3-week Study of Asenapine, Olanzapine and Placebo for Treatment of Bipolar Mania (P07009)

Study Overview
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Brief Summary
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Bipolar disorder is characterized by mood swings that range from high (manic) to low (depressed) states. Sometimes, symptoms of both depression and mania are present (mixed episodes). Asenapine is an investigational medication for the treatment of manic or mixed episodes of bipolar disorder. This is a 3-week study that will test the safety and efficacy of this medication. Participants will receive either asenapine, olanzapine (a medication that is already approved for the treatment of bipolar mania), or placebo (no active medication). Participants will be required to stay in the hospital for at least the first seven days of treatment. Participants who complete the 3 week study may be eligible to continue in extension studies for an additional 9 (study A7501006) to 49 (study A7501007) weeks.

Official Title
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A Phase III, Randomized, Placebo-Controlled, Double-Blind Trial Evaluating the Safety and Efficacy of Sublingual Asenapine vs. Olanzapine and Placebo in In-Patients With an Acute Manic Episode Clinical Trial Protocol 7501005 (Secondary Title: ARES)

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Drug: Asenapine
* Drug: Olanzapine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) diagnosis of bipolar I disorder, current episode manic or mixed. Exclusion Criteria: Participants with unstable medical conditions or clinically significant laboratory abnormalities or participants who are rapid cyclers (i.e., have had 4 or more (including current) mood episodes in the past 12 months); have any other psychiatric disorder other than bipolar I disorder as a primary diagnosis.

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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Asenapine | Drug: Asenapine<br>* Asenapine, 3 weeks<br>* Other names: Org 5222;|
| Active Comparator: Arm 2<br>Olanzapine | Drug: Olanzapine<br>* Olanzapine, 3 weeks<br>|
| Placebo Comparator: Arm 3<br>Placebo | Drug: Placebo<br>* placebo, 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Day 21 on the Young Mania Rating Scale (YMRS) Total Score |  | Baseline to Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Day 21 in the Clinical Global Impression Scale for use in Bipolar Disorder (CGI-BP) Severity of Mania |  | Baseline to Day 21 | 
| Change from Baseline to Day 21 in the Positive and Negative Symptom Scale (PANSS) Total Score |  | Baseline to Day 21 | 
| Change from Baseline to Day 21 in Montgomery Asberg Depression Rating Scale (MADRS) Total Score |  | Baseline to Day 21 | 
| Readiness for Discharge Questionnaire (RDQ) |  | Baseline to Day 21 | 
| Change from Baseline to Day 21 in Central Nervous System (CNS) Vital Signs |  | Baseline to Day 21 | 
| Change from Baseline to Day 21 in Short Form-36 (SF-36) - Physical Component Summary Scores |  | Baseline to Day 21 | 
| Change from Baseline to Day 21 in the Severity of Extrapyramidal Symptoms (EPS) |  | Baseline to Day 21 | 
| Concomitant Medication Usage |  | Up to Day 21 | 
| Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | Up to 30 days after last dose (Up to approximately 51 days) | 
| Change from Baseline to Each Time Point in YMRS Total Score |  | Days 2, 4, 7, 14, and 21 | 
| Change from Baseline to Day 21 in the CGI-BP Severity of Depression |  | Baseline to Day 21 | 
| Change from Baseline to Day 21 in the CGI-BP Severity of Overall Bipolar Illness |  | Baseline to Day 21 | 
| Change from Baseline to Day 21 in SF-36 - Mental Component Summary Scores |  | Baseline to Day 21 | 
| Treatment Satisfaction Questionnaire for Medicine (TSQM) Overall Impact Domain Score at Day 21 |  | Day 21 | 
| Mean Change from Baseline for Vital Signs |  | Baseline up to Day 21 | 
| Change from Baseline to Day 21 in Body Weight |  | Baseline to Day 21 | 
| Summary of Post-Baseline Markedly Abnormal Biochemistry Laboratory Changes/Values |  | Up to Day 21 | 
| Summary of Post-Baseline Markedly Abnormal Endocrinology/Miscellaneous Laboratory Changes/Values |  | Up to Day 21 | 
| Summary of Post-Baseline Markedly Abnormal Metabolic Chemistry Laboratory Changes/Values |  | Up to Day 21 | 
| Summary of Post-Baseline Markedly Abnormal Hematology Laboratory Values |  | Up to Day 21 | 
| Pharmacokinetics - Plasma asenapine concentrations |  | Day 1 (pre-dose), 7, 14 and 21 (or endpoint) |