Intramuscular Depot Formulation of Aripiprazole as Maintenance Treatment in Patients With Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: Aripiprazole depot; Placebo depot
Intervention description: Aripiprazole depot was supplied in 400 mg lyophilized vials. Patients received aripiprazole 300 mg if they were unable to tolerate aripiprazole 400 mg.; Placebo depot was supplied in 400 mg lyophilized vials.
Intervention MeSH terms: Aripiprazole
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 843.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Aripiprazole; Intramuscular (IM) depot; Schizophrenia

Summary:

      The purpose of the trial was to evaluate the efficacy, safety, and tolerability of an
      intramuscular depot formulation of aripiprazole as maintenance treatment in patients with
      schizophrenia.

      The trial was designed into 4 treatment phases. Phase 1 was designed to allow for a patient
      to be converted from their current antipsychotic treatment to oral non-generic aripiprazole
      monotherapy (oral conversion phase from 4 to 6 weeks). During Phase 2, the patient was
      stabilized on oral non-generic aripiprazole monotherapy (oral stabilization phase from a
      minimum of 4 weeks to a maximum of 12 weeks). Once the patient was stabilized in Phase 2,
      they entered Phase 3, the single-blind intramuscular (IM) depot aripiprazole stabilization
      phase. The goal of the phase was to stabilize the patient on the IM depot aripiprazole
      formulation for a minimum of 12 weeks to a maximum of 36 weeks. When the patient was
      stabilized, they were eligible to be randomized into the double-blind IM depot maintenance
      phase (Phase 4). During Phase 4, the patient was assessed for exacerbation of psychotic
      symptoms and/or impending relapse for up to 52 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects who are able to provide written informed consent and/or consent obtained from
             a legally acceptable representative (as required by the Institutional Review
             Board/Institutional Ethics Committee [IRB/IEC]), prior to the initiation of any
             protocol-required procedures.

          -  Male and female subjects 18 to 60 years of age, inclusive, at time of informed
             consent.

          -  Subjects with a current diagnosis of schizophrenia as defined by Diagnostic and
             Statistical Manual of Mental Disorders, 4th edition text revision (DSM-IV-TR) criteria
             and a history of the illness for at least 3 years prior to screening.

          -  Subjects who, in the investigator's judgment, require chronic treatment with an
             antipsychotic medication.

          -  Subjects able to understand the nature of the study and follow protocol requirements,
             including the prescribed dosage regimens, tablet ingestion, IM depot injection,
             discontinuation of prohibited concomitant medications; who can read and understand the
             written word in order to complete patient-reported outcomes measures; and who can be
             reliably rated on assessment scales.

        Exclusion Criteria:

          -  Subjects with a current DSM-IV-TR diagnosis other than schizophrenia, including
             schizoaffective disorder, major depressive disorder, bipolar disorder, delirium,
             dementia, or amnestic or other cognitive disorders. Also, subjects with borderline,
             paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder.

          -  Subjects with schizophrenia that are considered resistant/refractory to antipsychotic
             treatment by history or response only to clozapine.

          -  Subjects with a significant risk of violent behavior or a significant risk of
             committing suicide based on history or investigator's judgment.

          -  Subjects who currently meet DSM-IV-TR criteria for substance dependence, including
             alcohol and benzodiazepines, but excluding caffeine and nicotine; or 2 positive drug
             screens for cocaine.

          -  Subjects who are known to be allergic, intolerant, or unresponsive to prior treatment
             with aripiprazole or other quinolinones; or hypersensitivity to antipsychotic agents.

          -  Subjects with uncontrolled thyroid function abnormalities.

          -  Subjects with a history of seizures, neuroleptic malignant syndrome, clinically
             significant tardive dyskinesia, or other medical condition that would expose them to
             undue risk or interfere with study assessments.

          -  Subjects who are involuntary incarcerated.

          -  Subjects who have used an investigational agent within 30 days of screening or prior
             participation in a clinical study with aripiprazole IM depot.

          -  Subjects with clinically significant abnormalities in laboratory test results, vital
             signs, or ECG results; and subjects hospitalized for more than 30 days in the 90 days
             prior to Phase 1.

          -  Subjects who fail to wash-out from prohibited concomitant medications, including the
             use of CYP2D6 or CYP3A4 inhibitors or CYP3A4 inducers, antipsychotics, antidepressants
             (including monoamine oxidase inhibitors [MAOI}), and mood stabilizers during screening
             and/or Phase 1.