A Follow-on Study of the Long-Term Safety of Aripiprazole in Patients With Chronic Schizophrenia

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02435836
• Collaborator: (none)
• Enrollment: 631
• Arm: 1
• Duration (Months): 176

Study Details

Study Description

Brief Summary

The primary objective of the study was to determine the safety of aripiprazole administered long-term in doses ranging from 10 to 30 mg per day as a maintenance therapy in subjects with chronic or first episode of schizophrenia. Information on the continued efficacy of aripiprazole was also gathered in this long-term trial (until 31 Dec 2012 or until aripiprazole was otherwise available through marketed means and/or reimbursed).

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: Aripiprazole	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 631 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Follow-on Study of the Long-Term Safety of Aripiprazole in Patients With Chronic Schizophrenia
• Study Start Date: Apr 1, 1998
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aripiprazole All subjects began open-label treatment with 30 mg aripiprazole on the first day of participation in the current trial. Once a subject stabilized at the 30 mg per day dose, the investigator could adjust the dose within the range of 10 to 30 mg per day as needed (throughout this long-term trial), to manage AEs.	Drug: Aripiprazole; Other Names: Abilify

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score by Week [Baseline, Weeks 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108 continuing every 12 weeks, Last Visit]

   The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).

2. Mean Change From Baseline in PANSS Positive Sub-scale Score by Week [Baseline, Weeks 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108 continuing every 12 weeks, Last Visit]

   The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS positive subscale score was the sum of the rating scores for the 7 positive scale items from the PANSS panel. The 7 positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS Positive Subscale ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms).

3. Mean Change From Baseline in PANSS Negative Sub-scale Score by Week [Baseline, Weeks 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108 continuing every 12 weeks, Last Visit]

   The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS Negative Subscale ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms).

4. Mean Change From Baseline in Clinical Global Impression of Severity (CGI-S) by Week [Baseline, Weeks 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108 continuing every 12 weeks, Last Visit]

   The severity of illness for each participant was rated using the CGI-S scale. To assess CGI-S, the study physician answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?" Response choices included: 0 = not assessed; 1 = normal, not ill at all; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants.

5. Mean Clinical Global Impression of Improvement (CGI-I) by Week [Baseline, Weeks 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108 continuing every 12 weeks, Last Visit]

   The efficacy of trial medication were rated for each participant using the CGI-I scale. The study physician must rate the participant's total improvement whether or not it is due entirely to drug treatment. All responses were compared to the participant's condition at baseline. Response choices include: 0 = not assessed; 1 =very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 =minimally worse; 6 = much worse; and 7 = very much worse.

6. Mean Change From Baseline in Montgomery and Asberg Depression Rating Scale (MADRS) Total Score [Baseline, Weeks 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108 continuing every 12 weeks, Last Visit]

   The MADRS is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in participants with mood disorders. The questionnaire includes questions on the following symptoms. 1. Apparent sadness 2. Reported sadness 3. Inner tension 4. Reduced sleep 5. Reduced appetite 6. Concentration difficulties 7. Lassitude 8. Inability to feel 9. Pessimistic thoughts 10. Suicidal thoughts. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. The usual cut-off points are: 0 to 6 = normal/ symptom absent, 7 to 19 = mild depression, 20 to 34 = moderate depression, >34 = severe depression.

7. Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score by Week [Baseline, Weeks 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108 continuing every 12 weeks, Last Visit]

   The SAS is composed of 10 items. This scale contains 10 items: Gait, Arm dropping, Shoulder shaking, Elbow rigidity, Wrist rigidity, Head rotation, Glabella Tap, Tremor, Salivation, Akathisia. Grade of severity of each item is rated using a 5-point scale, 1 (normal) and 5 (most severe). The total score ranges from 10 to 50. Negative changes from baseline indicate an improvement, with higher negative values indicating better improvement.

8. Mean Change From Baseline in Barnes Akathisia Rating Scale Score (BARS) Total Score by Week [Baseline, Weeks 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108 continuing every 12 weeks, Last Visit]

   BARS consisted of 4 items: objective observation of akathisia by study physician, subjective feelings of restlessness by participant, participant distress due to akathisia, global evaluation of akathisia. The first 3 items were rated on a 4-point scale: 0 = absence of symptoms to 3 = severe condition. The global clinical evaluation were made on a 6-point scale, (0=absent, 1=questionable, 2=mild, 3=moderate, 4=marked, 5=severe). Participants were observed while they were seated and then stood for a minimum of 2 minutes in each position. Symptoms observed in other situations (e.g., while engaged in neutral conversation or engaged in activity on the ward) may also be rated. Subjective phenomena were elicited by direct questioning. The BARS Global Score was derived from the global clinical assessment of akathisia from the BARS panel. Total score ranges from 0 to 14. Negative changes from baseline indicate improvement, with higher negative values indicating better improvement.

9. Mean Change From Baseline in Abnormal Involuntary Movement Scale Score (AIMS) Total Score by Week [Baseline, Weeks 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108 continuing every 12 weeks, Last Visit]

   The AIMS assessment consisted of 10 items describing symptoms of dyskinesia. Facial and oral movements (items 1 through 4), extremity movements (items 5 and 6), and trunk movements (item 7) were observed unobtrusively while the participant was at rest (e.g., in the waiting room), and the study physician would make global judgments on the participant's dyskinesia's (items 8 through 10). For this scale, the participant was seated on a hard, firm chair. These items are rated on a five-point scale: 0 (none), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe). The total score ranges from 0 to 40. Negative changes from baseline indicate an improvement, with higher negative values indicating better improvement.

10. Number of Participants With Adverse Events (AEs) [Baseline to Last Visit]

    The AEs were one of the primary parameters to measure the safety and tolerability of individual participants. The AEs were captured for all participants from the time the ICF was signed until the end of the trial.

11. Percentage of Participants With Vital Signs of Potential Clinical Relevance [Baseline, Weeks 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108 continuing every 12 weeks, Last Visit]

    The vital signs were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance included abnormal values in heart rate, systolic and diastolic blood pressure, respiratory rate and weight that were identified based on pre-defined criteria.

12. Percentage of Participants With ECG Measurements of Potential Clinical Relevance [Baseline, Weeks 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108 continuing every 12 weeks, Last Visit]

    The measurement of ECG was one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in heart rate and ECG intervals of PR, QRS, QT, QTcB, and QTcF that were identified based on pre-defined criteria.

13. Percentage of Participants With Laboratory Values of Potential Clinical Relevance [Baseline, Weeks 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108 continuing every 12 weeks, Last Visit]

    The laboratory values were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal values in serum chemistry, hematology, urinalyses and prolactin tests that were identified based on pre-defined criteria.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Complete a Prior Study: each patient must meet one of the following conditions for completion of the prior study:

• A patient who has completed 52 weeks of post-randomization treatment in the prior double blind study (31-97-301 or 31-98-304-01) is eligible, with no further qualifications.

• A patient who was early-terminated from the study 31-97-301 or 31-98- 304-01 for either of the following two reasons is eligible to enter this open label study with no minimal required duration of prior double-blind participation:

• Early termination was due to a marked deterioration of clinical status and no serious adverse events (SAE) other than hospitalization has occurred. The marked clinical deterioration must be documented by at least a one-point increase in CGI-Severity score from the baseline and a score of 6 (much worse) or 7 (very much worse) in CGI-Global Improvement at the time of termination, or

• Early termination was due to a non-serious AE requiring discontinuation of the study drug

• A patient who was early terminated after a minimum of 4 weeks' participation in the double-blind treatment in study 31-97-301 or 31-98- 304-01 and the reason for early termination was withdrawal of consent due to lack of effect but not marked deterioration. This must be documented by no change from baseline in the CGI-Severity score and a score of 4 (no change) or 5 (minimally worse) on the CGI-Global Improvement scale.

