Major Depressive Disorder With Mixed Features
Conditions
Keywords
depression, Lurasidone, Latuda
Brief summary
Lurasidone HCl is a compound that is a candidate for the treatment of major depressive with mixed features.This clinical study is designed to test how well Lurasidone works to treat major depressive disorder with mixed features.
Interventions
DRUGLurasidone
20, 40, 60 mg, flexible dose, once daily PM 6 weeks
DRUGPlacebo
Placebo
Sponsors
Sumitomo Pharma America, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subject provides written informed consent and is willing and able to comply with the protocol in the opinion of the Investigator. * Subject is 18 to 75 years of age, inclusive. * Subject has MDD (diagnosed by DSM-IV-TR, and confirmed by the Structured - Clinical Interview for DSM-IV Disorders - Clinical Trial version \[SCID-CT\]). * Subject is currently experiencing a major depressive episode (diagnosed by DSM IV TR; at least 2 weeks in duration) AND two or three of the following manic symptoms occurring on most days over at least the last 2 weeks (confirmed by the SCID-CT modified for Study D1050304): * Elevated, expansive mood * Inflated self-esteem or grandiosity * More talkative than usual or pressure to keep talking * Flight of ideas or subjective experience that thoughts are racing * Increase in energy or goal-directed activity (either socially, at work or school, or sexually) * Increased or excessive involvement in activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments) * Decreased need for sleep (feeling rested despite sleeping less than usual; to be contrasted from insomnia)
Exclusion criteria
* Subject has Axis I or Axis II diagnosis other than MDD that has been the primary focus of treatment within the 3 months prior to screening. * Subject answers yes to Suicidal Ideation Item 4 or 5 on the C-SSRS (at time of evaluation) at screening or baseline visit. * Subject has attempted suicide within the past 3 months. * Subject has a lifetime history of any bipolar I manic or mixed manic episode. * Subject has any abnormal laboratory parameter at screening that indicates a clinically significant medical condition as determined by the Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to the 6-week Study Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Scores | Baseline to Week 6 | The MADRS consists of 10 items, each rated on a Likert scale, from 0=Normal to 6=Most Severe. The MADRS total score is calculated as the sum of the 10 items. The MADRS total score ranges from 0 to 60. Higher scores are associated with greater severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to Week 6 in the Young Mania Rating Scale (YMRS) Total Score | Baseline to Week 6 | The YMRS is an 11-item clinician-rated instrument used to assess the severity of mania. Seven items are rated on a 5-point scale, ranging from 0 to 4, and four items are rated on a 9-point scale, ranging from 0 to 8. The YMRS total score is calculated as the sum of the 11 individual items and ranges from 0 to 60. Higher scores are associated with greater severity of mania. |
| Mean Change From Baseline to Week 6 in the Sheehan Disability Scale (SDS) Total Score | Baseline to Week 6 | The SDS is a composite of three self-rated items designed to measure the extent to which three major sectors (work/school, social life/leisure, and family life/home responsibility) in the patient's life are impaired by depressive symptoms. These three items are responded to on a visual analogue scale (VAS) ranging through 0 (no impairment), 1-3 (mild), 4-6 (moderate), 7-9 (marked) and 10 (extreme) disability. The SDS total score is calculated as the sum of the three items and ranges from 0 (unimpaired) to 30 (highly impaired). |
| Mean Change From Baseline to the 6-week Study Endpoint in the Clinical Global Impression-Severity of Illness (CGI-S) Score | Baseline to Week 6 | The CGI-S score is a single value, clinician-rated assessment of illness severity and ranges from 1= 'Normal, not at all ill' to 7= 'Among the most extremely ill patients'. A higher score is associated with greater illness severity. |
| Percentage of Subjects Who Achieve a Response, Defined as ≥ 50% Reduction From Baseline on the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 6 (LOCF). | Baseline to Week 6 | — |
| Percentage of Subjects Who Achieve a Remission, Defined as a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of ≤ 12 at Week 6 (LOCF) | Baseline to Week 6 | — |
| Mean Change From Baseline to Week 6 in the Hamilton Rating Scale for Anxiety(HAM-A) Total Score | Baseline to Week 6 | The HAM-A is used to quantify the severity of anxiety symptomatology and consists of 14 items. Each item is rated on a 5-point scale, ranging from 0 (not present) to 4 (severe/disabling). The HAM-A total score is calculated as the sum of the 14 individual items and ranges from 0 to 56. Higher scores are associated with greater degree of anxiety. |
Countries
Russia, Serbia, Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lurasidone Lurasidone 20, 40 or 60 mg
Lurasidone: 20, 40, 60 mg, flexible dose, once daily PM 6 weeks | 109 |
| Placebo Placebo
Placebo: Placebo | 100 |
| Total | 209 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative | 0 | 1 |
| Overall Study | Adverse Event | 3 | 5 |
| Overall Study | Lack of Efficacy | 2 | 4 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Lurasidone | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 2 Participants | 4 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 106 Participants | 96 Participants | 202 Participants |
| Age, Continuous | 43.6 years STANDARD_DEVIATION 12.08 | 46.4 years STANDARD_DEVIATION 12.01 | 44.9 years STANDARD_DEVIATION 12.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 12 Participants | 26 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 94 Participants | 86 Participants | 180 Participants |
| Region of Enrollment Russian Federation | 18 participants | 13 participants | 31 participants |
| Region of Enrollment Serbia | 26 participants | 26 participants | 52 participants |
| Region of Enrollment Ukraine | 30 participants | 32 participants | 62 participants |
| Region of Enrollment United Kingdom | 1 participants | 3 participants | 4 participants |
| Region of Enrollment United States | 34 participants | 26 participants | 60 participants |
| Sex: Female, Male Female | 73 Participants | 72 Participants | 145 Participants |
| Sex: Female, Male Male | 36 Participants | 28 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 31 / 109 | 29 / 100 |
| serious Total, serious adverse events | 1 / 109 | 0 / 100 |
Outcome results
Primary
Mean Change From Baseline to the 6-week Study Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Scores
The MADRS consists of 10 items, each rated on a Likert scale, from 0=Normal to 6=Most Severe. The MADRS total score is calculated as the sum of the 10 items. The MADRS total score ranges from 0 to 60. Higher scores are associated with greater severity.
