvement scale is a 7 point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse.
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]
AIMS is a rating scale that was designed to measure involuntary movements (tardive dyskinesia). The AIMS test has a total of twelve items rating involuntary movements of various areas of the patient's body. These items are rated on a five-point scale of severity from 0-4. The scale is rated from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe). AIMS Total Score is from 0 to 28. A negative change score signifies improvement.
Change in Simpson-Angus Scale (SAS) Total Score During Extension Phase [End of Acute Phase (Week 10), Weeks 18,26, 40, 52]
The SAS is a 10-item instrument used to evaluate the presence and severity of parkinsonian symptomatology. It is the most commonly used rating scale for Parkinsonism in clinical trials over the past 25 years. The ten items focus on rigidity rather than bradykinesia, and do not assess subjective rigidity or slowness. Items are rated for severity on a 0-4 scale, with definitions given for each anchor point. The total SAS Score has a possible range from 10 to 50 (lower score=less severe). Negative change scores indicate improvement.
Change in Barnes Global Clinical Assessment of Akathisia Score During Extension Phase [End of Acute Phase (Week 10), Weeks 18,26, 40, 52]
The Barnes Akathisia Rating Scale is a 4-item scale to assess presence and severity of drug-induced akathisia, including both objective items and subjective items, together with a global clinical assessment of akathisia. Global assessment is made on a scale of 0 to 5 with comprehensive definitions provided for each anchor point on scale: 0=absent; 1=questionable; 2=mild akathisia; 3=moderate akathisia; 4=marked akathisia; 5=severe akathisia. Score has a possible range from 0 (absent) to 5 (severe akathisia). Negative change scores indicate improvement in akathisia.
Participants With Extrapyramidal Symptoms (EPS) Related Adverse Events During Extension Phase [Week 11 to Week 140]
Extrapyramidal symptoms (EPS) are various movement disorders such as acute dystonic reactions, pseudoparkinsonism, or akathisia
Participants Who Died, Experienced Serious Adverse Events (SAEs), Adverse Events (AEs) or Discontinuations Due to AE During Extension Phase [Week 11 to Week 140]
AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
Participants With a Potentially Clinically Significant Vital Sign Abnormality During Extension Phase [Week 11 to Week 140]
Systolic BP: increase defined as ≥180 and a ≥20-mmHg increase from baseline (BL); decrease defined as ≤90 and a ≤20mmHg decrease from BL. Diastolic BP: increase defined as ≥105 and a ≥15mmHg decrease from BL, decrease defined as ≤50 and a ≤15mmHg decrease from BL. Heart rate: increase defined as ≥120 and ≥15bpm increase from bBL, decrease defined as ≤50 and ≤15bpm decrease from BL; Weight: increase defined as ≥7% from baseline, decrease defined as ≤7% decrease BL. Criteria for identifying PCS measurements based on guidelines suggested by the FDA Division of Neuropharmacological Drug Products
Participants With a Potentially Clinically Significant Electrocardiogram Abnormalities During Extension Phase [Week 11 to Week 140]
Bradycardia:Heart rate ≤50 bpm and ≥15 bpm decrease from baseline; Supraventricular premature beat: ≥2 per 10 seconds and any increase from baseline; 1st degree A-V Block: PR ≥0.20 seconds and increase of ≥0.05 second from baseline; Intraventricular conduction block:QRS ≥0.12 second and increase of ≥0.02 second from baseline; QTcB= ≥450 msec and ≥10% increase from baseline; QTcN =≥450 msec and ≥10% increase from baseline. All other events were not present at baseline but observed during the study
Participants With Potentially Clinically Significant Laboratory Abnormalities During Extension Phase [Week 11 to Week 140]
Criteria for identifying potentially clinically significant laboratory values were based on guidelines suggested by the FDA Division of Neuropharmacological Drug Products.
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]
AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years to 95 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Otsuka Pharmaceutical Development & Commercialization, Inc.
Otsuka America Pharmaceutical

Investigators

Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

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Responsible Party:

Otsuka Pharmaceutical Development & Commercialization, Inc.

ClinicalTrials.gov Identifier:

NCT01438060

Other Study ID Numbers:

CN138-006

First Posted:

Sep 21, 2011

Last Update Posted:

Dec 2, 2013

Last Verified:

Nov 1, 2013

Additional relevant MeSH terms:

Dementia

Alzheimer Disease

Aripiprazole

Study Results

Participant Flow

Recruitment Details	232 participants were enrolled, 24 were not randomized (baseline failures).
Pre-assignment Detail

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks)	Acute Phase: Dosed at 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Period Title: Acute Phase: Double-blind, 10 Weeks
STARTED	102	106
COMPLETED	84	88
NOT COMPLETED	18	18
Period Title: Acute Phase: Double-blind, 10 Weeks
STARTED	80	81
COMPLETED	22	25
NOT COMPLETED	58	56
Period Title: Acute Phase: Double-blind, 10 Weeks
STARTED	0	9
COMPLETED	0	1
NOT COMPLETED	0	8

Baseline Characteristics

Arm/Group Title	Placebo	Aripiprazole	Total
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks)	Acute Phase: Dosed at 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).	Total of all reporting groups
Overall Participants	102	106	208
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	82.0	81.0	81.0
Sex: Female, Male (Count of Participants)
Female	74 72.5%	75 70.8%	149 71.6%
Male	28 27.5%	31 29.2%	59 28.4%
Race/Ethnicity, Customized (Number) [Number]
White	98 96.1%	105 99.1%	203 97.6%
Black	2 2%	1 0.9%	3 1.4%
Asian/ Pacific Islander	2 2%	0 0%	2 1%
Weight (kg) [Median (Full Range) ]
Median (Full Range) [kg]	58.8	59.0	59.0

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Neuropsychiatric Inventory (NPI) Psychosis Subscale Score at Week 10 in Acute Phase
Description	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.
Time Frame	Baseline (Day 0), Week 10

Outcome Measure Data

Analysis Population Description
Last Observation Carried forward (LOCF) data set, efficacy sample. Of the 208 randomized participants, 5 were excluded from the efficacy data sample: 2 from placebo (Withdrew Consent, Inadequate Caregiver Input.); 3 in aripiprazole group (Withdrew Consent-1, AE-2)

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	100	103
Baseline (Day 0)	12.12 (0.60)	12.29 (0.59)
Mean Change from Baseline at Week 10	-5.52 (0.66)	-6.55 (0.65)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aripiprazole
	Comments	Analysis at Baseline (Day 0)
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.802
	Comments	Baseline data was evaluated by analysis of variance (ANOVA) with treatment and study center as main effects.
	Method	ANOVA
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 95% -1.15 to 1.49
	Parameter Dispersion	Type: Value:
	Estimation Comments	Model based estimate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aripiprazole
	Comments	Analysis at Week 10
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.169
	Comments	ANCOVA model for LOCF data set included the baseline measure as covariate and the study center and treatment as main effects.
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.02
	Confidence Interval	(2-Sided) 95% -2.49 to 0.44
	Parameter Dispersion	Type: Value:
	Estimation Comments	Model based estimate

2. Secondary Outcome

Title	Change From Baseline in NPI Psychosis Subscale Score Through Week 8 in Acute Phase
Description	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.
Time Frame	Baseline (Day 0), Weeks 1, 2, 3, 4, 6, and 8

Outcome Measure Data

Analysis Population Description
LOCF data set, efficacy sample. Of the 208 randomized participants, 5 were excluded from the efficacy data sample: 2 from placebo (Withdrew Consent, Inadequate Caregiver Input.); 3 in aripiprazole group (Withdrew Consent-1, AE-2)

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	100	103
Baseline (Day 0)	12.12 (0.60)	12.29 (0.59)
Week 1	-3.33 (0.53)	-2.26 (0.52)
Week 2	-3.96 (0.67)	-3.81 (0.66)
Week 3	-4.54 (0.64)	-4.86 (0.64)
Week 4	-5.38 (0.61)	-5.66 (0.61)
Week 6	-4.87 (0.64)	-6.00 (0.63)
Week 8	-5.04 (0.69)	-6.01 (0.68)

3. Secondary Outcome

Title	Change From Baseline in NPI Total Score in Acute Phase
Description	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 Total Score is calculated by adding the Individual Item Scores for all 12 domains, to yield a possible NPI Total Score of 0 to 144. Lower score=less severity. A negative change score from baseline indicates improvement.
Time Frame	Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10

Outcome Measure Data

Analysis Population Description
LOCF data set, efficacy sample. Of the 208 randomized participants, 5 were excluded from the efficacy data sample: 2 from placebo (Withdrew Consent, Inadequate Caregiver Input.); 3 in aripiprazole group (Withdrew Consent-1, AE-2)

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	100	103
Baseline (Day 0)	40.08 (1.88)	39.82 (1.86)
Week 1	-6.26 (1.58)	-4.13 (1.57)
Week 2	-9.98 (1.86)	-8.40 (1.84)
Week 3	-10.85 (2.13)	-8.61 (2.11)
Week 4	-11.81 (1.87)	-11.74 (1.86)
Week 6	-10.47 (2.09)	-11.61 (2.07)
Week 8	-9.68 (2.32)	-10.71 (2.30)
Week 10	-9.75 (2.35)	-11.20 (2.33)

4. Secondary Outcome

Title	Participants Who Demonstrated a ≥ 50% Decrease From Baseline to Endpoint in the NPI Psychosis Subscale Score in Acute Phase
Description	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.
Time Frame	Weeks 1, 2, 3, 4, 6, 8, and 10

Outcome Measure Data

Analysis Population Description
LOCF data set, efficacy sample. Of the 208 randomized participants, 5 were excluded from the efficacy data sample: 2 from placebo (Withdrew Consent, Inadequate Caregiver Input.); 3 in aripiprazole group (Withdrew Consent-1, AE-2)

