Trial Outcomes & Findings for A Study to Evaluate the Efficacy of FK949E in Bipolar Disorder Patients With Major Depressive Episodes (NCT NCT01725308)

Japanese patients with bipolar I or bipolar II as specified in Diagnostic and Statistical Manual of Mental Disorders Ver. 4 Text Revision (DSM-IV-TR) whose most recent episode was diagnosed as a major depressive episode using the Mini-International Neuropsychiatric Interview (MINI) were recruited for this study.

Assignment of participants to the FK949E 150 mg group was discontinued with implementation of Version 3.0 of the protocol.

A Study to Evaluate the Efficacy of FK949E in Bipolar Disorder Patients With Major Depressive Episodes

The MADRS is a 10-item scale to measure the severity of depressive episodes, where each item is rated on a scale from 0 to 6. The MADRS total score ranges from 0 to 60 with lower scores indicating less depressive symptoms.

The MADRS is a 10-item scale to measure the severity of depressive episodes, where each item is rated on a scale from 0 to 6. The MADRS total score ranges from 0 to 60 with lower scores indicating less depressive symptoms.

The MADRS is a10-item scale to measure the severity of depressive episodes, where each item is rated on a scale from 0 to 6. The MADRS total score ranges from 0 to 60 with lower scores indicating less depressive symptoms. Baseline for Placebo / FK949E was at week 12 therefore no data were calculated for weeks 1-12.

A MADRS response was defined as a decrease in MADRS total score of 50% or more from baseline. The MADRS is a10-item scale to measure the severity of depressive episodes, where each item is rated on a scale from 0 to 6. The MADRS total score ranges from 0 to 60 with lower scores indicating less depressive symptoms.

A MADRS response was defined as a decrease in MADRS total score of 50% or more from baseline. The MADRS is a 10-item scale to measure the severity of depressive episodes, where each item is rated on a scale from 0 to 6. The MADRS total score ranges from 0 to 60 with lower scores indicating less depressive symptoms. Baseline for Placebo / FK949E was at week 12 therefore no data were calculated for weeks 1-12.

MADRS remission was defined as MADRS total score of 12 or less. The MADRS is a 10-item scale to measure the severity of depressive episodes, where each item is rated on a scale from 0 to 6. The MADRS total score ranges from 0 to 60 with lower scores indicating less depressive symptoms.

MADRS remission was defined as MADRS total score of 12 or less. The MADRS is a 10-item scale to measure the severity of depressive episodes, where each item is rated on a scale from 0 to 6. The MADRS total score ranges from 0 to 60 with lower scores indicating less depressive symptoms. Baseline for Placebo / FK949E was at week 12 therefore no data were calculated for weeks 1-10.

The HAM-D17 is a clinician-rated 17-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 52, where a higher score indicates a greater depressive state.

The HAM-D17 is a clinician-rated 17-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 52, where a higher score indicates a greater depressive state. Baseline for Placebo / FK949E was at week 12 therefore no data were calculated for weeks 1-12.

A HAM-D17 response was defined as a decrease in HAM-D17 total score of 50% or more from baseline. The HAM-D17 is a clinician-rated 17-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 52, where a higher score indicates a greater depressive state.

A HAM-D17 response was defined as a decrease in HAM-D17 total score of 50% or more from baseline. The HAM-D17 is a clinician-rated 17-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 52, where a higher score indicates a greater depressive state. Baseline for Placebo / FK949E was at week 12 therefore no data were calculated for weeks 1-12.

The CGI-BP-S is a scale which assesses a participant's severity of their overall bipolar illness, depression, and mania as assessed by the clinician using a scale from 1 (not ill) to 7 (very severely ill).

The CGI-BP-S is a scale which assesses a participant's severity of their overall bipolar illness, depression, and mania as assessed by the clinician using a scale from 1 (not ill) to 7 (very severely ill). Baseline for Placebo / FK949E was at week 12 therefore no data were calculated for weeks 1-12.

The CGI-BP-S is a scale which assesses a participant's severity of their overall bipolar illness, depression, and mania as assessed by the clinician with the scale from 1 (not ill) to 7 (very severely ill).

The CGI-BP-S is a scale which assesses a participant's severity of their overall bipolar illness, depression, and mania as assessed by the clinician using a scale from 1 (not ill) to 7 (very severely ill). Baseline for Placebo / FK949E was at week 12 therefore no data were calculated for weeks 1-12.

