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

Phase II/III Study of FK949E: Placebo-controlled, Double-blind, Parallel-group Comparative Study and Open-label, Non-controlled Extension Study in Bipolar Disorder Patients With Major Depressive Episodes

In period I, the treatment effect of FK949E was compared with that of placebo in a blind manner in bipolar disorder patients with major depressive episodes. In period II, the long-term safety and efficacy of FK949E was evaluated.

This study consisted of two parts. In Treatment Period I, FK949E or placebo was administered orally in a blind manner to bipolar disorder patients with major depressive episodes, with the aim of evaluating the superiority of FK949E over placebo and the dose response of two doses of FK949E based on changes in Montgomery-Asberg Depression Rating Scale (MADRS) total score. In Treatment Period II, the long-term safety, efficacy and pharmacokinetics of open-label FK949E was evaluated in patients who completed Treatment Period I. An analysis was performed for data in Treatment Period I and another analysis was done for data in combined Treatment Periods I and II.

Inclusion Criteria:

• Diagnosis of bipolar I or II disorder as specified in the Diagnostic and Statistical Manual of Mental Disorders Ver. 4 Text Revision (DSM-IV-TR,) with a major depressive episode
• The Hamilton Depression Rating Scale (HAM-D17) total score of 20 points or more and HAM-D17 depressed mood score of 2 points or more
• 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
• History of abuse or dependence of alcohol or substances other than caffeine and nicotine
• Treatment with a depot antipsychotic within the last 42 days before primary registration
• Unable to stop taking mood stabilizers (lithium carbonate and/or sodium valproate), lamotrigine, antipsychotics, or antidepressants from 7 days before secondary registration
• Unable to stop taking 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, after primary registration
• Electroconvulsive therapy within the last 76 days before primary registration
• The current major depressive episode persisting for more than 12 months or less than 4 weeks before informed consent
• A possible need of psychotherapy during the study period (unless the therapy has been commenced at least 76 days before primary registration and been maintained on a fixed level at fixed frequency)
• Documented or suspected conditions such as renal failure, hepatic failure, serious cardiac disease, hepatitis B, hepatitis C, or acquired immunodeficiency syndrome (AIDS) (or to be a carrier of hepatitis B, hepatitis C, or AIDS)
• Concurrence of malignancy or history of cured malignancy within 5 years
• Concurrence of uncontrolled hypertension (defined as a systolic blood pressure of 180 mmHg or more, or a diastolic blood pressure of 110 mmHg or more at primary registration) or unstable angina that may worsen with the study or may affect the study results based on the clinical judgment of the investigator or sub-investigator
• Concurrence of hypotension (defined as a systolic blood pressure of less than 100 mmHg at primary registration) or orthostatic hypotension
• History of transient, idiopathic orthostatic hypotension, with or without pre-syncope symptoms or syncope, or a current condition susceptible to transient hypotension, such as dehydration and decreased blood volume
• Concurrent or previous history of cerebrovascular disease or transient ischemic attack (TIA)
• Abnormal laboratory or electrocardiographic findings considered clinically significant in the investigator's or subinvestigator's opinion (in reference to grade 3 of the Adverse Drug Reactions Severity Grading Criteria [Notification No. 80 of the Safety Division, Pharmaceutical Affairs Bureau, Ministry of Health and Welfare dated 29 June 1992])
• Participation in another clinical study or post-marketing study within the last 12 weeks before informed consent
• History of quetiapine therapy during the current major depressive episode
• Pregnant or lactating women