1. Signing of Informed Consent Form: Prior to any procedure or drug administration, each patient must sign an informed consent form. In addition, if required by the Ethical Committee, each patient's next-of-kin or responsible caregiver will co-sign the patient's consent form or a separate consent form.

Exclusion Criteria:

1. Patients suffering from any significant somatic disease or medical problem that would obscure the results of treatment, or that might require frequent changes of concomitant medication.

2. Patients with any acute or unstable medical condition requiring pharmacotherapy, other than schizophrenia.

3. Patients with an abnormal laboratory test value in the most recent analysis (from the study 31-97-301 or 31-98-304-01) which is considered by the investigator as presenting a significant risk to the patient for continuing treatment with aripiprazole.

4. Patients who were early-terminated from the prior double-blind studies (31-97-301 or 31-98-304-01) due to a serious adverse event (SAE) other than worsening of psychosis or hospitalization.

5. Female patients of child bearing potential with a positive serum pregnancy test at the baseline (last visit of prior study) of this open-label follow-on study.

6. Patients who have positive result in the urine screen for drugs of abuse (except for cannabis or medically-prescribed analgesics or benzodiazepines.)

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
• ClinicalTrials.gov Identifier: NCT02435836
• Other Study ID Numbers: 31-97-303
• First Posted: May 6, 2015
• Last Update Posted: Sep 21, 2015
• Last Verified: Aug 1, 2015

• Additional relevant MeSH terms: Schizophrenia; Aripiprazole

Study Results

Participant Flow

Recruitment Details	This trial was conducted in 631 participants at 139 trial sites in 23 countries.
Pre-assignment Detail	All participants enrolled in this trial had previously participated in the double-blind aripiprazole; 89 participants from trial 31-97-301 and 542 participants from trial 31-98-304-01. NCT numbers were not available for these 2 trials as this was before the requirement. Studies were initiated in 1997 (31-97-201) and 1998 (31-98-304-01).

Arm/Group Title	Aripiprazole
Arm/Group Description	All participants began open-label treatment with 30 mg aripiprazole on the first day of participation in the current trial. Once a participant stabilized at the 30 mg per day dose, the study physician could adjust the dose within the range of 10 to 30 mg per day as needed (throughout this long-term trial), to manage adverse events.
Period Title: Overall Study
STARTED	631
COMPLETED	0
NOT COMPLETED	631

Baseline Characteristics

Arm/Group Title	Aripiprazole
Arm/Group Description	All participants began open-label treatment with 30 mg aripiprazole on the first day of participation in the current trial. Once a participant stabilized at the 30 mg per day dose, the study physician could adjust the dose within the range of 10 to 30 mg per day as needed (throughout this long-term trial), to manage adverse events.
Overall Participants	631
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	37.5 (11.0)
Sex: Female, Male (Count of Participants)
Female	264 41.8%
Male	367 58.2%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score by Week
Description	The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).
Time Frame	Baseline, Weeks 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108 continuing every 12 weeks, Last Visit

Outcome Measure Data

Analysis Population Description

All participants who had received at least one dose of study medication were included in both efficacy and safety analyses dataset.

Arm/Group Title	Aripiprazole
Arm/Group Description	All participants began open-label treatment with 30 mg aripiprazole on the first day of participation in the current trial. Once a participant stabilized at the 30 mg per day dose, the study physician could adjust the dose within the range of 10 to 30 mg per day as needed (throughout this long-term trial), to manage adverse events.
Measure Participants	631
Week 1 (N= 619)	-1.63 (7.92)
Week 2 (N= 595)	-3.19 (9.64)
Week 4 (N= 586)	-4.27 (10.90)
Week 6 (N= 573)	-4.93 (12.07)
Week 8 (N= 552)	-5.35 (13.03)
Week 12 (N= 532)	-5.47 (14.61)
Week 16 (N= 517)	-6.28 (14.44)
Week 24 (N= 489)	-6.78 (14.22)
Week 36 (N= 458)	-7.22 (14.17)
Week 48 (N= 426)	-8.07 (15.72)
Week 60 (N= 395)	-9.28 (14.71)
Week 72 (N= 382)	-9.81 (15.98)
Week 84 (N= 362)	-10.54 (15.92)
Week 96 (N= 340)	-10.68 (16.40)
Week 108 (N= 328)	-11.46 (16.56)
Week 120 (N= 316)	-11.43 (17.01)
Week 132 (N= 306)	-11.05 (17.37)
Week 144 (N= 288)	-11.70 (17.72)
Week 156 (N= 279)	-11.90 (17.47)
Week 168 (N= 272)	-11.69 (17.11)
Week 180 (N= 268)	-11.83 (17.41)
Week 192 (N= 255)	-11.46 (18.00)
Week 204 (N= 239)	-12.10 (17.72)
Week 216 (N= 238)	-11.54 (17.05)
Week 228 (N= 224)	-12.24 (17.53)
Week 240 (N= 183)	-12.14 (19.35)
Week 252 (N= 139)	-15.19 (18.61)
Week 264 (N= 83)	-22.16 (21.07)
Week 276 (N= 58)	-29.45 (20.33)
Week 288 (N= 56)	-28.79 (20.66)
Week 300 (N= 55)	-21.95 (19.91)
Week 312 (N= 37)	-25.35 (18.41)
Week 324 (N= 38)	-21.95 (17.45)
Week 336 (N= 28)	-24.86 (17.78)
Week 348 (N= 8)	-12.88 (14.71)
Week 360 (N= 10)	-17.70 (35.32)
Week 372 (N= 3)	-10.67 (4.16)
Week 384 (N= 5)	-4.60 (9.07)
Week 396 (N= 10)	-10.10 (12.67)
Week 408 (N= 9)	-5.56 (7.06)
Week 420 (N= 4)	-8.00 (2.83)
Week 432 (N= 3)	-13.67 (24.19)
Week 444 (N= 1)	-28.00 (NA)
Week 456 (N= 4)	-48.25 (32.12)
Week 468 (N= 2)	-36.00 (2.83)
Week 480 (N= 1)	-10.00 (NA)
Week 492 (N= 9)	-10.00 (13.52)
Week 504 (N= 2)	-9.50 (28.99)
Week 636 (N= 5)	-7.60 (22.35)
Week 648 (N= 2)	-10.00 (14.14)
Week 660 (N= 3)	-15.33 (19.66)
Week 672 (N= 1)	1.00 (NA)
Week 696 (N= 1)	-7.00 (NA)
Last Visit (N= 629)	-2.30 (22.21)

2. Primary Outcome

Title	Mean Change From Baseline in PANSS Positive Sub-scale Score by Week
Description	The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS positive subscale score was the sum of the rating scores for the 7 positive scale items from the PANSS panel. The 7 positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS Positive Subscale ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms).
Time Frame	Baseline, Weeks 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108 continuing every 12 weeks, Last Visit

Outcome Measure Data

Analysis Population Description

All participants who had received at least one dose of study medication were included in both efficacy and safety analyses dataset.

