3-Week Study of Asenapine, Olanzapine and Placebo for Treatment of Bipolar Mania (P07008)

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. Patients will receive either asenapine, olanzapine (a medication that is already approved for the treatment of bipolar mania), or placebo (no active medication). Patients will be required to stay in the hospital for at least the first seven days of treatment. Patients that 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 7501004 (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 DSMIV diagnosis of bipolar I disorder, current episode manic or mixed. Exclusion Criteria: Patients with unstable medical conditions or clinically significant laboratory abnormalities or patients who are rapid cyclers (ie. 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 |
| --- | --- |
| Active Comparator: 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 |
| --- | --- | --- |
| Changes in bipolar manic or mixed symptoms reflected in the scores on the YMRS (Young Mania Rating Scale) |  | The YMRS was administered at screening, baseline, Day 2, 4, 7, 14 and 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratings on the Clinical Global Impression scale in which severity and improvement of mania, depression, and overall bipolar state are rated. |  | The CGI assessment at days 1,7 and endpoint (day 21 or the time of the last assessment). | 
| The PANSS (Positive and Negative Symptom Scale) was used to assess psychotic symptoms |  | The PANSS was administered at Days 1, 7 and 21(or the time of the last assessment). | 
| The MADRS (Montgomery Asberg Depression Rating Scale) was used to assess depressive symptoms |  | The MADRS was administered on Days 1, 7 and 21(or at the time of the last assessment).l | 
| The Readiness for Discharge Questionaire (RDQ) was administered to characterize the subject's readiness for discharge. The investigator was to make the decision about discharging the subject. |  | The RDQ was administered on Day 1, 2, 4, 7 , 14 and 21 (or at the time of the last assessment) | 
| CogState, cognition battery, was used to assess changes in cognition |  | Cog State was administered at screening, Day 1 (baseline) and Days 7, 14, 21 (or endpoint). | 
| SF (short form)-36 and TSQM (Treatment Satisfaction Questionnaire for Medication) -- 2 measures of Quality of Life were administered. |  | The SF Health Survey was administered at Day 1 and Day 21 or endpoint. The TSMQ was administered at Day 21 or endpoint.. | 
| The SARS (Simpson Angus Rating Scale); the AIMS (Involuntary Movement Scale and the BARS (Barnes Akathisia Scale) were used to assess extrapyramidal symptoms |  | The SARS, AIMS and BARS assessments were administered at Days 1, 7 and 21 or endpoint. | 
| Concomitant medication use was recorded |  | Concomitant medication use was recorded whenever it occurred | 
| Physical examination, laboratory and electrocardiogram findings and weight/abdominal girth and vital signs were recorded. |  | Physical exam, ECG, laboratory and weight were recorded at screening and Day 21 or endpoint. Laboratory work was also done at baseline. | 
| Adverse events (AEs) |  | AEs were recorded whenever they occurred.. | 
| Pharmacokinetic analysis was done to determine the level of the drug in the blood |  | Pk samples were taken at Day 1, 7, 14 and 21 (or endpoint). |