Trial Outcomes & Findings for Open-label Study to Evaluate the Effectiveness of an Intramuscular Formulation of Aripiprazole (OPC-14597) as Maintenance Treatment in Patients With Bipolar I Disorder (NCT NCT01710709)
NCT ID: NCT01710709
Last Updated: 2018-09-21
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
748 participants
Primary outcome timeframe
Up to Week 52
Results posted on
2018-09-21
Participant Flow
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.
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).
Participant milestones
| Measure |
Phase C: Open-Label IM Depot Maintenance Phase
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).
|
|---|---|
|
Overall Study
STARTED
|
464
|
|
Overall Study
COMPLETED
|
291
|
|
Overall Study
NOT COMPLETED
|
173
|
Reasons for withdrawal
| Measure |
Phase C: Open-Label IM Depot Maintenance Phase
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).
|
|---|---|
|
Overall Study
Lost to Follow-up
|
29
|
|
Overall Study
Adverse Event
|
48
|
|
Overall Study
Participant met withdrawal criteria
|
33
|
|
Overall Study
Participant withdrawn by investigator
|
2
|
|
Overall Study
Withdrawal by Subject
|
53
|
|
Overall Study
Protocol Violation
|
5
|
|
Overall Study
Lack of Efficacy
|
3
|
Baseline Characteristics
Open-label Study to Evaluate the Effectiveness of an Intramuscular Formulation of Aripiprazole (OPC-14597) as Maintenance Treatment in Patients With Bipolar I Disorder
Baseline characteristics by cohort
| Measure |
Phase C: Open-label IM Depot Maintenance Phase
n=464 Participants
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.
|
|---|---|
|
Age, Continuous
|
41.1 Years
STANDARD_DEVIATION 11.8 • n=5 Participants
|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
458 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
268 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
196 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
South Korea
|
6 Participants
n=5 Participants
|
|
Region of Enrollment
Romania
|
10 Participants
n=5 Participants
|
|
Region of Enrollment
Hungary
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
322 Participants
n=5 Participants
|
|
Region of Enrollment
Japan
|
75 Participants
n=5 Participants
|
|
Region of Enrollment
Taiwan
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
28 Participants
n=5 Participants
|
|
Region of Enrollment
Malaysia
|
10 Participants
n=5 Participants
|
|
Region of Enrollment
France
|
5 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to Week 52Population: 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)
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.
Outcome measures
| Measure |
Phase C: Open-label IM Depot Maintenance Phase
n=464 Participants
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.
|
|---|---|
|
Number of Participants With Adverse Events
Participants with adverse events
|
374 Participants
|
|
Number of Participants With Adverse Events
Participants with TEAEs
|
374 Participants
|
|
Number of Participants With Adverse Events
Participants with serious TEAEs
|
30 Participants
|
|
Number of Participants With Adverse Events
Participants with severe TEAEs
|
41 Participants
|
|
Number of Participants With Adverse Events
Participants discontinued from IMP due to AEs
|
47 Participants
|
|
Number of Participants With Adverse Events
Participants discont. from IMP due to AEs or death
|
48 Participants
|
|
Number of Participants With Adverse Events
Deaths
|
1 Participants
|
PRIMARY outcome
Timeframe: Up to Week 52Population: 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.
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).
Outcome measures
| Measure |
Phase C: Open-label IM Depot Maintenance Phase
n=464 Participants
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.
