Armodafinil Treatment as Adjunctive Therapy in Adults With Major Depression Associated With Bipolar I Disorder

Study Overview
=================
Brief Summary
-----------------
The primary objective of the study is to determine if armodafinil treatment, at a dosage of 150 mg/day, is more effective than placebo treatment as adjunctive therapy for adults who are experiencing a major depressive episode associated with Bipolar I Disorder and who are inadequately responsive to their current treatment for a current major depressive episode.

Official Title
-----------------
An 8 Week Double Blind, Placebo-Controlled, Parallel Group, Fixed Dosage Study to Evaluate the Efficacy and Safety of Armodafinil Treatment (150mg/Day) as Adjunctive Therapy in Adults With Major Depression Associated With Bipolar I Disorder

Conditions
-----------------
Bipolar I Depression

Intervention / Treatment
-----------------
* Drug: Armodafinil
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: The patient has a diagnosis of Bipolar I Disorder and is currently experiencing a major depressive episode. The patient is currently being treated with 1 or 2 of the following drugs: lithium, olanzapine, or valproic acid. Key Exclusion Criteria: The patient has any Axis I disorder apart from Bipolar I Disorder that was the primary focus of treatment within 6 months before the screening visit (with the exception of nicotine dependence). The patient has any clinically significant uncontrolled medical or surgical condition. The patient has previously received modafinil or armodafinil, or the patient has a known sensitivity to any ingredients in the study drug tablets. The patient is a pregnant or lactating woman. (Any woman becoming pregnant during the study will be withdrawn from the study.)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Armodafinil<br> | Drug: Armodafinil<br>* Patients were randomly assigned to begin oral treatment with armodafinil, which was titrated to 150 mg/day (3 tablets). Armodafinil was titrated up to the target dosage of 150 mg/day (daily dose was administered each morning). Patients began taking blinded armodafinil at a dose of 50 mg/day (1 tablet) on the day following the baseline visit. Doses were increased by 50 mg/day (1 tablet) to a dose of 100 mg/day on Day 2 and 3, and then again by 50 mg /day on day 4 for a target dose of 150 mg/day. Following titration, patients continued taking 150 mg/day of armodafinil for the duration of the study. If a patient was unable to tolerate (recurrent or persistent adverse events) the study drug, 1 reduction in dosage (ie, minimum dosage 100 mg/day [2 tablets]) was allowed. The dosage could not be increased after it was decreased.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Patients were randomly assigned to begin oral treatment with placebo, which was titrated to 3 tablets. Placebo tablets matching the 50 mg armodafinil tablet were used in a manner identical to that of the armodafinil tablets. Study drug was titrated up to the target dosage of 3 tablets / day (daily dose was administered each morning). Patients began taking blinded study drug at a dose of 1 tablet daily on the day following the baseline visit. Doses were increased by 1 tablet to a dose of 2 tablets/day on Day 2 and 3, and then again by 1 tablet /day on day 4 for a target dose of 3 tablets/day. Following titration, patients continued taking 3 tablets/day of study drug for the duration of the study. If a patient was unable to tolerate (recurrent or persistent adverse events) the study drug, 1 reduction in dosage (ie, minimum dosage 2 tablets/day) was allowed. The dosage could not be increased after it was decreased.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Mean Change From Baseline to Endpoint (Week 8 or Last Observation After Baseline) in the 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30) | The IDS C30 is a standardized 30 item, clinician rated scale to assess the severity of a patient's depressive symptoms. The scale uses the 9 symptom domains of the DSM-IV criteria to measure symptom severity. The scores range from a minimum of 0 to a maximum score of 84. The higher the score the more severe the symptoms of depression. The data presented here summarizes the change from baseline to Endpoint (either week 8 or the last observation after baseline) in the total score of the IDS-C30. | Baseline and 8 weeks from start of study drug administration (or last observation after baseline) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Mean Change From Baseline to Week 1 in the 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30) | The IDS C30 is a standardized 30 item, clinician rated, scale to assess the severity of a patient's depressive symptoms. The scale uses the 9 symptom domains of the DSM-IV criteria to measure symptom severity. The scores range from a minimum of 0 to a maximum score of 84. The higher the score the more severe the symptoms of depression. The data presented here summarizes the change from baseline to Week 1 in the total score of the IDS-C30. | Baseline and 1 week following the start of study drug administration | 
