A Phase 3 interventional study of Aripiprazole (BMS-337039) and Placebo in Dementia, Alzheimer Type, sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc.. Completed. Open to participants aged 55 Years to 95 Years. Per ClinicalTrials.gov, last updated 2013-12-02.
Sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc. · Phase 3, Interventional, and Treatment
The primary objective of the study is to compare the efficacy of aripiprazole with placebo in patients with psychosis associated with Alzheimer's dementia.
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.
2,172 studies on the registry are indexed under Dementia; 541 are open to participants now.
This study's enrollment of 232 is above the median of 83 across 1,629 interventional studies indexed under Dementia.
Browse Dementia studies →Otsuka Pharmaceutical Development & Commercialization, Inc. is the lead sponsor of 289 studies on the registry; 18 are open to participants now.
Of its 104 completed or terminated interventional studies of FDA-regulated products, 69 (66%) have results posted.
Counted across the registry records on this site, refreshed daily.
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:
Double blind Acute Phase (Week 1 to Week 10), Open label Extension Phase (Week 11 to Week 140)
Drug: Aripiprazole (BMS-337039)
Double blind Acute Phase (Week 1 to Week 10)
Drug: Placebo
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
Acute Phase: Oral, Tablets, 0 mg, Once daily, 10 Weeks
Change From Baseline in Neuropsychiatric Inventory (NPI) Psychosis Subscale Score at Week 10 in Acute Phase
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
Change From Baseline in NPI Psychosis Subscale Score Through Week 8 in Acute Phase
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
Change From Baseline in NPI Total Score in Acute Phase
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
Participants Who Demonstrated a ≥ 50% Decrease From Baseline to Endpoint in the NPI Psychosis Subscale Score in Acute Phase
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
Participants Who Demonstrated a ≥ 50% Decrease From Baseline in the Total NPI Score in Acute Phase
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
Change From Baseline in NPI Psychosis Subscale Caregiver Distress Score in Acute Phase
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
Change From Baseline in NPI Total Caregiver Distress Score in Acute Phase
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
Change From Baseline in Clinical Global Impression (CGI) Severity of Illness Score in Acute Phase
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
CGI Improvement Score in Acute Phase
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
Change From Baseline in Brief Psychiatric Rating Scale (BPRS) Total Score in Acute Phase
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
Change From Baseline in Mini Mental State Examination (MMSE) Total Score in Acute Phase
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
Change From Baseline in NPI Individual Item Scores in Acute Phase: Delusions
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
Change From Baseline in NPI Individual Item Scores in Acute Phase: Hallucinations
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
Change From Baseline in NPI Individual Item Scores in Acute Phase: Agitation/Aggression
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
Change From Baseline in NPI Individual Item Scores in Acute Phase: Depression/Dysphoria
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
Change From Baseline in NPI Individual Item Scores in Acute Phase: Anxiety
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
Change From Baseline in NPI Individual Item Scores in Acute Phase: Apathy/Indifference
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
Change From Baseline in NPI Individual Item Scores in Acute Phase: Elation/Euphoria
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
Change From Baseline in NPI Individual Item Scores in Acute Phase: Disinhibition
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
Change From Baseline in NPI Individual Item Scores in Acute Phase: Irritability/Lability
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
Change From Baseline in NPI Individual Item Scores in Acute Phase: Aberrant Motor Behavior
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
Change From Baseline in NPI Individual Item Scores in Acute Phase: Appetite/Eating Behaviors
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
Change From Baseline in NPI Individual Item Scores in Acute Phase: Sleep
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
Change From Baseline in Simpson-Angus Scale (SAS) Total Score in Acute Phase
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
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score in Acute Phase
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
Change From Baseline in Barnes Global Clinical Assessment of Akathisia in Acute Phase
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
Participants With Extrapyramidal Symptoms (EPS) Related Adverse Events in Acute Phase
Extrapyramidal symptoms (EPS) are various movement disorders such as acute dystonic reactions, pseudoparkinsonism, or akathisia
Time frame: Week 1 to week 10
Participants Who Died, Experienced Serious Adverse Events (SAEs), Adverse Events (AEs) or Discontinuations Due to AEs in Acute Phase
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
Participants With Potentially Clinically Significant Laboratory Abnormalities in Acute Phase
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
Participants With Potentially Clinically Significant (PCS) Vital Sign Abnormalities in Acute Phase
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
Participants With Potentially Clinically Significant Electrocardiogram Abnormalities in Acute Phase
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
Change in Neuropsychiatric Inventory (NPI) Psychosis Subscale Score From Baseline During Extension Phase
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
Clinical Global Impression (CGI) Improvement Score During Extension Phase
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
Change in Abnormal Involuntary Movement Scale (AIMS) Total Score During Extension Phase
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
Change in Simpson-Angus Scale (SAS) Total Score During Extension Phase
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
Change in Barnes Global Clinical Assessment of Akathisia Score During Extension Phase
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
Participants With Extrapyramidal Symptoms (EPS) Related Adverse Events During Extension Phase
Extrapyramidal symptoms (EPS) are various movement disorders such as acute dystonic reactions, pseudoparkinsonism, or akathisia
Time frame: Week 11 to Week 140
Participants Who Died, Experienced Serious Adverse Events (SAEs), Adverse Events (AEs) or Discontinuations Due to AE During Extension Phase
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
Participants With a Potentially Clinically Significant Vital Sign Abnormality During Extension Phase
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
Participants With a Potentially Clinically Significant Electrocardiogram Abnormalities During Extension Phase
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
Participants With Potentially Clinically Significant Laboratory Abnormalities During Extension Phase
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
Participants Who Died, Experienced Serious Adverse Events (SAEs), Adverse Events (AEs) or Discontinuations Due to AE During Treatment Beyond 140 Weeks
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
232 participants were enrolled, 24 were not randomized (baseline failures).
