Bipolar I
Conditions
Keywords
Aripiprazole, Intramuscular (IM) Depot, Bipolar
Brief summary
This will be an open-label uncontrolled trial to evaluate the safety and tolerability of aripiprazole IM depot administered every 4 weeks for up to 52 weeks to patients with bipolar I disorder. The trial will enroll subjects who completed Trial 31-08-250 and de novo subjects not participating in Trial 31-08-250.
Detailed description
This will be an open-label, uncontrolled study which will enroll subjects completing Study 31-08-250 and new subjects. The treatment history of subjects prior to enrollment in the open-label study will vary according to the design of the pivotal double-blind study (i.e 31-08-250). This open-label study will be comprised of phases similar to the pivotal double-blind study (i.e. Study 250): a screening phase (if applicable), a conversion phase (Phase A, if applicable), an oral stabilization phase (Phase B, if applicable), and an IM depot open-label maintenance phase (Phase C). Phase C will be a minimum of 28 weeks up to a 52-week treatment period with a 4 week follow up period. During Phase C (the open-label maintenance phase) rescue medication will be allowed for subjects who do not meet stability criteria. This analysis focuses on Phase C due to ClinicalTrials.gov system limitations.
Interventions
DRUGAripiprazole
400mg or 300mg, intramuscular injections every 4 weeks.
Sponsors
H. Lundbeck A/S
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Completed participation in Trial 31-08-250 * De novo subjects not participating in Trial 31-08-250 * Subjects who are able to provide written informed consent. * Male and female subjects 18 years of age or older at time of informed consent * Subjects who, in the investigator's judgment, require chronic treatment with an antipsychotic medication for their bipolar I disorder and would benefit from extended treatment with a long-acting injectable formulation * Subjects who have a recurrence of mood episode or exacerbations of mood symptoms when they are not receiving treatment for their bipolar I disorder or are noncompliant with treatment for their bipolar I disorder * Have an outpatient status
Exclusion criteria
* Experienced 9 or more mood episodes within the past year * A current manic episode with a duration of \> 2 years * Currently meet DSM-IV-TR criteria for substance abuse or substance dependence; this includes the abuse of alcohol and benzodiazepines, but excludes the use of caffeine and/or nicotine * Hypothyroidism or hyperthyroidism, unless condition has been stabilized * Diagnosed with epilepsy or a history of seizures * Known to be allergic, intolerant, or unresponsive to prior treatment with aripiprazole or other quinolinones * Sexually active women of childbearing potential and sexually active men who will not commit to utilizing 2 of the approved birth control methods or who will not remain abstinent during this trial and for 180 days following the last dose of trial medication * Females breastfeeding or pregnant (positive blood pregnancy test prior to receiving trial drug) * Risk of committing suicide * Abnormal laboratory test results, vital signs and ECG results * Participated in any clinical trial other than Trial 250 with an investigational agent within the 30 days prior to screening * Had electroconvulsive therapy (ECT) treatment during the current episode or within 3 months * Subjects who have not met criteria for stabilization for 4 consecutive weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Injection Site Evaluations (Pain, Redness, Swelling, Induration) Measured by Investigator Rating | Up to Week 52 | 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). |
| Number of Participants With Adverse Events | Up to Week 52 | 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. |
| Injection Site Pain Measured by the Visual Analog Scale (VAS) | Up to Week 52 | 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). |
| Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECGs) | Up to Week 52 | 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. |
| Number of Participants With Clinically Significant Abnormal Laboratory Test Results | Up to Week 52 | 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. |
| Number of Participants With Clinically Significant Abnormal Vital Signs | Up to Week 52 | 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. |
| 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) | Baseline, Week 28, and Week 52 | 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. |
| Number of Participants Experiencing Suicidal Events and Their Classification According to the Completion of Columbia Suicide Severity Rating Scale (C-SSRS) | Up to Week 52 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Remained Stable at End of Treatment in Phase C | Up to Week 52 | 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. |
Countries
Canada, France, Hungary, Japan, Malaysia, Poland, Romania, South Korea, Taiwan, United States
Participant flow
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).
