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Open-label Study to Evaluate the Effectiveness of an Intramuscular Formulation of Aripiprazole (OPC-14597) as Maintenance Treatment in Patients With Bipolar I Disorder (ATLAS)

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ClinicalTrials.gov Identifier: NCT01710709
Recruitment Status : Completed
First Posted : October 19, 2012
Results First Posted : August 8, 2018
Last Update Posted : September 21, 2018
Sponsor:
Collaborator:
H. Lundbeck A/S
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Bipolar I
Intervention Drug: Aripiprazole
Enrollment 748
Recruitment Details This open-label, single-arm, uncontrolled trial evaluated aripiprazole intramuscular (IM) depot as maintenance treatment for participants with bipolar I disorder. Enrolled participants included those who had completed Trial 31-08-250 (NCT01567527) as well as de novo participants who had not participated in Trial 31-08-250.
Pre-assignment Details Screening period was from Day -42 to Day -2. Participants from the Trial 31-08-250 entered directly into the IM Depot Maintenance Phase of Trial 31-08-252. For de novo participants, this trial consisted of Phases A-C (Conversion Phase, Oral Stabilization Phase, and IM Depot Maintenance Phase).
Arm/Group Title Phase C: Open-Label IM Depot Maintenance Phase
Hide Arm/Group Description All de novo participants received open-label aripiprazole 400/300 mg IM depot and the participants who completed Trial 31-08-250 entered phase C on aripiprazole IM depot 400 mg, regardless of their last dose of IM depot. Aripiprazole IM depot injections were administered every 4 weeks for a maximum of 52 weeks. De novo participants also received daily supplemental oral aripiprazole (10 to 20 mg daily for non-Japanese sites; 6 to 18 mg for Japanese sites) for the first 2 weeks to maintain therapeutic plasma concentrations. Note: Data for Open-label aripiprazole IM depot maintenance phase (Phase C) is presented in the table below which included both rollover participants (those who had completed Trial 31-08-250 and entered into the Open-label aripiprazole IM depot maintenance phase directly) and de novo participants (ie, those who did not participate in Trial 31-08-250 and went through Screening phase, Conversion Phase, and Oral aripiprazole stabilization phase).
Period Title: Overall Study
Started 464
Completed 291
Not Completed 173
Reason Not Completed
Lost to Follow-up             29
Adverse Event             48
Participant met withdrawal criteria             33
Participant withdrawn by investigator             2
Withdrawal by Subject             53
Protocol Violation             5
Lack of Efficacy             3
Arm/Group Title Phase C: Open-label IM Depot Maintenance Phase
Hide Arm/Group Description All de novo participants received open-label aripiprazole 400/300 mg IM depot and the participants who completed Trial 31-08-250 entered phase C on aripiprazole IM depot 400 mg, regardless of their last dose of IM depot. Aripiprazole IM depot injections were administered every 4 weeks for a maximum of 52 weeks. Flexible dosing with aripiprazole IM depot 300 mg and 400 mg was permitted as often as necessary during the open-label treatment period. De novo participants also received daily supplemental oral aripiprazole (10 to 20 mg daily for non-Japanese sites; 6 to 18 mg for Japanese sites) for the first 2 weeks to maintain therapeutic plasma concentrations. For participants who completed Trial 31-08-250 (some of whom had received double-blind placebo), the use of supplemental oral aripiprazole for the first ≤ 2 weeks was at the investigator's discretion based on the clinical status of the participant.