| Milestone | Placebo | Aripiprazole |
|---|---|---|
| Started | 102 | 106 |
| Completed | 84 | 88 |
| Not completed | 18 | 18 |
| Withdrew: Adverse event | 7 | 9 |
| Withdrew: Lack of efficacy | 6 | 3 |
| Withdrew: Withdrawal by subject | 3 | 4 |
| Withdrew: Lost to follow-up | 1 | 0 |
| Withdrew: Death | 0 | 2 |
| Withdrew: Other reason | 1 | 0 |
| Milestone | Placebo | Aripiprazole |
|---|---|---|
| Started | 80 | 81 |
| Completed | 22 | 25 |
| Not completed | 58 | 56 |
| Withdrew: Adverse event | 15 | 16 |
| Withdrew: Lack of efficacy | 8 | 8 |
| Withdrew: Withdrawal by subject | 3 | 5 |
| Withdrew: Participant unreliability | 1 | 0 |
| Withdrew: Lost to follow-up | 2 | 0 |
| Withdrew: Death | 22 | 12 |
| Withdrew: Other reason | 7 | 15 |
| Milestone | Placebo | Aripiprazole |
|---|---|---|
| Started | 0 | 9 |
| Completed | 0 | 1 |
| Not completed | 0 | 8 |
| Withdrew: Adverse event | 0 | 2 |
| Withdrew: Lack of efficacy | 0 | 1 |
| Withdrew: Withdrawal by subject | 0 | 1 |
| Withdrew: Death | 0 | 1 |
| Withdrew: Other reason | 0 | 3 |
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.
| Units on a scale | Placebo | Aripiprazole |
|---|---|---|
| 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 |
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.
| Units on Scale | Placebo | Aripiprazole |
|---|---|---|
| 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 |
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.
| Units on a Scale | Placebo | Aripiprazole |
|---|---|---|
| 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 |
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 | Placebo | Aripiprazole |
|---|---|---|
| Week 1 | 24 | 18 |
| Week 2 | 37 | 34 |
| Week 3 | 45 | 44 |
| Week 4 | 52 | 47 |
| Week 6 | 53 | 56 |
| Week 8 | 58 | 64 |
| Week 10 | 60 | 70 |
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 | Placebo | Aripiprazole |
|---|---|---|
| Week 1 | 12 | 11 |
| Week 2 | 31 | 29 |
| Week 3 | 35 | 33 |
| Week 4 | 44 | 37 |
| Week 6 | 45 | 45 |
| Week 8 | 52 | 50 |
| Week 10 | 47 | 53 |
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.
| Unit on a Scale | Placebo | Aripiprazole |
|---|---|---|
| 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 |
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.
| Units on a Scale | Placebo | Aripiprazole |
|---|---|---|
| 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 |
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.
| Units on Scale | Placebo | Aripiprazole |
|---|---|---|
| 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 |
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.
| Units on Scale | Placebo | Aripiprazole |
|---|---|---|
| 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 |
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.
| Unit on Scale | Placebo | Aripiprazole |
|---|---|---|
| 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 |
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.
| Units on Scale | Placebo | Aripiprazole |
|---|---|---|
| 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 |
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.