Participants by arm
| Arm | Count |
|---|---|
| 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. 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. | 464 |
| Total | 464 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 48 |
| Overall Study | Lack of Efficacy | 3 |
| Overall Study | Lost to Follow-up | 29 |
| Overall Study | Participant met withdrawal criteria | 33 |
| Overall Study | Participant withdrawn by investigator | 2 |
| Overall Study | Protocol Violation | 5 |
| Overall Study | Withdrawal by Subject | 53 |
Baseline characteristics
| Characteristic | Phase C: Open-label IM Depot Maintenance Phase |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 458 Participants |
| Age, Continuous | 41.1 Years STANDARD_DEVIATION 11.8 |
| Region of Enrollment Canada | 3 Participants |
| Region of Enrollment France | 5 Participants |
| Region of Enrollment Hungary | 4 Participants |
| Region of Enrollment Japan | 75 Participants |
| Region of Enrollment Malaysia | 10 Participants |
| Region of Enrollment Poland | 28 Participants |
| Region of Enrollment Romania | 10 Participants |
| Region of Enrollment South Korea | 6 Participants |
| Region of Enrollment Taiwan | 1 Participants |
| Region of Enrollment United States | 322 Participants |
| Sex: Female, Male Female | 268 Participants |
| Sex: Female, Male Male | 196 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 464 |
| other Total, other adverse events | 367 / 464 |
| serious Total, serious adverse events | 30 / 464 |
Outcome results
Primary
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: 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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase C: Open-label IM Depot Maintenance Phase | 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 |
| Phase C: Open-label IM Depot Maintenance Phase | 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 |
| Phase C: Open-label IM Depot Maintenance Phase | 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 |
| Phase C: Open-label IM Depot Maintenance Phase | 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 |
| Phase C: Open-label IM Depot Maintenance Phase | 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 |
| Phase C: Open-label IM Depot Maintenance Phase | 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 |
| Phase C: Open-label IM Depot Maintenance Phase | 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 |
| Phase C: Open-label IM Depot Maintenance Phase | 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 0.6 |
Primary
Injection Site Pain Measured by the Visual Analog Scale (VAS)
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase C: Open-label IM Depot Maintenance Phase | Injection Site Pain Measured by the Visual Analog Scale (VAS) | 1ST Injection | 4.9 Units on a scale | Standard Deviation 10.7 |
| Phase C: Open-label IM Depot Maintenance Phase | Injection Site Pain Measured by the Visual Analog Scale (VAS) | 2ND Injection | 4.1 Units on a scale | Standard Deviation 8.4 |
| Phase C: Open-label IM Depot Maintenance Phase | Injection Site Pain Measured by the Visual Analog Scale (VAS) | 3RD Injection | 3.4 Units on a scale | Standard Deviation 7.5 |
| Phase C: Open-label IM Depot Maintenance Phase | Injection Site Pain Measured by the Visual Analog Scale (VAS) | 4TH Injection | 3.6 Units on a scale | Standard Deviation 8.6 |
| Phase C: Open-label IM Depot Maintenance Phase | Injection Site Pain Measured by the Visual Analog Scale (VAS) | 5TH Injection | 2.9 Units on a scale | Standard Deviation 7.9 |
| Phase C: Open-label IM Depot Maintenance Phase | Injection Site Pain Measured by the Visual Analog Scale (VAS) | 6TH Injection | 2.4 Units on a scale | Standard Deviation 5.8 |
| Phase C: Open-label IM Depot Maintenance Phase | Injection Site Pain Measured by the Visual Analog Scale (VAS) | 7TH Injection | 2.6 Units on a scale | Standard Deviation 7 |
| Phase C: Open-label IM Depot Maintenance Phase | Injection Site Pain Measured by the Visual Analog Scale (VAS) | 8TH Injection | 2.4 Units on a scale | Standard Deviation 4.9 |
| Phase C: Open-label IM Depot Maintenance Phase | Injection Site Pain Measured by the Visual Analog Scale (VAS) | 9TH Injection | 2.6 Units on a scale | Standard Deviation 6.6 |
| Phase C: Open-label IM Depot Maintenance Phase | Injection Site Pain Measured by the Visual Analog Scale (VAS) | 10TH Injection | 2.5 Units on a scale | Standard Deviation 7.5 |
