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

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

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.

Study Overview

• Status: Terminated
• Conditions: Bipolar 1 Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Lamotrigine; Drug: ELND005; Drug: Valproic acid

• Study Type: Interventional
• Enrollment (Actual): 309
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Kardzhali, Bulgaria, 6600
    • Elan Investigational Site
  • Pazardzhik, Bulgaria, 4400
    • Elan Investigational Site
  • Sofia, Bulgaria, 1000
    • Elan Investigational Site
  • Sofia, Bulgaria, 1431
    • Elan Investigational Site
  • Varna, Bulgaria, 9010
    • Elan Investigational Site
  • Vratsa, Bulgaria, 3000
    • Elan Investigational Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6L 6W6
      • Elan Investigational Site
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 1Z9
      • Elan Investigational Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2E2
      • Elan Investigational Site
  • Ontario
    • Chatham, Ontario, Canada, N7M 5L9
      • Elan Investigational Site
    • Kingston, Ontario, Canada, K7L 4X3
      • Elan Investigational Site
    • London, Ontario, Canada, N6A 4H1
      • Elan Investigational Site
    • Toronto, Ontario, Canada, M4N 3M5
      • Elan Investigational Site
    • Toronto, Ontario, Canada, M5T 2S8
      • Elan Investigational Site
• Czechia
  • Praha, Czechia, 100 00
    • Elan Investigational Site
  • Praha, Czechia, 120 00
    • Elan Investigational Site
  • Praha, Czechia, 160 00
    • Elan Investigational Site
  • Praha, Czechia, 18100
    • Elan Investigational Site
  • Strakonice, Czechia, 386 29
    • Elan Investigational Site
• France
  • Bully-Les-Mines, France, 62160
    • Elan Investigational Site
  • Dole, France, 39100
    • Elan Investigational Site
  • Elancourt, France, 78990
    • Elan Investigational Site
  • Nimes, France, 30029
    • Elan Investigational Site
  • Toulouse, France, 31000
    • Elan Investigational Site
  • Toulouse, France, 31200
    • Elan Investigational Site
• Poland
  • Bydgoszcz, Poland, 85-156
    • Elan Investigational Site
  • Gdansk, Poland, 80-546
    • Elan Investigational Site
  • Lodz, Poland, 91-229
    • Elan Investigational Site
  • Tuszyn, Poland, 95-080
    • Elan Investigational Site
• Romania
  • Brasov, Romania, 500366
    • Elan Investigational Site
  • Bucharest, Romania, 041914
    • Elan Investigational Site
  • Craiova, Romania, 200473
    • Elan Investigational Site
  • Sibiu, Romania, 550082
    • Elan Investigational Site
• Spain
  • Barcelona, Spain, 08036
    • Elan Investigational Site
  • Vitoria, Spain, 01004
    • Elan Investigational Site
  • Alicante
    • Torrevieja, Alicante, Spain, 03186
      • Elan Investigational Site
  • Asturias
    • Oviedo, Asturias, Spain, 33011
      • Elan Investigational Site
• Turkey
  • Ankara, Turkey, 06100
    • Elan Investigational Site
  • Diyarbakir, Turkey, 21280
    • Elan Investigational Site
  • Edirne, Turkey, 22030
    • Elan Investigational Site
  • Istanbul, Turkey, 34098
    • Elan Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Elan Investigational Site
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Elan Investigational Site
    • Phoenix, Arizona, United States, 85004
      • Elan Investigational Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72201
      • Elan Investigational Site
    • Little Rock, Arkansas, United States, 72211
      • Elan Investigational Site
  • California
    • Cerritos, California, United States, 90703
      • Elan Investigational Site
    • Costa Mesa, California, United States, 92626
      • Elan Investigational Site
    • Escondido, California, United States, 92025
      • Elan Investigational Site
    • Garden Grove, California, United States, 92845
      • Elan Investigational Site
    • National City, California, United States, 91950
      • Elan Investigational Site
    • Oceanside, California, United States, 92056
      • Elan Investigational Site
    • Palo Alto, California, United States, 94304
      • Elan Investigational Site
    • Riverside, California, United States, 92506
      • Elan Investigational Site
    • San Diego, California, United States, 92121
      • Elan Investigational Site
    • Santa Ana, California, United States, 92701
      • Elan Investigational Site
    • Stanford, California, United States, 94305
      • Elan Investigational Site
  • Connecticut
    • Norwich, Connecticut, United States, 06360
      • Elan Investigational Site
  • Florida
    • North Miami, Florida, United States, 33161
      • Elan Investigational Site
    • Oakland Park, Florida, United States, 33334
      • Elan Investigational Site
    • Tampa, Florida, United States, 33613
      • Elan Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Elan Investigational Site
    • Roswell, Georgia, United States, 30076
      • Elan Investigational Site
  • Missouri
    • Creve Coeur, Missouri, United States, 63141
      • Elan Investigational Site
    • Saint Louis, Missouri, United States, 63118
      • Elan Investigational Site
    • Saint Louis, Missouri, United States, 63128
      • Elan Investigational Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68526
      • Elan Investigational Site
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • Elan Investigational Site
  • New York
    • Fresh Meadows, New York, United States, 11366
      • Elan Investigational Site
    • New York, New York, United States, 10065
      • Elan Investigational Site
  • North Carolina
    • Raleigh, North Carolina, United States, 27609
      • Elan Investigational Site
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • Elan Investigational Site
    • Cincinnati, Ohio, United States, 45219
      • Elan Investigational Site
    • Cleveland, Ohio, United States, 44106
      • Elan Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Elan Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19139
      • Elan Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Elan Investigational Site
  • Texas
    • Houston, Texas, United States, 77054
      • Elan Investigational Site
    • Hurst, Texas, United States, 76053
      • Elan Investigational Site
    • San Antonio, Texas, United States, 78229
      • Elan Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Elan Investigational Site
  • Washington
    • Bellevue, Washington, United States, 98007
      • Elan Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: OPKO Health, Inc.
• Collaborators: Elan Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: August 24, 2012
• First Submitted That Met QC Criteria: August 24, 2012
• First Posted (Estimate): August 28, 2012

Study Record Updates

• Last Update Posted (Actual): October 21, 2019
• Last Update Submitted That Met QC Criteria: October 17, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Micronutrients; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; GABA Agents; Anticonvulsants; Sodium Channel Blockers; Antimanic Agents; Vitamins; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Vitamin B Complex; Lamotrigine; Valproic Acid; Inositol
• Other Study ID Numbers: ELND005-BPD201; 2012-001935-30 (EudraCT Number)