|
|---|---|
|
Injection Site Pain Measured by the Visual Analog Scale (VAS)
1ST Injection
|
4.9 Units on a scale
Standard Deviation 10.7
|
|
Injection Site Pain Measured by the Visual Analog Scale (VAS)
2ND Injection
|
4.1 Units on a scale
Standard Deviation 8.4
|
|
Injection Site Pain Measured by the Visual Analog Scale (VAS)
3RD Injection
|
3.4 Units on a scale
Standard Deviation 7.5
|
|
Injection Site Pain Measured by the Visual Analog Scale (VAS)
4TH Injection
|
3.6 Units on a scale
Standard Deviation 8.6
|
|
Injection Site Pain Measured by the Visual Analog Scale (VAS)
5TH Injection
|
2.9 Units on a scale
Standard Deviation 7.9
|
|
Injection Site Pain Measured by the Visual Analog Scale (VAS)
6TH Injection
|
2.4 Units on a scale
Standard Deviation 5.8
|
|
Injection Site Pain Measured by the Visual Analog Scale (VAS)
7TH Injection
|
2.6 Units on a scale
Standard Deviation 7.0
|
|
Injection Site Pain Measured by the Visual Analog Scale (VAS)
8TH Injection
|
2.4 Units on a scale
Standard Deviation 4.9
|
|
Injection Site Pain Measured by the Visual Analog Scale (VAS)
9TH Injection
|
2.6 Units on a scale
Standard Deviation 6.6
|
|
Injection Site Pain Measured by the Visual Analog Scale (VAS)
10TH Injection
|
2.5 Units on a scale
Standard Deviation 7.5
|
|
Injection Site Pain Measured by the Visual Analog Scale (VAS)
11TH Injection
|
2.4 Units on a scale
Standard Deviation 6.3
|
|
Injection Site Pain Measured by the Visual Analog Scale (VAS)
12TH Injection
|
1.8 Units on a scale
Standard Deviation 4.3
|
|
Injection Site Pain Measured by the Visual Analog Scale (VAS)
13TH Injection
|
2.2 Units on a scale
Standard Deviation 5.5
|
|
Injection Site Pain Measured by the Visual Analog Scale (VAS)
Last Injection
|
2.4 Units on a scale
Standard Deviation 5.9
|
PRIMARY outcome
Timeframe: Up to Week 52Population: IM Depot Maintenance Phase Safety Sample: All participants who received at least 1 dose of aripiprazole IM depot in the IM Depot Maintenance Phase.
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.
Outcome measures
| Measure |
Phase C: Open-label IM Depot Maintenance Phase
n=464 Participants
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.
|
|---|---|
|
Number of Participants With Clinically Significant Abnormal Laboratory Test Results
Fasting cholesterol
|
53 Participants
|
|
Number of Participants With Clinically Significant Abnormal Laboratory Test Results
Fasting glucose
|
39 Participants
|
|
Number of Participants With Clinically Significant Abnormal Laboratory Test Results
Fasting low-density lipoprotein cholesterol
|
32 Participants
|
|
Number of Participants With Clinically Significant Abnormal Laboratory Test Results
Fasting triglycerides
|
124 Participants
|
PRIMARY outcome
Timeframe: Up to Week 52Population: 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 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.
Outcome measures
| Measure |
Phase C: Open-label IM Depot Maintenance Phase
n=464 Participants
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.
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|---|---|
|
Number of Participants With Clinically Significant Abnormal Vital Signs
Weight gain of ≥ 7%
|
93 Participants
|
|
Number of Participants With Clinically Significant Abnormal Vital Signs
Weight loss of ≥ 7%
|
66 Participants
|
|
Number of Participants With Clinically Significant Abnormal Vital Signs
Blood pressure increased
|
4 Participants
|
|
Number of Participants With Clinically Significant Abnormal Vital Signs
Heart rate increased
|
3 Participants
|
|
Number of Participants With Clinically Significant Abnormal Vital Signs
Blood pressure decreased
|
2 Participants
|
|
Number of Participants With Clinically Significant Abnormal Vital Signs
Body temperature
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to Week 52Population: IM Depot Maintenance Phase Safety Sample: All participants who received at least 1 dose of aripiprazole IM depot in the IM Depot Maintenance Phase.
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.
Outcome measures
| Measure |
Phase C: Open-label IM Depot Maintenance Phase
n=464 Participants
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.
|
|---|---|
|
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECGs)
Symmetrical T-wave inversion
|
9 Participants
|
|
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECGs)
Supraventricular premature beat
|
8 Participants
|
|
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECGs)
Ventricular premature beat
|
4 Participants
|
|
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECGs)
Myocardial ischemia
|
2 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 28, and Week 52Population: IM Depot Maintenance Phase Safety Sample: All participants who received at least 1 dose of aripiprazole IM depot in the IM Depot Maintenance Phase.
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.
Outcome measures
| Measure |
Phase C: Open-label IM Depot Maintenance Phase
n=464 Participants
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.
|
|---|---|
|
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)
AIMS, Week 28
|
0.07 Units on a scale
Standard Deviation 1.00
|
|
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)
AIMS, Week 52
|
0.05 Units on a scale
Standard Deviation 0.97
|
|
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)
SAS, Week 28
|
0.21 Units on a scale
Standard Deviation 1.59
|
|
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)
SAS, Week 52
|
0.20 Units on a scale
Standard Deviation 1.58
|
|
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)
DIEPSS, Week 28
|
0.32 Units on a scale
Standard Deviation 1.29
|
|
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)
DIEPSS, Week 52
|
0.21 Units on a scale
Standard Deviation 1.11
|
|
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)
BARS, Week 28
|
0.05 Units on a scale
Standard Deviation 0.61
|
|
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)
BARS, Week 52
|
0.04 Units on a scale
Standard Deviation 0.60
|
PRIMARY outcome
Timeframe: Up to Week 52Population: IM Depot Maintenance Phase Safety Sample: All participants who received at least 1 dose of aripiprazole IM depot in the IM Depot Maintenance Phase.