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	100	103
Week 1	24 23.5%	18 17%
Week 2	37 36.3%	34 32.1%
Week 3	45 44.1%	44 41.5%
Week 4	52 51%	47 44.3%
Week 6	53 52%	56 52.8%
Week 8	58 56.9%	64 60.4%
Week 10	60 58.8%	70 66%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aripiprazole
	Comments	Analysis at Week 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.391
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Cochran-Mantel-Haenszel (CMH) test with controlling for treatment and study center

Method of Estimation	Estimation Parameter	Response ratio
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95% 0.47 to 1.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aripiprazole
	Comments	Analysis at Week 2
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.766
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	CMH test with controlling for treatment and study center

Method of Estimation	Estimation Parameter	Response ratio
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95% 0.69 to 1.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aripiprazole
	Comments	Analysis at Week 3
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.967
	Comments	CMH test with controlling for treatment and study center
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Response ratio
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95% 0.76 to 1.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aripiprazole
	Comments	Analysis at Week 4
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.505
	Comments	CMH test with controlling for treatment and study center
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Response ratio
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95% 0.71 to 1.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aripiprazole
	Comments	Analysis at Week 6
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.590
	Comments	CMH test with controlling for treatment and study center
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Response ratio
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95% 0.84 to 1.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aripiprazole
	Comments	Analysis at Week 8
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.374
	Comments	CMH test with controlling for treatment and study center
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Response ratio
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 95% 0.89 to 1.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aripiprazole
	Comments	Analysis at Week 10
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.175
	Comments	CMH test with controlling for treatment and study center
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Response ratio
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 95% 0.94 to 1.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Participants Who Demonstrated a ≥ 50% Decrease From Baseline in the Total NPI Score in Acute Phase
Description	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 Total Score is calculated by adding the Individual Item Scores for all 12 domains, to yield a possible NPI Total Score of 0 to 144. Lower score=less severity. A negative change score from baseline indicates improvement.
Time Frame	Weeks 1, 2, 3, 4, 6, 8, and 10

Outcome Measure Data

Analysis Population Description
LOCF data set, efficacy sample. Of the 208 randomized participants, 5 were excluded from the efficacy data sample: 2 from placebo (Withdrew Consent, Inadequate Caregiver Input.); 3 in aripiprazole group (Withdrew Consent-1, AE-2)

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	100	103
Week 1	12 11.8%	11 10.4%
Week 2	31 30.4%	29 27.4%
Week 3	35 34.3%	33 31.1%
Week 4	44 43.1%	37 34.9%
Week 6	45 44.1%	45 42.5%
Week 8	52 51%	50 47.2%
Week 10	47 46.1%	53 50%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aripiprazole
	Comments	Analysis at week 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.753
	Comments	CMH test with controlling for treatment and study center
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Response ratio
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95% 0.41 to 1.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aripiprazole
	Comments	Analysis at week 2
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.600
	Comments	CMH test with controlling for treatment and study center
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Response ratio
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95% 0.62 to 1.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aripiprazole
	Comments	Analysis at week 3
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.673
	Comments	CMH test with controlling for treatment and study center
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Response ratio
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95% 0.65 to 1.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aripiprazole
	Comments	Analysis at week 4
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.255
	Comments	CMH test with controlling for treatment and study center
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Response ratio
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95% 0.60 to 1.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aripiprazole
	Comments	Analysis at week 6
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.958
	Comments	CMH test with controlling for treatment and study center
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Response ratio
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95% 0.74 to 1.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aripiprazole
	Comments	Analysis at week 8
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.525
	Comments	CMH test with controlling for treatment and study center
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Response ratio
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95% 0.71 to 1.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aripiprazole
	Comments	Analysis at week 10
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.602
	Comments	CMH test with controlling for treatment and study center
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Response ratio
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95% 0.82 to 1.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in NPI Psychosis Subscale Caregiver Distress Score in Acute Phase
Description	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 Caregiver Distress Score is calculated by adding Individual Item Scores for the domains of Delusions and Hallucinations, to yield a possible total score of 0 to 10. Lower score=less severity. A negative change score from baseline=improvement.
Time Frame	Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10

Outcome Measure Data

Analysis Population Description
LOCF data set, efficacy sample. Of the 208 randomized participants, 5 were excluded from the efficacy data sample: 2 from placebo (Withdrew Consent, Inadequate Caregiver Input.); 3 in aripiprazole group (Withdrew Consent-1, AE-2)

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	100	103
Baseline (Day 0)	4.80 (0.25)	4.70 (0.25)
Week 1	-0.80 (0.21)	-0.64 (0.21)
Week 2	-0.84 (0.23)	-0.78 (0.23)
Week 3	-1.15 (0.24)	-0.93 (0.23)
Week 4	-1.31 (0.23)	-1.28 (0.23)
Week 6	-1.36 (0.27)	-1.62 (0.26)
Week 8	-1.18 (0.27)	-1.65 (0.27)
Week 10	-1.35 (0.26)	-1.79 (0.26)

7. Secondary Outcome

Title	Change From Baseline in NPI Total Caregiver Distress Score in Acute Phase
Description	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 total NPI Caregiver Distress Score is calculated by adding the 12 Caregiver Distress Individual Item Scores, to yield a possible total score of 0 to 60. Lower score=less severity. A negative change score from baseline indicates improvement.
Time Frame	Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10

Outcome Measure Data

Analysis Population Description
LOCF data set, efficacy sample. Of the 208 randomized participants, 5 were excluded from the efficacy data sample: 2 from placebo (Withdrew Consent, Inadequate Caregiver Input.); 3 in aripiprazole group (Withdrew Consent-1, AE-2)

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	100	103
Baseline (Day 0)	16.58 (0.87)	17.06 (0.86)
Week 1	-1.81 (0.65)	-1.64 (0.65)
Week 2	-3.25 (0.72)	-3.04 (0.72)
Week 3	-4.10 (0.81)	-2.58 (0.84)
Week 4	-4.01 (0.80)	-3.48 (0.80)
Week 6	-3.58 (0.98)	-3.72 (0.98)
Week 8	-3.20 (0.99)	-3.46 (0.99)
Week 10	-3.15 (1.03)	-3.53 (1.04)

8. Secondary Outcome

Title	Change From Baseline in Clinical Global Impression (CGI) Severity of Illness Score in Acute Phase
Description	The CGI rating scale, which measures symptom severity, treatment response and the efficacy of treatments, is used in clinical studies on mental disorders. CGI Severity scale is a 7-point scale that requires the clinician to rate the severity of the illness at the time of assessment, relative to the clinician's past experience with participants who have the same diagnosis. The assessment is based on severity of mental illness at the time of rating, 0=not assessed, 1=normal, 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; or 7=extremely ill.
Time Frame	Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10

Outcome Measure Data

Analysis Population Description
LOCF data set, efficacy sample. Of the 208 randomized participants, 5 were excluded from the efficacy data sample: 2 from placebo (Withdrew Consent, Inadequate Caregiver Input.); 3 in aripiprazole group (Withdrew Consent-1, AE-2). An additional participant did not have CGI-Severity score and was not included in the analysis

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	100	102
Baseline (Day 0)	4.84 (0.09)	4.83 (0.09)
Week 1	-0.19 (0.08)	-0.10 (0.08)
Week 2	-0.29 (0.11)	-0.19 (0.12)
Week 3	-0.44 (0.11)	-0.44 (0.11)
Week 4	-0.47 (0.12)	-0.49 (0.12)
Week 6	-0.44 (0.12)	-0.58 (0.12)
Week 8	-0.56 (0.13)	-0.65 (0.13)
Week 10	-0.54 (0.14)	-0.69 (0.14)

9. Secondary Outcome

Title	CGI Improvement Score in Acute Phase
Description	The CGI rating scale, which measures symptom severity, treatment response and the efficacy of treatments, is used in clinical studies on mental disorders. CGI Improvement scale is a 7 point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse.
Time Frame	Weeks 1, 2, 3, 4, 6, 8, and 10

Outcome Measure Data

Analysis Population Description
LOCF data set, efficacy sample. n = Participants who had both post baseline and baseline values. Of the 208 randomized participants, 5 were excluded from the efficacy data sample: 2 from placebo (Withdrew Consent, Inadequate Caregiver Input.); 3 in aripiprazole group (Withdrew Consent-1, AE-2)

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	100	103
Week 1; n=98, 102	3.81 (0.09)	3.96 (0.08)
Week 2; n=98, 102	3.55 (0.11)	3.71 (0.10)
Week 3; n=100, 103	3.37 (0.12)	3.49 (0.11)
Week 4; n=100, 103	3.28 (0.12)	3.32 (0.12)
Week 6; n=100, 103	3.26 (0.12)	3.23 (0.13)
Week 8; n=100, 103	3.11 (0.14)	3.16 (0.13)
Week 10; n=100, 103	3.07 (0.15)	3.17 (0.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aripiprazole
	Comments	Analysis at Week 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.133
	Comments	CMH Row Means test with controlling for study center
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aripiprazole
	Comments	Analysis at Week 2
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.282
	Comments	CMH Row Means test with controlling for study center
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aripiprazole
	Comments	Analysis at Week 3
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.571
	Comments	CMH Row Means test with controlling for study center
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aripiprazole
	Comments	Analysis at Week 4
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.895
	Comments	CMH Row Means test with controlling for study center
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aripiprazole
	Comments	Analysis at Week 6
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.817
	Comments	CMH Row Means test with controlling for study center
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aripiprazole
	Comments	Analysis at Week 8
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.795
	Comments	CMH Row Means test with controlling for study center
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aripiprazole
	Comments	Analysis at Week 10
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.564
	Comments	CMH Row Means test with controlling for study center
	Method	Cochran-Mantel-Haenszel
	Comments

