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

Phase 2

Terminated

Conditions: Bipolar 1 Disorder

Interventions: Drug: ELND005
Drug: Lamotrigine
Drug: Placebo
Drug: Valproic acid

Registration Number: NCT01674010

Lead Sponsor: OPKO Health, Inc.

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 309

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lamotrigine or Valproic acid + ELND005	ELND005	Lamotrigine or valproic acid plus ELND005 film coated tablets, 500mg BID for up to 48 weeks
Lamotrigine or Valproic acid + placebo	Placebo	Lamotrigine or valproic acid plus matched placebo BID for up to 48 weeks
Lamotrigine or Valproic acid + ELND005	Lamotrigine	Lamotrigine or valproic acid plus ELND005 film coated tablets, 500mg BID for up to 48 weeks
Lamotrigine or Valproic acid + ELND005	Valproic acid	Lamotrigine or valproic acid plus ELND005 film coated tablets, 500mg BID for up to 48 weeks
Lamotrigine or Valproic acid + placebo	Lamotrigine	Lamotrigine or valproic acid plus matched placebo BID for up to 48 weeks
Lamotrigine or Valproic acid + placebo	Valproic acid	Lamotrigine or valproic acid plus matched placebo BID for up to 48 weeks

Primary Outcome Measures

Name	Time	Method
Treatment Emergent Adverse Events	up to 48 weeks	The study was terminated early so no efficacy analysis was done, safety data are reported.

Secondary Outcome Measures

Name	Time	Method
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