| Phase C: Open-label IM Depot Maintenance Phase | Injection Site Pain Measured by the Visual Analog Scale (VAS) | 11TH Injection | 2.4 Units on a scale | Standard Deviation 6.3 |
| Phase C: Open-label IM Depot Maintenance Phase | Injection Site Pain Measured by the Visual Analog Scale (VAS) | 12TH Injection | 1.8 Units on a scale | Standard Deviation 4.3 |
| Phase C: Open-label IM Depot Maintenance Phase | Injection Site Pain Measured by the Visual Analog Scale (VAS) | 13TH Injection | 2.2 Units on a scale | Standard Deviation 5.5 |
| Phase C: Open-label IM Depot Maintenance Phase | Injection Site Pain Measured by the Visual Analog Scale (VAS) | Last Injection | 2.4 Units on a scale | Standard Deviation 5.9 |
Primary
Number of Participants Experiencing Suicidal Events and Their Classification According to the Completion of Columbia Suicide Severity Rating Scale (C-SSRS)
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
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase C: Open-label IM Depot Maintenance Phase | 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 |
| Phase C: Open-label IM Depot Maintenance Phase | 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 |
| Phase C: Open-label IM Depot Maintenance Phase | 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 |
| Phase C: Open-label IM Depot Maintenance Phase | 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 |
| Phase C: Open-label IM Depot Maintenance Phase | 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 |
Primary
Number of Participants With Adverse Events
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
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Adverse Events | Participants with adverse events | 374 Participants |
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Adverse Events | Participants with TEAEs | 374 Participants |
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Adverse Events | Participants with serious TEAEs | 30 Participants |
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Adverse Events | Participants with severe TEAEs | 41 Participants |
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Adverse Events | Participants discontinued from IMP due to AEs | 47 Participants |
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Adverse Events | Participants discont. from IMP due to AEs or death | 48 Participants |
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Adverse Events | Deaths | 1 Participants |
Primary
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECGs)
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
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECGs) | Symmetrical T-wave inversion | 9 Participants |
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECGs) | Supraventricular premature beat | 8 Participants |
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECGs) | Ventricular premature beat | 4 Participants |
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECGs) | Myocardial ischemia | 2 Participants |
Primary
Number of Participants With Clinically Significant Abnormal Laboratory Test Results
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
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Clinically Significant Abnormal Laboratory Test Results | Fasting cholesterol | 53 Participants |
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Clinically Significant Abnormal Laboratory Test Results | Fasting glucose | 39 Participants |
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Clinically Significant Abnormal Laboratory Test Results | Fasting low-density lipoprotein cholesterol | 32 Participants |
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Clinically Significant Abnormal Laboratory Test Results | Fasting triglycerides | 124 Participants |
Primary
Number of Participants With Clinically Significant Abnormal Vital Signs
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
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Clinically Significant Abnormal Vital Signs | Weight gain of ≥ 7% | 93 Participants |
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Clinically Significant Abnormal Vital Signs | Weight loss of ≥ 7% | 66 Participants |
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Clinically Significant Abnormal Vital Signs | Heart rate increased | 3 Participants |
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Clinically Significant Abnormal Vital Signs | Blood pressure decreased | 2 Participants |
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Clinically Significant Abnormal Vital Signs | Body temperature | 0 Participants |
