Depressive Disorder
Conditions
Brief summary
The purpose of this study is to determine the efficacy of duloxetine hydrochloride versus placebo in the treatment of Japanese children and adolescents with depressive disorder.
Interventions
DRUGDuloxetine Hydrochloride
Administered orally
DRUGPlacebo
Administered orally
Sponsors
Eli Lilly and Company
Shionogi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
9 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* 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. * Participants whose incipient age of depression was ≥7 years old. * Total score of CDRS-R is ≥40 and CGI-S score is ≥4 at both screening and baseline.
Exclusion criteria
* Have remarkable response to psycho-education (defined as \>30% decrease in the total score of CDRS-R between screening and baseline). * 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 * 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 * Have personality disorders, in the judgement of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline on the Children's Depression Rating Scale-Revised (CDRS-R) Total Score | Baseline, Week 6 | Change from baseline on the Children's Depression Rating Scale-Revised (CDRS-R) total score. 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 a higher number indicates a greater 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. Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach including treatment group, observation time-points, and interaction between treatment group and observation time-points as fixed effects, and baseline CDRS-R total score and age as covariates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Whose Children's Depression Rating Scale-Revised (CDRS-R) Total Score Decreased by More Than 30% From Baseline | Baseline, Week 6 | The 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 greater 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. |
| Percentage of Participants Whose CDRS-R Total Score Decreased by More Than 50% From Baseline | Baseline, Week 6 | The 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 with higher numbers indicating a greater degree of depression . The total sum of scores range from 17 to 113. 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. |
| Percentage of Participants With Total Children's Depression Rating Scale-Revised (CDRS-R) Score ≤ 28 | Baseline, Week 6 | The 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 greater 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. Remission was defined for the CDRS-R total score below 28. |
| Change From Baseline on Clinical Global Impression-Severity (CGI-S) | Baseline, Week 6 | CGI-S measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Presented here are the LS mean change from baseline on CGI-S calculated using a mixed-effects model repeated measures (MMRM) approach including treatment group, observation time-points, and interaction between treatment group and observation time-points as fixed effects, and baseline CGI-S and age as covariates. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Duloxetine 20 mg Duloxetine was administered 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 4 weeks. Lower doses Duloxetine were administered for 1 week during tapering off period. | 74 |
| Placebo Placebo was administered every day for 7 weeks. | 74 |
| Total | 148 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 2 |
| Overall Study | Difficult for regular visit | 0 | 1 |
| Overall Study | Protocol Deviation | 1 | 0 |
Baseline characteristics
| Characteristic | Duloxetine | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 14 years STANDARD_DEVIATION 1.9 | 14.6 years STANDARD_DEVIATION 2 | 14.5 years STANDARD_DEVIATION 1.9 |
| Children's Depression Rating Scale-Revised (CDRS-R) Total Score | 65.7 units on a scale STANDARD_DEVIATION 10.5 | 63.3 units on a scale STANDARD_DEVIATION 12.4 | 64.5 units on a scale STANDARD_DEVIATION 11.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 74 Participants | 74 Participants | 148 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 74 Participants | 74 Participants | 148 Participants |
| Sex: Female, Male Female | 46 Participants | 47 Participants | 93 Participants |
| Sex: Female, Male Male | 28 Participants | 27 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 75 | 0 / 74 |
| other Total, other adverse events | 59 / 75 | 46 / 74 |
| serious Total, serious adverse events | 0 / 75 | 0 / 74 |
Outcome results
Primary
Change From Baseline on the Children's Depression Rating Scale-Revised (CDRS-R) Total Score
Change from baseline on the Children's Depression Rating Scale-Revised (CDRS-R) total score. 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 a higher number indicates a greater 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. Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach including treatment group, observation time-points, and interaction between treatment group and observation time-points as fixed effects, and baseline CDRS-R total score and age as covariates.
