Major Depressive Disorder
Conditions
Brief summary
The purpose of this study is to verify the efficacy and evaluate the safety of 8-week once-daily oral administration of MD-120 in Japanese patients with depression.
Interventions
once daily dosing for 8 weeks
once daily dosing for 8 weeks
DRUGPlacebo
once daily dosing for 8 weeks
Sponsors
Pfizer
Mochida Pharmaceutical Company, 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 No maximum
Healthy volunteers
No
Inclusion criteria
* Patient with diagnosis of Major Depressive Disorder (MDD) based on the criteria in the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5). * Hamilton Depression Rating Scale-17 (HAM-D17) total score of ≥20.
Exclusion criteria
* Patient who meets DSM-5 criteria of the following disorders for current or past history. Schizophrenia spectrum and other psychotic disorders Bipolar and related disorders Substance use disorders (exclusive of tobacco and caffeine) * Patient who had suicidal behavior in Columbia-Suicide Severity Rating Scale (C-SSRS) within 1 year before start of screening phase.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Total MADRS Score From the Baseline to Week 8 Visit During the Treatment Period | 8 weeks | Montgomery-Asberg Depression Rating Scale (MADRS) Total Score: Scale ranges from 0 to 60 with a higher score indicating worsening symptoms of depression. Estimates were based on a Mixed-effects Model for Repeated Measures (MMRM) model with the treatment group, assessment timepoint, and the interaction between the treatment group and assessment timepoint as a factor and total MADRS score at baseline as a covariate. |
| Number of Participants With Adverse Events (AEs) | 10 weeks | An adverse event is any undesirable or unintended sign (including abnormal findings in general laboratory tests, body weight, and standard 12-lead ECG), symptom, or disease in a subject given the investigational drug, irrespective of the causal relationship to the investigational drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Total HAM-D17 Score From the Baseline to Week 8 Visit During the Treatment Period | 8 weeks | Hamilton Depression Rating Scale-17 (HAM-D17) Total Score: Scale ranges from 0 to 52 with a higher score indicating worsening symptoms of depression. Estimates were based on a MMRM model with the treatment group, assessment timepoint, and the interaction between the treatment group and assessment timepoint as a factor and total HAM-D17 score at baseline as a covariate. |
| Number of Participants With Adverse Drug Reactions (ADRs) | 10 weeks | — |
| Plasma Concentration of Desvenlafaxine | Week 2 through week 8 | — |
Countries
Japan
Participant flow
Recruitment details
Participants took part in the study at 82 investigational sites in Japan from 18 May 2020 to 14 September 2022.
Pre-assignment details
Participants who met entry criteria were enrolled placebo lead-in period for one week prior to randomization, after that participants randomized and enrolled in one of three treatment group (Placebo group, MD-120 50 mg group, MD-120 100 mg group) for 8 weeks as double-blind treatment period.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo, orally, once daily for up to Week 8 | 203 |
| MD-120 50 mg MD-120 50 mg, orally, once daily for up to Week 8 | 206 |
| MD-120 100 mg MD-120 50 mg, orally, once daily for up to Week 1, followed by MD-120 100 mg, orally, once daily for up to Week 8 | 204 |
| Total | 613 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 8 | 5 | 6 |
| Overall Study | Lack of Efficacy | 1 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 10 | 5 | 10 |
Baseline characteristics
| Characteristic | Placebo | MD-120 50 mg | MD-120 100 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 40.2 Years STANDARD_DEVIATION 12 | 39.8 Years STANDARD_DEVIATION 12.1 | 39.6 Years STANDARD_DEVIATION 12.7 | 39.8 Years STANDARD_DEVIATION 12.2 |
| Hamilton Depression Rating Scale-17 (HAM-D17) Total Score | 24.3 Scores on a scale STANDARD_DEVIATION 2.9 | 24.3 Scores on a scale STANDARD_DEVIATION 3 | 23.8 Scores on a scale STANDARD_DEVIATION 2.8 | 24.1 Scores on a scale STANDARD_DEVIATION 2.9 |
| Montgomery Asberg Depression Rating Scale (MADRS) Total Score | 31.6 Scores on a scale STANDARD_DEVIATION 4.9 | 32.0 Scores on a scale STANDARD_DEVIATION 4.7 | 31.5 Scores on a scale STANDARD_DEVIATION 4.7 | 31.7 Scores on a scale STANDARD_DEVIATION 4.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 203 Participants | 206 Participants | 204 Participants | 613 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 203 participants | 206 participants | 204 participants | 613 participants |
| Sex: Female, Male Female | 102 Participants | 104 Participants | 91 Participants | 297 Participants |
| Sex: Female, Male Male | 101 Participants | 102 Participants | 113 Participants | 316 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 204 | 0 / 206 | 0 / 204 |
| other Total, other adverse events | 43 / 204 | 67 / 206 | 71 / 204 |
| serious Total, serious adverse events | 2 / 204 | 3 / 206 | 2 / 204 |
Outcome results
Primary
Changes in Total MADRS Score From the Baseline to Week 8 Visit During the Treatment Period
Montgomery-Asberg Depression Rating Scale (MADRS) Total Score: Scale ranges from 0 to 60 with a higher score indicating worsening symptoms of depression. Estimates were based on a Mixed-effects Model for Repeated Measures (MMRM) model with the treatment group, assessment timepoint, and the interaction between the treatment group and assessment timepoint as a factor and total MADRS score at baseline as a covariate.
