Trial Outcomes & Findings for Long-term Study of FK949E in Elderly Bipolar Disorder Patients (NCT NCT01737268)
NCT ID: NCT01737268
Last Updated: 2024-11-19
Results Overview
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.
COMPLETED
PHASE3
20 participants
Baseline and week 52 (or the time of last assessment for participants who discontinued earlier)
2024-11-19
Participant Flow
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.
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.
Participant milestones
| Measure |
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.
|
|---|---|
|
Overall Study
STARTED
|
20
|
|
Overall Study
Treated
|
20
|
|
Overall Study
COMPLETED
|
11
|
|
Overall Study
NOT COMPLETED
|
9
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|
|
Overall Study
Adverse Event
|
6
|
|
Overall Study
Worsening of Target Disease
|
2
|
|
Overall Study
In consideration of the patient's safety
|
1
|
Baseline Characteristics
FAS
Baseline characteristics by cohort
| Measure |
FK949E Elderly Participants
n=19 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.
|
|---|---|
|
Age, Continuous
|
70.9 Years
STANDARD_DEVIATION 5.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
|
Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
|
25.1 Units of a scale
STANDARD_DEVIATION 6.4 • n=5 Participants • FAS
|
|
Hamilton Depression Scale (HAM-D17) Total Score
|
19.3 Units of a scale
STANDARD_DEVIATION 4.9 • n=5 Participants • FAS
|
PRIMARY outcome
Timeframe: Baseline and week 52 (or the time of last assessment for participants who discontinued earlier)Population: FAS population; last assessment value is used for participants who discontinued before week 52.
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.
Outcome measures
| Measure |
FK949E Elderly Participants
n=19 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.
|
|---|---|
|
Change From Baseline to Last Assessment in Treatment Period in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
|
-13.1 units on a scale
Standard Deviation 11.0
|
SECONDARY outcome
Timeframe: Baseline and week 52 (or the time of last assessment for participants who discontinued earlier)Population: FAS population; last assessment value is used for participants who discontinued before week 52.
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.
Outcome measures
| Measure |
FK949E Elderly Participants
n=19 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.
|
|---|---|
|
Change From Baseline to Last Assessment in Treatment Period in Hamilton Depression Scale (HAM-D17)
|
-10.5 units on a scale
Standard Deviation 8.2
|
SECONDARY outcome
Timeframe: Baseline and week 52 (or the time of last assessment for participants who discontinued earlier)Population: FAS population; last assessment value is used for participants who discontinued before week 52.
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).
Outcome measures
| Measure |
FK949E Elderly Participants
n=19 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.
|
|---|---|
|
Change From Baseline to Last Assessment in Treatment Period in Clinical Global Impression-Bipolar-Severity of Illness (CGI-BP-S): Overall Bipolar Illness
|
-1.2 units on a scale
Standard Deviation 1.5
|
SECONDARY outcome
Timeframe: Baseline and week 52 (or the time of last assessment for participants who discontinued earlier)Population: FAS population; last assessment value is used for participants who discontinued before week 52.
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).
Outcome measures
| Measure |
FK949E Elderly Participants
n=19 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.
|
|---|---|
|
Change From Baseline to Last Assessment in Treatment Period in CGI-BP-S: Depression
|
-1.3 units on a scale
Standard Deviation 1.5
|
SECONDARY outcome
Timeframe: Baseline and and week 52 (or the time of last assessment for participants who discontinued earlier)Population: FAS population; last assessment value is used for participants who discontinued before week 52.
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).
Outcome measures
| Measure |
FK949E Elderly Participants
n=19 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.
|
|---|---|
|
Change From Baseline to Last Assessment in Treatment Period in CGI-BP-S: Mania
|
0 units on a scale
Standard Deviation 0
|
SECONDARY outcome
Timeframe: Week 52 (or the time of last assessment for participants who discontinued earlier)Population: FAS population; last assessment value is used for participants who discontinued before week 52.
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.
