Long-term Study of FK949E in Elderly Bipolar Disorder Patients

Long-term Study of FK949E in Elderly Patients -Long-term Study in Elderly Bipolar Disorder Patients With Major Depressive Episodes-

FK949E was administered to elderly bipolar disorder patients with major depressive episode for 52 weeks. Its safety, efficacy, and plasma concentration change were evaluated in an open-label manner.

Study Overview

• Status: Completed
• Conditions: Bipolar Disorder; Elderly
• Intervention / Treatment: Drug: FK949E

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Chiba, Japan
    • Site JP00024
  • Fukuoka, Japan
    • Site JP00023
  • Fukuoka, Japan
    • Site JP00025
  • Fukushima, Japan
    • Site JP00015
  • Fukushima, Japan
    • Site JP00029
  • Hokkaido, Japan
    • Site JP00001
  • Hokkaido, Japan
    • Site JP00012
  • Hokkaido, Japan
    • Site JP00002
  • Hokkaido, Japan
    • Site JP00003
  • Hokkaido, Japan
    • Site JP00004
  • Hokkaido, Japan
    • Site JP00005
  • Hokkaido, Japan
    • Site JP00006
  • Hokkaido, Japan
    • Site JP00007
  • Hokkaido, Japan
    • Site JP00008
  • Hokkaido, Japan
    • Site JP00009
  • Hokkaido, Japan
    • Site JP00010
  • Hokkaido, Japan
    • Site JP00011
  • Hokkaido, Japan
    • Site JP00013
  • Hyogo, Japan
    • Site JP00028
  • Ibaraki, Japan
    • Site JP00031
  • Kanagawa, Japan
    • Site JP00017
  • Kanagawa, Japan
    • Site JP00032
  • Kumamoto, Japan
    • Site JP00019
  • Kyoto, Japan
    • Site JP00018
  • Osaka, Japan
    • Site JP00014
  • Tokyo, Japan
    • Site JP00016
  • Tokyo, Japan
    • Site JP00020
  • Tokyo, Japan
    • Site JP00027
  • Tokyo, Japan
    • Site JP00021
  • Tokyo, Japan
    • Site JP00022
  • Tokyo, Japan
    • Site JP00026
  • Tottori, Japan
    • Site JP00030

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of bipolar I or II disorder as specified in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR), with a major depressive episode
• Able to participate in the study with understanding of and compliance with subject requirements during the study in the investigator's or subinvestigator's opinion
• Male subjects must agree to take appropriate contraceptive measures with condoms during the study period.
• Female subjects must be confirmed to have no childbearing potential during the study period

Exclusion Criteria:

• Concurrent or previous history of DSM-IV-TR Axis I disorders, except bipolar disorder, within the last 6 months before informed consent
• Concurrence of DSM-IV-TR Axis II disorder that was considered to greatly affect patient's current mental status.
• The Young Mania Rating Scale (YMRS) total score of 13 points or more.
• Nine or more mood episodes within the last 12 months before informed consent.
• Lack of response to at least 6-week treatment with at least 2 antidepressants for the current major depressive episode in the investigator's or subinvestigator's opinion
• The current major depressive episode persisting for more than 12 months or less than 4 weeks before informed consent.
• History of substance dependence (other than caffeine and nicotine) or alcohol abuse or dependence.
• Treatment with a depot antipsychotic within the last 49 days before primary registration.
• Unable to suspend antipsychotics or antidepressants after primary registration
• Treatment with two or more of mood stabilizers (lithium carbonate and/or sodium valproate) and lamotrigine, if these drugs, except one of either drug, cannot be suspended after primary registration.
• Unable to suspend antiepileptics (except lamotrigine and sodium valproate), antianxiety agents, hypnotics, sedatives, psychostimulants, antiparkinsonian agents, cerebral ameliorators, antidementia agents, or anorectics, except those specified as conditionally-allowed concomitant drugs, from 7 days before primary registration
• Electroconvulsive therapy within the last 83 days before primary registration.
• A possible need of psychotherapy during the study period (unless the therapy has been commenced at least 83 days before primary registration).
• The Hamilton Depression Rating Scale (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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: FK949E Elderly Participants; After 2 days of dose-titration, elderly participants received either FK949E 150 mg or FK949E 300 mg once daily at bedtime from day 3 to week 52. Dose increase and reduction was allowed following dose increase or reduction guidelines and at the investigator's discretion. After which, participants went through a follow-up period of 1 week. For participants, who completed or discontinued treatment at FK949E 300 mg, a dose-tapering period was placed before proceeding to the follow-up period, and FK949E 150 mg was administered once daily for 1 week in this period.