| The Mean Change From Baseline to Week 2 in the 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30) | The IDS C30 is a standardized 30 item, clinician rated, scale to assess the severity of a patient's depressive symptoms. The scale uses the 9 symptom domains of the DSM-IV criteria to measure symptom severity. The scores range from a minimum of 0 to a maximum score of 84. The higher the score the more severe the symptoms of depression. The data presented here summarizes the change from baseline to Week 2 in the total score of the IDS-C30. | Baseline and 2 weeks following the start of study drug administration | 
| The Mean Change From Baseline to Week 3 in the 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30) | The IDS C30 is a standardized 30 item, clinician rated, scale to assess the severity of a patient's depressive symptoms. The scale uses the 9 symptom domains of the DSM-IV criteria to measure symptom severity. The scores range from a minimum of 0 to a maximum score of 84. The higher the score the more severe the symptoms of depression. The data presented here summarizes the change from baseline to Week 3 in the total score of the IDS-C30. | Baseline and 3 weeks following the start of study drug administration | 
| The Mean Change From Baseline to Week 4 in the 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30) | The IDS C30 is a standardized 30 item, clinician rated, scale to assess the severity of a patient's depressive symptoms. The scale uses the 9 symptom domains of the DSM-IV criteria to measure symptom severity. The scores range from a minimum of 0 to a maximum score of 84. The higher the score the more severe the symptoms of depression. The data presented here summarizes the change from baseline to Week 4 in the total score of the IDS-C30. | Baseline and 4 weeks following the start of study drug administration | 
| The Mean Change From Baseline to Week 6 in the 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30) | The IDS C30 is a standardized 30 item, clinician rated, scale to assess the severity of a patient's depressive symptoms. The scale uses the 9 symptom domains of the DSM-IV criteria to measure symptom severity. The scores range from a minimum of 0 to a maximum score of 84. The higher the score the more severe the symptoms of depression. The data presented here summarizes the change from baseline to Week 6 in the total score of the IDS-C30. | Baseline and 6 weeks following the start of study drug administration | 
| The Mean Change From Baseline to Week 8 in the 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30) | The IDS C30 is a standardized 30 item, clinician rated, scale to assess the severity of a patient's depressive symptoms. The scale uses the 9 symptom domains of the DSM-IV criteria to measure symptom severity. The scores range from a minimum of 0 to a maximum score of 84. The higher the score the more severe the symptoms of depression. The data presented here summarizes the change from baseline to Week 8 in the total score of the IDS-C30. | Baseline and 8 weeks following the start of study drug administration | 
| Number of Patients Achieving Remission at Endpoint According to the 30-item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) | The IDS C30 is a standardized 30 item, clinician rated, scale to assess the severity of a patient's depressive symptoms. The scale uses the 9 symptom domains of the DSM-IV criteria to measure symptom severity. The scores range from a minimum of 0 to a maximum score of 84. The higher the score the more severe the symptoms of depression. The data here summarizes the number of subjects in each treatment group who achieved a remission (total score <=11). | Baseline, 4 and 8 weeks following start of study drug administration (or last observation after baseline) | 
| Number of Patients Achieving Response at Endpoint According to the 30-item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) | The IDS C30 is a standardized 30 item, clinician rated, scale to assess the severity of a patient's depressive symptoms. The scale uses the 9 symptom domains of the DSM-IV criteria to measure symptom severity. The scores range from a minimum of 0 to a maximum score of 84. The higher the score the more severe the symptoms of depression. The data here summarizes the number of subjects in each treatment group who achieved a response (> 50% decrease from baseline in total score). | Baseline, 4 and 8 weeks following start of study drug administration (or last observation after baseline) | 
