Major Depressive Disorder
Conditions
Brief summary
The objective of the trial is to compare the efficacy of OPC-64005 at 20 mg vs placebo and to assess the safety and pharmacokinetics of OPC-64005 at 10 and 20 mg in patients with major depressive disorder (MDD).The primary endpoint is the mean change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Week 6 of the double-blind treatment period in the OPC-64005 20-mg group compared with the placebo group
Interventions
DRUGOPC-64005 20 mg , Once-daily
Active, High Dose
DRUGOPC-64005 10 mg , Once-daily
Active, Low Dose
DRUGPlacebo, Once-daily
Placebo
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Patients with a DSM-5 classification-based diagnosis of major depressive disorder, single episode or major depressive disorder, recurrent episode with the current episode persisting for ≥4 weeks to ≤1 year * Patients with a total score of ≥18 on the 17-item Hamilton Rating Scale for Depression (HAM-D)
Exclusion criteria
* Patients with a diagnosis of any of the following diseases according to DSM-5 Neurocognitive disorders, history or complication of schizophrenia spectrum or other psychotic disorder, history or complication of bipolar and related disorders, feeding and eating disorders, obsessive-compulsive disorder, panic disorder, posttraumatic stress disorder, personality disorders, neurodevelopmental disorders, substance-related and addictive disorders (within 180 days prior to informed consent) * Patients exhibiting mood-incongruent psychotic features in the current major depressive episode * Patients who, in the opinion of the investigator or subinvestigator, are judged to have treatment-resistant depression, ie, a certain degree of therapeutic effect is not obtained by administration of 2 or more antidepressants having different mechanisms of action at sufficient doses for at least 6 weeks for the current major depressive episode * Patients receiving augmentation treatment, such as antipsychotics, for the current major depressive episode (excluding the use of sulpiride for depression/depressive state or gastric/duodenal ulcer)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6 of the Double-blind Treatment Period | Baseline, Week 1, 2, 3, 4, 5, and 6 | The MADRS was a clinician-rated scale which evaluated the level of depression. The MADRS consists of following 10 depressive symptoms on 7 scales of 0 to 6, with higher scores indicating worse condition. 1\. Apparent sadness, 2. Reported sadness, 3. Inner tension, 4. Reduced sleep, 5. Reduced appetite, 6. Concentration difficulties, 7. Lassitude, 8. Inability to feel, 9. Pessimistic thoughts, and 10. Suicidal thoughts Summed subscales were combined to compute a total score. Total score ranges form 0 to 60, with higher scores indicating worse condition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MADRS Response Rate | Baseline, Week 1, 2, 3, 4, 5, and 6 | The MADRS response rate is the percentage of subjects with ≥50% reduction from baseline in MADRS total score at Week 6 of the double-blind treatment period. |
| MADRS Remission Rate | Week6 | MADRS remission rate is the percentage of subjects with MADRS total score ≤ 10 and ≥ 50% reduction from baseline in MADRS total score at Week 6 of the double-blind treatment period. |
Countries
Japan
Participant flow
Recruitment details
This trial was conducted in 273 subjects from 69 trial sites in Japan.
Pre-assignment details
Adult subjects with Major Depressive Disorder defined by criteria of the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5).