| Units on a Scale | Placebo | Aripiprazole |
|---|---|---|
| Baseline (Day 0) | 7.85 (7.29 to 8.41) | 8.11 (7.55 to 8.67) |
| Week 1 | -2.37 (-3.02 to -1.71) | -1.61 (-2.25 to -0.97) |
| Week 2 | -2.84 (-3.69 to -1.98) | -2.72 (-3.57 to -1.88) |
| Week 3 | -3.25 (-4.07 to -2.42) | -3.50 (-4.32 to -2.69) |
| Week 4 | -3.72 (-4.54 to -2.90) | -3.89 (-4.69 to -3.08) |
| Week 6 | -3.45 (-4.28 to -2.61) | -3.95 (-4.78 to -3.13) |
| Week 8 | -3.52 (-4.41 to -2.63) | -3.91 (-4.79 to -3.03) |
| Week 10 | -3.94 (-4.81 to -3.07) | -4.28 (-5.14 to -3.43) |
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.
| Units on a Scale | Placebo | Aripiprazole |
|---|---|---|
| Baseline (Day 0) | 4.27 (3.25 to 5.29) | 4.18 (3.17 to 5.19) |
| Week 1 | -0.98 (-1.63 to -0.32) | -0.65 (-1.30 to 0.00) |
| Week 2 | -1.15 (-1.86 to -0.43) | -1.09 (-1.80 to -0.38) |
| Week 3 | -1.34 (-2.05 to -0.63) | -1.37 (-2.08 to -0.67) |
| Week 4 | -1.71 (-2.31 to -1.10) | -1.79 (-2.40 to -1.19) |
| Week 6 | -1.43 (-2.02 to -0.84) | -2.03 (-2.62 to -1.45) |
| Week 8 | -1.57 (-2.22 to -0.91) | -2.12 (-2.77 to -1.47) |
| Week 10 | -1.65 (-2.28 to -1.03) | -2.30 (-2.92 to -1.67) |
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.
| Units on a Scale | Placebo | Aripiprazole |
|---|---|---|
| Baseline (Day 0) | 3.52 (2.68 to 4.37) | 4.04 (3.20 to 4.87) |
| Week 1 | -0.34 (-1.12 to 0.43) | 0.10 (-0.68 to 0.88) |
| Week 2 | -1.16 (-1.86 to -0.47) | -0.69 (-1.38 to 0.01) |
| Week 3 | -0.73 (-1.50 to 0.03) | -0.59 (-1.35 to 0.17) |
| Week 4 | -0.78 (-1.51 to -0.05) | -1.38 (-2.11 to -0.65) |
| Week 6 | -0.31 (-1.08 to 0.46) | -0.94 (-1.71 to -0.18) |
| Week 8 | -0.12 (-0.94 to 0.69) | -0.84 (-1.65 to -0.03) |
| Week 10 | -0.47 (-1.32 to 0.37) | -1.12 (-1.96 to -0.28) |
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.
| Units on a Scale | Placebo | Aripiprazole |
|---|---|---|
| Baseline (Day 0) | 3.27 (2.59 to 3.95) | 2.28 (1.60 to 2.95) |
| Week 1 | 0.21 (-0.39 to 0.81) | -0.04 (-0.62 to 0.54) |
| Week 2 | -0.44 (-1.01 to 0.13) | -0.36 (-0.91 to 0.19) |
| Week 3 | -0.77 (-1.28 to -0.25) | -0.33 (-0.84 to 0.17) |
| Week 4 | -0.72 (-1.22 to -0.22) | -0.50 (-0.99 to -0.02) |
| Week 6 | -0.47 (-1.04 to 0.10) | -0.55 (-1.10 to 0.00) |
| Week 8 | -0.65 (-1.20 to -0.11) | -0.54 (-1.07 to -0.01) |
| Week 10 | -0.32 (-0.95 to 0.32) | -0.42 (-1.04 to 0.19) |
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.
| Units on a Scale | Placebo | Aripiprazole |
|---|---|---|
| Baseline (Day 0) | 3.64 (2.81 to 4.46) | 3.17 (2.36 to 3.99) |
| Week 1 | 0.02 (-0.73 to 0.77) | 0.05 (-0.69 to 0.79) |
| Week 2 | -0.08 (-0.73 to 0.58) | 0.08 (-0.56 to 0.72) |
| Week 3 | -0.43 (-1.14 to 0.29) | 0.07 (-0.63 to 0.77) |
| Week 4 | -0.80 (-1.47 to -0.14) | -0.38 (-1.03 to 0.27) |
| Week 6 | -0.79 (-1.49 to -0.08) | -0.13 (-0.82 to 0.57) |
| Week 8 | -0.23 (-0.90 to 0.44) | -0.21 (-0.87 to 0.46) |
| Week 10 | -0.43 (-1.13 to 0.26) | -0.31 (-0.99 to 0.37) |
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.