10. Secondary Outcome

Title	Change From Baseline in Brief Psychiatric Rating Scale (BPRS) Total Score in Acute Phase
Description	The BPRS is designed to measure clinical change in participants and is used as a global measure of psychopathology. The BPRS includes 18 items with items devoted to hallucinatory behavior, suspiciousness, unusual thought content, etc. BPRS is an 18-item clinician rated scale with 11 general symptom items, 5 positive-symptom items, and 2 negative symptom items scored on a 7-point scale (1=not present and 7=extremely severe), with higher score indicating greater severity of symptom. Total possible score range=18 to 126. A negative change score signifies improvement.
Time Frame	Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10

Outcome Measure Data

Analysis Population Description
LOCF data set, efficacy sample. n = Participants who had both post baseline and baseline values. Of the 208 randomized participants, 5 were excluded from the efficacy data sample: 2 from placebo (Withdrew Consent, Inadequate Caregiver Input.); 3 in aripiprazole group (Withdrew Consent-1, AE-2)

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	100	103
Baseline (Day 0); n=95, 100	43.42 (1.32)	43.63 (1.28)
Week 2; n=87, 95	-4.65 (0.95)	-5.82 (0.94)
Week 4; n=95, 100	-5.80 (0.97)	-7.44 (0.95)
Week 6; n=95, 100	-6.13 (1.09)	-8.50 (1.07)
Week 8; n=95, 100	-6.45 (1.17)	-8.47 (1.14)
Week 10; n=95, 100	-6.28 (1.26)	-8.53 (1.23)

11. Secondary Outcome

Title	Change From Baseline in Mini Mental State Examination (MMSE) Total Score in Acute Phase
Description	The MMSE is a screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language). It is a 19 item scale, the total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement from baseline.
Time Frame	Baseline (Day 0), Week 10

Outcome Measure Data

Analysis Population Description
LOCF data set, efficacy sample. n=Participants who had both post baseline and baseline values. Of the 208 randomized participants, 5 were excluded from the efficacy data set: 2 from placebo (Withdrew Consent, Inadequate Caregiver Input.); 3 in aripiprazole group (Withdrew Consent-1, AE-2)

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	100	103
Baseline (Day 0); N=86,94	14.13 (0.60)	14.35 (0.58)
Week 10; n=82, 87	0.53 (0.37)	-0.81 (0.36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aripiprazole
	Comments	Analysis at baseline
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.733
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.23
	Confidence Interval	(2-Sided) 95% -1.08 to 1.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Aripiprazole
	Comments	Analysis at Week 10
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	ANOVA
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.35
	Confidence Interval	(2-Sided) 95% -2.16 to -0.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Change From Baseline in NPI Individual Item Scores in Acute Phase: Delusions
Description	The 12 individual items in NPI that quantify behavioral changes in dementia are delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, euphoria, aberrant motor behavior, nighttime behaviors, and appetite. For each behavioral domain there are 4 scores (refer to outcome 1 for the scoring for frequency, severity, total, caregiver distress). Presence of symptoms (0=no, 1=yes) x ratings for frequency and severity yield a total possible score of 0 to 12 for each item. Lower score=less severity. A negative change score from baseline indicates improvement.
Time Frame	Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10

Outcome Measure Data

Analysis Population Description
LOCF data set, efficacy sample. Of the 208 randomized participants, 5 were excluded from the efficacy data sample: 2 from placebo (Withdrew Consent, Inadequate Caregiver Input.); 3 in aripiprazole group (Withdrew Consent-1, AE-2)

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	100	103
Baseline (Day 0)	7.85	8.11
Week 1	-2.37	-1.61
Week 2	-2.84	-2.72
Week 3	-3.25	-3.50
Week 4	-3.72	-3.89
Week 6	-3.45	-3.95
Week 8	-3.52	-3.91
Week 10	-3.94	-4.28

13. Secondary Outcome

Title	Change From Baseline in NPI Individual Item Scores in Acute Phase: Hallucinations
Description	The 12 individual items in NPI that quantify behavioral changes in dementia are delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, euphoria, aberrant motor behavior, nighttime behaviors, and appetite. For each behavioral domain there are 4 scores (refer to outcome 1 for the scoring for frequency, severity, total, caregiver distress). Presence of symptoms (0=no, 1=yes) x ratings for frequency and severity yield a total possible score of 0 to 12 for each item. Lower score=less severity. A negative change score from baseline indicates improvement.
Time Frame	Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10

Outcome Measure Data

Analysis Population Description
LOCF data set, efficacy sample. Of the 208 randomized participants, 5 were excluded from the efficacy data sample: 2 from placebo (Withdrew Consent, Inadequate Caregiver Input.); 3 in aripiprazole group (Withdrew Consent-1, AE-2)

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	100	103
Baseline (Day 0)	4.27	4.18
Week 1	-0.98	-0.65
Week 2	-1.15	-1.09
Week 3	-1.34	-1.37
Week 4	-1.71	-1.79
Week 6	-1.43	-2.03
Week 8	-1.57	-2.12
Week 10	-1.65	-2.30

14. Secondary Outcome

Title	Change From Baseline in NPI Individual Item Scores in Acute Phase: Agitation/Aggression
Description	The 12 individual items in NPI that quantify behavioral changes in dementia are delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, euphoria, aberrant motor behavior, nighttime behaviors, and appetite. For each behavioral domain there are 4 scores (refer to outcome 1 for the scoring for frequency, severity, total, caregiver distress). Presence of symptoms (0=no, 1=yes) x ratings for frequency and severity yield a total possible score of 0 to 12 for each item. Lower score=less severity. A negative change score from baseline indicates improvement.
Time Frame	Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10

Outcome Measure Data

Analysis Population Description
LOCF data set, efficacy sample. Of the 208 randomized participants, 5 were excluded from the efficacy data sample: 2 from placebo (Withdrew Consent, Inadequate Caregiver Input.); 3 in aripiprazole group (Withdrew Consent-1, AE-2)

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	100	103
Baseline (Day 0)	3.52	4.04
Week 1	-0.34	0.10
Week 2	-1.16	-0.69
Week 3	-0.73	-0.59
Week 4	-0.78	-1.38
Week 6	-0.31	-0.94
Week 8	-0.12	-0.84
Week 10	-0.47	-1.12

15. Secondary Outcome

Title	Change From Baseline in NPI Individual Item Scores in Acute Phase: Depression/Dysphoria
Description	The 12 individual items in NPI that quantify behavioral changes in dementia are delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, euphoria, aberrant motor behavior, nighttime behaviors, and appetite. For each behavioral domain there are 4 scores (refer to outcome 1 for the scoring for frequency, severity, total, caregiver distress). Presence of symptoms (0=no, 1=yes) x ratings for frequency and severity yield a total possible score of 0 to 12 for each item. Lower score=less severity. A negative change score from baseline indicates improvement.
Time Frame	Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10

Outcome Measure Data

Analysis Population Description
LOCF data set, efficacy sample. Of the 208 randomized participants, 5 were excluded from the efficacy data sample: 2 from placebo (Withdrew Consent, Inadequate Caregiver Input.); 3 in aripiprazole group (Withdrew Consent-1, AE-2)

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	100	103
Baseline (Day 0)	3.27	2.28
Week 1	0.21	-0.04
Week 2	-0.44	-0.36
Week 3	-0.77	-0.33
Week 4	-0.72	-0.50
Week 6	-0.47	-0.55
Week 8	-0.65	-0.54
Week 10	-0.32	-0.42

16. Secondary Outcome

Title	Change From Baseline in NPI Individual Item Scores in Acute Phase: Anxiety
Description	The 12 individual items in NPI that quantify behavioral changes in dementia are delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, euphoria, aberrant motor behavior, nighttime behaviors, and appetite. For each behavioral domain there are 4 scores (refer to outcome 1 for the scoring for frequency, severity, total, caregiver distress). Presence of symptoms (0=no, 1=yes) x ratings for frequency and severity yield a total possible score of 0 to 12 for each item. Lower score=less severity. A negative change score from baseline indicates improvement.
Time Frame	Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10

Outcome Measure Data

Analysis Population Description
LOCF data set, efficacy sample. Of the 208 randomized participants, 5 were excluded from the efficacy data sample: 2 from placebo (Withdrew Consent, Inadequate Caregiver Input.); 3 in aripiprazole group (Withdrew Consent-1, AE-2)

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	100	103
Baseline (Day 0)	3.64	3.17
Week 1	0.02	0.05
Week 2	-0.08	0.08
Week 3	-0.43	0.07
Week 4	-0.80	-0.38
Week 6	-0.79	-0.13
Week 8	-0.23	-0.21
Week 10	-0.43	-0.31

17. Secondary Outcome

Title	Change From Baseline in NPI Individual Item Scores in Acute Phase: Apathy/Indifference
Description	The 12 individual items in NPI that quantify behavioral changes in dementia are delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, euphoria, aberrant motor behavior, nighttime behaviors, and appetite. For each behavioral domain there are 4 scores (refer to outcome 1 for the scoring for frequency, severity, total, caregiver distress). Presence of symptoms (0=no, 1=yes) x ratings for frequency and severity yield a total possible score of 0 to 12 for each item. Lower score=less severity. A negative change score from baseline indicates improvement.
Time Frame	Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10

Outcome Measure Data

Analysis Population Description
LOCF data set, efficacy sample. Of the 208 randomized participants, 5 were excluded from the efficacy data sample: 2 from placebo (Withdrew Consent, Inadequate Caregiver Input.); 3 in aripiprazole group (Withdrew Consent-1, AE-2)

