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-

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01737268

Enrollment

Registered

2012-11-29

Start date

2012-10-29

Completion date

2016-06-29

Last updated

2024-11-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Bipolar Disorder, Elderly

Keywords

patients, Major depressive episode, FK949E

Brief summary

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.

Interventions

DRUGFK949E

Oral tablet

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

65 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline to Last Assessment in Treatment Period in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score	Baseline and week 52 (or the time of last assessment for participants who discontinued earlier)	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.

Secondary

Measure	Time frame	Description
Change From Baseline to Last Assessment in Treatment Period in Clinical Global Impression-Bipolar-Severity of Illness (CGI-BP-S): Overall Bipolar Illness	Baseline and week 52 (or the time of last assessment for participants who discontinued earlier)	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).
Change From Baseline to Last Assessment in Treatment Period in CGI-BP-S: Depression	Baseline and week 52 (or the time of last assessment for participants who discontinued earlier)	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).
Change From Baseline to Last Assessment in Treatment Period in CGI-BP-S: Mania	Baseline and and week 52 (or the time of last assessment for participants who discontinued earlier)	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).
Change From Baseline to Last Assessment in Treatment Period in Hamilton Depression Scale (HAM-D17)	Baseline and week 52 (or the time of last assessment for participants who discontinued earlier)	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.
CGI-BP-C: Depression	Week 52 (or the time of last assessment for participants who discontinued earlier)	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.
CGI-BP-C: Mania	Week 52 (or the time of last assessment for participants who discontinued earlier)	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.
Number of Participants With Adverse Events	From first dose of study drug up to week 52 (52 weeks)	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.
Clinical Global Impression-Bipolar-Change (CGI-BP-C): Overall Bipolar Illness	Week 52 (or the time of last assessment for participants who discontinued earlier)	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.

Countries

Japan

Participant flow

Recruitment details

Elderly participants with documented clinical diagnosis meeting the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision criteria for bipolar I disorder or bipolar II disorder, with most recent episode depressed confirmed by the Mini-International Neuropsychiatric Interview were recruited from 32 sites in Japan.

Pre-assignment details

Participants who were not taking quetiapine or was at \< 50 mg/day at least 28 days prior to informed consent, FK949E was administered at an initial dose of 50 mg during the dose-titration period. Participants who were taking quetiapine at 50 to \< 300 mg/day or 300 mg/day, FK949E was administered at 150 mg/day during the dose-titration period.

Participants by arm

Arm	Count
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.	19
Total	19

Arm

Count

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.

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	6
Overall Study	In consideration of the patient's safety	1
Overall Study	Worsening of Target Disease	2

Baseline characteristics

Characteristic	FK949E Elderly Participants
Age, Continuous	70.9 Years STANDARD_DEVIATION 5.3
Hamilton Depression Scale (HAM-D17) Total Score	19.3 Units of a scale STANDARD_DEVIATION 4.9
Montgomery-Asberg Depression Rating Scale (MADRS) Total Score	25.1 Units of a scale STANDARD_DEVIATION 6.4
Sex: Female, Male Female	11 Participants
Sex: Female, Male Male	8 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 20
other Total, other adverse events	18 / 20
serious Total, serious adverse events	2 / 20

Outcome results

Primary

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.

Time frame: Baseline and week 52 (or the time of last assessment for participants who discontinued earlier)