| Number of Patients Achieving Sustained Remission at Endpoint According to the 30-item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) | The IDS C30 is a standardized 30 item, clinician rated, scale to assess the severity of a patient's depressive symptoms. The scale uses the 9 symptom domains of the DSM-IV criteria to measure symptom severity. The scores range from a minimum of 0 to a maximum score of 84. The higher the score the more severe the symptoms of depression. The data here summarizes the number of subjects in each treatment group who achieved a sustained remission (total score <= 11 that persists over the four week period from Week 4 to Week 8). | Baseline, 4 and 8 weeks following start of study drug administration (or last observation after baseline) | 
| Number of Patients Achieving Sustained Response at Endpoint According to the 30-item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) | The IDS C30 is a standardized 30 item, clinician rated, scale to assess the severity of a patient's depressive symptoms. The scale uses the 9 symptom domains of the DSM-IV criteria to measure symptom severity. The scores range from a minimum of 0 to a maximum score of 84. The higher the score the more severe the symptoms of depression. The data here summarizes the number of subjects in each treatment group who achieved a sustained response (> 50% decrease from baseline in total score that persisted over the four week period between Week 4 and Week 8). | Baseline, 4 and 8 weeks following start of study drug administration (or last observation after baseline) | 
| Change From Baseline to Endpoint (Week 8 or Last Observation After Baseline) on 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30) Combination of Items 1-3 | The IDS C30 is a standardized 30 item, clinician rated, scale to assess the severity of a patient's depressive symptoms. The scale uses the 9 symptom domains of the DSM-IV criteria to measure symptom severity. The scores range from a minimum of 0 to a maximum score of 84. The higher the score the more severe the symptoms of depression. Items 1 - 3 assess sleep onset insomnia, mid-nocturnal insomnia, and early morning insomnia respectively each on a 0 - 3 scale. The data presented here summarizes the change from baseline to Endpoint in the combined score of these three items assessing insomnia. | Baseline and 8 weeks (or last observation after baseline) | 
| Change From Baseline to Week 4 on 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30) Combination of Items 1-3 | The IDS C30 is a standardized 30 item, clinician rated, scale to assess the severity of a patient's depressive symptoms. The scale uses the 9 symptom domains of the DSM-IV criteria to measure symptom severity. The scores range from a minimum of 0 to a maximum score of 84. The higher the score the more severe the symptoms of depression. Items 1 - 3 assess sleep onset insomnia, mid-nocturnal insomnia, and early morning insomnia respectively each on a 0 - 3 scale. The data presented here summarizes the change from baseline to week 4 in the combined score of these three items assessing insomnia. | Baseline and 4 weeks following the start of study drug administration | 
| Change From Baseline to Week 8 on 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30) Combination of Items 1-3 | The IDS C30 is a standardized 30 item, clinician rated, scale to assess the severity of a patient's depressive symptoms. The scale uses the 9 symptom domains of the DSM-IV criteria to measure symptom severity. The scores range from a minimum of 0 to a maximum score of 84. The higher the score the more severe the symptoms of depression. Items 1 - 3 assess sleep onset insomnia, mid-nocturnal insomnia, and early morning insomnia respectively each on a 0 - 3 scale. The data presented here summarizes the change from baseline to week 8 in the combined score of these three items assessing insomnia. | Baseline and 8 weeks following the start of study drug administration | 
