40 Week Trial to Study the Safety of Asenapine When Added to Lithium or Valproate in the Treatment of Bipolar Disorder (A7501009)(P05786)

Study Overview
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Brief Summary
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The primary objective of this trial was to characterize the long-term (up to 40 weeks) safety and tolerability of asenapine in bipolar I disorder subjects who had not completely responded to continuing treatment with lithium or valproic acid (VPA) for the treatment of an acute manic or mixed episodes upon enrollment into the 12-week lead-in trial, A7501008 (NCT00145470). The safety comparison was between the group receiving lithium or VPA and placebo against the group receiving lithium or VPA and asenapine, with the caveat that all subjects may have received benzodiazepine and/or antidepressant rescue medication as needed.

Official Title
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A Phase 3, Placebo-Controlled, Double-Blinded Continuation Trial Evaluating the Safety and Efficacy of Asenapine in Subjects Completing a 12-week Lead-in Trial and Continuing Lithium or Valproic Acid/Divalproex Sodium for the Treatment of an Acute Manic or Mixed Episode

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Drug: Asenapine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have bipolar I disorder (current episode manic or mixed), be treated with lithium or valproic acid, and have completed the a 12-week lead-in trial Exclusion Criteria: Have an unstable medical condition or clinically significant laboratory abnormality. Have a primary diagnosis other than bipolar I disorder.

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Asenapine<br>Asenapine | Drug: Asenapine<br>* Asenapine 5 or 10 mg twice daily (BID) sublingually for 40 weeks<br>* Other names: Org 5222;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Fast-dissolving tablet; twice daily (BID) sublingually for 40 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced an Adverse Event | Participants who experienced treatment-emergent adverse events, defined as adverse events reported on or after the first dose of study medication in the 12-week lead-in study through the last dose of study drug + 7 days (or + 30 days for serious adverse events). | up to 52 weeks | 
| Number of Participants Who Discontinued Because of an Adverse Event | Participants who discontinued study medication due to adverse events. | 40 weeks | 
| Change From Baseline to Week 52 on the Young-Mania Rating Scale (Y-MRS) Score | The Y-MRS is an 11-item, clinician-rated instrument used for assessing the symptoms of mania. Y-MRS total score range = 0-60; higher scores indicate greater severity of symptoms. | Baseline and 52 Weeks | 
| Change From Baseline to Week 52 on the Montgomery Asberg Depression Rating Scale (MADRS) Score | The MADRS is a 10-item clinician-rated scale for assessing the severity of symptoms of depression. MADRS total score range = 0-60; higher scores indicate greater severity of symptoms. | Baseline and 52 Weeks |