A Study to Evaluate the Efficacy of FK949E in Bipolar Disorder Patients With Major Depressive Episodes
Phase II/III Study of FK949E: Placebo-controlled, Double-blind, Parallel-group Comparative Study and Open-label, Non-controlled Extension Study in Bipolar Disorder Patients With Major Depressive Episodes
1 other identifier
interventional
431
1 country
98
Brief Summary
In period I, the treatment effect of FK949E was compared with that of placebo in a blind manner in bipolar disorder patients with major depressive episodes. In period II, the long-term safety and efficacy of FK949E was evaluated.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Feb 2012
Typical duration for phase_2
98 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 7, 2012
CompletedFirst Submitted
Initial submission to the registry
November 8, 2012
CompletedFirst Posted
Study publicly available on registry
November 12, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
July 11, 2016
CompletedResults Posted
Study results publicly available
February 8, 2017
CompletedNovember 15, 2024
October 1, 2024
3.5 years
November 8, 2012
December 16, 2016
October 30, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change From Baseline to End of Treatment Period I 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 8
Secondary Outcomes (44)
Change From Baseline in MADRS Total Score (Treatment Period I)
Baseline and Weeks 1, 2, 3, 4, 6, 8
Change From Baseline in MADRS Total Score (Combined Treatment Period I and II)
Baseline (Week 0 for FK949E 150 mg/FK949E & FK949E 300 mg/FK949E and Week 12 for Placebo/FK949E) and Weeks 1, 2, 3, 4, 6, 8, 10, 12 13, 14, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52
Number of Participants With MADRS Response (Treatment Period I)
Baseline and Weeks 1, 2, 3, 4, 6, 8
Number of Participants With MADRS Response (Combined Treatment Period I and II)
Baseline (Week 0 for FK949E 150 mg/FK949E & FK949E 300 mg/FK949E and Week 12 for Placebo/FK949E) and Weeks 1, 2, 3, 4, 6, 8, 10, 12, 13, 14, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52
Number of Participants With MADRS Remission (Treatment Period I)
Weeks 1, 2, 3, 4, 6, 8
- +39 more secondary outcomes
Study Arms (6)
Placebo
PLACEBO COMPARATORParticipants who received placebo once daily at bedtime for 8 weeks in Treatment Period I and were evaluated against the transition criteria to transfer to Treatment Period II. If transition criteria were not met, participants underwent to a dose-tapering period (1 week) and a follow-up period (1 week) thereafter. If transition criteria were met, participants went into Treatment Period II.
FK949E 150 mg
EXPERIMENTALAfter 2 days of up-titration, participants who received FK949E 150 mg once daily at bedtime for 8 weeks in Treatment Period I and were evaluated against the transition criteria to transfer to Treatment Period II. If transition criteria were not met, participants underwent to a dose-tapering period (1 week) and a follow-up period (1 week) thereafter. If transition criteria were met, participants went into Treatment Period II.
FK949E 300 mg
EXPERIMENTALAfter 4 days of up-titration, participants who received FK949E 300 mg once daily at bedtime for 8 weeks in Treatment Period I and were evaluated against the transition criteria to transfer to Treatment Period II. If transition criteria were not met, participants underwent to a dose-tapering period (1 week) and a follow-up period (1 week) thereafter. If transition criteria were met, participants went into Treatment Period II.
Placebo / FK949E
EXPERIMENTALParticipants received placebo administered orally once daily at bedtime for 8 weeks in Treatment Period I. Participants who met the transition criteria continued to Treatment Period II which consisted of a transition period in which participants continued to receive placebo for 4 weeks, followed by a 1-week dose adjustment period, and a treatment period in which participants received either open-label FK949E 150 mg or 300 mg (depending on dose increase or reduction guidelines) administered orally for 39 weeks. Participants underwent a dose-tapering period (1 week) and a follow-up period (1 week) thereafter.