| Change From Baseline to Endpoint (Week 8 or Last Observation After Baseline) on 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30) - Item 4 | The IDS C30 is a standardized 30 item, clinician rated, scale to assess the severity of a patient's depressive symptoms. The scale uses the 9 symptom domains of the DSM-IV criteria to measure symptom severity. The scores range from a minimum of 0 to a maximum score of 84. The higher the score the more severe the symptoms of depression. Item 4 assesses hypersomnia on a scale from 0 (sleeps no longer than 7-8 hours a night) to 3 (sleeps longer than 12 hours in 24 hour period). The data presented here summarizes the change from baseline to Endpoint in the score of Item 4 assessing hypersomnia. | Baseline and 8 weeks (or last observation after baseline) | 
| Change From Baseline to Week 4 on 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30) - Item 4 | The IDS C30 is a standardized 30 item, clinician rated, scale to assess the severity of a patient's depressive symptoms. The scale uses the 9 symptom domains of the DSM-IV criteria to measure symptom severity. The scores range from a minimum of 0 to a maximum score of 84. The higher the score the more severe the symptoms of depression. Item 4 assesses hypersomnia on a scale from 0 (sleeps no longer than 7-8 hours a night) to 3 (sleeps longer than 12 hours in 24 hour period). The data presented here summarizes the change from baseline to week 4 in the score of Item 4 assessing hypersomnia. | Baseline and 4 weeks following the start of study drug administration | 
| Change From Baseline to Week 8 on 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30) - Item 4 | The IDS C30 is a standardized 30 item, clinician rated, scale to assess the severity of a patient's depressive symptoms. The scale uses the 9 symptom domains of the DSM-IV criteria to measure symptom severity. The scores range from a minimum of 0 to a maximum score of 84. The higher the score the more severe the symptoms of depression. Item 4 assesses hypersomnia on a scale from 0 (sleeps no longer than 7-8 hours a night) to 3 (sleeps longer than 12 hours in 24 hour period). The data presented here summarizes the change from baseline to week 8 in the score of Item 4 assessing hypersomnia. | Baseline and 8 weeks following the start of study drug administration | 
| Change From Baseline to Endpoint (Week 8 or Last Observation After Baseline) in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | The MADRS is a 10-item scale to evaluate the overall severity of a patient's depressive symptoms, that is completed by the physician. The rating scale makes use of both observational clues as to the subject's level of depression (eg. apparent sadness) and verbal indicators of depression expressed by the patient. Each of the 10 items is graded on a 6-point scale with anchors at 2 point intervals. Total scores range from 0 to 60, with the higher number indicating more severe symptoms of depression. Here we present data summarizing the change in MADRS from Baseline to Endpoint. | Baseline and Endpoint (8 weeks following the start of study drug administration or last observation after baseline) | 
| Change From Baseline to Week 4 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | The MADRS is a 10-item scale to evaluate the overall severity of a patient's depressive symptoms, that is completed by the physician. The rating scale makes use of both observational clues as to the subject's level of depression (eg. apparent sadness) and verbal indicators of depression expressed by the patient. Each of the 10 items is graded on a 6-point scale with anchors at 2 point intervals. Total scores range from 0 to 60, with the higher number indicating more severe symptoms of depression. Here we present data summarizing the difference in MADRS score from Baseline to Week 4. | Baseline and 4 weeks following the start of study drug administration | 
| Change From Baseline to Week 8 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | The MADRS is a 10-item scale to evaluate the overall severity of a patient's depressive symptoms, that is completed by the physician. The rating scale makes use of both observational clues as to the subject's level of depression (eg. apparent sadness) and verbal indicators of depression expressed by the patient. Each of the 10 items is graded on a 6-point scale with anchors at 2 point intervals. Total scores range from 0 to 60, with the higher number indicating more severe symptoms of depression. Here we present data summarizing the difference in MADRS score from Baseline to Week 8. | Baseline and 8 weeks following the start of study drug administration | 
| Change From Baseline to Endpoint (Week 8 or Last Observation After Baseline) in the Quick Inventory of Depressive Symptomatology - 16 Items (QIDS-SR16) | The QIDS-SR16 is a 16-item rating scale of depressive symptoms completed by the patient at each visit. It is a shorter version of the IDS-C30 that is completed by the patient rather than the examiner. The total score ranges from 0 to 27 (higher score signifies more severe depression) and is obtained by adding the scores for each of the 9 depression symptom domains of the DSM IV. The data presented here summarizes the change in QIDS-SR16 from Baseline to Endpoint (Week 8 or last observation after baseline). | Baseline and 8 weeks (or last observation after baseline) | 
