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

• ClinicalTrials.gov Identifier: NCT01725282
• Recruitment Status: Completed
• First Posted: November 12, 2012
• Results First Posted: August 28, 2014
• Last Update Posted: July 30, 2019
• Sponsor: Astellas Pharma Inc
• Information provided by (Responsible Party): Astellas Pharma Inc

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder	Drug: quetiapine extended release (XR); Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 172 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Phase 2 Study of FK949E - Double-blind, Placebo-controlled, Comparative Study in Major Depressive Disorder Patients With Inadequate Response to Existing Antidepressants
• Actual Study Start Date: December 14, 2011
• Actual Primary Completion Date: August 24, 2013
• Actual Study Completion Date: August 24, 2013

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Participants received matching placebo tablets once daily before bedtime for 7 weeks.	Drug: Placebo; matching tablets
Experimental: Quetiapine 50 mg; Participants received quetiapine extended release (XR) 50 mg tablets once daily before bedtime for 7 weeks.	Drug: quetiapine extended release (XR); Extended release tablets; Other Names: Seroquel XR; FK949E
Experimental: Quetiapine 150 mg; 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); Extended release tablets; Other Names: Seroquel XR; FK949E
Experimental: Quetiapine 300 mg; 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); Extended release tablets; Other Names: Seroquel XR; FK949E

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Baseline and Week 6 ]
   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.

Secondary Outcome Measures :

1. Change From Baseline in Hamilton Rating Score for Depression (HAM-D17) [ Time Frame: Baseline and Week 6 ]
   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.
2. Percentage of Participants With Improvement in Clinical Global Impressions-Improvement (CGI-I) [ Time Frame: Baseline and Week 6 ]

   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.

3. Change From Baseline in Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) [ Time Frame: Baseline and Week 6 ]

   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:

   1. Limitation in physical activities because of health problems.
   2. Limitations in usual role activities because of physical health problems.
   3. Bodily pain.
   4. Limitations in social activities because of physical or emotional problems.
   5. General mental health (psychological distress and well-being).
   6. Limitations in usual role activities because of emotional problems.
   7. Vitality (energy and fatigue).
   8. 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.

4. Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: Baseline and Week 6 ]
   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.
5. Safety Assessed by the Incidence of Adverse Events (AE), Vital Signs, Electrocardiogram (ECG) and Laboratory Tests [ Time Frame: Up to 8 weeks ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 64 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Japan

Hokkaidou, Japan

Kantou, Japan

Kinki, Japan

Sponsors and Collaborators

Astellas Pharma Inc

Investigators

• Study Director: Medical Director; Astellas Pharma Inc

More Information

Additional Information:

Link to results on Astellas Clinical Study Results website 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Fukushi R, Nomura Y, Katashima M, Komatsu K, Sato Y, Takada A. Approach to Evaluating QT Prolongation of Quetiapine Fumarate in Late Stage of Clinical Development Using Concentration-QTc Modeling and Simulation in Japanese Patients With Bipolar Disorder. Clin Ther. 2020 Aug;42(8):1483-1493.e1. doi: 10.1016/j.clinthera.2020.06.002. Epub 2020 Aug 11.

• Responsible Party: Astellas Pharma Inc
• ClinicalTrials.gov Identifier: NCT01725282
• Other Study ID Numbers: 6949-CL-0005
• First Posted: November 12, 2012
• Results First Posted: August 28, 2014
• Last Update Posted: July 30, 2019
• Last Verified: July 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• URL: https://www.clinicalstudydatarequest.com/

Keywords provided by Astellas Pharma Inc:

patients; FK949E

Additional relevant MeSH terms:

Depressive Disorder; Depression; Depressive Disorder, Major; Mood Disorders; Mental Disorders; Behavioral Symptoms; Quetiapine Fumarate; Antidepressive Agents; Psychotropic Drugs; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Physiological Effects of Drugs