Depressive Disorder
Conditions
Brief summary
The purpose of this long-term study is to evaluate the safety and efficacy of duloxetine hydrochloride in Japanese children and adolescents with depressive disorder.
Interventions
DRUGDuloxetine Hydrochloride
Administered orally
Sponsors
Eli Lilly and Company
Shionogi
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
9 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* a) Participants extended from B058(1701A3631) study. * b) New participants. Inclusion Criteria * a) Participants who have completed 7 weeks of dosing in the B058(1701A3631) study and give signed informed consent to continue duloxetine administration in this study. * b) Participants diagnosed with Major Depressive Disorder or persistent depressive disorder and completely meet the criteria of major depressive episode as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) with the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) ver.7.0.2. * b) Participants whose incipient age of depression was ≥7 years old.
Exclusion criteria
* a, b) Have a current or previous diagnosis (DSM-5) of the following as judged by the investigator: * Neurodevelopmental disorders * Schizophrenia spectrum and other psychotic disorders * Bipolar and related disorders * Trauma and stressor-related disorders * Disruptive · Impulse Control · and Conduct disorders * a, b) Have a current diagnosis (DSM-5) of the following as judged by the investigator: * Obsessive-compulsive and related disorders * Anorexia nervosa, Bulimia nervosa, Binge-eating disorder * Sleep-wake disorders * Neurocognitive disorders * Disruptive mood dysregulation disorder * a, b) Have personality disorders, in the judgment of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events (AEs), Drug Related Adverse Events (ADRs) or Any Serious Adverse Events (SAEs) | Baseline through Week 53 | A summary of AEs, ADRs (considered by the investigator) and SAEs is located in the Reported Adverse Events module. An AE was included if the onset date is on or after the first dose of study drug and within 7 days after the last dose, or it is consecutive from the preceding study at the initiation of study drug administration in this study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline on the Children's Depression Rating Scale-Revised (CDRS-R) | Baseline, Week 50 | Children's Depression Rating Scale-Revised (CDRS-R) Total score measures the presence and severity of depression in children. The scale consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. A rating of 1 indicates normal functioning and higher numbers indicate a higher degree of depression. The total sum of scores range from 17 to 113. In general, scores below 20 indicate an absence of depression, scores of 20 to 30 indicate borderline depression, scores of 40 to 60 indicate moderate depression, and scores greater than 60 indicate severe depression. |
| Change From Baseline on the Clinical Global Impression-Severity of Illness (CGI-S) | Baseline, Week 50 | CGI-S measures severity of illness at the time of assessment compared with start of treatment with scores ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). |
| Pharmacokinetics (PK): Trough Concentration of Duloxetine | Week 4 through Week 50 | Trough concentrations of duloxetine are defined as the plasma concentrations in 18 - 30 hours post the previous dose. PK samples were obtained from each subject from Week 4 to the end of treatment period (Week 50) for analysis of steady state duloxetine concentrations. If duloxetine dose changed, PK samples were taken after 2 week or more administration of the new dose. Principally 1 or 2 blood samples were drawn from each subject at pre-dose for trough concentrations. |
Countries
Japan
Participant flow
Recruitment details
59 and 64 subjects, respectively, were enrolled consecutively from the placebo- and duloxetine-group in the preceding study 1701A3631/F1J-JE-B058, NCT03315793. 28 new participants were also enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Duloxetine 20 mg Duloxetine was administered every day for 1 week. Then 40 mg Duloxetine was administered for 1 week. Then flexible doses of 40 mg or 60 mg Duloxetine were administered for 48 weeks till end of treatment period. Lower doses of Duloxetine were administered for 1 to 2 weeks during tapering off period. | 150 |
| Total | 150 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 20 |
| Overall Study | Discontinued visit | 1 |
| Overall Study | Early termination of overall study | 33 |
| Overall Study | Lack of Efficacy | 3 |
| Overall Study | Physician Decision | 4 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Refrain from visit due to COVID-19 | 1 |
| Overall Study | Withdrawal by Subject | 24 |
Baseline characteristics
| Characteristic | Duloxetine |
|---|---|
| Age, Continuous | 14.6 years STANDARD_DEVIATION 1.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 150 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 150 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Japan | 150 participants |
| Sex: Female, Male Female | 106 Participants |
| Sex: Female, Male Male | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 150 |
| other Total, other adverse events | 134 / 150 |
| serious Total, serious adverse events | 3 / 150 |
Outcome results
Primary
Percentage of Participants With Adverse Events (AEs), Drug Related Adverse Events (ADRs) or Any Serious Adverse Events (SAEs)
A summary of AEs, ADRs (considered by the investigator) and SAEs is located in the Reported Adverse Events module. An AE was included if the onset date is on or after the first dose of study drug and within 7 days after the last dose, or it is consecutive from the preceding study at the initiation of study drug administration in this study.