Arm/Group Title	Aripiprazole
Arm/Group Description	All participants began open-label treatment with 30 mg aripiprazole on the first day of participation in the current trial. Once a participant stabilized at the 30 mg per day dose, the study physician could adjust the dose within the range of 10 to 30 mg per day as needed (throughout this long-term trial), to manage adverse events.
Measure Participants	631
Week 1 (N= 619)	-0.39 (2.51)
Week 2 (N= 595)	-0.81 (3.15)
Week 4 (N= 586)	-1.13 (3.47)
Week 6 (N= 573)	-1.23 (3.70)
Week 8 (N= 552)	-1.30 (3.97)
Week 12 (N= 533)	-1.24 (4.43)
Week 16 (N= 517)	-1.43 (4.20)
Week 24 (N= 489)	-1.54 (4.26)
Week 36 (N= 458)	-1.56 (4.20)
Week 48 (N= 426)	-1.73 (4.64)
Week 60 (N= 395)	-2.01 (4.32)
Week 72 (N= 382)	-2.08 (4.63)
Week 84 (N= 362)	-2.26 (4.65)
Week 96 (N= 340)	-2.26 (4.81)
Week 108 (N= 328)	-2.50 (4.76)
Week 120 (N= 316)	-2.45 (4.84)
Week 132 (N= 306)	-2.25 (5.02)
Week 144 (N= 289)	-2.49 (5.03)
Week 156 (N= 279)	-2.46 (4.87)
Week 168 (N= 272)	-2.35 (4.62)
Week 180 (N= 268)	-2.40 (4.78)
Week 192 (N= 255)	-2.22 (4.91)
Week 204 (N= 239)	-2.48 (4.86)
Week 216 (N= 238)	-2.21 (4.57)
Week 228 (N= 224)	-2.42 (4.51)
Week 240 (N= 183)	-2.10 (5.16)
Week 252 (N= 139)	-2.74 (4.81)
Week 264 (N= 83)	-4.24 (5.69)
Week 276 (N= 58)	-5.90 (5.80)
Week 288 (N= 56)	-6.30 (5.61)
Week 300 (N= 55)	-4.16 (5.54)
Week 312 (N= 37)	-5.27 (5.57)
Week 324 (N= 38)	-4.45 (5.64)
Week 336 (N= 28)	-5.46 (5.73)
Week 348 (N= 8)	-0.75 (1.04)
Week 360 (N= 10)	-3.80 (7.60)
Week 372 (N= 3)	-0.67 (0.58)
Week 384 (N= 5)	-0.80 (3.96)
Week 396 (N= 10)	-2.40 (3.63)
Week 408 (N= 9)	-0.89 (2.80)
Week 420 (N= 4)	-0.75 (1.50)
Week 432 (N= 3)	-4.67 (8.08)
Week 444 (N= 1)	-9.00 (NA)
Week 456 (N= 4)	-10.50 (5.97)
Week 468 (N= 2)	-6.50 (3.54)
Week 480 (N= 1)	-2.00 (NA)
Week 492 (N= 9)	-2.00 (2.65)
Week 504 (N= 2)	-2.50 (7.78)
Week 636 (N= 5)	-1.80 (4.02)
Week 648 (N= 2)	-4.50 (7.78)
Week 660 (N= 3)	-2.00 (2.65)
Week 672 (N= 1)	1.00 (NA)
Week 696 (N= 1)	-1.00 (NA)
Last Visit (N= 629)	0.23 (6.58)

3. Primary Outcome

Title	Mean Change From Baseline in PANSS Negative Sub-scale Score by Week
Description	The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS Negative Subscale ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms).
Time Frame	Baseline, Weeks 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108 continuing every 12 weeks, Last Visit

Outcome Measure Data

Analysis Population Description

All participants who had received at least one dose of study medication were included in both efficacy and safety analyses dataset.

Arm/Group Title	Aripiprazole
Arm/Group Description	All participants began open-label treatment with 30 mg aripiprazole on the first day of participation in the current trial. Once a participant stabilized at the 30 mg per day dose, the study physician could adjust the dose within the range of 10 to 30 mg per day as needed (throughout this long-term trial), to manage adverse events.
Measure Participants	631
Week 1 (N= 619)	-0.35 (2.18)
Week 2 (N= 595)	-0.82 (2.59)
Week 4 (N= 586)	-1.05 (3.04)
Week 6 (N= 573)	-1.24 (3.38)
Week 8 (N= 552)	-1.41 (3.54)
Week 12 (N= 532)	-1.54 (4.01)
Week 16 (N= 517)	-1.85 (4.12)
Week 24 (N= 489)	-2.02 (4.13)
Week 36 (N= 458)	-2.16 (4.41)
Week 48 (N= 426)	-2.43 (4.71)
Week 60 (N= 395)	-2.75 (4.38)
Week 72 (N= 382)	-2.94 (4.79)
Week 84 (N= 362)	-3.17 (4.87)
Week 96 (N= 340)	-3.22 (4.99)
Week 108 (N= 328)	-3.36 (4.99)
Week 120 (N= 316)	-3.37 (5.25)
Week 132 (N= 306)	-3.41 (5.29)
Week 144 (N= 288)	-3.58 (5.43)
Week 156 (N= 279)	-3.70 (5.27)
Week 168 (N= 272)	-3.68 (5.28)
Week 180 (N= 268)	-3.69 (5.21)
Week 192 (N= 255)	-3.65 (5.40)
Week 204 (N= 239)	-3.79 (5.37)
Week 216 (N= 238)	-3.74 (5.17)
Week 228 (N= 224)	-3.90 (5.38)
Week 240 (N= 183)	-4.09 (5.86)
Week 252 (N= 139)	-4.88 (5.69)
Week 264 (N= 83)	-6.87 (6.50)
Week 276 (N= 58)	-8.71 (6.57)
Week 288 (N= 56)	-8.32 (6.85)
Week 300 (N= 55)	-6.58 (6.42)
Week 312 (N= 37)	-7.51 (5.43)
Week 324 (N= 38)	-6.63 (4.44)
Week 336 (N= 28)	-7.43 (4.59)
Week 348 (N= 8)	-4.88 (5.89)
Week 360 (N= 10)	-5.60 (9.40)
Week 372 (N= 3)	-4.33 (1.53)
Week 384 (N= 5)	0.00 (2.12)
Week 396 (N= 10)	-2.90 (3.67)
Week 408 (N= 9)	-1.22 (2.54)
Week 420 (N= 4)	-2.25 (2.22)
Week 432 (N= 3)	-2.67 (7.51)
Week 444 (N= 1)	-6.00 (NA)
Week 456 (N= 4)	-13.75 (9.95)
Week 468 (N= 2)	-9.00 (5.66)
Week 480 (N= 1)	-5.00 (NA)
Week 492 (N= 9)	-2.00 (3.61)
Week 504 (N= 2)	-1.50 (12.02)
Week 636 (N= 5)	-1.80 (5.85)
Week 648 (N= 2)	0.00 (0.00)
Week 660 (N= 3)	-4.67 (6.66)
Week 672 (N= 1)	1.00 (NA)
Week 696 (N= 1)	-3.00 (NA)
Last Visit (N= 629)	-1.34 (6.09)

4. Primary Outcome

Title	Mean Change From Baseline in Clinical Global Impression of Severity (CGI-S) by Week
Description	The severity of illness for each participant was rated using the CGI-S scale. To assess CGI-S, the study physician answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?" Response choices included: 0 = not assessed; 1 = normal, not ill at all; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants.
Time Frame	Baseline, Weeks 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108 continuing every 12 weeks, Last Visit

Outcome Measure Data

Analysis Population Description

All participants who had received at least one dose of study medication were included in both efficacy and safety analyses dataset.