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.
Outcome measures
| Measure |
Phase C: Open-label IM Depot Maintenance Phase
n=464 Participants
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.
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|---|---|
|
Number of Participants Experiencing Suicidal Events and Their Classification According to the Completion of Columbia Suicide Severity Rating Scale (C-SSRS)
Suicide Attempt
|
3 Participants
|
|
Number of Participants Experiencing Suicidal Events and Their Classification According to the Completion of Columbia Suicide Severity Rating Scale (C-SSRS)
Completed Suicide
|
0 Participants
|
|
Number of Participants Experiencing Suicidal Events and Their Classification According to the Completion of Columbia Suicide Severity Rating Scale (C-SSRS)
Preparatory action toward imminent suicide
|
4 Participants
|
|
Number of Participants Experiencing Suicidal Events and Their Classification According to the Completion of Columbia Suicide Severity Rating Scale (C-SSRS)
Suicidal ideation
|
46 Participants
|
|
Number of Participants Experiencing Suicidal Events and Their Classification According to the Completion of Columbia Suicide Severity Rating Scale (C-SSRS)
Non-suicidal self-injurious behavior
|
4 Participants
|
PRIMARY outcome
Timeframe: Up to Week 52Population: IM Depot Maintenance Phase Safety Sample: All participants who received at least 1 dose of aripiprazole IM depot in the IM Depot Maintenance Phase.
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).
Outcome measures
| Measure |
Phase C: Open-label IM Depot Maintenance Phase
n=464 Participants
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.
|
|---|---|
|
Number of Participants With Injection Site Evaluations (Pain, Redness, Swelling, Induration) Measured by Investigator Rating
Injection Site Bruising
|
2 Participants
|
|
Number of Participants With Injection Site Evaluations (Pain, Redness, Swelling, Induration) Measured by Investigator Rating
Injection Site Erythema
|
1 Participants
|
|
Number of Participants With Injection Site Evaluations (Pain, Redness, Swelling, Induration) Measured by Investigator Rating
Injection Site Induration
|
1 Participants
|
|
Number of Participants With Injection Site Evaluations (Pain, Redness, Swelling, Induration) Measured by Investigator Rating
Injection Site Mass
|
2 Participants
|
|
Number of Participants With Injection Site Evaluations (Pain, Redness, Swelling, Induration) Measured by Investigator Rating
Injection Site Pain
|
34 Participants
|
|
Number of Participants With Injection Site Evaluations (Pain, Redness, Swelling, Induration) Measured by Investigator Rating
Injection Site Swelling
|
4 Participants
|
SECONDARY outcome
Timeframe: Up to Week 52Population: 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.
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.
Outcome measures
| Measure |
Phase C: Open-label IM Depot Maintenance Phase
n=464 Participants
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.
|
|---|---|
|
Percentage of Participants Who Remained Stable at End of Treatment in Phase C
Week 16
|
96.46 Percentage of participants
|
|
Percentage of Participants Who Remained Stable at End of Treatment in Phase C
Baseline
|
100.00 Percentage of participants
|
|
Percentage of Participants Who Remained Stable at End of Treatment in Phase C
Week 2
|
96.98 Percentage of participants
|
|
Percentage of Participants Who Remained Stable at End of Treatment in Phase C
Week 4
|
97.22 Percentage of participants
|
|
Percentage of Participants Who Remained Stable at End of Treatment in Phase C
Week 8
|
95.64 Percentage of participants
|
|
Percentage of Participants Who Remained Stable at End of Treatment in Phase C
Week 12
|
96.31 Percentage of participants
|
|
Percentage of Participants Who Remained Stable at End of Treatment in Phase C
Week 20
|
95.54 Percentage of participants
|
|
Percentage of Participants Who Remained Stable at End of Treatment in Phase C
Week 24
|
96.40 Percentage of participants
|
|
Percentage of Participants Who Remained Stable at End of Treatment in Phase C
Week 28
|
95.09 Percentage of participants
|
|
Percentage of Participants Who Remained Stable at End of Treatment in Phase C
Week 32
|
97.91 Percentage of participants
|
|
Percentage of Participants Who Remained Stable at End of Treatment in Phase C
Week 36
|
95.94 Percentage of participants
|
|
Percentage of Participants Who Remained Stable at End of Treatment in Phase C
Week 40
|
98.04 Percentage of participants
|
|
Percentage of Participants Who Remained Stable at End of Treatment in Phase C
Week 44
|
97.59 Percentage of participants
|
|
Percentage of Participants Who Remained Stable at End of Treatment in Phase C
Week 48
|
97.53 Percentage of participants
|
|
Percentage of Participants Who Remained Stable at End of Treatment in Phase C
Week 52
|
95.78 Percentage of participants
|
|
Percentage of Participants Who Remained Stable at End of Treatment in Phase C
Last Visit
|
88.91 Percentage of participants
|
Adverse Events
Phase C: Open-Label IM Depot Maintenance Phase
Serious events: 30 serious events
Other events: 367 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Phase C: Open-Label IM Depot Maintenance Phase
n=464 participants at risk
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.