| Units on a Scale | Placebo | Aripiprazole |
|---|---|---|
| Baseline (Day 0) | 4.14 (3.41 to 4.86) | 3.47 (2.75 to 4.19) |
| Week 1 | 0.03 (-0.66 to 0.71) | -0.70 (-1.37 to -0.03) |
| Week 2 | -0.48 (-1.11 to 0.15) | -0.76 (-1.37 to -0.14) |
| Week 3 | -0.09 (-0.80 to 0.62) | -0.36 (-1.06 to 0.33) |
| Week 4 | -0.65 (-1.39 to 0.10) | -0.67 (-1.40 to 0.06) |
| Week 6 | -0.63 (-1.43 to 0.17) | -0.40 (-1.18 to 0.38) |
| Week 8 | -0.87 (-1.60 to -0.15) | -0.21 (-0.92 to 0.49) |
| Week 10 | -0.95 (-1.78 to -0.11) | -0.09 (-0.91 to 0.72) |
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.
| Units on a Scale | Placebo | Aripiprazole |
|---|---|---|
| Baseline (Day 0) | 0.56 (0.06 to 1.05) | 0.73 (0.24 to 1.23) |
| Week 1 | -0.48 (-0.75 to -0.22) | -0.26 (-0.52 to 0.01) |
| Week 2 | -0.37 (-0.63 to -0.11) | -0.18 (-0.43 to 0.08) |
| Week 3 | -0.48 (-0.76 to -0.20) | -0.27 (-0.54 to 0.01) |
| Week 4 | -0.47 (-0.66 to -0.28) | -0.40 (-0.59 to -0.21) |
| Week 6 | -0.38 (-0.58 to -0.18) | -0.39 (-0.59 to -0.20) |
| Week 8 | -0.32 (-0.59 to -0.04) | -0.25 (-0.52 to 0.03) |
| Week 10 | -0.42 (-0.65 to -0.19) | -0.36 (-0.59 to -0.14) |
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.
| Units on a Scale | Placebo | Aripiprazole |
|---|---|---|
| Baseline (Day 0) | 0.98 (0.39 to 1.57) | 1.36 (0.77 to 1.94) |
| Week 1 | -0.14 (-0.54 to 0.25) | -0.39 (-0.79 to 0.00) |
| Week 2 | -0.42 (-0.91 to 0.07) | -0.44 (-0.93 to 0.05) |
| Week 3 | -0.27 (-0.86 to 0.32) | -0.21 (-0.80 to 0.38) |
| Week 4 | -0.55 (-1.04 to -0.06) | -0.67 (-1.16 to -0.19) |
| Week 6 | -0.19 (-0.64 to 0.26) | -0.72 (-1.17 to -0.28) |
| Week 8 | -0.20 (-0.67 to 0.28) | -0.44 (-0.91 to 0.03) |
| Week 10 | 0.07 (-0.47 to 0.60) | -0.35 (-0.88 to 0.18) |
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.
| Units on a Scale | Placebo | Aripiprazole |
|---|---|---|
| Baseline (Day 0) | 3.73 (2.80 to 4.66) | 4.36 (3.44 to 5.28) |
| Week 1 | -0.73 (-1.48 to 0.02) | -0.09 (-0.84 to 0.66) |
| Week 2 | -0.89 (-1.65 to -0.12) | -0.69 (-1.45 to 0.08) |
| Week 3 | -1.11 (-1.89 to -0.32) | -1.09 (-1.87 to -0.30) |
| Week 4 | -0.75 (-1.53 to 0.02) | -1.53 (-2.30 to -0.76) |
| Week 6 | -0.42 (-1.19 to 0.36) | -1.29 (-2.06 to -0.51) |
| Week 8 | -0.33 (-1.16 to 0.50) | -0.99 (-1.82 to -0.16) |
| Week 10 | -0.24 (-1.02 to 0.53) | -1.26 (-2.03 to -0.48) |
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.
| Units on a Scale | Placebo | Aripiprazole |
|---|---|---|
| Baseline (Day 0) | 3.67 (2.69 to 4.66) | 3.61 (2.63 to 4.59) |
| Week 1 | -0.66 (-1.26 to -0.06) | 0.18 (-0.42 to 0.77) |
| Week 2 | -0.84 (-1.63 to -0.06) | -0.51 (-1.29 to 0.27) |
| Week 3 | -1.68 (-2.45 to -0.09) | -0.66 (-1.43 to 0.12) |
| Week 4 | -0.91 (-1.73 to -0.09) | -0.16 (-0.98 to 0.65) |
| Week 6 | -0.89 (-1.64 to -0.13) | -0.61 (-1.36 to 0.14) |
| Week 8 | -1.06 (-1.78 to -0.33) | -0.83 (-1.55 to -0.11) |
| Week 10 | -1.02 (-1.83 to -0.22) | -0.89 (-1.69 to -0.09) |
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.
