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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A 52-week, Multicenter, Open-label Study to Evaluate the Effectiveness of an Intramuscular Depot Formulation of Aripiprazole (OPC-14597) as Maintenance Treatment in Patients With Bipolar I Disorder

Conditions
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Bipolar I

Intervention / Treatment
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* Drug: Aripiprazole


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Aripiprazole, Intramuscular (IM) Depot | Drug: Aripiprazole<br>* 400mg or 300mg, intramuscular injections every 4 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to Week 52 | 
| 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). | Up to Week 52 | 
| 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. | Up to Week 52 | 
| 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. | Up to Week 52 | 
| 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. | Up to Week 52 | 
| 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. | Baseline, Week 28, and Week 52 | 
| 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. | Up to Week 52 | 
| 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). | Up to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aripiprazole, Intramuscular (IM) Depot, Bipolar