Arm/Group Title	Aripiprazole
Arm/Group Description	All participants began open-label treatment with 30 mg aripiprazole on the first day of participation in the current trial. Once a participant stabilized at the 30 mg per day dose, the study physician could adjust the dose within the range of 10 to 30 mg per day as needed (throughout this long-term trial), to manage adverse events.
Measure Participants	631
Week 1 (N= 619)	-0.07 (0.49)
Week 2 (N= 595)	-0.13 (0.60)
Week 4 (N= 586)	-0.20 (0.67)
Week 6 (N= 573)	-0.23 (0.78)
Week 8 (N= 552)	-0.25 (0.79)
Week 12 (N= 533)	-0.25 (0.86)
Week 16 (N= 517)	-0.30 (0.86)
Week 24 (N= 489)	-0.31 (0.89)
Week 36 (N= 458)	-0.32 (0.95)
Week 48 (N= 426)	-0.38 (0.94)
Week 60 (N= 395)	-0.45 (0.92)
Week 72 (N= 382)	-0.45 (0.93)
Week 84 (N= 362)	-0.49 (0.95)
Week 96 (N= 340)	-0.48 (0.99)
Week 108 (N= 328)	-0.51 (0.95)
Week 120 (N= 316)	-0.53 (0.98)
Week 132 (N= 306)	-0.48 (1.03)
Week 144 (N= 290)	-0.52 (1.04)
Week 156 (N= 279)	-0.53 (1.00)
Week 168 (N= 272)	-0.53 (0.96)
Week 180 (N= 268)	-0.55 (0.98)
Week 192 (N= 255)	-0.54 (1.04)
Week 204 (N= 239)	-0.55 (1.01)
Week 216 (N= 238)	-0.53 (0.99)
Week 228 (N= 232)	-0.56 (1.00)
Week 240 (N= 216)	-0.56 (1.06)
Week 252 (N= 208)	-0.58 (0.96)
Week 264 (N= 194)	-0.58 (1.04)
Week 276 (N= 187)	-0.61 (1.01)
Week 288 (N= 177)	-0.64 (1.02)
Week 300 (N= 167)	-0.63 (0.99)
Week 312 (N= 145)	-0.57 (1.01)
Week 324 (N= 137)	-0.60 (0.99)
Week 336 (N= 121)	-0.59 (0.95)
Week 348 (N= 114)	-0.48 (0.97)
Week 360 (N= 105)	-0.54 (0.98)
Week 372 (N= 93)	-0.49 (0.94)
Week 384 (N= 91)	-0.51 (0.94)
Week 396 (N= 80)	-0.53 (1.06)
Week 408 (N= 69)	-0.62 (0.96)
Week 420 (N= 61)	-0.70 (1.07)
Week 432 (N= 58)	-0.69 (1.16)
Week 444 (N= 51)	-0.59 (0.96)
Week 456 (N= 48)	-0.65 (1.10)
Week 468 (N= 37)	-0.46 (1.04)
Week 480 (N= 33)	-0.42 (0.83)
Week 492 (N= 31)	-0.55 (0.99)
Week 504 (N= 21)	-0.57 (0.93)
Week 516 (N= 19)	-0.53 (0.84)
Week 528 (N= 19)	-0.47 (0.90)
Week 540 (N= 18)	-0.61 (0.70)
Week 552 (N= 18)	-0.56 (0.86)
Week 564 (N= 17)	-0.41 (0.87)
Week 576 (N= 17)	-0.35 (0.86)
Week 588 (N= 17)	-0.41 (0.87)
Week 600 (N= 16)	-0.44 (0.89)
Week 612 (N= 16)	-0.44 (0.89)
Week 624 (N= 16)	-0.50 (0.73)
Week 636 (N= 16)	-0.44 (0.89)
Week 648 (N= 10)	-0.70 (0.67)
Week 660 (N= 8)	-0.50 (0.53)
Week 672 (N= 3)	-0.67 (0.58)
Week 684 (N= 1)	-1.00 (NA)
Week 696 (N= 1)	-1.00 (NA)
Last Visit (N= 629)	-0.00 (1.31)

5. Primary Outcome

Title	Mean Clinical Global Impression of Improvement (CGI-I) by Week
Description	The efficacy of trial medication were rated for each participant using the CGI-I scale. The study physician must rate the participant's total improvement whether or not it is due entirely to drug treatment. All responses were compared to the participant's condition at baseline. Response choices include: 0 = not assessed; 1 =very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 =minimally worse; 6 = much worse; and 7 = very much worse.
Time Frame	Baseline, Weeks 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108 continuing every 12 weeks, Last Visit

Outcome Measure Data

Analysis Population Description

All participants who had received at least one dose of study medication were included in both efficacy and safety analyses dataset.

Arm/Group Title	Aripiprazole
Arm/Group Description	All participants began open-label treatment with 30 mg aripiprazole on the first day of participation in the current trial. Once a participant stabilized at the 30 mg per day dose, the study physician could adjust the dose within the range of 10 to 30 mg per day as needed (throughout this long-term trial), to manage adverse events.
Measure Participants	631
Week 1 (N= 619)	3.60 (0.93)
Week 2 (N= 595)	3.42 (0.98)
Week 4 (N= 586)	3.29 (1.02)
Week 6 (N= 573)	3.21 (1.08)
Week 8 (N= 552)	3.17 (1.10)
Week 12 (N= 533)	3.16 (1.12)
Week 16 (N= 517)	3.08 (1.18)
Week 24 (N= 489)	3.03 (1.14)
Week 36 (N= 458)	2.95 (1.14)
Week 48 (N= 426)	2.88 (1.17)
Week 60 (N= 395)	2.76 (1.14)
Week 72 (N= 382)	2.73 (1.11)
Week 84 (N= 362)	2.67 (1.11)
Week 96 (N= 340)	2.67 (1.15)
Week 108 (N= 328)	2.60 (1.12)
Week 120 (N= 316)	2.58 (1.15)
Week 132 (N= 306)	2.62 (1.17)
Week 144 (N= 290)	2.59 (1.20)
Week 156 (N= 279)	2.58 (1.16)
Week 168 (N= 272)	2.57 (1.15)
Week 180 (N= 268)	2.57 (1.16)
Week 192 (N= 255)	2.59 (1.20)
Week 204 (N= 239)	2.56 (1.16)
Week 216 (N= 238)	2.56 (1.20)
Week 228 (N= 232)	2.49 (1.17)
Week 240 (N= 216)	2.48 (1.21)
Week 252 (N= 208)	2.37 (1.13)
Week 264 (N= 194)	2.14 (1.07)
Week 276 (N= 187)	2.16 (1.03)
Week 288 (N= 177)	2.26 (1.06)
Week 300 (N= 167)	2.26 (1.16)
Week 312 (N= 145)	2.18 (1.11)
Week 324 (N= 137)	2.23 (1.05)
Week 336 (N= 121)	2.03 (1.09)
Week 348 (N= 114)	2.45 (1.00)
Week 360 (N= 105)	2.53 (1.36)
Week 372 (N= 93)	2.14 (1.07)
Week 384 (N= 91)	2.50 (1.52)
Week 396 (N= 80)	3.00 (1.63)
Week 408 (N= 69)	2.50 (1.18)
Week 420 (N= 61)	2.43 (1.40)
Week 432 (N= 58)	2.00 (1.73)
Week 444 (N= 51)	1.00 (NA)
Week 456 (N= 48)	1.83 (0.75)
Week 468 (N= 37)	2.00 (0.00)
Week 480 (N= 33)	2.00 (NA)
Week 492 (N= 9)	2.33 (1.32)
Week 504 (N= 2)	2.50 (2.12)
Week 528 (N= 1)	4.00 (NA)
Week 636 (N= 5)	2.00 (0.00)
Week 648 (N= 2)	1.50 (0.71)
Week 660 (N= 3)	2.33 (1.15)
Week 672 (N= 3)	1.00 (NA)
Week 696 (N= 1)	1.00 (NA)
Last Visit (N= 629)	3.35 (1.60)