Overall Number of Baseline Participants 464
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 464 participants
<=18 years
0
   0.0%
Between 18 and 65 years
458
  98.7%
>=65 years
6
   1.3%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 464 participants
41.1  (11.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 464 participants
Female
268
  57.8%
Male
196
  42.2%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 464 participants
Canada 3
South Korea 6
Romania 10
Hungary 4
United States 322
Japan 75
Taiwan 1
Poland 28
Malaysia 10
France 5
1.Primary Outcome
Title Number of Participants With Adverse Events
Hide Description An adverse event (AE) is defined as any untoward medical occurrence in a patient or participant enrolled in the clinical trial and which does not necessarily have to have a causal relationship with the investigational medicinal product (IMP). AEs were assessed as a criteria for safety and tolerability.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
IM Depot Maintenance Phase Safety Sample: All participants who received at least 1 dose of aripiprazole IM depot in the IM Depot Maintenance Phase. TEAEs = Treatment-emergent adverse events. discount. = discontinued (used in the table below)
Arm/Group Title Phase C: Open-label IM Depot Maintenance Phase
Hide Arm/Group Description:
All de novo participants received open-label aripiprazole 400/300 mg IM depot and the participants who completed Trial 31-08-250 entered phase C on aripiprazole IM depot 400 mg, regardless of their last dose of IM depot. Aripiprazole IM depot injections were administered every 4 weeks for a maximum of 52 weeks. Flexible dosing with aripiprazole IM depot 300 mg and 400 mg was permitted as often as necessary during the open-label treatment period. De novo participants also received daily supplemental oral aripiprazole (10 to 20 mg daily for non-Japanese sites; 6 to 18 mg for Japanese sites) for the first 2 weeks to maintain therapeutic plasma concentrations. For participants who completed Trial 31-08-250 (some of whom had received double-blind placebo), the use of supplemental oral aripiprazole for the first ≤ 2 weeks was at the investigator's discretion based on the clinical status of the participant.
Overall Number of Participants Analyzed 464
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with adverse events 374
Participants with TEAEs 374
Participants with serious TEAEs 30
Participants with severe TEAEs 41
Participants discontinued from IMP due to AEs 47
Participants discont. from IMP due to AEs or death 48
Deaths 1
2.Primary Outcome
Title Injection Site Pain Measured by the Visual Analog Scale (VAS)
Hide Description Injection-site pain was evaluated by mean visual analog scale (VAS) scores as reported by the participant after each injection at visits where an injection occurred. Ratings ranged from 0 (no pain) to 100 (unbearably painful).
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description

All participants who received at least one dose of aripiprazole IM depot in Phase C. It is equivalent to safety set (SAF) for Phase C.

Number analyzed = Total number of participants with at least one observation of the given parameter.

Arm/Group Title Phase C: Open-label IM Depot Maintenance Phase
Hide Arm/Group Description:
All de novo participants received open-label aripiprazole 400/300 mg IM depot and the participants who completed Trial 31-08-250 entered phase C on aripiprazole IM depot 400 mg, regardless of their last dose of IM depot. Aripiprazole IM depot injections were administered every 4 weeks for a maximum of 52 weeks. Flexible dosing with aripiprazole IM depot 300 mg and 400 mg was permitted as often as necessary during the open-label treatment period. De novo participants also received daily supplemental oral aripiprazole (10 to 20 mg daily for non-Japanese sites; 6 to 18 mg for Japanese sites) for the first 2 weeks to maintain therapeutic plasma concentrations. For participants who completed Trial 31-08-250 (some of whom had received double-blind placebo), the use of supplemental oral aripiprazole for the first ≤ 2 weeks was at the investigator's discretion based on the clinical status of the participant.
Overall Number of Participants Analyzed 464
Mean (Standard Deviation)
Unit of Measure: Units on a scale
1ST Injection Number Analyzed 462 participants
4.9  (10.7)
2ND Injection Number Analyzed 435 participants
4.1  (8.4)
3RD Injection Number Analyzed 422 participants
3.4  (7.5)
4TH Injection Number Analyzed 402 participants
3.6  (8.6)
5TH Injection Number Analyzed 387 participants
2.9  (7.9)
6TH Injection Number Analyzed 366 participants
2.4  (5.8)
7TH Injection Number Analyzed 353 participants
2.6  (7.0)
8TH Injection Number Analyzed 293 participants
2.4  (4.9)
9TH Injection Number Analyzed 284 participants
2.6  (6.6)
10TH Injection Number Analyzed 264 participants
2.5  (7.5)
11TH Injection Number Analyzed 255 participants
2.4  (6.3)
12TH Injection Number Analyzed 247 participants
1.8  (4.3)
13TH Injection Number Analyzed 223 participants
2.2  (5.5)
Last Injection Number Analyzed 463 participants
2.4  (5.9)
3.Primary Outcome
Title Number of Participants With Clinically Significant Abnormal Laboratory Test Results
Hide Description Standard safety variables to be analyzed included clinical laboratory tests. Incidence of treatment emergent adverse events (TEAEs) of potential clinical relevance included abnormal values in serum chemistry, hematology, urinalysis, and other laboratory test that were identified based on pre-defined criteria. Abnormal laboratory values in participants were reported as serious adverse event/adverse events (SAE/AEs) and are reported in the SAE/other AE section of this report.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
IM Depot Maintenance Phase Safety Sample: All participants who received at least 1 dose of aripiprazole IM depot in the IM Depot Maintenance Phase.
