Bipolar Depression
Conditions
Keywords
major depressive episodes, FK949E, quetiapine, bipolar depression, bipolar disorder
Brief summary
The purpose of this study was to evaluate the efficacy, safety, and pharmacokinetics of switching FK949E (sustained-release quetiapine) 50-mg and 150-mg tablets to the other tablet at the equivalent total daily dose in bipolar disorder patients with major depressive episodes.
Interventions
DRUGFK949E
A tablet containing 50 mg or 150 mg of quetiapine taken orally.
Sponsors
Astellas Pharma Inc
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 64 Years
Healthy volunteers
No
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.
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 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. * The current major depressive episode persisting for 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 the start of the pre-treatment observation period. * Unable to suspend antipsychotics or antidepressants after the start of the pre-treatment observation period. * Treatment with more than one of the following three drugs, mood stabilizers (lithium carbonate and/or sodium valproate) and lamotrigine, if these drugs, except one of either drugs, cannot be suspended after the start of the pre-treatment observation period. * 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 the start of the pre-treatment observation period. * Unable to suspend CYP3A4 inhibitors or inducers, or monoamine oxidase (MAO) inhibitors from 7 days before the start of the pre-treatment observation period. * Electroconvulsive therapy within the last 83 days before the start of the pre-treatment observation period. * A possible need of psychotherapy during the study period (unless the therapy has been commenced at least 83 days before the start of the pre-treatment observation period). * 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 |
|---|---|---|
| Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Week 8 of each treatment period (Week 12 and Week 20) | 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 |
|---|---|---|
| Clinical Global Impression-Bipolar-Severity of Illness (CGI-BP-S): Overall Bipolar Illness | Week 8 of each treatment period (Week 12 and Week 20) | 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). |
| Clinical Global Impression-Bipolar-Severity of Illness (CGI-BP-S):Depression | Week 8 of each treatment period (Week 12 and Week 20) | 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). |
| Clinical Global Impression-Bipolar-Severity of Illness (CGI-BP-S): Mania | Week 8 of each treatment period (Week 12 and Week 20) | 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) |
| Hamilton Depression Scale (HAM-D17) | Week 8 of each treatment period (Week 12 and Week 20) | 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. |
| Clinical Global Impression-Bipolar-Change (CGI-BP-C):Depression | Week 8 of each treatment period (Week 12 and Week 20) | 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. |
| Clinical Global Impression-Bipolar-Change (CGI-BP-C):Mania | Week 8 of each treatment period (Week 12 and Week 20) | 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 | Up to 22 weeks | An adverse event (AE) is defined as any undesirable or unintended sign (including abnonmal 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, required or prolonged hospitalization or was considered medically important. |
| Clinical Global Impression-Bipolar-Change (CGI-BP-C):Overall Bipolar Illness | Week 8 of each treatment period (Week 12 and Week 20) | 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
Participants with documented clinical diagnosis meeting the DSM-IV-TR criteria for bipolar I disorder or bipolar II disorder, with most recent episode depressed (296.50 to 296.54 or 296.89) confirmed by the Mini-International Neuropsychiatric Interview (M.I.N.I.) were recruited from 10 sites in Japan.
Pre-assignment details
After informed consent was obtained and prior to randomization in Treatment Period II, participants entered Treatment Period I (4 weeks) to allow a dose titration and reduction for adjusting the dosage regimen of FK949E. Two participants did not enter Treatment Period II (due to an adverse event and withdrawal of consent, respectively).