The CGI-BP-S is a scale which assesses a participant's severity of their overall bipolar illness, depression, and mania as assessed by the clinician with the scale from 1 (not ill) to 7 (very severely ill).

The CGI-BP-S is a scale which assesses a participant's severity of their overall bipolar illness, depression, and mania as assessed by the clinician using a scale from 1 (not ill) to 7 (very severely ill). Baseline for Placebo / FK949E was at week 12 therefore no data were calculated for weeks 1-12.

The CGI-BP-C is a scale which assesses the degree of change or improvement from baseline for each of overall bipolar illness, depression and mania, by grading it using 8 grades, from 1 (very much improved) to 7 (very much worse) or 8 (not applicable). Grade 8 (not applicable) was regarded as a missing value for purposes of calculating the mean score.

The CGI-BP-C is a scale which assesses the degree of change or improvement from baseline for each of overall bipolar illness, depression and mania, by grading it using 8 grades, from 1 (very much improved) to 7 (very much worse) or 8 (not applicable). Grade 8 (not applicable) was regarded as a missing value for purposes of calculating the mean score. Baseline for Placebo / FK949E was at week 12 therefore no data were calculated for weeks 1-10.

The CGI-BP-C is a scale which assesses the degree of change or improvement from baseline for each of overall bipolar illness, depression and mania, by grading it using 8 grades, from 1 (very much improved) to 7 (very much worse) or 8 (not applicable). Grade 8 (not applicable) was regarded as a missing value for purposes of calculating the mean score.

The CGI-BP-C is a scale which assesses the degree of change or improvement from baseline for each of overall bipolar illness, depression and mania, by grading it using 8 grades, from 1 (very much improved) to 7 (very much worse) or 8 (not applicable). Grade 8 (not applicable) was regarded as a missing value for purposes of calculating the mean score. Baseline for Placebo / FK949E was at week 12 therefore no data were calculated for weeks 1-10.

The CGI-BP-C is a scale which assesses the degree of change or improvement from baseline for each of overall bipolar illness, depression and mania, by grading it using 8 grades, from 1 (very much improved) to 7 (very much worse) or 8 (not applicable). Grade 8 (not applicable) was regarded as a missing value for purposes of calculating the mean score.

The CGI-BP-C is a scale which assesses the degree of change or improvement from baseline for each of overall bipolar illness, depression and mania, by grading it using 8 grades, from 1 (very much improved) to 7 (very much worse) or 8 (not applicable). Grade 8 (not applicable) was regarded as a missing value for purposes of calculating the mean score. Baseline for Placebo / FK949E was at week 12 therefore no data were calculated for weeks 1-10.

An adverse event (AE) is defined as any undesirable or unintended sign (including abnormal laboratory test values), symptom, or disease occurring while the study drug was administered, regardless of whether or not there was a causal relationship with the study drug. A serious AE is defined as a an event resulting in death, persistent or significant disability/incapacity or congenital anomaly or birth defect, was life-threatening, required or prolonged hospitalization or was considered medically important.

An AE is defined as any undesirable or unintended sign (including abnormal laboratory test values), symptom, or disease occurring while the study drug was administered, regardless of whether or not there was a causal relationship with the study drug. A serious AE is defined as a an event resulting in death, persistent or significant disability/incapacity or congenital anomaly or birth defect, was life-threatening, required or prolonged hospitalization or was considered medically important. AEs reported are AEs that occurred after the start of the FK949E treatment for all groups.

The DIEPSS is a scale used to evaluate drug-induced extrapyramidal symptoms. DIEPSS is composed of 8 individual symptom parameters and a global assessment of severity, each rated on a 5-point scale, with lower scores indicating as "normal." The DIEPSS total score ranges from 0 (none, normal) to 32 (severe), and excludes the global assessment of severity.

The DIEPSS is a scale used to evaluate drug-induced extrapyramidal symptoms. DIEPSS is composed of 8 individual symptom parameters and a global assessment of severity, each rated on a 5-point scale, with lower scores indicating as "normal." The DIEPSS total score ranges from 0 (none, normal) to 32 (severe), and excludes the global assessment of severity. Baseline for Placebo / FK949E was at week 12 therefore no data were calculated for weeks 1-12.