Arm/Group Title Phase C: Open-label IM Depot Maintenance Phase
Hide Arm/Group Description:
All de novo participants received open-label aripiprazole 400/300 mg IM depot and the participants who completed Trial 31-08-250 entered phase C on aripiprazole IM depot 400 mg, regardless of their last dose of IM depot. Aripiprazole IM depot injections were administered every 4 weeks for a maximum of 52 weeks. Flexible dosing with aripiprazole IM depot 300 mg and 400 mg was permitted as often as necessary during the open-label treatment period. De novo participants also received daily supplemental oral aripiprazole (10 to 20 mg daily for non-Japanese sites; 6 to 18 mg for Japanese sites) for the first 2 weeks to maintain therapeutic plasma concentrations. For participants who completed Trial 31-08-250 (some of whom had received double-blind placebo), the use of supplemental oral aripiprazole for the first ≤ 2 weeks was at the investigator's discretion based on the clinical status of the participant.
Overall Number of Participants Analyzed 464
Measure Type: Count of Participants
Unit of Measure: Participants
Fasting cholesterol 53
Fasting glucose 39
Fasting low-density lipoprotein cholesterol 32
Fasting triglycerides 124
4.Primary Outcome
Title Number of Participants With Clinically Significant Abnormal Vital Signs
Hide Description TEAEs of potential clinical relevance included abnormal values in body weight, systolic and diastolic blood pressure, heart rate, and body temperature that were identified based on pre-defined criteria. Abnormal laboratory values in participants were reported as SAE/AEs and are reported in the SAE/other AE section of this report.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
IM Depot Maintenance Phase Safety Sample: All participants who received at least 1 dose of aripiprazole IM depot in the IM Depot Maintenance Phase.
Arm/Group Title Phase C: Open-label IM Depot Maintenance Phase
Hide Arm/Group Description:
All de novo participants received open-label aripiprazole 400/300 mg IM depot and the participants who completed Trial 31-08-250 entered phase C on aripiprazole IM depot 400 mg, regardless of their last dose of IM depot. Aripiprazole IM depot injections were administered every 4 weeks for a maximum of 52 weeks. Flexible dosing with aripiprazole IM depot 300 mg and 400 mg was permitted as often as necessary during the open-label treatment period. De novo participants also received daily supplemental oral aripiprazole (10 to 20 mg daily for non-Japanese sites; 6 to 18 mg for Japanese sites) for the first 2 weeks to maintain therapeutic plasma concentrations. For participants who completed Trial 31-08-250 (some of whom had received double-blind placebo), the use of supplemental oral aripiprazole for the first ≤ 2 weeks was at the investigator's discretion based on the clinical status of the participant.
Overall Number of Participants Analyzed 464
Measure Type: Count of Participants
Unit of Measure: Participants
Weight gain of ≥ 7% Number Analyzed 454 participants
93
  20.5%
Weight loss of ≥ 7% Number Analyzed 454 participants
66
  14.5%
Blood pressure increased Number Analyzed 464 participants
4
   0.9%
Heart rate increased Number Analyzed 464 participants
3
   0.6%
Blood pressure decreased Number Analyzed 464 participants
2
   0.4%
Body temperature Number Analyzed 464 participants
0
   0.0%
5.Primary Outcome
Title Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECGs)
Hide Description Twelve-lead ECGs were recorded at specified visits. For each time point, three 12-lead ECG recordings were obtained approximately 5 minutes apart. Additional 12-lead ECGs were permitted to be obtained at the investigator’s discretion and were to always be obtained in the event of an early termination. The ECGs were evaluated at the investigational site to determine the participant’s eligibility and to monitor safety during the trial.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
IM Depot Maintenance Phase Safety Sample: All participants who received at least 1 dose of aripiprazole IM depot in the IM Depot Maintenance Phase.