| Change From Baseline to Week 1 in the Quick Inventory of Depressive Symptomatology - 16 Items (QIDS-SR16) | The QIDS-SR16 is a 16-item rating scale of depressive symptoms completed by the patient at each visit. It is a shorter version of the IDS-C30 that is completed by the patient rather than the examiner. The total score ranges from 0 to 27 (higher score signifies more severe depression) and is obtained by adding the scores for each of the 9 depression symptom domains of the DSM IV. The data presented here summarizes the change in QIDS-SR16 from Baseline to Week 1 | Baseline and 1 week following the start of study drug administration | 
| Change From Baseline to Week 2 in the Quick Inventory of Depressive Symptomatology - 16 Items (QIDS-SR16) | The QIDS-SR16 is a 16-item rating scale of depressive symptoms completed by the patient at each visit. It is a shorter version of the IDS-C30 that is completed by the patient rather than the examiner. The total score ranges from 0 to 27 (higher score signifies more severe depression) and is obtained by adding the scores for each of the 9 depression symptom domains of the DSM IV. The data presented here summarizes the change in QIDS-SR16 from Baseline to Week 2 | Baseline and 2 weeks following the start of study drug administration | 
| Change From Baseline to Week 3 in the Quick Inventory of Depressive Symptomatology - 16 Items (QIDS-SR16) | The QIDS-SR16 is a 16-item rating scale of depressive symptoms completed by the patient at each visit. It is a shorter version of the IDS-C30 that is completed by the patient rather than the examiner. The total score ranges from 0 to 27 (higher score signifies more severe depression) and is obtained by adding the scores for each of the 9 depression symptom domains of the DSM IV. The data presented here summarizes the change in QIDS-SR16 from Baseline to Week 3. | Baseline and 3 weeks following the start of study drug administration | 
| Change From Baseline to Week 4 in the Quick Inventory of Depressive Symptomatology - 16 Items (QIDS-SR16) | The QIDS-SR16 is a 16-item rating scale of depressive symptoms completed by the patient at each visit. It is a shorter version of the IDS-C30 that is completed by the patient rather than the examiner. The total score ranges from 0 to 27 (higher score signifies more severe depression) and is obtained by adding the scores for each of the 9 depression symptom domains of the DSM IV. The data presented here summarizes the change in QIDS-SR16 from Baseline to Week 4. | Baseline and 4 weeks following the start of study drug administration | 
| Change From Baseline to Week 6 in the Quick Inventory of Depressive Symptomatology - 16 Items (QIDS-SR16) | The QIDS-SR16 is a 16-item rating scale of depressive symptoms completed by the patient at each visit. It is a shorter version of the IDS-C30 that is completed by the patient rather than the examiner. The total score ranges from 0 to 27 (higher score signifies more severe depression) and is obtained by adding the scores for each of the 9 depression symptom domains of the DSM IV. The data presented here summarizes the change in QIDS-SR16 from Baseline to Week 6. | Baseline and 6 weeks following the start of study drug administration | 
| Change From Baseline to Week 8 in the Quick Inventory of Depressive Symptomatology - 16 Items (QIDS-SR16) | The QIDS-SR16 is a 16-item rating scale of depressive symptoms completed by the patient at each visit. It is a shorter version of the IDS-C30 that is completed by the patient rather than the examiner. The total score ranges from 0 to 27 (higher score signifies more severe depression) and is obtained by adding the scores for each of the 9 depression symptom domains of the DSM IV. The data presented here summarizes the change in QIDS-SR16 from Baseline to Week 8. | Baseline and 8 weeks following the start of study drug administration | 
| Change From Baseline to Endpoint (Week 8 or Last Observation After Baseline) in the Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) | The Q-LES-Q-SF is an instrument designed to measure general activities of daily living. It is a patient-rated quality of life questionnaire and consists of 16 items, but only the first 14 are included in the total score. Each item is rated by the patient on a scale from 1 - 5 (1=very poor, 2=poor, 3=fair, 4=good, and 5=very good). The minimum score is 14 and the maximum score is 70, with lower scores indicating poorer quality of life. The data presented here summarizes the change in score from baseline to endpoint (8 weeks or last observation after baseline). | Baseline and 8 weeks (or last observation after baseline) | 