Outcome measures
| Measure |
FK949E Elderly Participants
n=19 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.
|
|---|---|
|
Clinical Global Impression-Bipolar-Change (CGI-BP-C): Overall Bipolar Illness
|
2.4 units on a scale
Standard Deviation 1.3
|
SECONDARY outcome
Timeframe: Week 52 (or the time of last assessment for participants who discontinued earlier)Population: FAS population; last assessment value is used for participants who discontinued before week 52.
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.
Outcome measures
| Measure |
FK949E Elderly Participants
n=19 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.
|
|---|---|
|
CGI-BP-C: Depression
|
2.4 units on a scale
Standard Deviation 1.3
|
SECONDARY outcome
Timeframe: Week 52 (or the time of last assessment for participants who discontinued earlier)Population: FAS population; last assessment value is used for participants who discontinued before week 52.
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.
Outcome measures
| Measure |
FK949E Elderly Participants
n=19 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.
|
|---|---|
|
CGI-BP-C: Mania
|
4.0 units on a scale
Standard Deviation 0.0
|
SECONDARY outcome
Timeframe: From first dose of study drug up to week 52 (52 weeks)Population: Safely Analysis Set (SAF), which included participants who received at least one dose of study drug.
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.
Outcome measures
| Measure |
FK949E Elderly Participants
n=20 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.
|
|---|---|
|
Number of Participants With Adverse Events
Any AE
|
18 Participants
|
|
Number of Participants With Adverse Events
Drug-related AEs
|
18 Participants
|
|
Number of Participants With Adverse Events
Deaths
|
0 Participants
|
|
Number of Participants With Adverse Events
Serious AEs
|
2 Participants
|
|
Number of Participants With Adverse Events
Drug-related SAEs
|
1 Participants
|
|
Number of Participants With Adverse Events
AEs that caused study drug discountinuation
|
8 Participants
|
|
Number of Participants With Adverse Events
Drug-related AEs that caused study drug discont.
|
7 Participants
|
Adverse Events
FK949E Elderly Participants
Serious adverse events
| Measure |
FK949E Elderly Participants
n=20 participants at risk
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.
|
|---|---|
|
General disorders
Malaise
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Psychiatric disorders
Depression
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
Other adverse events
| Measure |
FK949E Elderly Participants
n=20 participants at risk
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.
|
|---|---|
|
Endocrine disorders
Hypothyroidism
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Gastrointestinal disorders
Abdominal pain
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Gastrointestinal disorders
Constipation
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Gastrointestinal disorders
Gastritis
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Gastrointestinal disorders
Nausea
|
10.0%
2/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Gastrointestinal disorders
Salivary hypersecretion
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
General disorders
Fatigue
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
General disorders
Malaise
|
15.0%
3/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
General disorders
Thirst
|
35.0%
7/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Infections and infestations
Influenza
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Infections and infestations
Nasopharyngitis
|
20.0%
4/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Injury, poisoning and procedural complications
Fall
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Injury, poisoning and procedural complications
Wound
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Investigations
Blood creatine phosphokinase increased
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Investigations
Blood glucose decreased
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Investigations
Blood prolactin increased
|
20.0%
4/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Investigations
Blood thyroid stimulating hormone increased
|
10.0%
2/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Investigations
Blood triglycerides increased
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Investigations
Blood uric acid increased
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Investigations
Liver function test abnormal
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Investigations
Weight decreased
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Investigations
Platelet count increased
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Nervous system disorders
Dizziness
|
20.0%
4/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Nervous system disorders
Dizziness postural
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Nervous system disorders
Dysarthria
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Nervous system disorders
Dysgeusia
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Nervous system disorders
Headache
|
10.0%
2/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Nervous system disorders
Movement disorder
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Nervous system disorders
Somnolence
|
55.0%
11/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Psychiatric disorders
Depression
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Psychiatric disorders
Intentional self-injury
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Skin and subcutaneous tissue disorders
Rosacea
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
Vascular disorders
Hypertension
|
5.0%
1/20 • From first dose of study drug up to week 52 (52 weeks)
|
|
General disorders
Gait disturbance
|
10.0%
2/20 • From first dose of study drug up to week 52 (52 weeks)
|
Additional Information
Vice-President, Japan-Asia Clinical Development Administration
Astellas Pharma Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript prior to publication for review and comment.
- Publication restrictions are in place
Restriction type: OTHER