Arm/Group Title Phase C: Open-label IM Depot Maintenance Phase
Hide Arm/Group Description:
All de novo participants received open-label aripiprazole 400/300 mg IM depot and the participants who completed Trial 31-08-250 entered phase C on aripiprazole IM depot 400 mg, regardless of their last dose of IM depot. Aripiprazole IM depot injections were administered every 4 weeks for a maximum of 52 weeks. Flexible dosing with aripiprazole IM depot 300 mg and 400 mg was permitted as often as necessary during the open-label treatment period. De novo participants also received daily supplemental oral aripiprazole (10 to 20 mg daily for non-Japanese sites; 6 to 18 mg for Japanese sites) for the first 2 weeks to maintain therapeutic plasma concentrations. For participants who completed Trial 31-08-250 (some of whom had received double-blind placebo), the use of supplemental oral aripiprazole for the first ≤ 2 weeks was at the investigator's discretion based on the clinical status of the participant.
Overall Number of Participants Analyzed 464
Measure Type: Count of Participants
Unit of Measure: Participants
Symmetrical T-wave inversion Number Analyzed 412 participants
9
Supraventricular premature beat Number Analyzed 412 participants
8
Ventricular premature beat Number Analyzed 412 participants
4
Myocardial ischemia Number Analyzed 412 participants
2
6.Primary Outcome
Title Extrapyramidal Symptoms Will be Assessed by Mean Change From Baseline on Abnormal Involuntary Movement Scale(AIMS), Simpson-Angus Scale (SAS), Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS Only Used in Japan) and Barnes Akathisia Rating Scale (BARS)
Hide Description AIMS: 10 items described dyskinesia signs; 0-absence/no awareness; 4-severe condition/severe distress. Total score for Items 1-10 ranges from 0 to 40; a higher score reflects severe condition. SAS:Consisted of 10 parkinsonism signs;1-no symptoms;5-severe.Total score for Items 1-10 ranges from 1 to 50;a higher score reflects severe condition.DIEPSS:A 9-item rating scale (8 assessed individual symptoms [4 categories of parkinsonism, akathisia, dystonia & dyskinesia]+1 assessed general severity) was used;0-no symptoms/normal, 4-severe.Total score (8 individual symptom items) was in range of 0 to 32 (a higher score reflects severe condition).BARS:Consisted of 4 items related to akathisia:objective observation, subjective feelings of restlessness, distress, global clinical evaluation.Only BARS global clinical assessment score has been presented and rated using scale:0-absence of symptoms;5-severe akathisia.Total BARS global score ranges from 0 to 5,a higher score reflects severe condition.
Time Frame Baseline, Week 28, and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
IM Depot Maintenance Phase Safety Sample: All participants who received at least 1 dose of aripiprazole IM depot in the IM Depot Maintenance Phase.
Arm/Group Title Phase C: Open-label IM Depot Maintenance Phase
Hide Arm/Group Description:
All de novo participants received open-label aripiprazole 400/300 mg IM depot and the participants who completed Trial 31-08-250 entered phase C on aripiprazole IM depot 400 mg, regardless of their last dose of IM depot. Aripiprazole IM depot injections were administered every 4 weeks for a maximum of 52 weeks. Flexible dosing with aripiprazole IM depot 300 mg and 400 mg was permitted as often as necessary during the open-label treatment period. De novo participants also received daily supplemental oral aripiprazole (10 to 20 mg daily for non-Japanese sites; 6 to 18 mg for Japanese sites) for the first 2 weeks to maintain therapeutic plasma concentrations. For participants who completed Trial 31-08-250 (some of whom had received double-blind placebo), the use of supplemental oral aripiprazole for the first ≤ 2 weeks was at the investigator's discretion based on the clinical status of the participant. Results using last observation carried forward (LOCF) were presented.