| Units on a Scale | Placebo | Aripiprazole |
|---|---|---|
| Baseline (Day 0) | 1.78 (1.18 to 2.39) | 1.47 (0.87 to 2.07) |
| Week 1 | -0.24 (-0.73 to 0.25) | -0.18 (-0.66 to 0.30) |
| Week 2 | -0.36 (-0.84 to 0.12) | -0.21 (-0.68 to 0.26) |
| Week 3 | -0.14 (-0.65 to 0.36) | 0.23 (-0.27 to 0.73) |
| Week 4 | -0.44 (-0.96 to 0.07) | -0.04 (-0.55 to 0.47) |
| Week 6 | -0.27 (-0.96 to 0.42) | 0.23 (-0.45 to 0.91) |
| Week 8 | -0.11 (-0.72 to 0.49) | 0.45 (-0.15 to 1.05) |
| Week 10 | -0.17 (-0.79 to 0.46) | 0.56 (-0.05 to 1.17) |
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.
| Units on a Scale | Placebo | Aripiprazole |
|---|---|---|
| Baseline (Day 0) | 2.67 (1.78 to 3.55) | 3.03 (2.15 to 3.91) |
| Week 1 | -0.10 (-0.84 to 0.64) | -0.07 (-0.81 to 0.67) |
| Week 2 | -0.20 (-0.95 to 0.55) | -0.07 (-0.82 to 0.67) |
| Week 3 | -0.20 (-0.98 to 0.58) | 0.10 (-0.68 to 0.87) |
| Week 4 | 0.02 (-0.65 to 0.70) | 0.15 (-0.53 to 0.82) |
| Week 6 | -0.39 (-1.12 to 0.34) | -0.03 (-0.76 to 0.69) |
| Week 8 | -0.06 (-0.80 to 0.68) | -0.06 (-0.79 to 0.68) |
| Week 10 | 0.05 (-0.69 to 0.79) | -0.06 (-0.80 to 0.67) |
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.
| Units on scale | Placebo | Aripiprazole |
|---|---|---|
| Baseline (Day 0); n=97, 100 | 14.41 ± NA | 14.47 ± NA |
| Week 2; n=89, 94 | 0.02 (-0.49 to 0.52) | -0.35 (-0.84 to 0.14) |
| Week 4; n=93, 96 | -0.15 (-0.76 to 0.45) | -0.06 (-0.65 to 0.54) |
| Week 10; n=82, 85 | -0.44 (-1.19 to 0.31) | 0.33 (-0.40 to 1.07) |
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.
| Units on scale | Placebo | Aripiprazole |
|---|---|---|
| Baseline (Day 0); n=99, 101 | 0.87 (0.32 to 1.42) | 0.93 (0.39 to 1.48) |
| Week 2; n=91, 95 | -0.10 (-0.25 to 0.04) | -0.17 (-0.32 to -0.03) |
| Week 4; n=97, 97 | -0.05 (-0.30 to 0.19) | -0.08 (-0.33 to 0.17) |
| Week 8; n=87, 87 | 0.07 (-0.30 to 0.44) | -0.14 (-0.51 to 0.23) |
| Week 10; n=85, 87 | 0.05 (-0.33 to 0.43) | -0.17 (-0.55 to 0.20) |
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.
| Unit on scale | Placebo | Aripiprazole |
|---|---|---|
| Baseline (Day 0); n=100,101 | 0.20 (0.09 to 0.31) | 0.19 (0.07 to 0.30) |
| Week 1; n=99, 101 | -0.06 (-0.12 to 0.00) | -0.06 (-0.12 to 0.00) |
| Week 2; n=91, 95 | -0.02 (-0.07 to 0.03) | -0.05 (-0.11 to 0.00) |
| Week 3; n=95, 99 | -0.03 (-0.08 to 0.02) | -0.06 (-0.11 to -0.01) |
| Week 4; n=97, 98 | 0.00 ± NA | -0.08 (-0.15 to -0.02) |
| Week 6; n=91, 92 | -0.07 (-0.14 to -0.01) | -0.02 (-0.09 to 0.04) |
| Week 8; n=87, 87 | -0.05 (-0.11 to 0.01) | -0.03 (-0.09 to 0.03) |
| Week 10; n=85, 87 | -0.05 (-0.11 to 0.00) | -0.05 (-0.11 to 0.01) |
Extrapyramidal symptoms (EPS) are various movement disorders such as acute dystonic reactions, pseudoparkinsonism, or akathisia
| Participants | Placebo | Aripiprazole |
|---|---|---|
| Dyskinesia | 2 | 0 |
| Extrapyramidal syndrome | 1 | 2 |
| Hypertonia | 1 | 1 |
| Hypokinesia | 0 | 1 |
| Tremor | 0 | 2 |
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 | Placebo | Aripiprazole |
|---|---|---|
| Any adverse event (AE) | 53 | 67 |
| Serious adverse event | 9 | 16 |
| Deaths | 0 | 4 |
| Discontinuations due to AE | 7 | 11 |
