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

OPKO Health

Status and phase: Terminated; Phase 2

Conditions: Bipolar 1 Disorder

Treatments: Drug: Lamotrigine; Drug: Placebo; Drug: Valproic acid; Drug: ELND005

Study type: Interventional

Funder types: Industry

Identifiers

NCT01674010

2012-001935-30 (EudraCT Number)

ELND005-BPD201

Details and patient eligibility

About

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.

Enrollment: 309 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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309 participants in 2 patient groups, including a placebo group

Lamotrigine or Valproic acid + ELND005

Experimental group

Description:

Lamotrigine or valproic acid plus ELND005 film coated tablets, 500mg BID for up to 48 weeks

Treatment:

Drug: ELND005

Drug: Valproic acid

Drug: Lamotrigine

Lamotrigine or Valproic acid + placebo

Placebo Comparator group

Description:

Lamotrigine or valproic acid plus matched placebo BID for up to 48 weeks

Treatment:

Drug: Placebo

Drug: Valproic acid

Drug: Lamotrigine