Oral Multiple-dose Study in Patients With Major Depressive Disorder

Phase I Study of FK949E - Phase I Oral Multiple-dose Study in Patients With Major Depressive Disorder

A study was to evaluate the safety and plasma concentration changes of quetiapine after repeated administration of FK949E (extended-release formulation of quetiapine) in patients with major depressive disorder (MDD).

The objective of the study was to evaluate the safety and pharmacokinetics of multiple oral doses of FK949E (extended-release formulation of quetiapine) of three doses in patients with major depressive disorder (MDD).

Inclusion Criteria:

• Diagnosis of major depressive disorder by the M.I.N.I. according to the DSM-IV-TR
• Female patients of childbearing potential with a negative serum pregnancy test result and who were willing and able to use a reliable method of birth control during the study.
• Patients who could understand and comply with the requirements of the study, as judged by the investigator/sub-investigator.

Exclusion Criteria:

• A current or past history of a DSM-IV-TR Axis I disorder other than major depressive disorder within 6 months prior to provision of written informed consent.
• Diagnosis of a DSM-IV-TR Axis II disorder that was considered to have a major impact on the patient's current psychiatric status.
• A history of substance or alcohol abuse or dependence excluding caffeine and nicotine.
• Patients who were unable to abstain from drugs that induce or inhibit the drug-metabolizing enzyme CYP3A4 from 14 days prior to screening assessment and throughout the study period.
• Patients showing evidence or signs of renal or hepatic failure, serious heart disease, cerebrovascular disease, viral hepatitis B or C, or acquired immunodeficiency syndrome (AIDS) (carrier).
• Patients being treated for hypertension or patients with clinical finding that in the opinion of the investigator/sub-investigator could be negatively affected by the study or that would affect the study results (e.g., hypertension, unstable angina).
• Patients with concomitant hypotension or orthostatic hypotension (hypotension is defined as systolic blood pressure of less than 100 mmHg)
• Conditions that could affect absorption and metabolism of the study medication (e.g., malabsorption syndrome, liver disease)
• A current diagnosis of malignant tumor unless in remission for at least 5 years (except basal or squamous cell skin carcinoma).
• A history of transient ischemic attack (TIA).
• A history of seizure disorder, except for febrile convulsions
• Application of electroconvulsive therapy within 90 days prior to the start of study drug administration
• Use of a depot antipsychotic injection and inability to be off the drug for a period of twice the dosing interval prior to screening assessment and throughout the study period
• A score of ≥ 3 on the HAM-D17 Item (suicide) or a suicide attempt within the past 6 months. Patients judged to be at serious suicidal or homicidal risk in the opinion of the investigator/sub-investigator.