Oral Multiple-dose Study in Patients With Major Depressive Disorder

Study Overview
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Brief Summary
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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).

Detailed Description
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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).

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

Conditions
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Major Depressive Disorder

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 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.

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: Group 1 (FK949E lower dose)<br>Oral | Drug: FK949E<br>* Oral<br>* Other names: extended-release formulation of quetiapine;|
| Experimental: Group 2 (FK949E middle dose)<br>Oral | Drug: FK949E<br>* Oral<br>* Other names: extended-release formulation of quetiapine;|
| Experimental: Group 3 (FK949E higher dose)<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 | 
| AUC24h (area under the curve for 24hr) of unchanged quetiapine |  | for 24 hours after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| trough value of plasma concentration of unchanged quetiapine |  | for 24 hours after dosing | 
| t1/2 of plasma concentration of unchanged quetiapine |  | for 24 hours after dosing | 
| Maximum plasma concentration (Cmax) of quetiapine metabolites |  | for 24 hours after dosing | 
| AUC (area under the curve) of quetiapine metabolites |  | for 24 hours after dosing | 
| trough value of plasma concentration of quetiapine metabolites |  | for 24 hours after dosing | 
| tmax of plasma concentration of quetiapine metabolites |  | for 24 hours after dosing | 
| t1/2 of plasma concentration of quetiapine metabolites |  | for 24 hours after dosing | 
| Safety assessed by the incidence of adverse events, clinical tab tests, vital signs, 12-lead ECGs and physical exam |  | Up to Day 14 | 

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