|
|---|---|
|
Cardiac disorders
Acute Myocardial Infarction
|
0.22%
1/464 • Number of events 1 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Cardiac disorders
Cardiac Arrest
|
0.22%
1/464 • Number of events 1 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Cardiac disorders
Myocardial Infarction
|
0.22%
1/464 • Number of events 1 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Cardiac disorders
Prinzmetal Angina
|
0.22%
1/464 • Number of events 3 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Endocrine disorders
Hyperprolactinaemia
|
0.22%
1/464 • Number of events 1 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
General disorders
Chest Pain
|
0.43%
2/464 • Number of events 2 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Hepatobiliary disorders
Cholecystitis Acute
|
0.22%
1/464 • Number of events 1 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Infections and infestations
Kidney Infection
|
0.22%
1/464 • Number of events 1 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Injury, poisoning and procedural complications
Arthropod Bite
|
0.22%
1/464 • Number of events 1 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Metabolism and nutrition disorders
Diabetes Mellitus
|
0.22%
1/464 • Number of events 1 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Metabolism and nutrition disorders
Diabetes Mellitus Inadequate Control
|
0.22%
1/464 • Number of events 1 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Metabolism and nutrition disorders
Obesity
|
0.22%
1/464 • Number of events 1 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer
|
0.22%
1/464 • Number of events 1 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Nervous system disorders
Somnolence
|
0.22%
1/464 • Number of events 1 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Nervous system disorders
Tardive Dyskinesia
|
0.22%
1/464 • Number of events 1 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Psychiatric disorders
Aggression
|
0.22%
1/464 • Number of events 2 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Psychiatric disorders
Bipolar Disorder
|
0.43%
2/464 • Number of events 2 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Psychiatric disorders
Bipolar I Disorder
|
0.86%
4/464 • Number of events 4 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Psychiatric disorders
Major Depression
|
0.22%
1/464 • Number of events 1 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Psychiatric disorders
Mania
|
0.65%
3/464 • Number of events 3 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Psychiatric disorders
Social Avoidant Behaviour
|
0.22%
1/464 • Number of events 1 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Psychiatric disorders
Suicidal Ideation
|
0.86%
4/464 • Number of events 4 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Psychiatric disorders
Suicide Attempt
|
0.22%
1/464 • Number of events 1 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.22%
1/464 • Number of events 1 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
Other adverse events
| Measure |
Phase C: Open-Label IM Depot Maintenance Phase
n=464 participants at risk
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.
|
|---|---|
|
General disorders
Injection site pain
|
7.3%
34/464 • Number of events 50 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Infections and infestations
Nasopharyngitis
|
12.1%
56/464 • Number of events 87 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Infections and infestations
Upper respiratory tract infection
|
5.2%
24/464 • Number of events 27 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Investigations
Weight increased
|
13.4%
62/464 • Number of events 66 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Nervous system disorders
Akathisia
|
14.7%
68/464 • Number of events 79 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Nervous system disorders
Headache
|
6.2%
29/464 • Number of events 37 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Nervous system disorders
Tremor
|
6.0%
28/464 • Number of events 38 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Psychiatric disorders
Anxiety
|
9.9%
46/464 • Number of events 60 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Psychiatric disorders
Depression
|
5.6%
26/464 • Number of events 35 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Psychiatric disorders
Insomnia
|
11.0%
51/464 • Number of events 54 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
|
Psychiatric disorders
Restlessness
|
5.0%
23/464 • Number of events 27 • Phase C week 1 to week 52/early termination.
All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
|
Additional Information
Global Clinical Development
Otsuka Pharmaceutical Development & Commercialization, Inc.
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER