Study to Evaluate the Effects of Switching Different Strength Forms of FK949E in Bipolar Disorder Patients With Major Depressive Episodes

Study Overview
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Brief Summary
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The purpose of this study was to evaluate the efficacy, safety, and pharmacokinetics of switching FK949E (sustained-release quetiapine) 50-mg and 150-mg tablets to the other tablet at the equivalent total daily dose in bipolar disorder patients with major depressive episodes.

Official Title
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Study of FK949E - An Open-label, Two-way Crossover Study to Evaluate the Effects of Switching Different Strength Forms of FK949E in Bipolar Disorder Patients With Major Depressive Episodes

Conditions
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Bipolar Depression

Intervention / Treatment
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* Drug: FK949E


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of bipolar I or II disorder as specified in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR), with a major depressive episode. Able to participate in the study with understanding of and compliance with subject requirements during the study in the investigator's or subinvestigator's opinion. Exclusion Criteria: Concurrent or previous history of DSM-IV-TR Axis I disorders, except bipolar disorder, within the last 6 months before informed consent. Concurrence of DSM-IV-TR Axis II disorder that is considered to greatly affect patient's current mental status. The Young Mania Rating Scale (YMRS) total score of 13 points or more. Nine or more mood episodes within the last 12 months before informed consent. Lack of response to at least 6-week treatment with at least 2 antidepressants for the current major depressive episode in the investigator's or subinvestigator's opinion. The current major depressive episode persisting for less than 4 weeks before informed consent. History of substance dependence (other than caffeine and nicotine) or alcohol abuse or dependence. Treatment with a depot antipsychotic within the last 49 days before the start of the pre-treatment observation period. Unable to suspend antipsychotics or antidepressants after the start of the pre-treatment observation period. Treatment with more than one of the following three drugs, mood stabilizers (lithium carbonate and/or sodium valproate) and lamotrigine, if these drugs, except one of either drugs, cannot be suspended after the start of the pre-treatment observation period. Unable to suspend antiepileptics (except lamotrigine and sodium valproate), antianxiety agents, hypnotics, sedatives, psychostimulants, antiparkinsonian agents, cerebral ameliorators, antidementia agents, or anorectics, except those specified as conditionally-allowed concomitant drugs, from 7 days before the start of the pre-treatment observation period. Unable to suspend CYP3A4 inhibitors or inducers, or monoamine oxidase (MAO) inhibitors from 7 days before the start of the pre-treatment observation period. Electroconvulsive therapy within the last 83 days before the start of the pre-treatment observation period. A possible need of psychotherapy during the study period (unless the therapy has been commenced at least 83 days before the start of the pre-treatment observation period). The Hamilton Depression Rating Scale (HAM-D17) suicide score of 3 points or more, history of suicide attempt within the last 6 months before informed consent, or the risk of suicide in the investigator's or subinvestigator's opinion.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 64 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FK949E 50 MG / FK949E 150 MG<br>Participants who received the 50 mg tablet once daily during Treatment Period II (8 weeks) and 150 mg tablet once daily during Treatment Period III (8 weeks). | Drug: FK949E<br>* A tablet containing 50 mg or 150 mg of quetiapine taken orally.<br>* Other names: quetiapine;|
| Experimental: FK949E 150 MG / FK949E 50 MG<br>Participants who received the 150 mg tablet once daily during Treatment Period II (8 weeks) and 50 mg tablet once daily during Treatment Period III (8 weeks). | Drug: FK949E<br>* A tablet containing 50 mg or 150 mg of quetiapine taken orally.<br>* Other names: quetiapine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | 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. | Week 8 of each treatment period (Week 12 and Week 20) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Depression Scale (HAM-D17) | 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 with lower scores indicating less depressive symptoms. | Week 8 of each treatment period (Week 12 and Week 20) | 
| Clinical Global Impression-Bipolar-Severity of Illness (CGI-BP-S): Overall Bipolar Illness | 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 with the scale from 1 (Normal, not ill) to 7 (very severely ill). | Week 8 of each treatment period (Week 12 and Week 20) | 
| Clinical Global Impression-Bipolar-Severity of Illness (CGI-BP-S):Depression | 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 with the scale from 1 (Normal, not ill) to 7 (very severely ill). | Week 8 of each treatment period (Week 12 and Week 20) | 
| Clinical Global Impression-Bipolar-Severity of Illness (CGI-BP-S): Mania | 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 with the scale from 1 (Normal, not ill) to 7 (very severely ill) | Week 8 of each treatment period (Week 12 and Week 20) | 
| Clinical Global Impression-Bipolar-Change (CGI-BP-C):Overall Bipolar Illness | 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. | Week 8 of each treatment period (Week 12 and Week 20) | 
| Clinical Global Impression-Bipolar-Change (CGI-BP-C):Depression | 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. | Week 8 of each treatment period (Week 12 and Week 20) | 
| Clinical Global Impression-Bipolar-Change (CGI-BP-C):Mania | 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. | Week 8 of each treatment period (Week 12 and Week 20) | 
| Number of Participants With Adverse Events | An adverse event (AE) is defined as any undesirable or unintended sign (including abnonmal 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. | Up to 22 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bipolar disorder, major depressive episodes, FK949E, quetiapine, bipolar depression