FK949E 150 mg / FK949E
EXPERIMENTALAfter 2 days of up-titration, participants received FK949E 150 mg administered orally once daily at bedtime for 8 weeks in Treatment Period I. Participants who met the transition criteria continued to Treatment Period II which consisted of a transition period in which participants continued to receive FK949E 150 mg for 4 weeks followed by a 1-week dose-adjustment period and a treatment period in which participants received either open-label FK949E 150 mg or 300 mg (depending on dose increase or reduction guidelines) administered orally for 39 weeks. Participants underwent a dose-tapering period (1 week) and a follow-up period (1 week) thereafter.
FK949E 300 mg / FK949E
EXPERIMENTALAfter 4 days of up-titration, participants received FK949E 300 mg administered orally once daily at bedtime for 8 weeks in Treatment Period I. Participants who met the transition criteria continued to Treatment Period II which consisted of a transition period in which participants continued to receive FK949E 300 mg for 4 weeks followed by a 1-week dose-adjustment period and a treatment period in which participants received either open-label FK949E 150 mg or 300 mg (depending on dose increase or reduction guidelines) administered orally for 39 weeks. Participants underwent a dose-tapering period (1 week) and a follow-up period (1 week) thereafter.
Interventions
Eligibility Criteria
You may qualify if:
- Diagnosis of bipolar I or II disorder as specified in the Diagnostic and Statistical Manual of Mental Disorders Ver. 4 Text Revision (DSM-IV-TR,) with a major depressive episode
- 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
- 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
You may not qualify if:
- 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 is 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
- History of abuse or dependence of alcohol or substances other than caffeine and nicotine
- Treatment with a depot antipsychotic within the last 42 days before primary registration
- Unable to stop taking mood stabilizers (lithium carbonate and/or sodium valproate), lamotrigine, antipsychotics, or antidepressants from 7 days before secondary registration
- Unable to stop taking 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, after primary registration
- Electroconvulsive therapy within the last 76 days before primary registration
- The current major depressive episode persisting for more than 12 months or less than 4 weeks before informed consent
- A possible need of psychotherapy during the study period (unless the therapy has been commenced at least 76 days before primary registration and been maintained on a fixed level at fixed frequency)
- Documented or suspected conditions such as renal failure, hepatic failure, serious cardiac disease, hepatitis B, hepatitis C, or acquired immunodeficiency syndrome (AIDS) (or to be a carrier of hepatitis B, hepatitis C, or AIDS)
- Concurrence of malignancy or history of cured malignancy within 5 years
- 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 sub-investigator
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (98)
Site JP00030
Aichi, Japan
Site JP00031
Aichi, Japan
Site JP00052
Aichi, Japan
Site JP00055
Aichi, Japan
Site JP00072
Aichi, Japan
Site JP00092
Aichi, Japan
Site JP00003
Akita, Japan
Site JP00008
Chiba, Japan
Site JP00009
Chiba, Japan
Site JP00002
Fukuoka, Japan
Site JP00037
Fukuoka, Japan
Site JP00038
Fukuoka, Japan
Site JP00039
Fukuoka, Japan
Site JP00040
Fukuoka, Japan
Site JP00041
Fukuoka, Japan
Site JP00058
Fukuoka, Japan