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 | Placebo | Aripiprazole |
|---|---|---|
| Alanine aminotransferase ≥3 x ULN; n=98, 98 | 1 | 3 |
| Aspartate aminotransferase ≥3 x ULN; n=98, 98 | 1 | 1 |
| Alkaline phosphatase ≥3 x ULN; n=98, 98 | 1 | 0 |
| Creatine phosphokinase (total) ≥3 x ULN; n=98, 98 | 1 | 2 |
| Creatinine ≥ 2.0 mg/dL; n=98, 98 | 2 | 2 |
| Uric acid ≥8.5 mg/dL (F);≥10.5 mg/dL(M); n=98, 98 | 5 | 2 |
| Calcium ≥ 10.6 mg/dL; n=98, 98 | 1 | 2 |
| Calcium ≤ 8.4 mg/dL; n=98, 98 | 4 | 5 |
| Serum Chloride ≥ 113 mEq/L; n=98, 98 | 6 | 4 |
| Serum Chloride ≤ 93 mEq/L; n=98, 98 | 5 | 6 |
| Cholesterol Total > ULN; n=98, 98 | 47 | 36 |
| Cholesterol Total < LLN; n=98, 98 | 1 | 0 |
| Serum Glucose Fasting > ULN; n=36, 31 | 13 | 16 |
| Serum Potassium ≥ 5.6 mEq/L; n=98, 98 | 7 | 7 |
| Serum Potassium ≤ 3.4 mEq/L; n=98, 98 | 4 | 4 |
| Serum Sodium ≥ 148 mEq/L; n=98, 98 | 2 | 1 |
| Serum Sodium ≤ 132 mEq/L; n=98, 98 | 3 | 3 |
| Urea ≥ 10.1mmol/L; n=98, 97 | 19 | 14 |
| Platelet ≥ 700,000 mm3; n=97, 96 | 0 | 1 |
| Platelet ≤ 75,000 mm3; n=97, 96 | 1 | 0 |
| Eosinophils ≥ 10%; n=97, 96 | 1 | 1 |
| Hematocrit ≤ 37% (M)/≤ 32% (F); n=97, 96 | 7 | 6 |
| Hemoglobin ≤ 11.5 (M)/≤ 9.5 g/dL (F); n=97, 96 | 6 | 4 |
| Urine Glucose ≥ 2-unit increase; n=92, 93 | 2 | 0 |
| Urine Protein ≥ 2-unit increase; n=92, 93 | 2 | 1 |
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 | Placebo | Aripiprazole |
|---|---|---|
| Increased Systolic BP, standing; n=99, 100 | 5 | 5 |
| Decreased Systolic BP, standing; n=99, 100 | 1 | 1 |
| Increased Systolic BP, supine; n=101, 102 | 6 | 2 |
| Decreased Systolic BP, supine; n=101, 102 | 0 | 2 |
| Decreased Systolic BP, sitting; n=13, 20 | 0 | 1 |
| Increased Diastolic BP, standing; n=99, 100 | 2 | 2 |
| Decreased Diastolic BP, standing; n=99, 100 | 6 | 3 |
| Increased Diastolic BP, supine; n=101, 102 | 2 | 0 |
| Decreased Diastolic BP, supine; n=101, 102 | 4 | 3 |
| Decreased Diastolic BP, sitting; n=13, 20 | 2 | 0 |
| Increased Heart rate, standing; n=99, 100 | 1 | 0 |
| Decreased Heart rate, standing; n=99, 100 | 0 | 1 |
| Decreased Heart rate, supine; n=101, 102 | 1 | 3 |
| Increased Weight; n=89, 93 | 3 | 5 |
| Decreased Weight; n=89,93 | 5 | 5 |
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
| Participants | Placebo | Aripiprazole |
|---|---|---|
| Bradycardia; n=99, 102 | 3 | 1 |
| Sinus Bradycardia; n=99, 102 | 2 | 1 |
| Supraventricular premature beat; n=99, 102 | 10 | 7 |
| Ventricular premature beat; n=99, 102 | 7 | 12 |
| Supraventricular tachycardia; n=99, 102 | 1 | 0 |
| Atrial fibrillation; n=99, 102 | 3 | 1 |
| Atrial flutter; n=99, 102 | 0 | 1 |
| 1st degree A-V Block; n=95, 97 | 2 | 0 |
| Left bundle branch block; n=99, 102 | 1 | 2 |
| Right bundle branch block; n=99, 102 | 2 | 1 |
| Other intraventricular conduction block; n=99, 102 | 0 | 2 |
| Subacute infarction; n=99, 102 | 1 | 0 |
| Old infarction; n=99, 102 | 2 | 2 |
| Myocardial ischemia; n=99, 102 | 3 | 4 |
| Symmetrical T-wave inversion; n=99, 102 | 2 | 1 |
| Inc QTcB (≥450 msec≥,10% from baseline); n=99, 102 | 5 | 5 |
| Inc QTcN (≥450 msec,≥10% from baseline); n=99, 102 | 1 | 2 |
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.
