Study to Evaluate the Effect and Safety of Quetiapine Extended Release (XR) (FK949E) in Major Depressive Disorder

Study Overview
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Brief Summary
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In this study, quetiapine XR or placebo will be administered orally for 6 weeks to major depressive disorder patients with lack of response to existing antidepressants, with the aim of evaluating the efficacy of quetiapine XR and dose-response in three quetiapine XR dose groups based on changes in Montgomery-Asberg Depression Rating Scale (MADRS) scores.

Official Title
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Phase 2 Study of FK949E - Double-blind, Placebo-controlled, Comparative Study in Major Depressive Disorder Patients With Inadequate Response to Existing Antidepressants

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: quetiapine extended release (XR)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of major depressive disorder as specified in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR) with the use of the Mini-International Neuropsychiatric Interview (M.I.N.I.) Documented appropriate treatment history (i.e., lack of response to treatment at labeled dosage for at least 4 weeks) for the current major depression episode with an antidepressant other than that used concomitantly with the study drug 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 Exclusion Criteria: Concurrent or previous history of DSM-IV-TR Axis I disorders, except major depressive 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 duration of the current major depression episode is shorter than 4 weeks or longer than 24 months at informed consent History of dependence of substances other than caffeine and nicotine or history of abuse or dependence of alcohol The 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 Concurrent or previous history of diabetes mellitus. HbA1c levels of 6.1% (Japan Diabetes Society values) or more within the past 2 months Electroconvulsive therapy within the last 62 days before primary registration (within the last 90 days before secondary registration) Treatment with a depot antipsychotic within the last 28 days Documented or suspected (to be a carrier of) conditions such as renal failure, hepatic failure, serious cardiac disease (or current use of antiarrhythmic drugs), hepatitis B, hepatitis C, or acquired immunodeficiency syndrome (AIDS) 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 subinvestigator Concurrence of hypotension (defined as a systolic blood pressure of less than 100 mmHg at primary registration) or orthostatic hypotension Concurrence of malabsorption syndrome, hepatic disease, or other conditions that may affect the absorption and/or metabolism of the study drug Concurrent or previous history of cerebrovascular disease or transient ischemic attack (TIA) Known hypersensitivity to quetiapine or any component of FK949E tablets

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received matching placebo tablets once daily before bedtime for 7 weeks. | Drug: Placebo<br>* matching tablets<br>|
| Experimental: Quetiapine 50 mg<br>Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks. | Drug: quetiapine extended release (XR)<br>* Extended release tablets<br>* Other names: FK949E;|
| Experimental: Quetiapine 150 mg<br>After 2 days of up-titration, participants received quetiapine XR 150 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 50 mg tablets once daily for 1 week. | Drug: quetiapine extended release (XR)<br>* Extended release tablets<br>* Other names: FK949E;|
| Experimental: Quetiapine 300 mg<br>After 4 days of up-titration, participants received quetiapine XR 300 mg tablets once daily before bedtime for 6 weeks followed by quetiapine XR 150 mg tablets once daily for 1 week. | Drug: quetiapine extended release (XR)<br>* Extended release tablets<br>* Other names: FK949E;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | The Montgomery Åsberg Depression Rating Scale (MADRS) is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). Decrease in the total score or on individual items indicates improvement. | Baseline and Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hamilton Rating Score for Depression (HAM-D17) | The 17-item Hamilton Depression Scale (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 range is from 0 to 52 where a higher score indicates a greater depressive state. | Baseline and Week 6 | 
| Percentage of Participants With Improvement in Clinical Global Impressions-Improvement (CGI-I) | The Clinical Global Impression - global improvement assesses the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale: 1, markedly improved; 2, moderately improved; 3, minimally improved; 4, no change; 5, minimally worsened; 6, moderately worsened; or 7, markedly worsened. Improvement is defined as a score of 1 or 2. | Baseline and Week 6 | 
| Change From Baseline in Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) | The Medical Outcomes Study SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. The 8 health concepts are: Limitation in physical activities because of health problems. Limitations in usual role activities because of physical health problems. Bodily pain. Limitations in social activities because of physical or emotional problems. General mental health (psychological distress and well-being). Limitations in usual role activities because of emotional problems. Vitality (energy and fatigue). General health perception. Each scale ranges from 0 to 100, with 0 indicating the least favorable status and 100 being the most favorable health status. | Baseline and Week 6 | 
| Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) | The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate seven component scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction, each on a scale from 0 (best) to 3 (worst). The sum of scores for these seven components yields one global score, ranging from 0 to 21, with higher scores indicative of poor sleep quality. | Baseline and Week 6 | 
| Safety Assessed by the Incidence of Adverse Events (AE), Vital Signs, Electrocardiogram (ECG) and Laboratory Tests | An AE is defined as any untoward medical occurrence in a patient administered a study drug, and which does not necessarily have a causal relationship with this treatment. Abnormal laboratory parameters, vital signs or ECG data were defined as AEs if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. A serious AE was 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. AEs were assessed by the Investigator for intensity as mild, moderate or severe and for causal relationship to study drug. | Up to 8 weeks | 

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