Time frame: Baseline, Week 6
Population: All randomized participants who received 1 dose of study drug and had 1 post-baseline CDRS-S score. One participant in the duloxetine group had no post-dose CDRS-R Total Score and was not included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Change From Baseline on the Children's Depression Rating Scale-Revised (CDRS-R) Total Score | -21.03 units on a scale | Standard Error 2.04 |
| Placebo | Change From Baseline on the Children's Depression Rating Scale-Revised (CDRS-R) Total Score | -22.42 units on a scale | Standard Error 2.05 |
p-value: 0.558798% CI: [-3.3, 6.08]mixed-effects model repeated measures
Secondary
Change From Baseline on Clinical Global Impression-Severity (CGI-S)
CGI-S measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Presented here are the LS mean change from baseline on CGI-S calculated using a mixed-effects model repeated measures (MMRM) approach including treatment group, observation time-points, and interaction between treatment group and observation time-points as fixed effects, and baseline CGI-S and age as covariates.
Time frame: Baseline, Week 6
Population: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose CDRS-R Total score. One duloxetine participant had no post-dose CDRS-R Total Score and was not included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Change From Baseline on Clinical Global Impression-Severity (CGI-S) | -1.24 units on a scale | Standard Error 0.14 |
| Placebo | Change From Baseline on Clinical Global Impression-Severity (CGI-S) | -1.38 units on a scale | Standard Error 0.14 |
p-value: 0.383695% CI: [-0.18, 0.46]mixed-effects model repeated measures
Secondary
Percentage of Participants Whose CDRS-R Total Score Decreased by More Than 50% From Baseline
The 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 with higher numbers indicating a greater degree of depression . The total sum of scores range from 17 to 113. 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 6
Population: All randomized participants who received at least one dose of study drug and had at least 1 post-dose CDRS-R Total Score. One participant in the duloxetine group had no post-dose CDRS-R Total Score and was not included in the analysis. The last observation carried forward (LOCF) method was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duloxetine | Percentage of Participants Whose CDRS-R Total Score Decreased by More Than 50% From Baseline | 21.6 percentage of participants |
| Placebo | Percentage of Participants Whose CDRS-R Total Score Decreased by More Than 50% From Baseline | 21.6 percentage of participants |
p-value: 195% CI: [-13.5, 13.5]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Whose Children's Depression Rating Scale-Revised (CDRS-R) Total Score Decreased by More Than 30% From Baseline
The 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 greater 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 6
Population: All randomized participants who received at least one dose of study drug and had at least 1 post-dose CDRS-R Total Score. One participant in the duloxetine group had no post-dose CDRS-R Total Score and was not included in the analysis. The last observation carried forward (LOCF) method was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duloxetine | Percentage of Participants Whose Children's Depression Rating Scale-Revised (CDRS-R) Total Score Decreased by More Than 30% From Baseline | 48.6 percentage of participants |
| Placebo | Percentage of Participants Whose Children's Depression Rating Scale-Revised (CDRS-R) Total Score Decreased by More Than 30% From Baseline | 43.2 percentage of participants |
p-value: 0.511195% CI: [-10.7, 21.5]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Total Children's Depression Rating Scale-Revised (CDRS-R) Score ≤ 28
The 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 greater 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. Remission was defined for the CDRS-R total score below 28.
Time frame: Baseline, Week 6
Population: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose CDRS-R Total Score. One participant in the duloxetine group had no post-dose CDRS-R Total Score and was not included in the analysis. The last observation carried forward (LOCF) method was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duloxetine | Percentage of Participants With Total Children's Depression Rating Scale-Revised (CDRS-R) Score ≤ 28 | 9.5 percentage of participants |
| Placebo | Percentage of Participants With Total Children's Depression Rating Scale-Revised (CDRS-R) Score ≤ 28 | 13.5 percentage of participants |
p-value: 0.442395% CI: [-14.4, 6.3]Cochran-Mantel-Haenszel