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Clinically Significant Abnormal Vital Signs | Blood pressure increased | 4 Participants |
Primary
Number of Participants With Injection Site Evaluations (Pain, Redness, Swelling, Induration) Measured by Investigator Rating
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
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Injection Site Evaluations (Pain, Redness, Swelling, Induration) Measured by Investigator Rating | Injection Site Bruising | 2 Participants |
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Injection Site Evaluations (Pain, Redness, Swelling, Induration) Measured by Investigator Rating | Injection Site Erythema | 1 Participants |
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Injection Site Evaluations (Pain, Redness, Swelling, Induration) Measured by Investigator Rating | Injection Site Induration | 1 Participants |
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Injection Site Evaluations (Pain, Redness, Swelling, Induration) Measured by Investigator Rating | Injection Site Mass | 2 Participants |
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Injection Site Evaluations (Pain, Redness, Swelling, Induration) Measured by Investigator Rating | Injection Site Pain | 34 Participants |
| Phase C: Open-label IM Depot Maintenance Phase | Number of Participants With Injection Site Evaluations (Pain, Redness, Swelling, Induration) Measured by Investigator Rating | Injection Site Swelling | 4 Participants |
Secondary
Percentage of Participants Who Remained Stable at End of Treatment in Phase C
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase C: Open-label IM Depot Maintenance Phase | Percentage of Participants Who Remained Stable at End of Treatment in Phase C | Baseline | 100.00 Percentage of participants |
| Phase C: Open-label IM Depot Maintenance Phase | Percentage of Participants Who Remained Stable at End of Treatment in Phase C | Week 2 | 96.98 Percentage of participants |
| Phase C: Open-label IM Depot Maintenance Phase | Percentage of Participants Who Remained Stable at End of Treatment in Phase C | Week 4 | 97.22 Percentage of participants |
| Phase C: Open-label IM Depot Maintenance Phase | Percentage of Participants Who Remained Stable at End of Treatment in Phase C | Week 8 | 95.64 Percentage of participants |
| Phase C: Open-label IM Depot Maintenance Phase | Percentage of Participants Who Remained Stable at End of Treatment in Phase C | Week 12 | 96.31 Percentage of participants |
| Phase C: Open-label IM Depot Maintenance Phase | Percentage of Participants Who Remained Stable at End of Treatment in Phase C | Week 16 | 96.46 Percentage of participants |
| Phase C: Open-label IM Depot Maintenance Phase | Percentage of Participants Who Remained Stable at End of Treatment in Phase C | Week 20 | 95.54 Percentage of participants |
| Phase C: Open-label IM Depot Maintenance Phase | Percentage of Participants Who Remained Stable at End of Treatment in Phase C | Week 24 | 96.40 Percentage of participants |
| Phase C: Open-label IM Depot Maintenance Phase | Percentage of Participants Who Remained Stable at End of Treatment in Phase C | Week 28 | 95.09 Percentage of participants |
| Phase C: Open-label IM Depot Maintenance Phase | Percentage of Participants Who Remained Stable at End of Treatment in Phase C | Week 32 | 97.91 Percentage of participants |
| Phase C: Open-label IM Depot Maintenance Phase | Percentage of Participants Who Remained Stable at End of Treatment in Phase C | Week 36 | 95.94 Percentage of participants |
| Phase C: Open-label IM Depot Maintenance Phase | Percentage of Participants Who Remained Stable at End of Treatment in Phase C | Week 40 | 98.04 Percentage of participants |
| Phase C: Open-label IM Depot Maintenance Phase | Percentage of Participants Who Remained Stable at End of Treatment in Phase C | Week 44 | 97.59 Percentage of participants |
| Phase C: Open-label IM Depot Maintenance Phase | Percentage of Participants Who Remained Stable at End of Treatment in Phase C | Week 48 | 97.53 Percentage of participants |
| Phase C: Open-label IM Depot Maintenance Phase | Percentage of Participants Who Remained Stable at End of Treatment in Phase C | Week 52 | 95.78 Percentage of participants |
| Phase C: Open-label IM Depot Maintenance Phase | Percentage of Participants Who Remained Stable at End of Treatment in Phase C | Last Visit | 88.91 Percentage of participants |