| Units on a Scale | Aripiprazole |
|---|---|
| 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 |
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.
| Units on Scale | Aripiprazole |
|---|---|
| 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 |
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.
| Units on Scale | Aripiprazole |
|---|---|
| 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 |
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.
| Units on Scale | Aripiprazole |
|---|---|
| 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 |
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.
| units on a scale | Aripiprazole |
|---|---|
| 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 |
Extrapyramidal symptoms (EPS) are various movement disorders such as acute dystonic reactions, pseudoparkinsonism, or akathisia
| Participants | Aripiprazole |
|---|---|
| Dyskinesia | 2 |
| Muscle Rigidity | 3 |
| Extrapyramidal Disorder | 14 |
| Hypokinesia | 8 |
| Tremor | 8 |
| Akinesia | 1 |
| Bradykinesia | 1 |
| Parkinsonian Gait | 1 |
| Muscle Twitching | 1 |
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 | Aripiprazole |
|---|---|
| Death | 41 |
| SAE | 59 |
| AE | 148 |
| Discontinuation due to AE | 66 |
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 | Aripiprazole |
|---|---|
| Increased Systolic BP, standing; n=159 | 6 |
| Decreased Systolic BP, standing; n=159 | 9 |
| Increased Systolic BP, supine; n=158 | 6 |
| Decreased Systolic BP, supine; n=158 | 7 |
| Decreased Systolic BP, sitting; n=45 | 1 |
| Increased Diastolic BP, standing; n=159 | 4 |
| Decreased Diastolic BP, standing; n=159 | 19 |
| Increased Diastolic BP, supine; n=158 | 1 |
| Decreased Diastolic BP, supine; n=158 | 25 |
| Decreased Diastolic BP, sitting; n=45 | 1 |
| Increased Heart rate, standing; n=159 | 2 |
| Decreased Heart rate, standing; n=159 | 3 |
| Increased Heart rate, supine; n=158 | 1 |
| Decreased Heart rate, supine; n=158 | 5 |
| Increased Weight; n=133 | 28 |
| Decreased Weight; n=133 | 58 |
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 | Aripiprazole |
|---|---|
| Atrial Fibrillation; n=145 | 5 |
| Atrial Flutter; n=145 | 1 |
| Bradycardia; n=145 | 4 |
| Left Bundle Branch Block; n=145 | 5 |
| Myocardial Ischemia; n=145 | 10 |
| Old Infarction; n=145 | 2 |
| Right Bundle Branch Block; n=145 | 3 |
| Sinus Bradycardia; n=145 | 2 |
| Sinus Tachycardia; n=145 | 2 |
| Supraventricular Premature Beat; n=145 | 12 |
| Supraventricular Tachycardia; n=145 | 2 |
| Symmetrical T-wave Inversions; n=145 | 8 |
| Tachycardia; n=145 | 4 |
| Ventricular premature Beat; n=145 | 13 |
Criteria for identifying potentially clinically significant laboratory values were based on guidelines suggested by the FDA Division of Neuropharmacological Drug Products.