6. Primary Outcome

Title	Mean Change From Baseline in Montgomery and Asberg Depression Rating Scale (MADRS) Total Score
Description	The MADRS is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in participants with mood disorders. The questionnaire includes questions on the following symptoms. 1. Apparent sadness 2. Reported sadness 3. Inner tension 4. Reduced sleep 5. Reduced appetite 6. Concentration difficulties 7. Lassitude 8. Inability to feel 9. Pessimistic thoughts 10. Suicidal thoughts. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. The usual cut-off points are: 0 to 6 = normal/ symptom absent, 7 to 19 = mild depression, 20 to 34 = moderate depression, >34 = severe depression.
Time Frame	Baseline, Weeks 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108 continuing every 12 weeks, Last Visit

Outcome Measure Data

Analysis Population Description

All participants who had received at least one dose of study medication were included in both efficacy and safety analyses dataset.

Arm/Group Title	Aripiprazole
Arm/Group Description	All participants began open-label treatment with 30 mg aripiprazole on the first day of participation in the current trial. Once a participant stabilized at the 30 mg per day dose, the study physician could adjust the dose within the range of 10 to 30 mg per day as needed (throughout this long-term trial), to manage adverse events.
Measure Participants	631
Week 1 (N= 619)	-0.78 (3.62)
Week 2 (N= 595)	-1.13 (4.09)
Week 4 (N= 586)	-1.38 (4.73)
Week 6 (N= 572)	-1.54 (5.15)
Week 8 (N= 552)	-1.40 (4.98)
Week 12 (N= 533)	-1.31 (5.77)
Week 16 (N= 517)	-1.60 (5.41)
Week 24 (N= 489)	-1.61 (5.75)
Week 36 (N= 458)	-1.66 (5.75)
Week 48 (N= 425)	-1.75 (5.47)
Week 60 (N= 395)	-2.13 (5.41)
Week 72 (N= 382)	-2.21 (5.29)
Week 84 (N= 362)	-2.33 (5.51)
Week 96 (N= 339)	-2.26 (5.70)
Week 108 (N= 328)	-2.30 (5.68)
Week 120 (N= 316)	-2.40 (5.67)
Week 132 (N= 306)	-2.22 (5.85)
Week 144 (N= 291)	-2.47 (5.85)
Week 156 (N= 279)	-2.51 (5.64)
Week 168 (N= 272)	-2.51 (5.49)
Week 180 (N= 268)	-2.73 (5.67)
Week 192 (N= 255)	-2.53 (6.05)
Week 204 (N= 239)	-2.69 (6.20)
Week 216 (N= 238)	-2.50 (5.87)
Week 228 (N= 224)	-2.62 (5.82)
Week 240 (N= 183)	-2.92 (6.50)
Week 252 (N= 139)	-3.63 (6.53)
Week 264 (N= 83)	-5.52 (7.89)
Week 276 (N= 58)	-7.71 (8.88)
Week 288 (N= 56)	-7.57 (8.64)
Week 300 (N= 55)	-6.15 (7.52)
Week 312 (N= 37)	-7.24 (8.51)
Week 324 (N= 38)	-6.32 (8.76)
Week 336 (N= 28)	-7.21 (8.01)
Week 348 (N= 8)	-4.00 (7.45)
Week 360 (N= 10)	-2.80 (16.09)
Week 372 (N= 3)	-2.67 (2.08)
Week 384 (N= 5)	0.00 (0.00)
Week 396 (N= 10)	-1.40 (2.95)
Week 408 (N= 9)	-1.89 (1.27)
Week 420 (N= 4)	0.75 (4.11)
Week 432 (N= 3)	-2.33 (5.86)
Week 444 (N= 1)	-1.00 (NA)
Week 456 (N= 5)	-9.60 (8.85)
Week 468 (N= 2)	-3.00 (2.83)
Week 480 (N= 1)	0.00 (NA)
Week 492 (N= 9)	-6.56 (8.44)
Week 504 (N= 2)	-13.50 (13.44)
Week 636 (N= 5)	0.40 (3.36)
Week 648 (N= 2)	-1.00 (1.41)
Week 660 (N= 3)	-4.33 (2.31)
Week 672 (N= 1)	-2.00 (NA)
Week 696 (N= 1)	-1.00 (NA)
Last Visit (N= 629)	-0.31 (8.02)

7. Primary Outcome

Title	Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score by Week
Description	The SAS is composed of 10 items. This scale contains 10 items: Gait, Arm dropping, Shoulder shaking, Elbow rigidity, Wrist rigidity, Head rotation, Glabella Tap, Tremor, Salivation, Akathisia. Grade of severity of each item is rated using a 5-point scale, 1 (normal) and 5 (most severe). The total score ranges from 10 to 50. Negative changes from baseline indicate an improvement, with higher negative values indicating better improvement.
Time Frame	Baseline, Weeks 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108 continuing every 12 weeks, Last Visit

Outcome Measure Data

Analysis Population Description

All participants who had received at least one dose of study medication were included in both efficacy and safety analyses dataset.

Arm/Group Title	Aripiprazole
Arm/Group Description	All participants began open-label treatment with 30 mg aripiprazole on the first day of participation in the current trial. Once a participant stabilized at the 30 mg per day dose, the study physician could adjust the dose within the range of 10 to 30 mg per day as needed (throughout this long-term trial), to manage adverse events.
Measure Participants	631
Week 1 (N= 618)	-0.78 (3.05)
Week 2 (N= 594)	-1.01 (3.32)
Week 4 (N= 585)	-1.06 (3.68)
Week 6 (N= 572)	-1.14 (3.94)
Week 8 (N= 550)	-1.19 (4.00)
Week 12 (N= 532)	-1.28 (4.03)
Week 16 (N= 516)	-1.27 (4.18)
Week 24 (N= 488)	-1.24 (3.91)
Week 36 (N= 456)	-1.10 (3.79)
Week 48 (N= 426)	-1.33 (4.14)
Week 60 (N= 395)	-1.25 (3.89)
Week 72 (N= 382)	-1.36 (4.07)
Week 84 (N= 362)	-1.33 (4.16)
Week 96 (N= 338)	-1.24 (3.92)
Week 108 (N= 328)	-1.29 (3.83)
Week 120 (N= 316)	-1.22 (3.83)
Week 132 (N= 306)	-1.26 (3.88)
Week 144 (N= 289)	-1.26 (3.99)
Week 156 (N= 278)	-1.33 (4.04)
Week 168 (N= 272)	-1.31 (3.92)
Week 180 (N= 268)	-1.43 (4.08)
Week 192 (N= 255)	-1.46 (4.07)
Week 204 (N= 239)	-1.49 (4.16)
Week 216 (N= 238)	-1.39 (3.48)
Week 228 (N= 224)	-1.44 (3.55)
Week 240 (N= 183)	-1.68 (3.72)
Week 252 (N= 139)	-2.11 (4.16)
Week 264 (N= 83)	-2.89 (4.99)
Week 276 (N= 58)	-3.84 (5.64)
Week 288 (N= 56)	-3.88 (5.77)
Week 300 (N= 55)	-2.53 (4.55)
Week 312 (N= 37)	-2.30 (4.07)
Week 324 (N= 38)	-1.76 (4.10)
Week 336 (N= 28)	-1.64 (3.90)
Week 348 (N= 8)	-2.00 (2.78)
Week 360 (N= 9)	-0.44 (5.75)
Week 372 (N= 3)	-1.00 (0.00)
Week 384 (N= 5)	-0.20 (0.45)
Week 396 (N= 10)	-0.30 (1.16)
Week 408 (N= 9)	-0.89 (1.27)
Week 420 (N= 4)	-1.25 (1.50)
Week 432 (N= 3)	-1.00 (1.73)
Week 444 (N= 1)	1.00 (NA)
Week 456 (N= 5)	-7.20 (8.87)
Week 468 (N= 2)	0.00 (0.00)
Week 480 (N= 1)	-1.00 (NA)
Week 492 (N= 9)	-3.22 (5.33)
Week 504 (N= 2)	-3.00 (4.24)
Week 636 (N= 5)	-0.20 (0.45)
Week 648 (N= 2)	0.00 (0.00)
Week 660 (N= 3)	-1.00 (1.00)
Week 672 (N= 1)	-3.00 (NA)
Week 696 (N= 1)	-7.00 (NA)
Last Visit (N= 628)	-1.36 (4.31)