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Participants who received either FK949E 50 mg tablets or FK949E 150 mg tablets once daily. The analysis population was the Full Analysis Set (FAS), which consisted of all participants who received at least one dose of the study drug and who had at least one efficacy measurement after the start of treatment with the study drug. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period III | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 39.7 Years STANDARD_DEVIATION 10.3 |
| HAMILTON DEPRESSION SCALE (HAM-D17) TOTAL SCORE | 14.5 UNITS ON A SCALE STANDARD_DEVIATION 6.4 |
| MONTGOMERY-ASBERG DEPRESSION RATING SCALE (MADRS) TOTAL SCORE | 19.8 UNITS ON A SCALE STANDARD_DEVIATION 8.6 |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 9 | 2 / 11 | 5 / 9 | 2 / 11 |
| serious Total, serious adverse events | 0 / 9 | 0 / 11 | 0 / 9 | 0 / 11 |
Outcome results
Primary
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: Week 8 of each treatment period (Week 12 and Week 20)
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| FK949E 50 mg Tablets | Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | 7.4 UNITS ON A SCALE |
| FK949E 150 mg Tablets | Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | 7.9 UNITS ON A SCALE |
95% CI: [-3.4, 2.3]
Secondary
Clinical Global Impression-Bipolar-Change (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.
Time frame: Week 8 of each treatment period (Week 12 and Week 20)
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| FK949E 50 mg Tablets | Clinical Global Impression-Bipolar-Change (CGI-BP-C):Depression | 2.0 Units on a scale |
| FK949E 150 mg Tablets | Clinical Global Impression-Bipolar-Change (CGI-BP-C):Depression | 2.0 Units on a scale |
95% CI: [-0.5, 0.5]
Secondary
Clinical Global Impression-Bipolar-Change (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.
Time frame: Week 8 of each treatment period (Week 12 and Week 20)
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FK949E 50 mg Tablets | Clinical Global Impression-Bipolar-Change (CGI-BP-C):Mania | 4.0 Units on a scale | Standard Deviation 0 |
| FK949E 150 mg Tablets | Clinical Global Impression-Bipolar-Change (CGI-BP-C):Mania | 4.0 Units on a scale | Standard Deviation 0 |
Secondary
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.
Time frame: Week 8 of each treatment period (Week 12 and Week 20)
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| FK949E 50 mg Tablets | Clinical Global Impression-Bipolar-Change (CGI-BP-C):Overall Bipolar Illness | 2.0 Units on a scale |
| FK949E 150 mg Tablets | Clinical Global Impression-Bipolar-Change (CGI-BP-C):Overall Bipolar Illness | 2.0 Units on a scale |
95% CI: [-0.5, 0.5]
Secondary
Clinical Global Impression-Bipolar-Severity of Illness (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).
Time frame: Week 8 of each treatment period (Week 12 and Week 20)
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| FK949E 50 mg Tablets | Clinical Global Impression-Bipolar-Severity of Illness (CGI-BP-S):Depression | 2.1 Units on a scale |
| FK949E 150 mg Tablets | Clinical Global Impression-Bipolar-Severity of Illness (CGI-BP-S):Depression | 2.0 Units on a scale |
95% CI: [-0.3, 0.4]
Secondary
Clinical Global Impression-Bipolar-Severity of Illness (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)
Time frame: Week 8 of each treatment period (Week 12 and Week 20)
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FK949E 50 mg Tablets | Clinical Global Impression-Bipolar-Severity of Illness (CGI-BP-S): Mania | 1.0 Units on a scale | Standard Deviation 0 |
| FK949E 150 mg Tablets | Clinical Global Impression-Bipolar-Severity of Illness (CGI-BP-S): Mania | 1.0 Units on a scale | Standard Deviation 0 |
Secondary
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).
Time frame: Week 8 of each treatment period (Week 12 and Week 20)
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| FK949E 50 mg Tablets | Clinical Global Impression-Bipolar-Severity of Illness (CGI-BP-S): Overall Bipolar Illness | 2.1 Units on a scale |
| FK949E 150 mg Tablets | Clinical Global Impression-Bipolar-Severity of Illness (CGI-BP-S): Overall Bipolar Illness | 2.0 Units on a scale |
95% CI: [-0.3, 0.4]
Secondary
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.