Time frame: 8 weeks
Population: Of subjects registered for randomization, those meeting all the following items were included in the full analysis set (FAS).~1. Subjects who received the investigational drug at least once during the treatment period.~2. Subjects who were evaluated for the total MADRS score at the baseline and at least one timepoint after the start of the treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Changes in Total MADRS Score From the Baseline to Week 8 Visit During the Treatment Period | -10.4 Score on a scale | Standard Error 0.7 |
| MD-120 50 mg | Changes in Total MADRS Score From the Baseline to Week 8 Visit During the Treatment Period | -11.1 Score on a scale | Standard Error 0.7 |
| MD-120 100 mg | Changes in Total MADRS Score From the Baseline to Week 8 Visit During the Treatment Period | -11.9 Score on a scale | Standard Error 0.7 |
p-value: 0.50995% CI: [-2.5, 1.2]MMRM
p-value: 0.13195% CI: [-3.3, 0.4]MMRM
Primary
Number of Participants With Adverse Events (AEs)
An adverse event is any undesirable or unintended sign (including abnormal findings in general laboratory tests, body weight, and standard 12-lead ECG), symptom, or disease in a subject given the investigational drug, irrespective of the causal relationship to the investigational drug.
Time frame: 10 weeks
Population: Of subjects registered for randomization, those meeting all the following items will be included in the safety analysis set in treatment period.~1. Subjects who have received the investigational drug at least once during the treatment period.~2. Subjects in whom the safety evaluation data after the dose of the investigational drug in the treatment period are available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Adverse Events (AEs) | 102 Participants |
| MD-120 50 mg | Number of Participants With Adverse Events (AEs) | 117 Participants |
| MD-120 100 mg | Number of Participants With Adverse Events (AEs) | 124 Participants |
Secondary
Changes in Total HAM-D17 Score From the Baseline to Week 8 Visit During the Treatment Period
Hamilton Depression Rating Scale-17 (HAM-D17) Total Score: Scale ranges from 0 to 52 with a higher score indicating worsening symptoms of depression. Estimates were based on a MMRM model with the treatment group, assessment timepoint, and the interaction between the treatment group and assessment timepoint as a factor and total HAM-D17 score at baseline as a covariate.
Time frame: 8 weeks
Population: Of subjects registered for randomization, those meeting all the following items were included in the FAS.~1. Subjects who received the investigational drug at least once during the treatment period.~2. Subjects who were evaluated for the total MADRS score at the baseline and at least one timepoint after the start of the treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Changes in Total HAM-D17 Score From the Baseline to Week 8 Visit During the Treatment Period | -8.3 Scores on a scale | Standard Error 0.5 |
| MD-120 50 mg | Changes in Total HAM-D17 Score From the Baseline to Week 8 Visit During the Treatment Period | -8.4 Scores on a scale | Standard Error 0.5 |
| MD-120 100 mg | Changes in Total HAM-D17 Score From the Baseline to Week 8 Visit During the Treatment Period | -8.8 Scores on a scale | Standard Error 0.5 |
p-value: 0.81195% CI: [-1.5, 1.2]MMRM
p-value: 0.42495% CI: [-1.9, 0.8]MMRM
Secondary
Number of Participants With Adverse Drug Reactions (ADRs)
Time frame: 10 weeks
Secondary
Plasma Concentration of Desvenlafaxine
Time frame: Week 2 through week 8