A Randomized, Double-blind, Placebo-controlled, Flexible-dose, Parallel-group Study of Lurasidone Adjunctive to Lithium or Divalproex for the Prevention of Recurrence in Subjects With Bipolar I Disorder
Overview
- Phase
- Phase 3
- Intervention
- Lurasidone
- Conditions
- Bipolar I Disorder
- Sponsor
- Sumitomo Pharma America, Inc.
- Enrollment
- 965
- Locations
- 104
- Primary Endpoint
- Time to Recurrence of Mood Event During the Double Blind Treatment Phase
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
This is a multi-center, randomized, placebo-controlled, flexible-dose, parallel-group study designed to evaluate the efficacy and safety of lurasidone (in combination with lithium or divalproex) for the maintenance treatment of bipolar I disorder in subjects with or without rapid cycling and /or psychotic features.
Detailed Description
This study is to evaluate the efficacy and safety of lurasidone (in combination with lithium or divalproex) for the maintenance treatment of bipolar I disorder in subjects with or without rapid cycling and/or psychotic features.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Open-label Phase
- •18 years of age or older
- •Diagnostic and Statistical Manual of Mental Disorders, 4th Ed., Text Revision (DSM-IV-TR) diagnosis of bipolar I disorder
- •≥ 1 manic, mixed manic, or depressed episode in past 2 years
- •YMRS or MADRS total score ≥ 14 if on lithium or divalproex; ≥ 18 if not on lithium or divalproex
- •Double-blind Phase
- •Inclusion Criteria:
- •Subjects must achieve consistent clinical stability, defined as total scores ≤ 12 on the YMRS and MADRS over at least 12 weeks, with the allowance of two excursions (YMRS and/or MADRS total scores up to 13 or 14, respectively) except during the last 4 weeks before randomization
Exclusion Criteria
- •Open Label Phase
- •Diagnosis of an Axis I or Axis II disorder, other than bipolar I disorder, that is the primary focus of treatment within 3 months of screening
- •Subjects for whom diagnostic agreement between the Investigator and United BioSource Corporation (Boston) (UBC) cannot be reached
- •Ultra-fast rapid cycling (defined as ≥ 8 mood episodes over the previous 12-month period)
- •Subjects who test positive for drugs of abuse at screening. In the event a subject tests positive for cannabinoids (tetrahydrocannabinol), the Investigator will evaluate the subject's ability to abstain from cannabis during the study
- •Unstable/inadequately treated medical illness
- •The subjects answers "yes" to "Suicidal Ideation" items 4 or 5 on the C-SSRS (at time of evaluation)
- •Double Blind Phase
- •Subjects who in the Investigator's judgment have not been compliant with study medication during the stabilization phase
- •Subjects who have not stabilized during the open-label phase (within 20 weeks)
Arms & Interventions
Lurasidone 20-80 mg flexible dose
Intervention: Lurasidone
Placebo
Intervention: Placebo
Outcomes
Primary Outcomes
Time to Recurrence of Mood Event During the Double Blind Treatment Phase
Time Frame: 28 weeks (up to 33 weeks)
A mood event is defined as one of the following during the double-blind phase: (1) Fulfilled Diagnostic and Statistical Manual of Mental Disorders, 4th Ed., Text Revision (DSM-IV-TR) criteria for manic, mixed manic, hypomanic, or depressive episode. (2) Required treatment intervention for manic, mixed manic, hypomanic, or depressive symptoms with any antipsychotic (other than study drug), antidepressant, mood stabilizer (other than lithium or divalproex), anxiolytic agents, benzodiazepine (beyond dosage allowed for anxiety, agitation, or insomnia). (3) Psychiatric hospitalization for any bipolar mood episode. (4) Young Mania Rating Scale (YMRS) or Montgomery-Asberg Depression Rating Scale (MADRS) total score ≥ 18 or Clinical Global Impression Bipolar Version, Severity of Illness (CGI BP S) score ≥ 4 at 2 consecutive assessments no more than 10 days apart. (5) Discontinuation from the study because of a mood event (as determined by the Investigator).
Secondary Outcomes
- Time to All-cause Discontinuation(28 weeks (up to 33 weeks))
- Time to Recurrence of a Manic, Mixed Manic, Hypomanic, or Depressed Episode(28 weeks (up to 33 weeks))
- Percentage of Subjects Who Experience a Recurrence of a Manic, Mixed Manic, Hypomanic, or Depressed Episode(28 weeks)
- Change From Double-blind Baseline to Week 28 (LOCF) in CGI-BP-S Overall Score(Double-blind Baseline to week 28)
- Change From Double -Blind Baseline to Week 28 (LOCF) in CGI-BP-S Mania Score(Double-blind Baseline to week 28)
- Change From Double-blind Baseline to Week 28 (LOCF) in CGI+-BP-S Depression Score(Double-blind Baseline to week 28)
- Change From Double-blind Baseline to Week 28 (LOCF) in YMRS Total Score(Double-blind Baseline to week 28)
- Change From Double-blind Baseline to Week 28 (LOCF) in MADRS Total Score(Double-blind Baseline to week 28)
- Change Fro Double-blind Baseline to Week 28 (LOCF) in QIDS-SR(16) Total Score(Double-blind Baseline to week 28)
- Change From Double-blind Baseline to Week 28 (LOF) in PANSS Positive Symptom (PANNS-P) Subscale Score(Double-blind Baseline to week 28)
- Change From Double-blind Baseline to Week 28 (LOCF) in SDS Total Score(Double-blind Baseline to week 28)
- Change From Double-blind Baseline to Week 28 (LOCF) in PIRS-2 Total Score(Double-blind Baseline to week 28)
- Change From Double-blind Baseline to Week 28 (LOCF) in Q-LES-Q-SF Percent Maximum Possible Score(Double-blind Baseline to week 28)