Site JP00082
Fukuoka, Japan
Site JP00083
Fukuoka, Japan
Site JP00091
Fukuoka, Japan
Site JP00094
Fukuoka, Japan
Site JP00095
Fukuoka, Japan
Site JP00096
Fukuoka, Japan
Site JP00097
Fukuoka, Japan
Site JP00098
Fukuoka, Japan
Site JP00004
Fukushima, Japan
Site JP00028
Gifu, Japan
Site JP00006
Gunma, Japan
Site JP00007
Gunma, Japan
Site JP00035
Hiroshima, Japan
Site JP00056
Hiroshima, Japan
Site JP00067
Hiroshima, Japan
Site JP00001
Hokkaido, Japan
Site JP00059
Hokkaido, Japan
Site JP00061
Hokkaido, Japan
Site JP00062
Hokkaido, Japan
Site JP00068
Hokkaido, Japan
Site JP00069
Hokkaido, Japan
Site JP00073
Hokkaido, Japan
Site JP00074
Hokkaido, Japan
Site JP00076
Hokkaido, Japan
Site JP00005
Ibaraki, Japan
Site JP00049
Kagawa, Japan
Site JP00021
Kanagawa, Japan
Site JP00022
Kanagawa, Japan
Site JP00023
Kanagawa, Japan
Site JP00024
Kanagawa, Japan
Site JP00025
Kanagawa, Japan
Site JP00042
Kumamoto, Japan
Site JP00050
Kumamoto, Japan
Site JP00032
Kyoto, Japan
Site JP00084
Kyoto, Japan
Site JP00077
Miyagi, Japan
Site JP00027
Nagano, Japan
Site JP00075
Nara, Japan
Site JP00054
Okayama, Japan
Site JP00079
Okayama, Japan
Site JP00043
Okinawa, Japan
Site JP00046
Okinawa, Japan
Site JP00033
Osaka, Japan
Site JP00034
Osaka, Japan
Site JP00047
Osaka, Japan
Site JP00063
Osaka, Japan
Site JP00053
Ōita, Japan
Site JP00029
Shizuoka, Japan
Site JP00036
Tokushima, Japan
Site JP00010
Tokyo, Japan
Site JP00011
Tokyo, Japan
Site JP00012
Tokyo, Japan
Site JP00013
Tokyo, Japan
Site JP00014
Tokyo, Japan
Site JP00015
Tokyo, Japan
Site JP00016
Tokyo, Japan
Site JP00017
Tokyo, Japan
Site JP00018
Tokyo, Japan
Site JP00019
Tokyo, Japan
Site JP00020
Tokyo, Japan
Site JP00045
Tokyo, Japan
Site JP00048
Tokyo, Japan
Site JP00051
Tokyo, Japan
Site JP00057
Tokyo, Japan
Site JP00060
Tokyo, Japan
Site JP00064
Tokyo, Japan
Site JP00065
Tokyo, Japan
Site JP00066
Tokyo, Japan
Site JP00070
Tokyo, Japan
Site JP00071
Tokyo, Japan
Site JP00078
Tokyo, Japan
Site JP00081
Tokyo, Japan
Site JP00085
Tokyo, Japan
Site JP00086
Tokyo, Japan
Site JP00087
Tokyo, Japan
Site JP00088
Tokyo, Japan
Site JP00089
Tokyo, Japan
Site JP00090
Tokyo, Japan
Site JP00093
Tokyo, Japan
Site JP00099
Tokyo, Japan
Site JP00044
Tottori, Japan
Site JP00026
Toyama, Japan
Related Publications (3)
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.
PMID: 32792252DERIVEDFukushi R, Nomura Y, Katashima M, Komatsu K, Sato Y, Takada A. Population Pharmacokinetics Analysis of Quetiapine Extended-release Formulation in Japanese Patients with Bipolar Depression. Clin Ther. 2020 Jun;42(6):1067-1076.e2. doi: 10.1016/j.clinthera.2020.04.006. Epub 2020 Jun 6.
PMID: 32518042DERIVEDKanba S, Murasaki M, Koyama T, Takeuchi M, Shimizu Y, Arita E, Kuroishi K, Takeuchi M, Kamei S. Long-term mood/antidepressant effects of quetiapine extended-release formulation: an open-label, non-controlled extension study in Japanese patients with bipolar depression. BMC Psychiatry. 2019 Jun 26;19(1):198. doi: 10.1186/s12888-019-2181-9.
PMID: 31242884DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Head of Clinical Development Administration
- Organization
- Astellas Pharma Inc.
Study Officials
- STUDY DIRECTOR
Medical Director
Astellas Pharma Inc
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 8, 2012
First Posted
November 12, 2012
Study Start
February 7, 2012
Primary Completion
August 1, 2015
Study Completion
July 11, 2016
Last Updated
November 15, 2024
Results First Posted
February 8, 2017
Record last verified: 2024-10
Data Sharing
- IPD Sharing
- Will not share
Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.