Safety and Efficacy Study of ELND005 as an Adjunctive Maintenance Treatment in Bipolar I Disorder

Study Overview
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Brief Summary
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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.

Official Title
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A Prospective, Randomized, Double-Blind, Placebo-Controlled, Phase 2 Safety and Efficacy Study of Oral ELND005 as an Adjunctive Maintenance Treatment in Patients With Bipolar I Disorder

Conditions
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Bipolar 1 Disorder

Intervention / Treatment
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* Drug: ELND005
* Drug: Lamotrigine
* Drug: Valproic acid
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lamotrigine or Valproic acid + ELND005<br>Lamotrigine or valproic acid plus ELND005 film coated tablets, 500mg BID for up to 48 weeks | Drug: ELND005<br> <br> * Other names: Scyllo-inositol;Drug: Lamotrigine<br> <br> Drug: Valproic acid<br> <br> |
| Placebo Comparator: Lamotrigine or Valproic acid + placebo<br>Lamotrigine or valproic acid plus matched placebo BID for up to 48 weeks | Drug: Lamotrigine<br> <br> Drug: Valproic acid<br> <br> Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Emergent Adverse Events | The study was terminated early so no efficacy analysis was done, safety data are reported. | up to 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Study Participants With Recurrence of Any Mood Episode |  | up to 48 weeks | 
| Time to Recurrence of a Depressive Episode |  | up to 48 weeks | 
| Time to Recurrence of a Manic/Hypomanic or a Mixed Episode |  | up to 48 weeks |