Overall Number of Participants Analyzed 464
Mean (Standard Deviation)
Unit of Measure: Units on a scale
AIMS, Week 28 Number Analyzed 457 participants
0.07  (1.00)
AIMS, Week 52 Number Analyzed 457 participants
0.05  (0.97)
SAS, Week 28 Number Analyzed 377 participants
0.21  (1.59)
SAS, Week 52 Number Analyzed 377 participants
0.20  (1.58)
DIEPSS, Week 28 Number Analyzed 75 participants
0.32  (1.29)
DIEPSS, Week 52 Number Analyzed 75 participants
0.21  (1.11)
BARS, Week 28 Number Analyzed 457 participants
0.05  (0.61)
BARS, Week 52 Number Analyzed 457 participants
0.04  (0.60)
7.Primary Outcome
Title Number of Participants Experiencing Suicidal Events and Their Classification According to the Completion of Columbia Suicide Severity Rating Scale (C-SSRS)
Hide Description Suicidality was monitored throughout the trial using the C-SSRS at every visit. The C-SSRS scale consisted of a screening/baseline evaluation that assessed the participant's lifetime experience and experience over the last 90 days with suicide events and suicidal ideation and a post-baseline/ “Since Last Visit” evaluation that focused on suicidality since the last trial visit.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
IM Depot Maintenance Phase Safety Sample: All participants who received at least 1 dose of aripiprazole IM depot in the IM Depot Maintenance Phase.
Arm/Group Title Phase C: Open-label IM Depot Maintenance Phase
Hide Arm/Group Description:
All de novo participants received open-label aripiprazole 400/300 mg IM depot and the participants who completed Trial 31-08-250 entered phase C on aripiprazole IM depot 400 mg, regardless of their last dose of IM depot. Aripiprazole IM depot injections were administered every 4 weeks for a maximum of 52 weeks. Flexible dosing with aripiprazole IM depot 300 mg and 400 mg was permitted as often as necessary during the open-label treatment period. De novo participants also received daily supplemental oral aripiprazole (10 to 20 mg daily for non-Japanese sites; 6 to 18 mg for Japanese sites) for the first 2 weeks to maintain therapeutic plasma concentrations. For participants who completed Trial 31-08-250 (some of whom had received double-blind placebo), the use of supplemental oral aripiprazole for the first ≤ 2 weeks was at the investigator's discretion based on the clinical status of the participant.
Overall Number of Participants Analyzed 464
Measure Type: Count of Participants
Unit of Measure: Participants
Completed Suicide Number Analyzed 463 participants
0
   0.0%
Suicide Attempt Number Analyzed 463 participants
3
   0.6%
Preparatory action toward imminent suicide Number Analyzed 463 participants
4
   0.9%
Suicidal ideation Number Analyzed 463 participants
46
   9.9%
Non-suicidal self-injurious behavior Number Analyzed 463 participants
4
   0.9%
8.Primary Outcome
Title Number of Participants With Injection Site Evaluations (Pain, Redness, Swelling, Induration) Measured by Investigator Rating
Hide Description Injection-site reactions were assessed by the investigator (or qualified designee) and the participant. Investigators rated localized pain, redness, swelling, and induration at the most recent injection site using a 4-point categorical scale (absent, mild, moderate, severe) . The participant indicated the degree of pain at the most recent injection site using a VAS. Ratings ranged from 0 (no pain) to 100 (unbearably painful). Ratings included were: 0 = absent, 1 = mild, 2 = moderate, 3 = severe. These assessments occurred at trial visits where injections occurred (scheduled and unscheduled), beginning with the first dose of open-label aripiprazole IM depot administered at the final visit of the Oral Stabilization Phase and continued through the last injection prior to the end of the IM Depot Maintenance Phase/Early termination (ET) visit (ie, evaluations were not done at end of the IM Depot Maintenance Phase/ET visit).
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
IM Depot Maintenance Phase Safety Sample: All participants who received at least 1 dose of aripiprazole IM depot in the IM Depot Maintenance Phase.
