Efficacy, Safety, and Tolerability of an Intramuscular Formulation of Aripiprazole (OPC-14597) as Maintenance Treatment in Bipolar I Patients
Condition: Bipolar I Disorder
Intervention: Intramuscular (IM) Depot Aripiprazole; Intramuscular (IM) Depot Placebo
Intervention description: Formulation: Intramuscular (IM) Depot Aripiprazole Formulation 400 mg or 300 mg, once a month injection; Formulation: Intramuscular (IM) Depot Placebo 400 mg or 300 mg, once a month injection
Intervention MeSH terms: Aripiprazole
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 731.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Aripiprazole; Intramuscular (IM) Depot; Bipolar

Summary:

      This will be a randomized, double-blind, placebo-controlled trial to assess the time to
      recurrence of any mood episode in subjects with bipolar I disorder who have maintained
      stability on aripiprazole IM depot for at least 8 weeks. This trial will include male and
      female subjects 18 to 65 years of age, inclusive, with a diagnosis of bipolar I disorder,
      according to DSM-IV-TR criteria and confirmed by the Mini International Neuropsychiatric
      Interview (MINI), who have experienced at least one previous manic episode of sufficient
      severity to require hospitalization and/or treatment with a mood stabilizer or antipsychotic
      agent in addition to their current manic episode. All subjects must be experiencing a manic
      episode (per DSM-IV-TR criteria) with a YMRS total score ≥ 20 at trial entry. Both inpatients
      and outpatients are eligible for this trial.

      This trial will consist of a screening phase followed by 4 treatment phases. Subjects will
      undergo screening for eligibility, followed by a conversion to oral aripiprazole monotherapy
      phase, if needed, an oral aripiprazole stabilization phase, a single-blind aripiprazole IM
      depot stabilization phase, and, a double-blind, placebo-controlled phase.
    

Eligibility criteria:

        Key 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 and a history of 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, 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.

        Key Exclusion Criteria:

          1. Subjects with a current Axis I (DSM-IV-TR) diagnosis other than bipolar I disorder.

          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 a
             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 unresponsive 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 with a current manic episode with a 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.