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	100	103
Baseline (Day 0)	4.14	3.47
Week 1	0.03	-0.70
Week 2	-0.48	-0.76
Week 3	-0.09	-0.36
Week 4	-0.65	-0.67
Week 6	-0.63	-0.40
Week 8	-0.87	-0.21
Week 10	-0.95	-0.09

18. Secondary Outcome

Title	Change From Baseline in NPI Individual Item Scores in Acute Phase: Elation/Euphoria
Description	The 12 individual items in NPI that quantify behavioral changes in dementia are delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, euphoria, aberrant motor behavior, nighttime behaviors, and appetite. For each behavioral domain there are 4 scores (refer to outcome 1 for the scoring for frequency, severity, total, caregiver distress). Presence of symptoms (0=no, 1=yes) x ratings for frequency and severity yield a total possible score of 0 to 12 for each item. Lower score=less severity. A negative change score from baseline indicates improvement.
Time Frame	Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10

Outcome Measure Data

Analysis Population Description
LOCF data set, efficacy sample. Of the 208 randomized participants, 5 were excluded from the efficacy data sample: 2 from placebo (Withdrew Consent, Inadequate Caregiver Input.); 3 in aripiprazole group (Withdrew Consent-1, AE-2)

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	100	103
Baseline (Day 0)	0.56	0.73
Week 1	-0.48	-0.26
Week 2	-0.37	-0.18
Week 3	-0.48	-0.27
Week 4	-0.47	-0.40
Week 6	-0.38	-0.39
Week 8	-0.32	-0.25
Week 10	-0.42	-0.36

19. Secondary Outcome

Title	Change From Baseline in NPI Individual Item Scores in Acute Phase: Disinhibition
Description	The 12 individual items in NPI that quantify behavioral changes in dementia are delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, euphoria, aberrant motor behavior, nighttime behaviors, and appetite. For each behavioral domain there are 4 scores (refer to outcome 1 for the scoring for frequency, severity, total, caregiver distress). Presence of symptoms (0=no, 1=yes) x ratings for frequency and severity yield a total possible score of 0 to 12 for each item. Lower score=less severity. A negative change score from baseline indicates improvement.
Time Frame	Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10

Outcome Measure Data

Analysis Population Description
LOCF data set, efficacy sample. Of the 208 randomized participants, 5 were excluded from the efficacy data sample: 2 from placebo (Withdrew Consent, Inadequate Caregiver Input.); 3 in aripiprazole group (Withdrew Consent-1, AE-2)

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	100	103
Baseline (Day 0)	0.98	1.36
Week 1	-0.14	-0.39
Week 2	-0.42	-0.44
Week 3	-0.27	-0.21
Week 4	-0.55	-0.67
Week 6	-0.19	-0.72
Week 8	-0.20	-0.44
Week 10	0.07	-0.35

20. Secondary Outcome

Title	Change From Baseline in NPI Individual Item Scores in Acute Phase: Irritability/Lability
Description	The 12 individual items in NPI that quantify behavioral changes in dementia are delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, euphoria, aberrant motor behavior, nighttime behaviors, and appetite. For each behavioral domain there are 4 scores (refer to outcome 1 for the scoring for frequency, severity, total, caregiver distress). Presence of symptoms (0=no, 1=yes) x ratings for frequency and severity yield a total possible score of 0 to 12 for each item. Lower score=less severity. A negative change score from baseline indicates improvement.
Time Frame	Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10

Outcome Measure Data

Analysis Population Description
LOCF data set, efficacy sample. Of the 208 randomized participants, 5 were excluded from the efficacy data sample: 2 from placebo (Withdrew Consent, Inadequate Caregiver Input.); 3 in aripiprazole group (Withdrew Consent-1, AE-2)

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	100	103
Baseline (Day 0)	3.73	4.36
Week 1	-0.73	-0.09
Week 2	-0.89	-0.69
Week 3	-1.11	-1.09
Week 4	-0.75	-1.53
Week 6	-0.42	-1.29
Week 8	-0.33	-0.99
Week 10	-0.24	-1.26

21. Secondary Outcome

Title	Change From Baseline in NPI Individual Item Scores in Acute Phase: Aberrant Motor Behavior
Description	The 12 individual items in NPI that quantify behavioral changes in dementia are delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, euphoria, aberrant motor behavior, nighttime behaviors, and appetite. For each behavioral domain there are 4 scores (refer to outcome 1 for the scoring for frequency, severity, total, caregiver distress). Presence of symptoms (0=no, 1=yes) x ratings for frequency and severity yield a total possible score of 0 to 12 for each item. Lower score=less severity. A negative change score from baseline indicates improvement.
Time Frame	Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10

Outcome Measure Data

Analysis Population Description
LOCF data set, efficacy sample. Of the 208 randomized participants, 5 were excluded from the efficacy data sample: 2 from placebo (Withdrew Consent, Inadequate Caregiver Input.); 3 in aripiprazole group (Withdrew Consent-1, AE-2)

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	100	103
Baseline (Day 0)	3.67	3.61
Week 1	-0.66	0.18
Week 2	-0.84	-0.51
Week 3	-1.68	-0.66
Week 4	-0.91	-0.16
Week 6	-0.89	-0.61
Week 8	-1.06	-0.83
Week 10	-1.02	-0.89

22. Secondary Outcome

Title	Change From Baseline in NPI Individual Item Scores in Acute Phase: Appetite/Eating Behaviors
Description	The 12 individual items in NPI that quantify behavioral changes in dementia are delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, euphoria, aberrant motor behavior, nighttime behaviors, and appetite. For each behavioral domain there are 4 scores (refer to outcome 1 for the scoring for frequency, severity, total, caregiver distress). Presence of symptoms (0=no, 1=yes) x ratings for frequency and severity yield a total possible score of 0 to 12 for each item. Lower score=less severity. A negative change score from baseline indicates improvement.
Time Frame	Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10

Outcome Measure Data

Analysis Population Description
LOCF data set, efficacy sample. Of the 208 randomized participants, 5 were excluded from the efficacy data sample: 2 from placebo (Withdrew Consent, Inadequate Caregiver Input.); 3 in aripiprazole group (Withdrew Consent-1, AE-2)

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	100	103
Baseline (Day 0)	1.78	1.47
Week 1	-0.24	-0.18
Week 2	-0.36	-0.21
Week 3	-0.14	0.23
Week 4	-0.44	-0.04
Week 6	-0.27	0.23
Week 8	-0.11	0.45
Week 10	-0.17	0.56

23. Secondary Outcome

Title	Change From Baseline in NPI Individual Item Scores in Acute Phase: Sleep
Description	The 12 individual items in NPI that quantify behavioral changes in dementia are delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, euphoria, aberrant motor behavior, nighttime behaviors, and appetite. For each behavioral domain there are 4 scores (refer to outcome 1 for the scoring for frequency, severity, total, caregiver distress). Presence of symptoms (0=no, 1=yes) x ratings for frequency and severity yield a total possible score of 0 to 12 for each item. Lower score=less severity. A negative change score from baseline indicates improvement.
Time Frame	Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10

Outcome Measure Data

Analysis Population Description
LOCF data set, efficacy sample. Of the 208 randomized participants, 5 were excluded from the efficacy data sample: 2 from placebo (Withdrew Consent, Inadequate Caregiver Input.); 3 in aripiprazole group (Withdrew Consent-1, AE-2)

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	100	103
Baseline (Day 0)	2.67	3.03
Week 1	-0.10	-0.07
Week 2	-0.20	-0.07
Week 3	-0.20	0.10
Week 4	0.02	0.15
Week 6	-0.39	-0.03
Week 8	-0.06	-0.06
Week 10	0.05	-0.06

24. Secondary Outcome

Title	Change From Baseline in Simpson-Angus Scale (SAS) Total Score in Acute Phase
Description	The SAS is a 10-item instrument used to evaluate the presence and severity of parkinsonian symptomatology. It is the most commonly used rating scale for Parkinsonism in clinical trials over the past 25 years. The ten items focus on rigidity rather than bradykinesia, and do not assess subjective rigidity or slowness. Items are rated for severity on a 0-4 scale, with definitions given for each anchor point. The total SAS Score has a possible range from 10 to 50.(lower score=less severe). Negative change scores indicate improvement.
Time Frame	Baseline (Day 0), Weeks 2, 4, and 10

Outcome Measure Data

Analysis Population Description
Observed cases data set, Efficacy Sample. n=Participants who had both post baseline and baseline values. Of the 208 randomized participants, 5 were excluded from the efficacy data set: 2 from placebo (Withdrew Consent, Inadequate Caregiver Input.); 3 in aripiprazole group (Withdrew Consent-1, AE-2)

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	100	103
Baseline (Day 0); n=97, 100	14.41 (NA)	14.47 (NA)
Week 2; n=89, 94	0.02	-0.35
Week 4; n=93, 96	-0.15	-0.06
Week 10; n=82, 85	-0.44	0.33

25. Secondary Outcome

Title	Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score in Acute Phase
Description	The Abnormal Involuntary Movement Scale (AIMS) is a rating scale that was designed to measure involuntary movements (tardive dyskinesia). The AIMS test has a total of twelve items rating involuntary movements of various areas of the patient's body. These items are rated on a five-point scale of severity from 0-4. The scale is rated from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe). AIMS Total Score is from 0 to 28. A negative change score signifies improvement.
Time Frame	Baseline (Day 0), Weeks 2, 4, 8, and 10

Outcome Measure Data

Analysis Population Description
Observed Cased data set, efficacy sample. n=Participants who had both post baseline and baseline values. Of the 208 randomized participants, 5 were excluded from the efficacy data set: 2 from placebo (Withdrew Consent, Inadequate Caregiver Input.); 3 in aripiprazole group (Withdrew Consent-1, AE-2)

