Efficacy, Safety and Tolerability of an Intramuscular Formulation of Aripiprazole (OPC-14597) compared with placebo as Maintenance Treatment in Bipolar I Patients

Phase 1

• Conditions: Bipolar I disorder; MedDRA version: 18.0Level: PTClassification code 10004939Term: Bipolar I disorderSystem Organ Class: 10037175 - Psychiatric disorders; Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]

• Registration Number: EUCTR2012-002870-30-PL
• Lead Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-12-18
• Last Update Posted: 8 May 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

1. Male and female subjects 18 to 65 years of age, inclusive, at time of informed consent.
2. Subjects with a current diagnosis of bipolar I disorder, as defined by DSM-IV-TR criteria and confirmed by the MINI, who have experienced at least 1 previous manic or mixed episode with manic symptoms of sufficient severity to require one of the following interventions: hospitalization and/or treatment with a mood stabilizer, and/or treatment with an antipsychotic agent, in addition to their current manic episode. Require is defined as an intervention that occurred rather than one that was recommended. Rapid cyclers with 8 or fewer episodes in the previous year will be included.
3. Subjects currently experiencing a manic episode with a YMRS total score of =20 at the Screening Visit.
4. Subjects can have an inpatient or outpatient status prior to entry into Phase C (IM depot stabilization).
5. In the investigator's opinion, subjects who are able to understand the nature of the trial and follow protocol requirements, including the prescribed dosage regimens, tablet ingestion, aripiprazole IM depot injection, and discontinuation of prohibited concomitant medications; who can read and understand the written word in order to complete subject-reported outcomes measures; and who can be reliably rated on assessment scales.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 600
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Subjects with a current Axis I (DSM-IV-TR) diagnosis other than bipolar I disorder. All other current diagnoses must be discussed with
the medical monitor.
2. Subjects who have NOT experienced at least one previous manic or
mixed episode with manic symptoms of sufficient severity to require one of the following interventions: hospitalization and/or treatment with a mood stabilizer, and/or treatment with an antipsychotic agent,
excluding their current manic episode. Require is defined as an
intervention that occurred rather than one that was recommended.
3. Subjects with bipolar I disorder who are considered resistant/refractory to treatment for manic symptoms by history.
4. Subjects who are unresponsive to clozapine or those who only respond to clozapine for treatment of mania.
5. Subjects with a significant risk of committing suicide based on history, mental status examination, investigator's judgment, or C-SSRS answer of yes to question 4 or 5 (current or within the last 90 days).
6. Subjects who have a current manic episode with duration of >2 years.
7. Subjects who currently (within the past month) 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.
8. Subjects who have a history or evidence of a medical condition that would expose them to an undue risk of a significant adverse event (AE) or interfere with assessments of safety or efficacy during the course of the trial, including but not limited to hepatic, renal, respiratory, cardiovascular, endocrine, neurologic, hematologic, or immunologic disease as determined by the clinical judgment of the investigator.
9. Subjects who are currently experiencing a mixed or a depressive episode (per DSM-IV-TR criteria).
10. Subjects with a history of hypersensitivity to antipsychotic agents.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this trial is to evaluate the efficacy of aripiprazole IM depot compared with placebo, as measured by time to recurrence of any mood episode in subjects with bipolar I disorder who have maintained stability on aripiprazole IM depot<br>for at least 8 weeks.;Secondary Objective: The secondary objective is to evaluate the safety and tolerability of aripiprazole IM depot as maintenance therapy in subjects with bipolar I disorder.;Primary end point(s): Time from randomization to recurrence of any mood episode during Double-Bind Placebo Controlled phase.;Timepoint(s) of evaluation of this end point: Up to 52 weeks from randomization

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Proportion of subjects meeting criteria for recurrence of any mood episode(manic, mixed, depressive) <br>2. Mean change from randomization to endpoint in the CGI-BP-S (mania) score <br>3. Time from randomization to recurrence defined by hospitalization for a mood episode. <br><br>;Timepoint(s) of evaluation of this end point: Up to 52 weeks from randomization