Arm/Group Title Phase C: Open-label IM Depot Maintenance Phase
Hide Arm/Group Description:
All de novo participants received open-label aripiprazole 400/300 mg IM depot and the participants who completed Trial 31-08-250 entered phase C on aripiprazole IM depot 400 mg, regardless of their last dose of IM depot. Aripiprazole IM depot injections were administered every 4 weeks for a maximum of 52 weeks. Flexible dosing with aripiprazole IM depot 300 mg and 400 mg was permitted as often as necessary during the open-label treatment period. De novo participants also received daily supplemental oral aripiprazole (10 to 20 mg daily for non-Japanese sites; 6 to 18 mg for Japanese sites) for the first 2 weeks to maintain therapeutic plasma concentrations. For participants who completed Trial 31-08-250 (some of whom had received double-blind placebo), the use of supplemental oral aripiprazole for the first ≤ 2 weeks was at the investigator's discretion based on the clinical status of the participant.
Overall Number of Participants Analyzed 464
Measure Type: Count of Participants
Unit of Measure: Participants
Injection Site Bruising
2
   0.4%
Injection Site Erythema
1
   0.2%
Injection Site Induration
1
   0.2%
Injection Site Mass
2
   0.4%
Injection Site Pain
34
   7.3%
Injection Site Swelling
4
   0.9%
9.Secondary Outcome
Title Percentage of Participants Who Remained Stable at End of Treatment in Phase C
Hide Description The secondary objective was to evaluate the efficacy, as measured by the percentage of stable participants at baseline who remained stable at the end of treatment in the IM depot maintenance phase, of aripiprazole IM depot administered every 4 weeks for up to 52 weeks to subjects with bipolar I disorder.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
IM Depot Maintenance Phase Efficacy Sample: All participants who entered the IM Depot Maintenance Phase, received at least 1 dose of aripiprazole IM depot, and had at least 1 post-baseline efficacy evaluation in the IM Depot Maintenance Phase. Number analyzed is the number of participants evaluated at the specified trial week.
Arm/Group Title Phase C: Open-label IM Depot Maintenance Phase
Hide Arm/Group Description:
All de novo participants received open-label aripiprazole 400/300 mg IM depot and the participants who completed Trial 31-08-250 entered phase C on aripiprazole IM depot 400 mg, regardless of their last dose of IM depot. Aripiprazole IM depot injections were administered every 4 weeks for a maximum of 52 weeks. Flexible dosing with aripiprazole IM depot 300 mg and 400 mg was permitted as often as necessary during the open-label treatment period. De novo participants also received daily supplemental oral aripiprazole (10 to 20 mg daily for non-Japanese sites; 6 to 18 mg for Japanese sites) for the first 2 weeks to maintain therapeutic plasma concentrations. For participants who completed Trial 31-08-250 (some of whom had received double-blind placebo), the use of supplemental oral aripiprazole for the first ≤ 2 weeks was at the investigator's discretion based on the clinical status of the participant.
Overall Number of Participants Analyzed 464
Measure Type: Number
Unit of Measure: Percentage of participants
Baseline Number Analyzed 463 participants
100.00
Week 2 Number Analyzed 430 participants
96.98
Week 4 Number Analyzed 432 participants
97.22
Week 8 Number Analyzed 413 participants
95.64
Week 12 Number Analyzed 406 participants
96.31
Week 16 Number Analyzed 396 participants
96.46
Week 20 Number Analyzed 381 participants
95.54
Week 24 Number Analyzed 361 participants
96.40
Week 28 Number Analyzed 346 participants
95.09
Week 32 Number Analyzed 287 participants
97.91
Week 36 Number Analyzed 271 participants
95.94
Week 40 Number Analyzed 255 participants
98.04
Week 44 Number Analyzed 249 participants
97.59
Week 48 Number Analyzed 243 participants
97.53
Week 52 Number Analyzed 237 participants
95.78
Last Visit Number Analyzed 460 participants
88.91
Time Frame Phase C week 1 to week 52/early termination.