Time frame: Week 8 of each treatment period (Week 12 and Week 20)
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| FK949E 50 mg Tablets | Hamilton Depression Scale (HAM-D17) | 5.5 Units on a scale |
| FK949E 150 mg Tablets | Hamilton Depression Scale (HAM-D17) | 5.4 Units on a scale |
95% CI: [-1.7, 1.9]
Secondary
Number of Participants With Adverse Events
An adverse event (AE) is defined as any undesirable or unintended sign (including abnonmal 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, required or prolonged hospitalization or was considered medically important.
Time frame: Up to 22 weeks
Population: Safety Analysis Set (SAF), which included participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FK949E 50 mg Tablets | Number of Participants With Adverse Events | Any AE | 1 Participants |
| FK949E 50 mg Tablets | Number of Participants With Adverse Events | AEs that caused study drug discontinuation | 0 Participants |
| FK949E 50 mg Tablets | Number of Participants With Adverse Events | Drug-related SAEs | 0 Participants |
| FK949E 50 mg Tablets | Number of Participants With Adverse Events | Drug-related AEs | 0 Participants |
| FK949E 50 mg Tablets | Number of Participants With Adverse Events | Drug-related AEs that caused study drug discont. | 0 Participants |
| FK949E 50 mg Tablets | Number of Participants With Adverse Events | Deaths | 0 Participants |
| FK949E 50 mg Tablets | Number of Participants With Adverse Events | Serious AEs | 0 Participants |
| FK949E 150 mg Tablets | Number of Participants With Adverse Events | AEs that caused study drug discontinuation | 0 Participants |
| FK949E 150 mg Tablets | Number of Participants With Adverse Events | Serious AEs | 0 Participants |
| FK949E 150 mg Tablets | Number of Participants With Adverse Events | Deaths | 0 Participants |
| FK949E 150 mg Tablets | Number of Participants With Adverse Events | Drug-related SAEs | 0 Participants |
| FK949E 150 mg Tablets | Number of Participants With Adverse Events | Drug-related AEs that caused study drug discont. | 0 Participants |
| FK949E 150 mg Tablets | Number of Participants With Adverse Events | Drug-related AEs | 1 Participants |
| FK949E 150 mg Tablets | Number of Participants With Adverse Events | Any AE | 2 Participants |
| Treatment Period III FK949E 150 mg | Number of Participants With Adverse Events | Serious AEs | 0 Participants |
| Treatment Period III FK949E 150 mg | Number of Participants With Adverse Events | Any AE | 5 Participants |
| Treatment Period III FK949E 150 mg | Number of Participants With Adverse Events | Drug-related AEs | 2 Participants |
| Treatment Period III FK949E 150 mg | Number of Participants With Adverse Events | Deaths | 0 Participants |
| Treatment Period III FK949E 150 mg | Number of Participants With Adverse Events | Drug-related SAEs | 0 Participants |
| Treatment Period III FK949E 150 mg | Number of Participants With Adverse Events | AEs that caused study drug discontinuation | 0 Participants |
| Treatment Period III FK949E 150 mg | Number of Participants With Adverse Events | Drug-related AEs that caused study drug discont. | 0 Participants |
| Treatment Period III FK949E 50 mg | Number of Participants With Adverse Events | Deaths | 0 Participants |
| Treatment Period III FK949E 50 mg | Number of Participants With Adverse Events | Drug-related AEs that caused study drug discont. | 0 Participants |
| Treatment Period III FK949E 50 mg | Number of Participants With Adverse Events | AEs that caused study drug discontinuation | 0 Participants |
| Treatment Period III FK949E 50 mg | Number of Participants With Adverse Events | Drug-related AEs | 0 Participants |
| Treatment Period III FK949E 50 mg | Number of Participants With Adverse Events | Any AE | 2 Participants |
| Treatment Period III FK949E 50 mg | Number of Participants With Adverse Events | Drug-related SAEs | 0 Participants |
| Treatment Period III FK949E 50 mg | Number of Participants With Adverse Events | Serious AEs | 0 Participants |