Safety and Efficacy Study of ELND005 as an Adjunctive Maintenance Treatment in Bipolar I Disorder
Condition: Bipolar 1 Disorder
Intervention: ELND005; Lamotrigine; Valproic acid; Placebo
Intervention MeSH terms: Inositol; Lamotrigine; Valproic Acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 309.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      The primary purpose of this study is to determine whether ELND005 is effective in the
      maintenance treatment of bipolar 1 disorder when added to other therapies.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Meets the DSM-IV-TR criteria for BPD I by the SCID, prior to the Screening Visit.

          -  Has a history in the last 3 years of ≥ 1 manic or mixed episodes of sufficient
             severity that required hospitalization and/or treatment with a mood stabilizer or
             antipsychotic, or confirmed by a family member or medical records to ensure the
             episode fulfills the DSM-IV-TR criteria.

          -  Has experienced a mood episode of any polarity within 4 months prior to the Screening
             Visit and responded to StOC therapy.

          -  Is euthymic at the Screening Visit (ie, score of ≤ 12 on the MADRS and a score of ≤ 12
             on the Y-MRS).

          -  Is receiving maintenance treatment for his or her BPD I with either LTG or VPA; on
             stable doses for past 4 weeks and therapeutic drug levels (total VPA 50--125 µg/mL and
             LTG 10-50 µmol/L or as deemed appropriate by the investigator). Dose adjustments made
             for tolerability reasons will be acceptable.

        A study patient must meet the following additional criteria to be eligible for
        randomization in the Double-blind Randomization Phase of this study:

        - Maintained in a stable euthymic state during Phase 1, defined as Y-MRS and MADRS scores
        of ≤ 12, with the following exceptions: a maximum of 2 nonconsecutive excursions will be
        allowed throughout Phase 1. Excursions are defined as Y-MRS or MADRS scores >12 but ≤ 16.

        Exclusion Criteria:

          -  Woman of childbearing potential who is unwilling or unable to use an acceptable method
             of birth control or is using a prohibited contraceptive method.

          -  Is found to be actively suicidal on the C-SSRS (answer of "yes" to question 4 or 5
             [current or over the last 30 days]) or a score of ≥4 on the MADRS item 10 at the
             Screening Visit.

          -  Has suboptimally treated thyroid disease as evidenced by thyroid-stimulating hormone
             (TSH) >3 mIU/L at the Screening Visit.

          -  Has received electroconvulsive therapy (ECT) during the current episode or within 6
             months prior to the Screening Visit.

          -  Has an estimated glomerular filtration rate <40 mL/min/1.73 m2 according to the
             Modification of Diet in Renal Disease formula.

        A study patient who meets ANY of the above and ANY of the criteria below will not be
        eligible for enrollment in the Double-blind Randomization Phase of this study:

          -  Has current signs or symptoms of psychosis.

          -  Has become actively suicidal as defined by C-SSRS answer of "yes" to question 4 or 5
             (current or over the last 30 days) and/or has a score of ≥4 on MADRS item 10.