8. Primary Outcome

Title	Mean Change From Baseline in Barnes Akathisia Rating Scale Score (BARS) Total Score by Week
Description	BARS consisted of 4 items: objective observation of akathisia by study physician, subjective feelings of restlessness by participant, participant distress due to akathisia, global evaluation of akathisia. The first 3 items were rated on a 4-point scale: 0 = absence of symptoms to 3 = severe condition. The global clinical evaluation were made on a 6-point scale, (0=absent, 1=questionable, 2=mild, 3=moderate, 4=marked, 5=severe). Participants were observed while they were seated and then stood for a minimum of 2 minutes in each position. Symptoms observed in other situations (e.g., while engaged in neutral conversation or engaged in activity on the ward) may also be rated. Subjective phenomena were elicited by direct questioning. The BARS Global Score was derived from the global clinical assessment of akathisia from the BARS panel. Total score ranges from 0 to 14. Negative changes from baseline indicate improvement, with higher negative values indicating better improvement.
Time Frame	Baseline, Weeks 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108 continuing every 12 weeks, Last Visit

Outcome Measure Data

Analysis Population Description

All participants who had received at least one dose of study medication were included in both efficacy and safety analyses dataset.

Arm/Group Title	Aripiprazole
Arm/Group Description	All participants began open-label treatment with 30 mg aripiprazole on the first day of participation in the current trial. Once a participant stabilized at the 30 mg per day dose, the study physician could adjust the dose within the range of 10 to 30 mg per day as needed (throughout this long-term trial), to manage adverse events.
Measure Participants	631
Week 1 (N= 618)	-0.15 (0.67)
Week 2 (N= 595)	-0.20 (0.70)
Week 4 (N= 586)	-0.20 (0.74)
Week 6 (N= 572)	-0.23 (0.76)
Week 8 (N= 552)	-0.22 (0.79)
Week 12 (N= 533)	-0.22 (0.78)
Week 16 (N= 517)	-0.22 (0.77)
Week 24 (N= 489)	-0.22 (0.74)
Week 36 (N= 458)	-0.21 (0.75)
Week 48 (N= 425)	-0.20 (0.75)
Week 60 (N= 395)	-0.20 (0.70)
Week 72 (N= 382)	-0.19 (0.73)
Week 84 (N= 362)	-0.21 (0.74)
Week 96 (N= 340)	-0.21 (0.79)
Week 108 (N= 327)	-0.21 (0.77)
Week 120 (N= 316)	-0.20 (0.75)
Week 132 (N= 306)	-0.22 (0.76)
Week 144 (N= 291)	-0.22 (0.79)
Week 156 (N= 278)	-0.24 (0.79)
Week 168 (N= 272)	-0.22 (0.78)
Week 180 (N= 268)	-0.24 (0.81)
Week 192 (N= 255)	-0.29 (0.79)
Week 204 (N= 238)	-0.29 (0.80)
Week 216 (N= 237)	-0.26 (0.76)
Week 228 (N= 223)	-0.26 (0.78)
Week 240 (N= 183)	-0.24 (0.75)
Week 252 (N= 139)	-0.29 (0.81)
Week 264 (N= 83)	-0.51 (1.06)
Week 276 (N= 58)	-0.69 (1.16)
Week 288 (N= 56)	-0.64 (1.09)
Week 300 (N= 55)	-0.51 (0.96)
Week 312 (N= 37)	-0.35 (0.68)
Week 324 (N= 38)	-0.26 (0.60)
Week 336 (N= 28)	-0.29 (0.66)
Week 348 (N= 8)	-0.75 (1.04)
Week 360 (N= 9)	-0.22 (0.67)
Week 372 (N= 3)	0.00 (0.00)
Week 384 (N= 5)	0.00 (0.00)
Week 396 (N= 10)	-0.10 (0.32)
Week 408 (N= 9)	-0.33 (0.71)
Week 420 (N= 4)	-0.25 (0.50)
Week 432 (N= 3)	0.00 (0.00)
Week 444 (N= 1)	0.00 (NA)
Week 456 (N= 5)	-1.40 (1.67)
Week 468 (N= 2)	0.00 (0.00)
Week 480 (N= 1)	0.00 (NA)
Week 492 (N= 9)	-0.56 (1.01)
Week 504 (N= 2)	-1.50 (0.71)
Week 636 (N= 5)	-0.40 (0.89)
Week 648 (N= 2)	0.00 (0.00)
Week 660 (N= 3)	-0.67 (1.15)
Week 672 (N= 1)	-4.00 (NA)
Week 696 (N= 1)	0.00 (NA)
Last Visit (N= 629)	-0.26 (0.85)

9. Primary Outcome

Title	Mean Change From Baseline in Abnormal Involuntary Movement Scale Score (AIMS) Total Score by Week
Description	The AIMS assessment consisted of 10 items describing symptoms of dyskinesia. Facial and oral movements (items 1 through 4), extremity movements (items 5 and 6), and trunk movements (item 7) were observed unobtrusively while the participant was at rest (e.g., in the waiting room), and the study physician would make global judgments on the participant's dyskinesia's (items 8 through 10). For this scale, the participant was seated on a hard, firm chair. These items are rated on a five-point scale: 0 (none), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe). The total score ranges from 0 to 40. Negative changes from baseline indicate an improvement, with higher negative values indicating better improvement.
Time Frame	Baseline, Weeks 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108 continuing every 12 weeks, Last Visit

Outcome Measure Data

Analysis Population Description

All participants who had received at least one dose of study medication were included in both efficacy and safety analyses dataset.