Participants by arm
| Arm | Count |
|---|---|
| OPC-64005 10-mg One placebo tablet and one OPC-64005 10-mg tablet administered orally once daily for 6 weeks | 31 |
| OPC-64005 20-mg One placebo tablet and one OPC-64005 10-mg tablet administered orally once daily for 1 week, followed by two OPC-64005 10-mg tablets for 5 weeks | 121 |
| Placebo Two placebo tablets administered orally once daily for 6 weeks | 121 |
| Total | 273 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 4 |
| Overall Study | Non-Compliance With Study Drug | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 6 |
Baseline characteristics
| Characteristic | OPC-64005 10-mg | OPC-64005 20-mg | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 121 Participants | 121 Participants | 273 Participants |
| Age, Continuous | 37.5 years STANDARD_DEVIATION 11 | 39.5 years STANDARD_DEVIATION 11.4 | 38.3 years STANDARD_DEVIATION 11.1 | 38.8 years STANDARD_DEVIATION 11.2 |
| Race/Ethnicity, Customized Asian | 31 Participants | 121 Participants | 121 Participants | 273 Participants |
| Region of Enrollment Japan | 31 participants | 121 participants | 121 participants | 273 participants |
| Sex: Female, Male Female | 17 Participants | 56 Participants | 58 Participants | 131 Participants |
| Sex: Female, Male Male | 14 Participants | 65 Participants | 63 Participants | 142 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 121 | 0 / 121 |
| other Total, other adverse events | 7 / 31 | 19 / 121 | 19 / 121 |
| serious Total, serious adverse events | 0 / 31 | 2 / 121 | 1 / 121 |
Outcome results
Primary
Mean Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6 of the Double-blind Treatment Period
The MADRS was a clinician-rated scale which evaluated the level of depression. The MADRS consists of following 10 depressive symptoms on 7 scales of 0 to 6, with higher scores indicating worse condition. 1\. Apparent sadness, 2. Reported sadness, 3. Inner tension, 4. Reduced sleep, 5. Reduced appetite, 6. Concentration difficulties, 7. Lassitude, 8. Inability to feel, 9. Pessimistic thoughts, and 10. Suicidal thoughts Summed subscales were combined to compute a total score. Total score ranges form 0 to 60, with higher scores indicating worse condition.
Time frame: Baseline, Week 1, 2, 3, 4, 5, and 6
Population: The full analysis set (FAS) includes all subjects who were administered at least 1 dose of double-blind IMP and have MADRS total scores at baseline and at least one time point after the start of double-blind treatment. FAS excluded one subject in the placebo group for whom no MADRS total score was obtained after start of double-blind treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OPC-64005 10-mg | Mean Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6 of the Double-blind Treatment Period | 1Week | -1.9 Units on a scale | Standard Error 0.8 |
| OPC-64005 10-mg | Mean Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6 of the Double-blind Treatment Period | 2Week | -3.9 Units on a scale | Standard Error 1 |
| OPC-64005 10-mg | Mean Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6 of the Double-blind Treatment Period | 3Week | -7.1 Units on a scale | Standard Error 1.2 |
| OPC-64005 10-mg | Mean Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6 of the Double-blind Treatment Period | 4Week | -9.5 Units on a scale | Standard Error 1.3 |
| OPC-64005 10-mg | Mean Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6 of the Double-blind Treatment Period | 5Week | -10.6 Units on a scale | Standard Error 1.4 |
| OPC-64005 10-mg | Mean Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6 of the Double-blind Treatment Period | 6Week | -11.2 Units on a scale | Standard Error 1.5 |
| OPC-64005 20-mg | Mean Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6 of the Double-blind Treatment Period | 6Week | -10.7 Units on a scale | Standard Error 0.8 |
| OPC-64005 20-mg | Mean Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6 of the Double-blind Treatment Period | 1Week | -1.6 Units on a scale | Standard Error 0.4 |
| OPC-64005 20-mg | Mean Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6 of the Double-blind Treatment Period | 4Week | -7.5 Units on a scale | Standard Error 0.7 |
| OPC-64005 20-mg | Mean Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6 of the Double-blind Treatment Period | 5Week | -8.9 Units on a scale | Standard Error 0.7 |
| OPC-64005 20-mg | Mean Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6 of the Double-blind Treatment Period | 2Week | -3.4 Units on a scale | Standard Error 0.5 |
| OPC-64005 20-mg | Mean Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6 of the Double-blind Treatment Period | 3Week | -5.7 Units on a scale | Standard Error 0.6 |
| Placebo | Mean Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6 of the Double-blind Treatment Period | 2Week | -3.6 Units on a scale | Standard Error 0.5 |
| Placebo | Mean Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6 of the Double-blind Treatment Period | 3Week | -5.2 Units on a scale | Standard Error 0.6 |
| Placebo | Mean Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6 of the Double-blind Treatment Period | 6Week | -9.5 Units on a scale | Standard Error 0.8 |
| Placebo | Mean Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6 of the Double-blind Treatment Period | 4Week | -6.3 Units on a scale | Standard Error 0.7 |
| Placebo | Mean Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6 of the Double-blind Treatment Period | 1Week | -2.1 Units on a scale | Standard Error 0.4 |
| Placebo | Mean Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6 of the Double-blind Treatment Period | 5Week | -8.1 Units on a scale | Standard Error 0.7 |
Comparison: The statistical analysis was performed at Week 6 to compare the OPC-64005 20-mg group and placebo group.p-value: 0.28895% CI: [-3.3, 1]Mixed-model repeated measures
Secondary
MADRS Remission Rate
MADRS remission rate is the percentage of subjects with MADRS total score ≤ 10 and ≥ 50% reduction from baseline in MADRS total score at Week 6 of the double-blind treatment period.