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	100	103
Baseline (Day 0); n=99, 101	0.87	0.93
Week 2; n=91, 95	-0.10	-0.17
Week 4; n=97, 97	-0.05	-0.08
Week 8; n=87, 87	0.07	-0.14
Week 10; n=85, 87	0.05	-0.17

26. Secondary Outcome

Title	Change From Baseline in Barnes Global Clinical Assessment of Akathisia in Acute Phase
Description	The Barnes Akathisia Rating Scale is a 4-item scale to assess presence and severity of drug-induced akathisia, including both objective items and subjective items, together with a global clinical assessment of akathisia. Global assessment is made on a scale of 0 to 5 with comprehensive definitions provided for each anchor point on scale: 0=absent; 1=questionable; 2=mild akathisia; 3=moderate akathisia; 4=marked akathisia; 5=severe akathisia. Score has a possible range from 0 (absent) to 5 (severe akathisia). Negative change scores indicate improvement in akathisia.
Time Frame	Baseline (Day 0), Weeks 1, 2, 3, 4, 6, 8, and 10

Outcome Measure Data

Analysis Population Description
Observed cases data set, efficacy sample. n=Participants with both post-baseline and baseline measures. Of the 208 randomized participants, 5 were excluded from the efficacy data sample: 2 from placebo (Withdrew Consent, Inadequate Caregiver Input.); 3 in aripiprazole group (Withdrew Consent-1, AE-2)

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	100	103
Baseline (Day 0); n=100,101	0.20	0.19
Week 1; n=99, 101	-0.06	-0.06
Week 2; n=91, 95	-0.02	-0.05
Week 3; n=95, 99	-0.03	-0.06
Week 4; n=97, 98	0.00 (NA)	-0.08
Week 6; n=91, 92	-0.07	-0.02
Week 8; n=87, 87	-0.05	-0.03
Week 10; n=85, 87	-0.05	-0.05

27. Secondary Outcome

Title	Participants With Extrapyramidal Symptoms (EPS) Related Adverse Events in Acute Phase
Description	Extrapyramidal symptoms (EPS) are various movement disorders such as acute dystonic reactions, pseudoparkinsonism, or akathisia
Time Frame	Week 1 to week 10

Outcome Measure Data

Analysis Population Description
Of the 208 randomized participants, one (randomized to aripiprazole) was excluded from the Safety Sample as the participant withdrew consent prior to receiving study medication.

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	102	105
Dyskinesia	2 2%	0 0%
Extrapyramidal syndrome	1 1%	2 1.9%
Hypertonia	1 1%	1 0.9%
Hypokinesia	0 0%	1 0.9%
Tremor	0 0%	2 1.9%

28. Secondary Outcome

Title	Participants Who Died, Experienced Serious Adverse Events (SAEs), Adverse Events (AEs) or Discontinuations Due to AEs in Acute Phase
Description	AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
Time Frame	Week 1 to week 10

Outcome Measure Data

Analysis Population Description
Of the 208 randomized participants, one (randomized to aripiprazole) was excluded from the Safety Sample as the participant withdrew consent prior to receiving study medication.

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	102	105
Any adverse event (AE)	53 52%	67 63.2%
Serious adverse event	9 8.8%	16 15.1%
Deaths	0 0%	4 3.8%
Discontinuations due to AE	7 6.9%	11 10.4%

29. Secondary Outcome

Title	Participants With Potentially Clinically Significant Laboratory Abnormalities in Acute Phase
Description	Criteria for identifying potentially clinically significant laboratory values were based on guidelines suggested by the FDA Division of Neuropharmacological Drug Products. Normal ranges are local lab data and vary according to the site. M=male, F=female. Criteria for hematocrit also includes a 3 point shift from baseline.
Time Frame	Week 1 to Week 10

Outcome Measure Data

Analysis Population Description
Of the 208 randomized participants, one (randomized to aripiprazole) was excluded from the Safety Sample as the participant withdrew consent prior to receiving study medication. n=Participants with values for laboratory findings

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	102	105
Alanine aminotransferase ≥3 x ULN; n=98, 98	1 1%	3 2.8%
Aspartate aminotransferase ≥3 x ULN; n=98, 98	1 1%	1 0.9%
Alkaline phosphatase ≥3 x ULN; n=98, 98	1 1%	0 0%
Creatine phosphokinase (total) ≥3 x ULN; n=98, 98	1 1%	2 1.9%
Creatinine ≥ 2.0 mg/dL; n=98, 98	2 2%	2 1.9%
Uric acid ≥8.5 mg/dL (F);≥10.5 mg/dL(M); n=98, 98	5 4.9%	2 1.9%
Calcium ≥ 10.6 mg/dL; n=98, 98	1 1%	2 1.9%
Calcium ≤ 8.4 mg/dL; n=98, 98	4 3.9%	5 4.7%
Serum Chloride ≥ 113 mEq/L; n=98, 98	6 5.9%	4 3.8%
Serum Chloride ≤ 93 mEq/L; n=98, 98	5 4.9%	6 5.7%
Cholesterol Total > ULN; n=98, 98	47 46.1%	36 34%
Cholesterol Total < LLN; n=98, 98	1 1%	0 0%
Serum Glucose Fasting > ULN; n=36, 31	13 12.7%	16 15.1%
Serum Potassium ≥ 5.6 mEq/L; n=98, 98	7 6.9%	7 6.6%
Serum Potassium ≤ 3.4 mEq/L; n=98, 98	4 3.9%	4 3.8%
Serum Sodium ≥ 148 mEq/L; n=98, 98	2 2%	1 0.9%
Serum Sodium ≤ 132 mEq/L; n=98, 98	3 2.9%	3 2.8%
Urea ≥ 10.1mmol/L; n=98, 97	19 18.6%	14 13.2%
Platelet ≥ 700,000 mm3; n=97, 96	0 0%	1 0.9%
Platelet ≤ 75,000 mm3; n=97, 96	1 1%	0 0%
Eosinophils ≥ 10%; n=97, 96	1 1%	1 0.9%
Hematocrit ≤ 37% (M)/≤ 32% (F); n=97, 96	7 6.9%	6 5.7%
Hemoglobin ≤ 11.5 (M)/≤ 9.5 g/dL (F); n=97, 96	6 5.9%	4 3.8%
Urine Glucose ≥ 2-unit increase; n=92, 93	2 2%	0 0%
Urine Protein ≥ 2-unit increase; n=92, 93	2 2%	1 0.9%

30. Secondary Outcome

Title	Participants With Potentially Clinically Significant (PCS) Vital Sign Abnormalities in Acute Phase
Description	Systolic BP: increase defined as ≥180 and a ≥20-mmHg increase from baseline (BL); decrease defined as ≤90 and a ≥20mmHg decrease from BL. Diastolic BP: increase defined as ≥105 and a ≥15mmHg decrease from BL, decrease defined as ≤50 and a ≥15mmHg decrease from BL. Heart rate: increase defined as ≥120 and ≥15bpm increase from BL, decrease defined as ≤50 and ≥15bpm decrease from BL; Weight: increase defined as ≥7% from BL, decrease defined as ≤7% decrease BL. Criteria for identifying PCS measurements are based on guidelines suggested by the FDA Division of Neuropharmacological Drug Products
Time Frame	Week 1 to week 10

Outcome Measure Data

Analysis Population Description
Of the 208 randomized participants, one (randomized to aripiprazole) was excluded from the Safety Sample as the participant withdrew consent prior to receiving study medication. n=Participants with values for vital signs

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks)	Acute Phase: Dosed at 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	102	105
Increased Systolic BP, standing; n=99, 100	5 4.9%	5 4.7%
Decreased Systolic BP, standing; n=99, 100	1 1%	1 0.9%
Increased Systolic BP, supine; n=101, 102	6 5.9%	2 1.9%
Decreased Systolic BP, supine; n=101, 102	0 0%	2 1.9%
Decreased Systolic BP, sitting; n=13, 20	0 0%	1 0.9%
Increased Diastolic BP, standing; n=99, 100	2 2%	2 1.9%
Decreased Diastolic BP, standing; n=99, 100	6 5.9%	3 2.8%
Increased Diastolic BP, supine; n=101, 102	2 2%	0 0%
Decreased Diastolic BP, supine; n=101, 102	4 3.9%	3 2.8%
Decreased Diastolic BP, sitting; n=13, 20	2 2%	0 0%
Increased Heart rate, standing; n=99, 100	1 1%	0 0%
Decreased Heart rate, standing; n=99, 100	0 0%	1 0.9%
Decreased Heart rate, supine; n=101, 102	1 1%	3 2.8%
Increased Weight; n=89, 93	3 2.9%	5 4.7%
Decreased Weight; n=89,93	5 4.9%	5 4.7%

31. Secondary Outcome

Title	Participants With Potentially Clinically Significant Electrocardiogram Abnormalities in Acute Phase
Description	Bradycardia:Heart rate ≤50 bpm and ≥15 bpm decrease from baseline; Supraventricular premature beat: ≥2 per 10 seconds and any increase from baseline; 1st degree A-V Block: PR ≥0.20 seconds and increase of ≥0.05 second from baseline; Intraventricular conduction block:QRS ≥0.12 second and increase of ≥0.02 second from baseline; QTcB= ≥450 msec and ≥10% increase from baseline; QTcN =≥450 msec and ≥10% increase from baseline. All other events were not present at baseline but observed during the study. Inc=increase
Time Frame	Week 1 to Week 10

Outcome Measure Data

Analysis Population Description
Of the 208 randomized participants, one (randomized to aripiprazole) was excluded from the Safety Sample as the participant withdrew consent prior to receiving study medication. n=Participants who were evaluated for electrocardiogram

