Study to Evaluate Safety and Tolerability of FK949E in Patients With Major Depressive Disorder

Study Overview
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Brief Summary
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The objective of the study was to evaluate the safety and plasma concentration changes of quetiapine after multiple oral administration of FK949E (extended-release formulation of quetiapine) in patients with major depressive disorder (MDD).

Detailed Description
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This is a dose-titration study. In low-dose-group, patients receive prescribed dose on Day 5 after 3-step dose increases. In high-dose-group patients receive prescribed dose on Day 7 after 4-step dose increases. Patients receive prescribed dose of FK949E for 7 days in each group. The dosage period is 12 days in low dose group and 14 days in high dose group.

Official Title
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Phase I Study of FK949E - Multiple Dose Study of Non-Elderly Adult Patients With Major Depressive Disorder (MDD)

Conditions
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Major Depressive Disorder Patients

Intervention / Treatment
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* Drug: FK949E


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of major depressive disorder according to the DSM-IV-TR (Text Revision of the Diagnostic and Statistical Manual of Mental Disorders version-4) 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 the study 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 the start of study drug administration and throughout the study period Pregnant or lactating women 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) A 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) 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 current or past diagnosis 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 the start of study drug administration and throughout the study period Patients could require psychotherapy (other than supportive psychotherapy) during the study period, unless psychotherapy had been ongoing for a minimum of 90 days prior to the start of study drug administration A score of ≥ 3 on the HAM-D17 Item (suicide) or a suicide attempt within the past 6 months, and those judged to be at serious suicidal or homicidal risk in the opinion of the investigator/sub-investigator A current or past history of diabetes mellitus* or glycated hemoglobin (HbA1c) of ≥ 6.5% at screening within 2 months before the start of study drug administration (*refer to the guidelines for monitoring blood glucose levels in patients treated with atypical antipsychotics) A white blood cell count (WBC) of ≤ 3,000/mm3 at screening assessment Elevation of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values at screening assessment (grade 2 or higher according to the Criteria for Classification of the Grade of Adverse Drug Reactions to Pharmaceutical Products (Pharmaceutical Affairs Bureau Safety Division's Notification No. 80 issued on 29 June 1992)) A known history of hypersensitivity to quetiapine or to any other component in the FK949E tablets at the time of providing written informed consent Treatment with quetiapine for depressive symptoms or bipolar disorder (mania) at the time of providing written informed consent Participation in another clinical study or post-marketing study within 12 weeks prior to the start of study drug administration

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: Other
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: low-dose group FK949E<br>oral | Drug: FK949E<br>* oral<br>* Other names: extended release formulation of quetiapine;|
| Experimental: high-dose group FK949E<br>oral | Drug: FK949E<br>* oral<br>* Other names: extended release formulation of quetiapine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) of unchanged quetiapine |  | For 24 hours after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC (area under the curve) of unchanged quetiapine |  | For 24 hours after dosing | 
| tmax of plasma concentration of unchanged quetiapine |  | For 24 hours after dosing | 
| t1/2 of plasma concentration of unchanged quetiapine |  | For 24 hours after dosing | 
| Safety assessed by the incidence of adverse events, clinical lab tests, vital signs, 12-lead ECGs and physical exam |  | Up to 21 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FK949E, Antipsychotic, Quetiapine