The DIEPSS is a scale used to evaluate drug-induced extrapyramidal symptoms. DIEPSS is composed of 8 individual symptom parameters and a global assessment of severity, each rated on a 5-point scale, with lower scores indicating as "normal." Parkinsonism is a total of the gait disturbance, bradykinesia, salivation, muscle rigidity, and tremor scores and ranges from 0 (none, normal) to 20 (severe).

The DIEPSS is a scale used to evaluate drug-induced extrapyramidal symptoms. DIEPSS is composed of 8 individual symptom parameters and a global assessment of severity, each rated on a 5-point scale, with lower scores indicating as "normal." Parkinsonism is a total of the gait disturbance, bradykinesia, salivation, muscle rigidity, and tremor scores and ranges from 0 (none, normal) to 20 (severe). Baseline for Placebo / FK949E was at week 12 therefore no data were calculated for weeks 1-12.

The YMRS is a scale used to evaluate manic symptoms. The YMRS total score was the total assessment of assessed points for 11 items, ranges from 0 to 60 (each item is scored from either 0-4 or 0-8 by severity (0 = absent and 4/8 = displays mood/behavior to a greater degree). A lower score indicates "Absent" or "Normal."

The YMRS is a scale used to evaluate manic symptoms. The YMRS total score was the total assessment of assessed points for 11 items, ranges from 0 to 60 (each item is scored from either 0-4 or 0-8 by severity (0 = absent and 4/8 = displays mood/behavior to a greater degree). A lower score indicates "Absent" or "Normal." Baseline for Placebo / FK949E was at week 12 therefore no data were calculated for weeks 1-12.

The C-SSRS is a scale for assessing risk for suicidal behavior and suicide ideation and was administered by the clinician. Affirmative or negative responses were provided to 5 items for suicide ideation (1. Wish to be dead; 2. Suicidal thoughts; 3. Suicidal thoughts with a method (no specific plan or intent to act); 4. Suicidal intent (without a specific plan); 5. Suicidal intent with specific plan. If participants responded with a negative response for questions 1 and 2, the remaining questions are skipped. If question 2 was responded to with a positive response, the remaining questions need to be asked.

The C-SSRS is a scale for assessing risk for suicidal behavior and suicide ideation and was administered by the clinician. Affirmative or negative responses were provided to 5 items for suicide ideation (1. Wish to be dead; 2. Suicidal thoughts; 3. Suicidal thoughts with a method (no specific plan or intent to act); 4. Suicidal intent (without a specific plan); 5. Suicidal intent with specific plan. If participants responded with a negative response for questions 1 and 2, the remaining questions are skipped. If question 2 was responded to with a positive response, the remaining questions need to be asked. Baseline for Placebo / FK949E was at week 12 therefore no data were calculated for weeks 1-10.

The C-SSRS is a scale for assessing risk for suicidal behavior and suicide ideation and was administered by the clinician. Affirmative or negative responses were provided to 5 items for suicide ideation (1. Wish to be dead; 2. Suicidal thoughts; 3. Suicidal thoughts with a method (no specific plan or intent to act); 4. Suicidal intent (without a specific plan); 5. Suicidal intent with specific plan. If participants responded with a negative response for questions 1 and 2, the remaining questions are skipped. If question 2 was responded to with a positive response, the remaining questions need to be asked. Baseline for Placebo / FK949E was at week 12 therefore no data were calculated for weeks 1-10.

The C-SSRS is a scale for assessing risk for suicidal behavior and suicide ideation and was administered by the clinician. Affirmative or negative responses were provided to 5 items for suicide ideation (1. Wish to be dead; 2. Suicidal thoughts; 3. Suicidal thoughts with a method (no specific plan or intent to act); 4. Suicidal intent (without a specific plan); 5. Suicidal intent with specific plan. If participants responded with a negative response for questions 1 and 2, the remaining questions are skipped. If question 2 was responded to with a positive response, the remaining questions need to be asked. Baseline for Placebo / FK949E was at week 12 therefore no data were calculated for weeks 1-10.