Arm/Group Title	Placebo	Aripiprazole
Arm/Group Description	Acute Phase: 0 mg, Once daily (10 Weeks	Acute Phase: 2 mg/day (Week 1-2), 2-5 mg/day (Week 3-4), 2-10 mg/day (Week 5-6), 2-15 mg/day (Weeks 7-10).
Measure Participants	102	105
Bradycardia; n=99, 102	3 2.9%	1 0.9%
Sinus Bradycardia; n=99, 102	2 2%	1 0.9%
Supraventricular premature beat; n=99, 102	10 9.8%	7 6.6%
Ventricular premature beat; n=99, 102	7 6.9%	12 11.3%
Supraventricular tachycardia; n=99, 102	1 1%	0 0%
Atrial fibrillation; n=99, 102	3 2.9%	1 0.9%
Atrial flutter; n=99, 102	0 0%	1 0.9%
1st degree A-V Block; n=95, 97	2 2%	0 0%
Left bundle branch block; n=99, 102	1 1%	2 1.9%
Right bundle branch block; n=99, 102	2 2%	1 0.9%
Other intraventricular conduction block; n=99, 102	0 0%	2 1.9%
Subacute infarction; n=99, 102	1 1%	0 0%
Old infarction; n=99, 102	2 2%	2 1.9%
Myocardial ischemia; n=99, 102	3 2.9%	4 3.8%
Symmetrical T-wave inversion; n=99, 102	2 2%	1 0.9%
Inc QTcB (≥450 msec≥,10% from baseline); n=99, 102	5 4.9%	5 4.7%
Inc QTcN (≥450 msec,≥10% from baseline); n=99, 102	1 1%	2 1.9%

32. Secondary Outcome

Title	Change in Neuropsychiatric Inventory (NPI) Psychosis Subscale Score From Baseline During Extension Phase
Description	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.
Time Frame	Baseline (Day 0), Weeks 18,26,40,52,68,84,100,116,132,140

Outcome Measure Data

Analysis Population Description
Observed Cases data set, Efficacy Sample. n=participants with both post-baseline and baseline values Of the 161 participants (80 in placebo and 81 in aripiprazole group), 158 were included in the Extension Phase Efficacy Sample, (3 treated participants had no efficacy measurements).

Arm/Group Title	Aripiprazole
Arm/Group Description	Aripiprazole dosed at 2 mg (Week 11), 2-5 mg/day (Weeks 12-13), 2-10 mg/day (Weeks 14-15), 2-15 mg/day (Weeks 16-140).
Measure Participants	158
Baseline, Day 0 (n=154)	12.312 (0.426)
Week 18 (n=151)	-8.589 (0.548)
Week 26 (n=139)	-8.993 (0.589)
Week 40 (n=115)	-8.270 (0.677)
Week 52 (n=98)	-8.582 (0.672)
Week 68 (n=69)	-9.232 (0.824)
Week 84 (n=62)	-10.18 (0.848)
Week 100 (n=52)	-10.06 (1.031)
Week 116 (n=47)	-10.19 (1.183)
Week 132 (n=31)	-11.68 (1.554)
Week 140 (n=25)	-13.12 (1.586)

33. Secondary Outcome

Title	Clinical Global Impression (CGI) Improvement Score During Extension Phase
Description	The CGI rating scale, which measures symptom severity, treatment response and the efficacy of treatments, is used in clinical studies on mental disorders. CGI Improvement scale is a 7 point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse.
Time Frame	Weeks 12, 14, 18, 22, 26, 30, 34, 40, 46, 52, 68, 84, 100, 116, 132, 140

Outcome Measure Data

Analysis Population Description
Observed Cases data set, Efficacy Sample. n=participants with both post-baseline and baseline values. Of the 161 participants, 158 were included in the Extension Phase Efficacy Sample, (3 treated participants had no efficacy measurements).

Arm/Group Title	Aripiprazole
Arm/Group Description	Aripiprazole dosed at 2 mg (Week 11), 2-5 mg/day (Weeks 12-13), 2-10 mg/day (Weeks 14-15), 2-15 mg/day (Weeks 16-140).
Measure Participants	158
Week 12; n=158	2.873 (0.089)
Week 14; n=151	2.709 (0.084)
Week 18; n=152	2.625 (0.091)
Week 22; n=145	2.552 (0.087)
Week 26; n=140	2.707 (0.113)
Week 30; n=129	2.636 (0.113)
Week 34; n=121	2.554 (0.106)
Week 40; n=114	2.482 (0.121)
Week 46; n=103	2.592 (0.130)
Week 52; n=100	2.580 (0.138)
Week 68; n=70	2.514 (0.155)
Week 84; n=62	2.306 (0.150)
Week 100; n=53	2.660 (0.196)
Week 116; n=47	2.787 (0.233)
Week 132; n=36	3.028 (0.289)
Week 140; n=26	2.385 (0.299)

34. Secondary Outcome

Title	Change in Abnormal Involuntary Movement Scale (AIMS) Total Score During Extension Phase
Description	AIMS is a rating scale that was designed to measure involuntary movements (tardive dyskinesia). The AIMS test has a total of twelve items rating involuntary movements of various areas of the patient's body. These items are rated on a five-point scale of severity from 0-4. The scale is rated from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe). AIMS Total Score is from 0 to 28. A negative change score signifies improvement.
Time Frame	End of Acute Phase (Week 10), Weeks 14, 18, 22, 26, 30, 34, 40, 46, 52, 68, 84, 100, 116, 140

Outcome Measure Data

Analysis Population Description
Observed Cases data set, Efficacy Sample. n=participants with both post-baseline and baseline values. Of the 161 participants (80 in placebo and 81 in aripiprazole group), 158 were included in the Extension Phase Efficacy Sample, (3 treated participants had no efficacy measurements).

Arm/Group Title	Aripiprazole
Arm/Group Description	Aripiprazole dosed at 2 mg (Week 11), 2-5 mg/day (Weeks 12-13), 2-10 mg/day (Weeks 14-15), 2-15 mg/day (Weeks 16-140).
Measure Participants	158
End of Acute Phase (Week 10); n=157	0.95 (0.20)
Week 14; n=151	0.25 (0.12)
Week 18; n=152	0.09 (0.11)
Week 22; n=145	0.02 (0.13)
Week 26; n=140	-0.12 (0.13)
Week 30; n=128	-0.01 (0.10)
Week 34; n=121	-0.10 (0.15)
Week 40; n=115	-0.01 (0.16)
Week 46; n=104	-0.02 (0.15)
Week 52; n=100	-0.02 (0.20)
Week 68; n=70	-0.29 (0.17)
Week 84; n=62	-0.24 (0.17)
Week 100; n=52	-0.21 (0.15)
Week 116; n=47	-0.21 (0.20)
Week 140; n=15	0.00 (0.20)
Endpoint (LOCF data set); n=157	-0.03 (0.15)

35. Secondary Outcome

Title	Change in Simpson-Angus Scale (SAS) Total Score During Extension Phase
Description	The SAS is a 10-item instrument used to evaluate the presence and severity of parkinsonian symptomatology. It is the most commonly used rating scale for Parkinsonism in clinical trials over the past 25 years. The ten items focus on rigidity rather than bradykinesia, and do not assess subjective rigidity or slowness. Items are rated for severity on a 0-4 scale, with definitions given for each anchor point. The total SAS Score has a possible range from 10 to 50 (lower score=less severe). Negative change scores indicate improvement.
Time Frame	End of Acute Phase (Week 10), Weeks 18,26, 40, 52

Outcome Measure Data

Analysis Population Description
Observed Cases data set, Efficacy Sample. n=participants with both post-baseline and baseline values. Of the 161 participants, 158 were included in the Extension Phase Efficacy Sample, (3 treated participants had no efficacy measurements).

Arm/Group Title	Aripiprazole
Arm/Group Description	Aripiprazole dosed at 2 mg (Week 11), 2-5 mg/day (Weeks 12-13), 2-10 mg/day (Weeks 14-15), 2-15 mg/day (Weeks 16-140).
Measure Participants	158
End of Acute Phase (Week 10); n=153	14.34 (0.40)
Week 18; n=148	0.62 (0.23)
Week 26; n=132	1.24 (0.31)
Week 40; n=107	1.25 (0.39)
Week 52; n=95	1.14 (0.40)
Endpoint (LOCF data set); n=153	2.01 (0.37)

36. Secondary Outcome

Title	Change in Barnes Global Clinical Assessment of Akathisia Score During Extension Phase
Description	The Barnes Akathisia Rating Scale is a 4-item scale to assess presence and severity of drug-induced akathisia, including both objective items and subjective items, together with a global clinical assessment of akathisia. Global assessment is made on a scale of 0 to 5 with comprehensive definitions provided for each anchor point on scale: 0=absent; 1=questionable; 2=mild akathisia; 3=moderate akathisia; 4=marked akathisia; 5=severe akathisia. Score has a possible range from 0 (absent) to 5 (severe akathisia). Negative change scores indicate improvement in akathisia.
Time Frame	End of Acute Phase (Week 10), Weeks 18,26, 40, 52

Outcome Measure Data

Analysis Population Description
Observed Cases data set, Efficacy Sample. n=participants with both post-baseline and baseline values. Of the 161 participants, 158 were included in the Extension Phase Efficacy Sample, (3 treated participants had no efficacy measurements).