Drug: FK949E; Oral tablet; Other Names: quetiapine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Last Assessment in Treatment Period in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score	The MADRS is a 10-item scale to measure the severity of depressive episodes, where each item is rated on a scale from 0 to 6. The MADRS total score ranges from 0 to 60 with lower scores indicating less depressive symptoms.	Baseline and week 52 (or the time of last assessment for participants who discontinued earlier)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Last Assessment in Treatment Period in Hamilton Depression Scale (HAM-D17)	The 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 ranges from 0 to 52 with lower scores indicating less depressive symptoms.	Baseline and week 52 (or the time of last assessment for participants who discontinued earlier)
Change From Baseline to Last Assessment in Treatment Period in Clinical Global Impression-Bipolar-Severity of Illness (CGI-BP-S): Overall Bipolar Illness	The CGI-BP-S is a scale which assesses a participant's severity of their overall bipolar illness, depression, and mania as assessed by the clinician using a scale from with the scale from 1 (Normal, not ill) to 7 (very severely ill).	Baseline and week 52 (or the time of last assessment for participants who discontinued earlier)
Change From Baseline to Last Assessment in Treatment Period in CGI-BP-S: Depression	The CGI-BP-S is a scale which assesses a participant's severity of their overall bipolar illness, depression, and mania as assessed by the clinician using a scale from with the scale from 1 (Normal, not ill) to 7 (very severely ill).	Baseline and week 52 (or the time of last assessment for participants who discontinued earlier)
Change From Baseline to Last Assessment in Treatment Period in CGI-BP-S: Mania	The CGI-BP-S is a scale which assesses a participant's severity of their overall bipolar illness, depression, and mania as assessed by the clinician using a scale from with the scale from 1 (Normal, not ill) to 7 (very severely ill).	Baseline and and week 52 (or the time of last assessment for participants who discontinued earlier)
Clinical Global Impression-Bipolar-Change (CGI-BP-C): Overall Bipolar Illness	The CGI-BP-C is a scale which assesses the degree of change or improvement from baseline for each of overall bipolar illness, depression and mania, by grading it using 8 grades, from 1 (very much improved) to 7 (very much worse) or 8 (not applicable). Grade 8 (not applicable) was regarded as a missing value for purposes of calculating the mean score.	Week 52 (or the time of last assessment for participants who discontinued earlier)
CGI-BP-C: Depression	The CGI-BP-C is a scale which assesses the degree of change or improvement from baseline for each of overall bipolar illness, depression and mania, by grading it using 8 grades, from 1 (very much improved) to 7 (very much worse) or 8 (not applicable). Grade 8 (not applicable) was regarded as a missing value for purposes of calculating the mean score.	Week 52 (or the time of last assessment for participants who discontinued earlier)
CGI-BP-C: Mania	The CGI-BP-C is a scale which assesses the degree of change or improvement from baseline for each of overall bipolar illness, depression and mania, by grading it using 8 grades, from 1 (very much improved) to 7 (very much worse) or 8 (not applicable). Grade 8 (not applicable) was regarded as a missing value for purposes of calculating the mean score.	Week 52 (or the time of last assessment for participants who discontinued earlier)
Number of Participants With Adverse Events	An adverse event (AE) is defined as any undesirable or unintended sign (including abnormal laboratory test values), symptom, or disease occurring while the study drug was administered, regardless of whether or not there was a causal relationship with the study drug. A serious AE is defined as a an event resulting in death, persistent or significant disability/incapacity or congenital anomaly or birth defect, was life-threatening, re quire d or prolonged hospitalization or was considered medically important.	From first dose of study drug up to week 52 (52 weeks)

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc

Publications and helpful links

General Publications

• 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.

Helpful Links

• Link to results on Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2012
• Primary Completion (Actual): June 29, 2016
• Study Completion (Actual): June 29, 2016

Study Registration Dates

• First Submitted: November 8, 2012
• First Submitted That Met QC Criteria: November 27, 2012
• First Posted (Estimate): November 29, 2012

Study Record Updates

• Last Update Posted (Actual): January 29, 2019
• Last Update Submitted That Met QC Criteria: January 10, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: patients; FK949E; Major depressive episode
• Additional Relevant MeSH Terms: Mental Disorders; Bipolar and Related Disorders; Bipolar Disorder; Physiological Effects of Drugs; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Quetiapine Fumarate
• Other Study ID Numbers: 6949-CL-0022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."