The C-SSRS is a scale for assessing risk for suicidal behavior and suicide ideation and was administered by the clinician. Affirmative or negative responses were provided to 5 items for suicide ideation (1. Wish to be dead; 2. Suicidal thoughts; 3. Suicidal thoughts with a method (no specific plan or intent to act); 4. Suicidal intent (without a specific plan); 5. Suicidal intent with specific plan. If participants responded with a negative response for questions 1 and 2, the remaining questions are skipped. If question 2 was responded to with a positive response, the remaining questions need to be asked. Baseline for Placebo / FK949E was at week 12 therefore no data were calculated for weeks 1-10.

The C-SSRS is a scale for assessing risk for suicidal behavior and suicide ideation and was administered by the clinician. Affirmative or negative responses were provided to 5 items for suicide ideation (1. Wish to be dead; 2. Suicidal thoughts; 3. Suicidal thoughts with a method (no specific plan or intent to act); 4. Suicidal intent (without a specific plan); 5. Suicidal intent with specific plan. If participants responded with a negative response for questions 1 and 2, the remaining questions are skipped. If question 2 was responded to with a positive response, the remaining questions need to be asked. Baseline for Placebo / FK949E was at week 12 therefore no data were calculated for weeks 1-10.

The C-SSRS is a scale for assessing risk for suicidal behavior and suicide ideation and was administered by the clinician. Affirmative or negative responses were provided to 7 items to suicidal behaviors (1. suicide attempt; 2. Self-injury without suicide intent; 3. discontinued suicide attempt; 4. interrupted suicide attempt; 5. preliminary action to suicide; 6. suicidal behavior; 7. completed suicide).

The C-SSRS is a scale for assessing risk for suicidal behavior and suicide ideation and was administered by the clinician. Affirmative or negative responses were provided to 7 items to suicidal behaviors (1. suicide attempt; 2. Self-injury without suicide intent; 3. discontinued suicide attempt; 4. interrupted suicide attempt; 5. preliminary action to suicide; 6. suicidal behavior; 7. completed suicide). Baseline for Placebo / FK949E was at week 12 therefore no data were calculated for weeks 1-10.

The C-SSRS is a scale for assessing risk for suicidal behavior and suicide ideation and was administered by the clinician. Affirmative or negative responses were provided to 7 items to suicidal behaviors (1. suicide attempt; 2. Self-injury without suicide intent; 3. discontinued suicide attempt; 4. interrupted suicide attempt; 5. preliminary action to suicide; 6. suicidal behavior; 7. completed suicide). Baseline for Placebo / FK949E was at week 12 therefore no data were calculated for weeks 1-10.

The C-SSRS is a scale for assessing risk for suicidal behavior and suicide ideation and was administered by the clinician. Affirmative or negative responses were provided to 7 items to suicidal behaviors (1. suicide attempt; 2. Self-injury without suicide intent; 3. discontinued suicide attempt; 4. interrupted suicide attempt; 5. preliminary action to suicide; 6. suicidal behavior; 7. completed suicide). Baseline for Placebo / FK949E was at week 12 therefore no data were calculated for weeks 1-10.

The C-SSRS is a scale for assessing risk for suicidal behavior and suicide ideation and was administered by the clinician. Affirmative or negative responses were provided to 7 items to suicidal behaviors (1. suicide attempt; 2. Self-injury without suicide intent; 3. discontinued suicide attempt; 4. interrupted suicide attempt; 5. preliminary action to suicide; 6. suicidal behavior; 7. completed suicide). Baseline for Placebo / FK949E was at week 12 therefore no data were calculated for weeks 1-10.

The C-SSRS is a scale for assessing risk for suicidal behavior and suicide ideation and was administered by the clinician. Affirmative or negative responses were provided to 7 items to suicidal behaviors (1. suicide attempt; 2. Self-injury without suicide intent; 3. discontinued suicide attempt; 4. interrupted suicide attempt; 5. preliminary action to suicide; 6. suicidal behavior; 7. completed suicide). Baseline for Placebo / FK949E was at week 12 therefore no data were calculated for weeks 1-10.

The C-SSRS is a scale for assessing risk for suicidal behavior and suicide ideation and was administered by the clinician. Affirmative or negative responses were provided to 7 items to suicidal behaviors (1. suicide attempt; 2. Self-injury without suicide intent; 3. discontinued suicide attempt; 4. interrupted suicide attempt; 5. preliminary action to suicide; 6. suicidal behavior; 7. completed suicide). Baseline for Placebo / FK949E was at week 12 therefore no data were calculated for weeks 1-10