Arm/Group Title	Aripiprazole
Arm/Group Description	Aripiprazole dosed at 2 mg (Week 11), 2-5 mg/day (Weeks 12-13), 2-10 mg/day (Weeks 14-15), 2-15 mg/day (Weeks 16-140).
Measure Participants	158
End of Acute Phase (Week 10); n=155	0.14 (0.03)
Week 18; n=151	0.04 (0.03)
Week 26; n=139	0.03 (0.04)
Week 40; n=114	0.04 (0.04)
Week 52; n=99	0.06 (0.03)
Endpoint (LOCF data set); n=155	0.06 (0.03)

37. Secondary Outcome

Title	Participants With Extrapyramidal Symptoms (EPS) Related Adverse Events During Extension Phase
Description	Extrapyramidal symptoms (EPS) are various movement disorders such as acute dystonic reactions, pseudoparkinsonism, or akathisia
Time Frame	Week 11 to Week 140

Outcome Measure Data

Analysis Population Description
All the 161 participants (80 in placebo and 81 in aripiprazole group)were included in the Extension Phase Safety Sample.

Arm/Group Title	Aripiprazole
Arm/Group Description	Aripiprazole dosed at 2 mg (Week 11), 2-5 mg/day (Weeks 12-13), 2-10 mg/day (Weeks 14-15), 2-15 mg/day (Weeks 16-140).
Measure Participants	161
Dyskinesia	2 2%
Muscle Rigidity	3 2.9%
Extrapyramidal Disorder	14 13.7%
Hypokinesia	8 7.8%
Tremor	8 7.8%
Akinesia	1 1%
Bradykinesia	1 1%
Parkinsonian Gait	1 1%
Muscle Twitching	1 1%

38. Secondary Outcome

Title	Participants Who Died, Experienced Serious Adverse Events (SAEs), Adverse Events (AEs) or Discontinuations Due to AE During Extension Phase
Description	AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
Time Frame	Week 11 to Week 140

Outcome Measure Data

Analysis Population Description
All the 161 participants (80 in placebo and 81 in aripiprazole group)were included in the Extension Phase Safety Sample.

Arm/Group Title	Aripiprazole
Arm/Group Description	Aripiprazole dosed at 2 mg (Week 11), 2-5 mg/day (Weeks 12-13), 2-10 mg/day (Weeks 14-15), 2-15 mg/day (Weeks 16-140).
Measure Participants	161
Death	41 40.2%
SAE	59 57.8%
AE	148 145.1%
Discontinuation due to AE	66 64.7%

39. Secondary Outcome

Title	Participants With a Potentially Clinically Significant Vital Sign Abnormality During Extension Phase
Description	Systolic BP: increase defined as ≥180 and a ≥20-mmHg increase from baseline (BL); decrease defined as ≤90 and a ≤20mmHg decrease from BL. Diastolic BP: increase defined as ≥105 and a ≥15mmHg decrease from BL, decrease defined as ≤50 and a ≤15mmHg decrease from BL. Heart rate: increase defined as ≥120 and ≥15bpm increase from bBL, decrease defined as ≤50 and ≤15bpm decrease from BL; Weight: increase defined as ≥7% from baseline, decrease defined as ≤7% decrease BL. Criteria for identifying PCS measurements based on guidelines suggested by the FDA Division of Neuropharmacological Drug Products
Time Frame	Week 11 to Week 140

Outcome Measure Data

Analysis Population Description
All the 161 participants (80 in placebo and 81 in aripiprazole group) were included in the Extension Phase Safety Sample.

Arm/Group Title	Aripiprazole
Arm/Group Description	Aripiprazole dosed at 2 mg (Week 11), 2-5 mg/day (Weeks 12-13), 2-10 mg/day (Weeks 14-15), 2-15 mg/day (Weeks 16-140).
Measure Participants	161
Increased Systolic BP, standing; n=159	6 5.9%
Decreased Systolic BP, standing; n=159	9 8.8%
Increased Systolic BP, supine; n=158	6 5.9%
Decreased Systolic BP, supine; n=158	7 6.9%
Decreased Systolic BP, sitting; n=45	1 1%
Increased Diastolic BP, standing; n=159	4 3.9%
Decreased Diastolic BP, standing; n=159	19 18.6%
Increased Diastolic BP, supine; n=158	1 1%
Decreased Diastolic BP, supine; n=158	25 24.5%
Decreased Diastolic BP, sitting; n=45	1 1%
Increased Heart rate, standing; n=159	2 2%
Decreased Heart rate, standing; n=159	3 2.9%
Increased Heart rate, supine; n=158	1 1%
Decreased Heart rate, supine; n=158	5 4.9%
Increased Weight; n=133	28 27.5%
Decreased Weight; n=133	58 56.9%

40. Secondary Outcome

Title	Participants With a Potentially Clinically Significant Electrocardiogram Abnormalities During Extension Phase
Description	Bradycardia:Heart rate ≤50 bpm and ≥15 bpm decrease from baseline; Supraventricular premature beat: ≥2 per 10 seconds and any increase from baseline; 1st degree A-V Block: PR ≥0.20 seconds and increase of ≥0.05 second from baseline; Intraventricular conduction block:QRS ≥0.12 second and increase of ≥0.02 second from baseline; QTcB= ≥450 msec and ≥10% increase from baseline; QTcN =≥450 msec and ≥10% increase from baseline. All other events were not present at baseline but observed during the study
Time Frame	Week 11 to Week 140

Outcome Measure Data

Analysis Population Description
All the 161 participants (80 in placebo and 81 in aripiprazole group) were included in the Extension Phase Safety Sample.

Arm/Group Title	Aripiprazole
Arm/Group Description	Aripiprazole dosed at 2 mg (Week 11), 2-5 mg/day (Weeks 12-13), 2-10 mg/day (Weeks 14-15), 2-15 mg/day (Weeks 16-140).
Measure Participants	161
Atrial Fibrillation; n=145	5 4.9%
Atrial Flutter; n=145	1 1%
Bradycardia; n=145	4 3.9%
Left Bundle Branch Block; n=145	5 4.9%
Myocardial Ischemia; n=145	10 9.8%
Old Infarction; n=145	2 2%
Right Bundle Branch Block; n=145	3 2.9%
Sinus Bradycardia; n=145	2 2%
Sinus Tachycardia; n=145	2 2%
Supraventricular Premature Beat; n=145	12 11.8%
Supraventricular Tachycardia; n=145	2 2%
Symmetrical T-wave Inversions; n=145	8 7.8%
Tachycardia; n=145	4 3.9%
Ventricular premature Beat; n=145	13 12.7%

41. Secondary Outcome

Title	Participants With Potentially Clinically Significant Laboratory Abnormalities During Extension Phase
Description	Criteria for identifying potentially clinically significant laboratory values were based on guidelines suggested by the FDA Division of Neuropharmacological Drug Products.
Time Frame	Week 11 to Week 140

Outcome Measure Data

Analysis Population Description
All the 161 participants (80 in placebo and 81 in aripiprazole group) were included in the Extension Phase Safety Sample.

Arm/Group Title	Aripiprazole
Arm/Group Description	Aripiprazole dosed at 2 mg (Week 11), 2-5 mg/day (Weeks 12-13), 2-10 mg/day (Weeks 14-15), 2-15 mg/day (Weeks 16-140).
Measure Participants	161
High Alanine aminotransferase; ≥ 41 U/L	0 0%
High Aspartate aminotransferase; ≥ 38 U/L	1 1%
High Alkaline phosphatase; ≥ 117 U/L	2 2%
High Lactate dehydrogenase; >480 U/L	1 1%
High Urea; >8.4 mmol/L	56 54.9%
High Creatinine; ≥ 2.0 mg/dL	8 7.8%
High Uric acid; >5.7 mg/dL	9 8.8%
High Total Billirubin; > 1 mg/dL	0 0%
High Creatinine Kinase; ≥ 170 U/L	2 2%
High Serum Glucose Fasting; >118 mg/dL	36 35.3%
High Serum Glucose Non-fasting; >118 mg/dL	17 16.7%
High Cholesterol Total; > 220mg/dL	131 128.4%
High Serum Calcium; >10.2 mg/dL	5 4.9%
Low Serum Calcium; <8.6 mg/dL	26 25.5%
High Serum Chloride; >108 mEq/L	24 23.5%
Low Serum Chloride; <96 mEq/L	36 35.3%
High Serum Potassium; >5.1 mEq/L	36 35.3%
Low Serum Potassium; <3.3mEq/L	11 10.8%
High Serum Sodium; > 145 mEq/L	13 12.7%
Low Serum Sodium; < 133 mEq/L	12 11.8%
Low Hematocrit; <37%	21 20.6%
Low Hemoglobin; < 12 g/dL	19 18.6%
High Leukocyte count; > 10.8 x 10^3 c/uL	7 6.9%
Low Leukocyte count: < 4.8 x 10^3 c/uL	4 3.9%
High Eosinophil count; > 5%	3 2.9%
High Platelet count; >450 x 10^9 c/L	0 0%
Low Platelet count; < 150 x 10^9 c/L	1 1%
High Urine Protein; ≥ 2-unit increase	2 2%
High Urine Glucose; ≥ 2-unit increase	3 2.9%

42. Secondary Outcome

Title	Participants Who Died, Experienced Serious Adverse Events (SAEs), Adverse Events (AEs) or Discontinuations Due to AE During Treatment Beyond 140 Weeks
Description	AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
Time Frame	Week 140 to Week 328

Outcome Measure Data

Analysis Population Description
Participants in France who completed the 130-week open-label extension phase and continued beyond Week 140 were included in safety sample.