| Change From Baseline to Week 4 in the Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) | The Q-LES-Q-SF is an instrument designed to measure general activities of daily living. It is a patient-rated quality of life questionnaire and consists of 16 items, but only the first 14 are included in the total score. Each item is rated by the patient on a scale from 1 - 5 (1=very poor, 2=poor, 3=fair, 4=good, and 5=very good). The minimum score is 14 and the maximum score is 70, with lower scores indicating poorer quality of life. The data presented here summarizes the change in score from baseline to 4 weeks. | Baseline and 4 weeks following the start of study drug administration | 
| Change From Baseline to Week 8 in the Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) | The Q-LES-Q-SF is an instrument designed to measure general activities of daily living. It is a patient-rated quality of life questionnaire and consists of 16 items, but only the first 14 are included in the total score. Each item is rated by the patient on a scale from 1 - 5 (1=very poor, 2=poor, 3=fair, 4=good, and 5=very good). The minimum score is 14 and the maximum score is 70, with lower scores indicating poorer quality of life. The data presented here summarizes the change in score from baseline to 8 weeks. | Baseline and 8 weeks following the start of study drug administration | 
| Change From Baseline to Endpoint (8 Weeks or Last Observation After Baseline) in Hamilton Anxiety Scale (HAM-A) Total Score | The HAM-A is a clinician-rated 14 item scale that provides an overall measure of global anxiety, including psychic (mental agitation and psychological distress) and somatic (physical complaints related to anxiety) symptoms. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0 - 56, where less than 17 indicates mild anxiety, 18 - 24 mild to moderate anxiety, 25-30 moderate to severe, >30 very severe. The data presented here summarizes the change in HAM-A score from Baseline to Endpoint (8 weeks or last observation after baseline). | baseline and 8 weeks (or last observation after baseline) | 
| Change From Baseline to 4 Weeks in the Hamilton Anxiety Scale (HAM A) Total Score | The HAM-A is a clinician-rated 14 item scale that provides an overall measure of global anxiety, including psychic (mental agitation and psychological distress) and somatic (physical complaints related to anxiety) symptoms. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0 - 56, where less than 17 indicates mild anxiety, 18 - 24 mild to moderate anxiety and 25-30 moderate to severe. The data presented here summarizes the change in HAM-A score from Baseline to 4 Weeks | Baseline and 4 weeks following the start of study drug administration | 
| Change From Baseline to 8 Weeks in the Hamilton Anxiety Scale (HAM A) Total Score | The HAM-A is a clinician-rated 14 item scale that provides an overall measure of global anxiety, including psychic (mental agitation and psychological distress) and somatic (physical complaints related to anxiety) symptoms. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0 - 56, where less than 17 indicates mild anxiety, 18 - 24 mild to moderate anxiety and 25-30 moderate to severe. The data presented here summarizes the change in HAM-A score from Baseline to 8 Weeks | Baseline and 8 weeks following the start of study drug administration | 
| The Number of Responders According to the Clinical Global Impression of Change - Bipolar Version (CGI BP) Measure of Depression at Endpoint (Week 8 or Last Observation After Baseline) | CGI-BP is a standardized, clinician-rated assessment which allows the clinician to rate the bipolar illness at various time points compared with baseline. At Screening and Baseline visits the physician rated the severity of the illness using 7 categories (1=normal through 7=very severely ill). At subsequent visits the clinician assessed the change in severity of the condition using 7 categories (1=very much improved through 7=very much worse). Subjects were considered responders if they had a rating of much improved or very much improved. The number of responders at Endpoint are presented. | Baseline and 8 weeks (or last observation after baseline) | 