Arm/Group Title	Aripiprazole
Arm/Group Description	All participants began open-label treatment with 30 mg aripiprazole on the first day of participation in the current trial. Once a participant stabilized at the 30 mg per day dose, the study physician could adjust the dose within the range of 10 to 30 mg per day as needed (throughout this long-term trial), to manage adverse events.
Measure Participants	631
Week 1 (N= 619)	-0.21 (1.61)
Week 2 (N= 595)	-0.29 (1.77)
Week 4 (N= 586)	-0.28 (1.96)
Week 6 (N= 572)	-0.34 (2.25)
Week 8 (N= 552)	-0.34 (2.22)
Week 12 (N= 533)	-0.37 (2.26)
Week 16 (N= 517)	-0.39 (2.31)
Week 24 (N= 489)	-0.35 (2.08)
Week 36 (N= 458)	-0.21 (1.85)
Week 48 (N= 425)	-0.35 (2.17)
Week 60 (N= 395)	-0.33 (2.02)
Week 72 (N= 382)	-0.31 (2.10)
Week 84 (N= 362)	-0.31 (2.12)
Week 96 (N= 340)	-0.25 (1.84)
Week 108 (N= 328)	-0.27 (1.88)
Week 120 (N= 316)	-0.26 (1.85)
Week 132 (N= 306)	-0.26 (1.91)
Week 144 (N= 290)	-0.29 (1.97)
Week 156 (N= 279)	-0.31 (2.04)
Week 168 (N= 272)	-0.29 (1.87)
Week 180 (N= 268)	-0.34 (2.08)
Week 192 (N= 255)	-0.35 (2.08)
Week 204 (N= 239)	-0.30 (2.06)
Week 216 (N= 238)	-0.26 (1.50)
Week 228 (N= 224)	-0.31 (1.41)
Week 240 (N= 183)	-0.31 (1.44)
Week 252 (N= 139)	-0.40 (1.59)
Week 264 (N= 83)	-0.61 (1.95)
Week 276 (N= 58)	-0.76 (2.30)
Week 288 (N= 56)	-0.57 (2.72)
Week 300 (N= 55)	-0.18 (1.45)
Week 312 (N= 37)	-0.35 (0.68)
Week 324 (N= 38)	-0.32 (0.57)
Week 336 (N= 28)	-0.36 (0.56)
Week 348 (N= 8)	-0.50 (1.07)
Week 360 (N= 9)	-0.44 (0.73)
Week 372 (N= 3)	0.00 (0.00)
Week 384 (N= 5)	0.00 (0.00)
Week 396 (N= 10)	0.00 (0.00)
Week 408 (N= 9)	0.00 (0.00)
Week 420 (N= 4)	0.00 (0.00)
Week 432 (N= 3)	0.00 (0.00)
Week 444 (N= 1)	0.00 (NA)
Week 456 (N= 5)	-1.00 (2.24)
Week 468 (N= 2)	0.00 (0.00)
Week 480 (N= 1)	0.00 (NA)
Week 492 (N= 9)	-0.44 (0.53)
Week 504 (N= 2)	-0.50 (0.71)
Week 636 (N= 5)	0.20 (0.45)
Week 648 (N= 2)	0.00 (0.00)
Week 660 (N= 3)	0.00 (0.00)
Week 672 (N= 1)	0.00 (NA)
Week 696 (N= 1)	0.00 (NA)
Last Visit (N= 629)	-0.39 (2.36)

10. Primary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	The AEs were one of the primary parameters to measure the safety and tolerability of individual participants. The AEs were captured for all participants from the time the ICF was signed until the end of the trial.
Time Frame	Baseline to Last Visit

Outcome Measure Data

Analysis Population Description

Safety Sample includes all randomized participants who receive at least one dose of study medication.

Arm/Group Title	Aripiprazole
Arm/Group Description	All participants began open-label treatment with 30 mg aripiprazole on the first day of participation in the current trial. Once a participant stabilized at the 30 mg per day dose, the study physician could adjust the dose within the range of 10 to 30 mg per day as needed (throughout this long-term trial), to manage adverse events.
Measure Participants	631
Participants with serious TEAEs	179 28.4%
Participants with severe TEAEs	116 18.4%
Participants discontinued medication due to AE	140 22.2%
Participants with TEAEs	523 82.9%
Participants discontinued due to AEs or death	140 22.2%

11. Primary Outcome

Title	Percentage of Participants With Vital Signs of Potential Clinical Relevance
Description	The vital signs were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance included abnormal values in heart rate, systolic and diastolic blood pressure, respiratory rate and weight that were identified based on pre-defined criteria.
Time Frame	Baseline, Weeks 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108 continuing every 12 weeks, Last Visit

Outcome Measure Data

Analysis Population Description

Safety Sample includes all randomized participants who receive at least one dose of study medication.

Arm/Group Title	Aripiprazole
Arm/Group Description	All participants began open-label treatment with 30 mg aripiprazole on the first day of participation in the current trial. Once a participant stabilized at the 30 mg per day dose, the study physician could adjust the dose within the range of 10 to 30 mg per day as needed (throughout this long-term trial), to manage adverse events.
Measure Participants	631
Heart rate sitting increase ≥15 bpm (N=625)	0.5 0.1%
Systolic sitting BP increase ≥20 mmHg (N=627)	0.8 0.1%
Systolic sitting BP decrease ≥20 mmHg (N=627)	1.3 0.2%
Diastolic sitting BP increase ≥15mmHg (N=627)	3.0 0.5%
Weight gain ≥7% (N=622)	38.9 6.2%
Weight loss ≥7% (N=622)	23.6 3.7%

12. Primary Outcome

Title	Percentage of Participants With ECG Measurements of Potential Clinical Relevance
Description	The measurement of ECG was one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in heart rate and ECG intervals of PR, QRS, QT, QTcB, and QTcF that were identified based on pre-defined criteria.
Time Frame	Baseline, Weeks 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108 continuing every 12 weeks, Last Visit

Outcome Measure Data

Analysis Population Description

Safety Sample includes all randomized participants who receive at least one dose of study medication.

Arm/Group Title	Aripiprazole
Arm/Group Description	All participants began open-label treatment with 30 mg aripiprazole on the first day of participation in the current trial. Once a participant stabilized at the 30 mg per day dose, the study physician could adjust the dose within the range of 10 to 30 mg per day as needed (throughout this long-term trial), to manage adverse events.
Measure Participants	631
Tachycardia (N=612)	0.8 0.1%
Bradycardia (N=612)	7.5 1.2%
Sinus tachycardia (N=612)	0.8 0.1%
Sinus bradycardia (N=612)	7.4 1.2%
Ventricular premature beat (N=612)	2.9 0.5%
Primary atrioventricular block (N=606)	2.5 0.4%
Secondary atrioventricular block (N=612)	0.2 0%
Left bundle branch block (N=612)	0.2 0%
Right bundle branch block (N=612)	16.0 2.5%
Pre-excitation syndrome (N=612)	0.3 0%
Other intraventricular conduction block (N=611)	1.8 0.3%
Acute infarction (N=612)	0.2 0%
Old infarction (N=612)	0.7 0.1%
QTcB (N=612)	8.0 1.3%
QTcF (N=611)	2.1 0.3%
QTcN (N=611)	2.3 0.4%

13. Primary Outcome

Title	Percentage of Participants With Laboratory Values of Potential Clinical Relevance
Description	The laboratory values were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal values in serum chemistry, hematology, urinalyses and prolactin tests that were identified based on pre-defined criteria.
Time Frame	Baseline, Weeks 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108 continuing every 12 weeks, Last Visit

Outcome Measure Data

Analysis Population Description

Safety Sample includes all randomized participants who receive at least one dose of study medication.