Time frame: Week6
Population: The full analysis set (FAS) included all subjects who were administered at least 1 dose of double-blind IMP and had MADRS total scores at baseline and at least one time point after the start of double-blind treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OPC-64005 10-mg | MADRS Remission Rate | 16.1 percentage of participants |
| OPC-64005 20-mg | MADRS Remission Rate | 14.9 percentage of participants |
| Placebo | MADRS Remission Rate | 13.3 percentage of participants |
Comparison: The statistical analysis was performed at Week 6 to compare the OPC-64005 20-mg group and placebo group.p-value: 0.73195% CI: [-7.2, 10.3]χ2 test
Secondary
MADRS Response Rate
The MADRS response rate is the percentage of subjects with ≥50% reduction from baseline in MADRS total score at Week 6 of the double-blind treatment period.
Time frame: Baseline, Week 1, 2, 3, 4, 5, and 6
Population: The full analysis set (FAS) included all subjects who were administered at least 1 dose of double-blind IMP and had MADRS total scores at baseline and at least one time point after the start of double-blind treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| OPC-64005 10-mg | MADRS Response Rate | 1Week | 0.0 percentage of participants |
| OPC-64005 10-mg | MADRS Response Rate | 2Week | 3.2 percentage of participants |
| OPC-64005 10-mg | MADRS Response Rate | 3Week | 12.9 percentage of participants |
| OPC-64005 10-mg | MADRS Response Rate | 4Week | 22.6 percentage of participants |
| OPC-64005 10-mg | MADRS Response Rate | 5Week | 25.8 percentage of participants |
| OPC-64005 10-mg | MADRS Response Rate | 6Week | 32.3 percentage of participants |
| OPC-64005 20-mg | MADRS Response Rate | 6Week | 29.8 percentage of participants |
| OPC-64005 20-mg | MADRS Response Rate | 1Week | 0.8 percentage of participants |
| OPC-64005 20-mg | MADRS Response Rate | 4Week | 14.9 percentage of participants |
| OPC-64005 20-mg | MADRS Response Rate | 5Week | 18.2 percentage of participants |
| OPC-64005 20-mg | MADRS Response Rate | 2Week | 5.0 percentage of participants |
| OPC-64005 20-mg | MADRS Response Rate | 3Week | 9.9 percentage of participants |
| Placebo | MADRS Response Rate | 2Week | 3.3 percentage of participants |
| Placebo | MADRS Response Rate | 3Week | 6.7 percentage of participants |
| Placebo | MADRS Response Rate | 6Week | 24.2 percentage of participants |
| Placebo | MADRS Response Rate | 4Week | 10.0 percentage of participants |
| Placebo | MADRS Response Rate | 1Week | 0.8 percentage of participants |
| Placebo | MADRS Response Rate | 5Week | 18.3 percentage of participants |
Comparison: The statistical analysis was performed at Week 6 to compare the OPC-64005 20-mg group and placebo group.p-value: 0.32995% CI: [-5.6, 16.8]χ2 test