| Participants | Aripiprazole |
|---|---|
| High Alanine aminotransferase; ≥ 41 U/L | 0 |
| High Aspartate aminotransferase; ≥ 38 U/L | 1 |
| High Alkaline phosphatase; ≥ 117 U/L | 2 |
| High Lactate dehydrogenase; >480 U/L | 1 |
| High Urea; >8.4 mmol/L | 56 |
| High Creatinine; ≥ 2.0 mg/dL | 8 |
| High Uric acid; >5.7 mg/dL | 9 |
| High Total Billirubin; > 1 mg/dL | 0 |
| High Creatinine Kinase; ≥ 170 U/L | 2 |
| High Serum Glucose Fasting; >118 mg/dL | 36 |
| High Serum Glucose Non-fasting; >118 mg/dL | 17 |
| High Cholesterol Total; > 220mg/dL | 131 |
| High Serum Calcium; >10.2 mg/dL | 5 |
| Low Serum Calcium; <8.6 mg/dL | 26 |
| High Serum Chloride; >108 mEq/L | 24 |
| Low Serum Chloride; <96 mEq/L | 36 |
| High Serum Potassium; >5.1 mEq/L | 36 |
| Low Serum Potassium; <3.3mEq/L | 11 |
| High Serum Sodium; > 145 mEq/L | 13 |
| Low Serum Sodium; < 133 mEq/L | 12 |
| Low Hematocrit; <37% | 21 |
| Low Hemoglobin; < 12 g/dL | 19 |
| High Leukocyte count; > 10.8 x 10^3 c/uL | 7 |
| Low Leukocyte count: < 4.8 x 10^3 c/uL | 4 |
| High Eosinophil count; > 5% | 3 |
| High Platelet count; >450 x 10^9 c/L | 0 |
| Low Platelet count; < 150 x 10^9 c/L | 1 |
| High Urine Protein; ≥ 2-unit increase | 2 |
| High Urine Glucose; ≥ 2-unit increase | 3 |
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 | Aripiprazole |
|---|---|
| Any AE | 7 |
| SAE | 1 |
| Death | 1 |
| Discontinuation due to AE | 3 |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| 1 Double Blind Aripiprazole | — | 16/105 (15.2%) | 31/105 (29.5%) |
| 2 Double Blind Placebo | — | 8/102 (7.8%) | 27/102 (26.5%) |
| 3 Ext - Aripiprazole | — | 84/161 (52.2%) | 101/161 (62.7%) |
| Event | 1 Double Blind Aripiprazole | 2 Double Blind Placebo | 3 Ext - Aripiprazole |
|---|---|---|---|
| CARDIAC ARRESTCardiac disorders | 0/105 | 0/102 | 10/161 |
| FEMORAL NECK FRACTUREInjury, poisoning and procedural complications | 2/105 | 0/102 | 6/161 |
| LUNG DISORDERRespiratory, thoracic and mediastinal disorders | 0/105 | 0/102 | 5/161 |
| DEATHGeneral disorders | 2/105 | 0/102 | 4/161 |
| FEMUR FRACTUREInjury, poisoning and procedural complications | 0/105 | 0/102 | 4/161 |
| MYOCARDIAL INFARCTIONCardiac disorders | 0/105 | 0/102 | 4/161 |
| PSYCHOSOCIAL SUPPORTSurgical and medical procedures | 2/105 | 0/102 | 1/161 |
| AGGRESSIONPsychiatric disorders | 2/105 | 0/102 | 0/161 |
| SEPSISInfections and infestations | 0/105 | 0/102 | 3/161 |
| DYSPNOEARespiratory, thoracic and mediastinal disorders | 0/105 | 0/102 | 3/161 |
| Event | 1 Double Blind Aripiprazole | 2 Double Blind Placebo | 3 Ext - Aripiprazole |
|---|---|---|---|
| SOMNOLENCENervous system disorders | 8/105 | 2/102 | 30/161 |
| URINARY TRACT INFECTIONInfections and infestations | 8/105 | 14/102 | 27/161 |
| BRONCHITISInfections and infestations | 4/105 | 3/102 | 27/161 |
| FALLInjury, poisoning and procedural complications | 3/105 | 4/102 | 18/161 |
| DIARRHOEAGastrointestinal disorders | 3/105 | 1/102 | 16/161 |
| INSOMNIAPsychiatric disorders | 2/105 | 4/102 | 14/161 |
| EXTRAPYRAMIDAL DISORDERNervous system disorders | 2/105 | 1/102 | 14/161 |
| APATHYPsychiatric disorders | 0/105 | 0/102 | 13/161 |
| OEDEMA PERIPHERALGeneral disorders | 1/105 | 0/102 | 11/161 |
| CONSTIPATIONGastrointestinal disorders | 2/105 | 0/102 | 10/161 |
| Age Continuous(years) | Placebo | Aripiprazole | Total |
|---|---|---|---|
| Median | 82.0 (59 to 99) | 81.0 (56 to 95) | 81.0 (56 to 99) |
| Sex: Female, Male(Participants) | Placebo | Aripiprazole | Total |
|---|---|---|---|
| Female | 74 | 75 | 149 |
| Male | 28 | 31 | 59 |
| Race/Ethnicity, Customized(Participants) | Placebo | Aripiprazole | Total |
|---|---|---|---|
| White | 98 | 105 | 203 |
| Black | 2 | 1 | 3 |
| Asian/ Pacific Islander | 2 | 0 | 2 |
| Weight(kg) | Placebo | Aripiprazole | Total |
|---|---|---|---|
| Median | 58.8 (33 to 102) | 59.0 (35 to 100) | 59.0 (33 to 102) |
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