Arm/Group Title	Aripiprazole
Arm/Group Description	All participants began open-label treatment with 30 mg aripiprazole on the first day of participation in the current trial. Once a participant stabilized at the 30 mg per day dose, the study physician could adjust the dose within the range of 10 to 30 mg per day as needed (throughout this long-term trial), to manage adverse events.
Measure Participants	631
Alanine aminotransferase (IU/L) (N=626)	1.1 0.2%
Aspartate aminotransferase (IU/L) (N=626)	1.0 0.2%
Bilirubin (mg/dl) (high)(N=626)	3.0 0.5%
Calcium (mg/dl) (low) (N=626)	3.4 0.5%
Chloride (meq/l) (low) (N=626)	0.5 0.1%
Chloride (meq/l) (high) (N=626)	0.2 0%
Creatinine phosphokinase (IU/L) (N=626)	14.9 2.4%
Creatinine (mg/dl) (N=617)	0.5 0.1%
Glucose (mg/dl) (N=626)	3.0 0.5%
Lactic dehydrogenase (IU/L) (N=626)	0.2 0%
Potassium (meq/l) (low) (N=626)	0.2 0%
Potassium (meq/l) (high) (N=626)	5.3 0.8%
Sodium (meq/l) (low) (N=626)	0.5 0.1%
Sodium (meq/l) (high) (N=626)	0.2 0%
Urea nitrogen (mg/dl) (N=626)	0.8 0.1%
Uric acid (mg/dl) (N=626)	1.0 0.2%
Eosinophils (%) (N=624)	3.2 0.5%
Hematocrit (%) (N=623)	2.7 0.4%
Hemoglobin (g/dl) (N=625)	2.4 0.4%
Platelet count (per cubic mm) (low) (N=625)	0.2 0%
Platelet count (per cubic mm) (high) (N=625)	0.3 0%
White blood count (thou/mcl) (low) (N=625)	1.1 0.2%
White blood count (thou/mcl) (high) (N=625)	3.8 0.6%
Glucose, urine (N=613)	1.6 0.3%
Protein, urine (N=599)	1.8 0.3%

Adverse Events

Time Frame	From the signing of the informed consent to 30 days after the end of study treatment. The investigator continued to report any significant follow-up information on the AE up to the time the event had been resolved.
Arm/Group Title	Aripiprazole
Arm/Group Description	All participants began open-label treatment with 30 mg aripiprazole on the first day of participation in the current trial. Once a participant stabilized at the 30 mg per day dose, the study physician could adjust the dose within the range of 10 to 30 mg per day as needed (throughout this long-term trial), to manage adverse events.
All Cause Mortality
	Aripiprazole
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Aripiprazole
	Affected / at Risk (%)	# Events
Total	179/631 (28.4%)
Blood and lymphatic system disorders
Anemia	1/631 (0.2%)
Cardiac disorders
Atrial flutter	1/631 (0.2%)
Cardiac failure	2/631 (0.3%)
Myocardial infarction	1/631 (0.2%)
Myocardial ischaemia	1/631 (0.2%)
Palpitations	1/631 (0.2%)
Eye disorders
Cataract	1/631 (0.2%)
Glaucoma	1/631 (0.2%)
Gastrointestinal disorders
Abdominal pain	1/631 (0.2%)
Duodenal ulcer perforation	1/631 (0.2%)
Gastric ulcer haemorrhage	1/631 (0.2%)
Inguinal hernia	1/631 (0.2%)
Umbilical hernia	1/631 (0.2%)
Infections and infestations
Appendicitis	1/631 (0.2%)
Gangrene	1/631 (0.2%)
Pneumonia	1/631 (0.2%)
Syphilis	1/631 (0.2%)
Injury, poisoning and procedural complications
Foreign body	1/631 (0.2%)
Overdose	3/631 (0.5%)
Toxicity to various agents	2/631 (0.3%)
Traumatic liver injury	1/631 (0.2%)
Investigations
Blood creatinine phosphokinase increased	1/631 (0.2%)
Electrocardiogram QT prolonged	1/631 (0.2%)
Weight decreased	2/631 (0.3%)
Metabolism and nutrition disorders
Decreased appetite	1/631 (0.2%)
Diabetes mellitus	2/631 (0.3%)
Type 2 diabetes mellitus	1/631 (0.2%)
Musculoskeletal and connective tissue disorders
Back pain	1/631 (0.2%)
Myopathy	1/631 (0.2%)
Metastases to liver	1/631 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bronchial carcinoma	1/631 (0.2%)
Colon cancer	1/631 (0.2%)
Malignant melanoma	1/631 (0.2%)
Metastatic malignant melanoma	1/631 (0.2%)
Nervous system disorders
Akathisia	2/631 (0.3%)
Carpal tunnel syndrome	1/631 (0.2%)
Dizziness	1/631 (0.2%)
Multiple sclerosis	1/631 (0.2%)
Psychiatric disorders
Abnormal behaviour	2/631 (0.3%)
Adjustment disorder	1/631 (0.2%)
Agression	4/631 (0.6%)
Agitation	2/631 (0.3%)
Alcohol abuse	1/631 (0.2%)
Anxiety	10/631 (1.6%)
Completed suicide	4/631 (0.6%)
Confusional state	1/631 (0.2%)
Delusion	2/631 (0.3%)
Depressed mood	1/631 (0.2%)
Depression	2/631 (0.3%)
Depressive symptom	1/631 (0.2%)
Drug abuse	1/631 (0.2%)
Hallucination	4/631 (0.6%)
Hypomania	1/631 (0.2%)
Illusion	1/631 (0.2%)
Insomnia	1/631 (0.2%)
Intentional self-injury	1/631 (0.2%)
Persecutory delusion	1/631 (0.2%)
Psychotic disorder	20/631 (3.2%)
Restlessness	1/631 (0.2%)
Schizophrenia	85/631 (13.5%)
Schizophrenia, paranoid type	1/631 (0.2%)
Suicidal ideation	2/631 (0.3%)
Suicidal attempt	6/631 (1%)
Reproductive system and breast disorders
Bartholin's cyst	1/631 (0.2%)
Menorrhagia	1/631 (0.2%)
Ovarian cyst	1/631 (0.2%)
Prostatic disorder	1/631 (0.2%)
Uterine haemorrhage	1/631 (0.2%)
Respiratory, thoracic and mediastinal disorders
Bronchitis chronic	1/631 (0.2%)
Chronic obstructive pulmonary disease	1/631 (0.2%)
Pulmonary thrombosis	1/631 (0.2%)
Respiratory failure	1/631 (0.2%)
Social circumstances
Homicide	1/631 (0.2%)
Respite care	2/631 (0.3%)
Social stay hospitalisation	16/631 (2.5%)
Substance use	1/631 (0.2%)
Vascular disorders
Hypertension	1/631 (0.2%)
Other (Not Including Serious) Adverse Events
	Aripiprazole
	Affected / at Risk (%)	# Events
Total	364/631 (57.7%)
Infections and infestations
Influenza	47/631 (7.4%)
Investigations
Weight increased	56/631 (8.9%)
Nervous system disorders
Akathisia	84/631 (13.3%)
Extrapyramidal disorder	50/631 (7.9%)
Headache	48/631 (7.6%)
Tremor	50/631 (7.9%)
Psychiatric disorders
Anxiety	73/631 (11.6%)
Insomnia	118/631 (18.7%)
Schizophrenia	79/631 (12.5%)

Limitations/Caveats

The study was terminated prematurely by the sponsor. The protocol specified that the study would run until Abilify (aripiprazole) was commercially available in all site countries.

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.