Adverse Event Reporting Description All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
 
Arm/Group Title Phase C: Open-Label IM Depot Maintenance Phase
Hide Arm/Group Description All de novo participants received open-label aripiprazole 400/300 mg IM depot and the participants who completed Trial 31-08-250 entered phase C on aripiprazole IM depot 400 mg, regardless of their last dose of IM depot. Aripiprazole IM depot injections were administered every 4 weeks for a maximum of 52 weeks. Flexible dosing with aripiprazole IM depot 300 mg and 400 mg was permitted as often as necessary during the open-label treatment period. De novo participants also received daily supplemental oral aripiprazole (10 to 20 mg daily for non-Japanese sites; 6 to 18 mg for Japanese sites) for the first 2 weeks to maintain therapeutic plasma concentrations. For participants who completed Trial 31-08-250 (some of whom had received double-blind placebo), the use of supplemental oral aripiprazole for the first ≤ 2 weeks was at the investigator's discretion based on the clinical status of the participant.
All-Cause Mortality
Phase C: Open-Label IM Depot Maintenance Phase
Affected / at Risk (%)
Total   1/464 (0.22%)    
Show Serious Adverse Events Hide Serious Adverse Events
Phase C: Open-Label IM Depot Maintenance Phase
Affected / at Risk (%) # Events
Total   30/464 (6.47%)    
Cardiac disorders   
Acute Myocardial Infarction * 1  1/464 (0.22%)  1
Cardiac Arrest * 1  1/464 (0.22%)  1
Myocardial Infarction * 1  1/464 (0.22%)  1
Prinzmetal Angina * 1  1/464 (0.22%)  3
Endocrine disorders   
Hyperprolactinaemia * 1  1/464 (0.22%)  1
General disorders   
Chest Pain * 1  2/464 (0.43%)  2
Hepatobiliary disorders   
Cholecystitis Acute * 1  1/464 (0.22%)  1
Infections and infestations   
Kidney Infection * 1  1/464 (0.22%)  1
Injury, poisoning and procedural complications   
Arthropod Bite * 1  1/464 (0.22%)  1
Metabolism and nutrition disorders   
Diabetes Mellitus * 1  1/464 (0.22%)  1
Diabetes Mellitus Inadequate Control * 1  1/464 (0.22%)  1
Obesity * 1  1/464 (0.22%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Breast Cancer * 1  1/464 (0.22%)  1
Nervous system disorders   
Somnolence * 1  1/464 (0.22%)  1
Tardive Dyskinesia * 1  1/464 (0.22%)  1
Psychiatric disorders   
Aggression * 1  1/464 (0.22%)  2
Bipolar Disorder * 1  2/464 (0.43%)  2
Bipolar I Disorder * 1  4/464 (0.86%)  4
Major Depression * 1  1/464 (0.22%)  1
Mania * 1  3/464 (0.65%)  3
Social Avoidant Behaviour * 1  1/464 (0.22%)  1
Suicidal Ideation * 1  4/464 (0.86%)  4
Suicide Attempt * 1  1/464 (0.22%)  1
Respiratory, thoracic and mediastinal disorders   
Dyspnoea * 1  1/464 (0.22%)  1
1
Term from vocabulary, MedDRA 19.0
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Phase C: Open-Label IM Depot Maintenance Phase
Affected / at Risk (%) # Events
Total   367/464 (79.09%)    
General disorders   
Injection site pain * 1  34/464 (7.33%)  50
Infections and infestations   
Nasopharyngitis * 1  56/464 (12.07%)  87
Upper respiratory tract infection * 1  24/464 (5.17%)  27
Investigations   
Weight increased * 1  62/464 (13.36%)  66
Nervous system disorders   
Akathisia * 1  68/464 (14.66%)  79
Headache * 1  29/464 (6.25%)  37
Tremor * 1  28/464 (6.03%)  38
Psychiatric disorders   
Anxiety * 1  46/464 (9.91%)  60
Depression * 1  26/464 (5.60%)  35
Insomnia * 1  51/464 (10.99%)  54
Restlessness * 1  23/464 (4.96%)  27
1
Term from vocabulary, MedDRA 19.0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
 
Results Point of Contact
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Name/Title: Global Clinical Development
Organization: Otsuka Pharmaceutical Development & Commercialization, Inc.
EMail: DT-inquiry@otsuka.jp
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Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01710709     History of Changes
Other Study ID Numbers: 31-08-252
First Submitted: October 17, 2012
First Posted: October 19, 2012
Results First Submitted: November 30, 2017
Results First Posted: August 8, 2018
Last Update Posted: September 21, 2018