Time frame: Baseline through Week 53
Population: All enrolled participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine | Percentage of Participants With Adverse Events (AEs), Drug Related Adverse Events (ADRs) or Any Serious Adverse Events (SAEs) | Serious Adverse Event | 2 percentage of participants |
| Duloxetine | Percentage of Participants With Adverse Events (AEs), Drug Related Adverse Events (ADRs) or Any Serious Adverse Events (SAEs) | Adverse Event including Serious Adverse Event | 89.3 percentage of participants |
| Duloxetine | Percentage of Participants With Adverse Events (AEs), Drug Related Adverse Events (ADRs) or Any Serious Adverse Events (SAEs) | Drug-Related Adverse Event | 73.3 percentage of participants |
Secondary
Change From Baseline on the Children's Depression Rating Scale-Revised (CDRS-R)
Children's Depression Rating Scale-Revised (CDRS-R) Total score measures the presence and severity of depression in children. The scale consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. A rating of 1 indicates normal functioning and higher numbers indicate a higher degree of depression. The total sum of scores range from 17 to 113. In general, scores below 20 indicate an absence of depression, scores of 20 to 30 indicate borderline depression, scores of 40 to 60 indicate moderate depression, and scores greater than 60 indicate severe depression.
Time frame: Baseline, Week 50
Population: All enrolled participants who received at least one dose of study drug and had at least 1 post-dose CDRS-R Total score. Missing values due to discontinuation of study or missing data were imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Change From Baseline on the Children's Depression Rating Scale-Revised (CDRS-R) | -12.8 units on a scale | Standard Deviation 16.7 |
Secondary
Change From Baseline on the Clinical Global Impression-Severity of Illness (CGI-S)
CGI-S measures severity of illness at the time of assessment compared with start of treatment with scores ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill participants).
Time frame: Baseline, Week 50
Population: All enrolled participants who received at least one dose of study drug and had at least 1 post-dose CDRS-R Total score. Missing values due to discontinuation of study or missing data were imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Change From Baseline on the Clinical Global Impression-Severity of Illness (CGI-S) | -0.9 units on a scale | Standard Deviation 1.3 |
Secondary
Pharmacokinetics (PK): Trough Concentration of Duloxetine
Trough concentrations of duloxetine are defined as the plasma concentrations in 18 - 30 hours post the previous dose. PK samples were obtained from each subject from Week 4 to the end of treatment period (Week 50) for analysis of steady state duloxetine concentrations. If duloxetine dose changed, PK samples were taken after 2 week or more administration of the new dose. Principally 1 or 2 blood samples were drawn from each subject at pre-dose for trough concentrations.
Time frame: Week 4 through Week 50
Population: All enrolled participants who received at least 1 dose of study drug. 512 plasma concentrations were from 141 subjects, 20 of which were excluded due to discontinuation, overdose and subjects being non-Japanese. 492 concentration values from 136 Japanese subjects were included in the analysis. Of the 492 concentration values, 133 from 106 subjects were trough concentrations. Sum of subjects(3, 47, 6, 54) is 110, 4 more than 106, as 4 subjects of 12-17 years old are redundant in 40mg and 60mg.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Pharmacokinetics (PK): Trough Concentration of Duloxetine | 8.51 ng/mL | Standard Deviation 7.22 |
| Duloxetine 40 mg (12 to 17 Years Old) | Pharmacokinetics (PK): Trough Concentration of Duloxetine | 18 ng/mL | Standard Deviation 15.2 |
| Duloxetine 60 mg (9 to 11 Years Old) | Pharmacokinetics (PK): Trough Concentration of Duloxetine | 33.4 ng/mL | Standard Deviation 30.7 |
| Duloxetine 60 mg (12 to 17 Years Old) | Pharmacokinetics (PK): Trough Concentration of Duloxetine | 39.5 ng/mL | Standard Deviation 52.1 |