| The Number of Responders According to the Clinical Global Impression of Change - Bipolar Version (CGI BP) Measure of Depression at Week 1 | CGI-BP is a standardized, clinician-rated assessment which allows the clinician to rate the bipolar illness at various time points compared with baseline. At Screening and Baseline visits the physician rated the severity of the illness using 7 categories (1=normal through 7=very severely ill). At subsequent visits the clinician assessed the change in severity of the condition using 7 categories (1=very much improved through 7=very much worse). Subjects were considered responders if they had a rating of much improved or very much improved. The number of responders at Week 1 are presented. | Baseline and 1 week following the start of study drug administration | 
| The Number of Responders According to the Clinical Global Impression of Change - Bipolar Version (CGI BP) Measure of Depression at Week 2 | CGI-BP is a standardized, clinician-rated assessment which allows the clinician to rate the bipolar illness at various time points compared with baseline. At Screening and Baseline visits the physician rated the severity of the illness using 7 categories (1=normal through 7=very severely ill). At subsequent visits the clinician assessed the change in severity of the condition using 7 categories (1=very much improved through 7=very much worse). Subjects were considered responders if they had a rating of much improved or very much improved. The number of responders at Week 2 are presented. | Baseline and 2 weeks following the start of study drug administration | 
| The Number of Responders According to the Clinical Global Impression of Change - Bipolar Version (CGI BP) Measure of Depression at Week 3 | CGI-BP is a standardized, clinician-rated assessment which allows the clinician to rate the bipolar illness at various time points compared with baseline. At Screening and Baseline visits the physician rated the severity of the illness using 7 categories (1=normal through 7=very severely ill). At subsequent visits the clinician assessed the change in severity of the condition using 7 categories (1=very much improved through 7=very much worse). Subjects were considered responders if they had a rating of much improved or very much improved. The number of responders at Week 3 are presented. | Baseline and 3 weeks following the start of study drug administration | 
| The Number of Responders According to the Clinical Global Impression of Change - Bipolar Version (CGI BP) Measure of Depression at Week 4 | CGI-BP is a standardized, clinician-rated assessment which allows the clinician to rate the bipolar illness at various time points compared with baseline. At Screening and Baseline visits the physician rated the severity of the illness using 7 categories (1=normal through 7=very severely ill). At subsequent visits the clinician assessed the change in severity of the condition using 7 categories (1=very much improved through 7=very much worse). Subjects were considered responders if they had a rating of much improved or very much improved. The number of responders at Week 4 are presented. | Baseline and 4 weeks following the start of study drug administration | 
| The Number of Responders According to the Clinical Global Impression of Change - Bipolar Version (CGI BP) Measure of Depression at Week 6 | CGI-BP is a standardized, clinician-rated assessment which allows the clinician to rate the bipolar illness at various time points compared with baseline. At Screening and Baseline visits the physician rated the severity of the illness using 7 categories (1=normal through 7=very severely ill). At subsequent visits the clinician assessed the change in severity of the condition using 7 categories (1=very much improved through 7=very much worse). Subjects were considered responders if they had a rating of much improved or very much improved. The number of responders at Week 6 are presented. | Baseline and 6 weeks following the start of study drug administration | 
| The Number of Responders According to the Clinical Global Impression of Change - Bipolar Version (CGI BP) Measure of Depression at Week 8 | CGI-BP is a standardized, clinician-rated assessment which allows the clinician to rate the bipolar illness at various time points compared with baseline. At Screening and Baseline visits the physician rated the severity of the illness using 7 categories (1=normal through 7=very severely ill). At subsequent visits the clinician assessed the change in severity of the condition using 7 categories (1=very much improved through 7=very much worse). Subjects were considered responders if they had a rating of much improved or very much improved. The number of responders at Week 8 are presented. | Baseline and 8 weeks following the start of study drug administration |