Arm/Group Title	Aripiprazole
Arm/Group Description	Treatment beyond 140 weeks: Dosed at 2-15 mg/day (flexible dosing).
Measure Participants	9
Any AE	7 6.9%
SAE	1 1%
Death	1 1%
Discontinuation due to AE	3 2.9%

Adverse Events

Arm/Group Description
Time Frame
Adverse Event Reporting Description

Arm/Group Title	1 Double Blind Aripiprazole		2 Double Blind Placebo		3 Ext - Aripiprazole
All Cause Mortality
	1 Double Blind Aripiprazole		2 Double Blind Placebo		3 Ext - Aripiprazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	1 Double Blind Aripiprazole		2 Double Blind Placebo		3 Ext - Aripiprazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/105 (15.2%)		8/102 (7.8%)		84/161 (52.2%)
Blood and lymphatic system disorders
LEUKOPENIA	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
ANAEMIA	0/105 (0%)		0/102 (0%)		2/161 (1.2%)
Cardiac disorders
CARDIOVASCULAR INSUFFICIENCY	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
CARDIAC ARREST	0/105 (0%)		0/102 (0%)		10/161 (6.2%)
CARDIAC FAILURE ACUTE	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
CARDIOPULMONARY FAILURE	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
ATRIAL FLUTTER	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
MYOCARDIAL INFARCTION	0/105 (0%)		0/102 (0%)		4/161 (2.5%)
CARDIAC FAILURE	1/105 (1%)		0/102 (0%)		2/161 (1.2%)
CARDIO-RESPIRATORY ARREST	0/105 (0%)		0/102 (0%)		2/161 (1.2%)
BRADYCARDIA	1/105 (1%)		1/102 (1%)		0/161 (0%)
MYOCARDIAL ISCHAEMIA	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
Eye disorders
CATARACT	1/105 (1%)		1/102 (1%)		0/161 (0%)
Gastrointestinal disorders
SALIVARY HYPERSECRETION	1/105 (1%)		0/102 (0%)		0/161 (0%)
FAECALOMA	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
INTESTINAL OBSTRUCTION	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
DIARRHOEA	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
HAEMATEMESIS	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
VOMITING	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
ABDOMINAL PAIN	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
General disorders
DEATH	2/105 (1.9%)		0/102 (0%)		4/161 (2.5%)
ASTHENIA	0/105 (0%)		0/102 (0%)		2/161 (1.2%)
MALAISE	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
PYREXIA	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
SUDDEN CARDIAC DEATH	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
CHEST PAIN	0/105 (0%)		1/102 (1%)		0/161 (0%)
CHILLS	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
SUDDEN DEATH	0/105 (0%)		0/102 (0%)		2/161 (1.2%)
Hepatobiliary disorders
HEPATITIS ACUTE	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
CHOLECYSTITIS	1/105 (1%)		0/102 (0%)		1/161 (0.6%)
Infections and infestations
ESCHERICHIA SEPSIS	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
SEPSIS	0/105 (0%)		0/102 (0%)		3/161 (1.9%)
URINARY TRACT INFECTION	0/105 (0%)		0/102 (0%)		2/161 (1.2%)
PYELONEPHRITIS	0/105 (0%)		0/102 (0%)		2/161 (1.2%)
ERYSIPELAS	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
INFECTION	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
PNEUMONIA	0/105 (0%)		0/102 (0%)		3/161 (1.9%)
SEPTIC SHOCK	1/105 (1%)		0/102 (0%)		0/161 (0%)
BRONCHOPNEUMONIA	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
BRONCHITIS	1/105 (1%)		0/102 (0%)		3/161 (1.9%)
LUNG INFECTION	1/105 (1%)		0/102 (0%)		3/161 (1.9%)
Injury, poisoning and procedural complications
FEMUR FRACTURE	0/105 (0%)		0/102 (0%)		4/161 (2.5%)
FALL	1/105 (1%)		1/102 (1%)		1/161 (0.6%)
JAW FRACTURE	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
HUMERUS FRACTURE	1/105 (1%)		0/102 (0%)		0/161 (0%)
FEMORAL NECK FRACTURE	2/105 (1.9%)		0/102 (0%)		6/161 (3.7%)
HAND FRACTURE	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
HIP FRACTURE	1/105 (1%)		0/102 (0%)		1/161 (0.6%)
PELVIC FRACTURE	1/105 (1%)		0/102 (0%)		0/161 (0%)
Investigations
BLOOD GLUCOSE INCREASED	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
Metabolism and nutrition disorders
DEHYDRATION	1/105 (1%)		0/102 (0%)		3/161 (1.9%)
DIABETES MELLITUS	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
MALNUTRITION	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
Musculoskeletal and connective tissue disorders
MUSCLE RIGIDITY	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
MUSCULOSKELETAL STIFFNESS	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
OSTEOARTHRITIS	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PROSTATE CANCER	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
SALIVARY GLAND NEOPLASM	0/105 (0%)		1/102 (1%)		0/161 (0%)
PANCREATIC CARCINOMA METASTATIC	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
Nervous system disorders
DIABETIC COMA	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
DEMENTIA ALZHEIMER'S TYPE	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
EPILEPSY	0/105 (0%)		1/102 (1%)		0/161 (0%)
ISCHAEMIC STROKE	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
LETHARGY	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
VASCULAR DEMENTIA	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
CEREBROVASCULAR ACCIDENT	0/105 (0%)		0/102 (0%)		3/161 (1.9%)
SCIATICA	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
SYNCOPE	0/105 (0%)		0/102 (0%)		2/161 (1.2%)
DEMENTIA	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
LOSS OF CONSCIOUSNESS	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
TRANSIENT ISCHAEMIC ATTACK	0/105 (0%)		1/102 (1%)		0/161 (0%)
Psychiatric disorders
CONFUSIONAL STATE	1/105 (1%)		0/102 (0%)		1/161 (0.6%)
DELIRIUM	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
PSYCHOTIC DISORDER	0/105 (0%)		1/102 (1%)		0/161 (0%)
AGGRESSION	2/105 (1.9%)		0/102 (0%)		0/161 (0%)
Renal and urinary disorders
URINARY RETENTION	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
RENAL FAILURE	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
Respiratory, thoracic and mediastinal disorders
ACQUIRED DIAPHRAGMATIC EVENTRATION	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
ACUTE RESPIRATORY DISTRESS SYNDROME	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
HAEMOPTYSIS	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
LUNG DISORDER	0/105 (0%)		0/102 (0%)		5/161 (3.1%)
BRONCHOPNEUMOPATHY	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
DYSPNOEA	0/105 (0%)		0/102 (0%)		3/161 (1.9%)
PULMONARY EMBOLISM	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
ACUTE PULMONARY OEDEMA	0/105 (0%)		0/102 (0%)		2/161 (1.2%)
PNEUMONIA ASPIRATION	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
PULMONARY OEDEMA	0/105 (0%)		0/102 (0%)		2/161 (1.2%)
RESPIRATORY ARREST	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
MENDELSON'S SYNDROME	0/105 (0%)		0/102 (0%)		2/161 (1.2%)
RESPIRATORY DISTRESS	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
Skin and subcutaneous tissue disorders
ECZEMA VESICULAR	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
Social circumstances
SOCIAL PROBLEM	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
Surgical and medical procedures
PSYCHOSOCIAL SUPPORT	2/105 (1.9%)		0/102 (0%)		1/161 (0.6%)
Vascular disorders
CIRCULATORY COLLAPSE	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
PERIPHERAL ISCHAEMIA	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
EMBOLISM	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
VARICOSE VEIN	1/105 (1%)		0/102 (0%)		0/161 (0%)
THROMBOSIS	0/105 (0%)		0/102 (0%)		1/161 (0.6%)
Other (Not Including Serious) Adverse Events
	1 Double Blind Aripiprazole		2 Double Blind Placebo		3 Ext - Aripiprazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/105 (29.5%)		27/102 (26.5%)		101/161 (62.7%)
Gastrointestinal disorders
CONSTIPATION	2/105 (1.9%)		0/102 (0%)		10/161 (6.2%)
DIARRHOEA	3/105 (2.9%)		1/102 (1%)		16/161 (9.9%)
VOMITING	1/105 (1%)		2/102 (2%)		10/161 (6.2%)
General disorders
OEDEMA PERIPHERAL	1/105 (1%)		0/102 (0%)		11/161 (6.8%)
Infections and infestations
URINARY TRACT INFECTION	8/105 (7.6%)		14/102 (13.7%)		27/161 (16.8%)
BRONCHITIS	4/105 (3.8%)		3/102 (2.9%)		27/161 (16.8%)
Injury, poisoning and procedural complications
FALL	3/105 (2.9%)		4/102 (3.9%)		18/161 (11.2%)
Musculoskeletal and connective tissue disorders
OSTEOARTHRITIS	3/105 (2.9%)		0/102 (0%)		10/161 (6.2%)
Nervous system disorders
SOMNOLENCE	8/105 (7.6%)		2/102 (2%)		30/161 (18.6%)
EXTRAPYRAMIDAL DISORDER	2/105 (1.9%)		1/102 (1%)		14/161 (8.7%)
Psychiatric disorders
INSOMNIA	2/105 (1.9%)		4/102 (3.9%)		14/161 (8.7%)
ANXIETY	1/105 (1%)		2/102 (2%)		10/161 (6.2%)
APATHY	0/105 (0%)		0/102 (0%)		13/161 (8.1%)

Limitations/Caveats

Limitations of the study, such as early termination leading to small numbers of subjects analyzed and technical problems with measurement leading to unreliable or uninterpretable data

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication

Results Point of Contact

Name/Title	BMS Study Director
Organization	Bristol-Myers Squibb
Phone
Email	Clinical.Trials@bms.com

Responsible Party:

Otsuka Pharmaceutical Development & Commercialization, Inc.

ClinicalTrials.gov Identifier:

NCT01438060

Other Study ID Numbers:

CN138-006

First Posted:

Sep 21, 2011

Last Update Posted:

Dec 2, 2013

Last Verified:

Nov 1, 2013