Time frame: Baseline to Week 6
Population: Intent to treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lurasidone | Mean Change From Baseline to the 6-week Study Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Scores | -20.5 units on a scale | Standard Error 0.95 |
| Placebo | Mean Change From Baseline to the 6-week Study Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Scores | -13.0 units on a scale | Standard Error 1 |
p-value: <0.000195% CI: [-10.2, -4.8]Mixed Models Analysis
Secondary
Mean Change From Baseline to the 6-week Study Endpoint in the Clinical Global Impression-Severity of Illness (CGI-S) Score
The CGI-S score is a single value, clinician-rated assessment of illness severity and ranges from 1= 'Normal, not at all ill' to 7= 'Among the most extremely ill patients'. A higher score is associated with greater illness severity.
Time frame: Baseline to Week 6
Population: Intent to treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lurasidone | Mean Change From Baseline to the 6-week Study Endpoint in the Clinical Global Impression-Severity of Illness (CGI-S) Score | -1.83 units on a scale | Standard Error 0.109 |
| Placebo | Mean Change From Baseline to the 6-week Study Endpoint in the Clinical Global Impression-Severity of Illness (CGI-S) Score | -1.18 units on a scale | Standard Error 0.115 |
p-value: <0.000195% CI: [-0.96, -0.34]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 6 in the Hamilton Rating Scale for Anxiety(HAM-A) Total Score
The HAM-A is used to quantify the severity of anxiety symptomatology and consists of 14 items. Each item is rated on a 5-point scale, ranging from 0 (not present) to 4 (severe/disabling). The HAM-A total score is calculated as the sum of the 14 individual items and ranges from 0 to 56. Higher scores are associated with greater degree of anxiety.
Time frame: Baseline to Week 6
Population: Intent to treat population. 3 Lurasidone subjects and 2 placebo subjects did not have post-baseline HAM-A assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lurasidone | Mean Change From Baseline to Week 6 in the Hamilton Rating Scale for Anxiety(HAM-A) Total Score | -9.9 units on a scale | Standard Error 0.58 |
| Placebo | Mean Change From Baseline to Week 6 in the Hamilton Rating Scale for Anxiety(HAM-A) Total Score | -5.4 units on a scale | Standard Error 0.59 |
p-value: <0.000195% CI: [-6.1, -2.9]ANCOVA
Secondary
Mean Change From Baseline to Week 6 in the Sheehan Disability Scale (SDS) Total Score
The SDS is a composite of three self-rated items designed to measure the extent to which three major sectors (work/school, social life/leisure, and family life/home responsibility) in the patient's life are impaired by depressive symptoms. These three items are responded to on a visual analogue scale (VAS) ranging through 0 (no impairment), 1-3 (mild), 4-6 (moderate), 7-9 (marked) and 10 (extreme) disability. The SDS total score is calculated as the sum of the three items and ranges from 0 (unimpaired) to 30 (highly impaired).
Time frame: Baseline to Week 6
Population: Intent to treat population: If a subject has not worked/studied at all during the past week for reasons unrelated to the disorder, the SDS total score will be set to missing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lurasidone | Mean Change From Baseline to Week 6 in the Sheehan Disability Scale (SDS) Total Score | -11.2 units on a scale | Standard Error 0.88 |
| Placebo | Mean Change From Baseline to Week 6 in the Sheehan Disability Scale (SDS) Total Score | -6.4 units on a scale | Standard Error 0.88 |
p-value: 0.000195% CI: [-7.2, -2.4]ANCOVA
Secondary
Mean Change From Baseline to Week 6 in the Young Mania Rating Scale (YMRS) Total Score
The YMRS is an 11-item clinician-rated instrument used to assess the severity of mania. Seven items are rated on a 5-point scale, ranging from 0 to 4, and four items are rated on a 9-point scale, ranging from 0 to 8. The YMRS total score is calculated as the sum of the 11 individual items and ranges from 0 to 60. Higher scores are associated with greater severity of mania.
Time frame: Baseline to Week 6
Population: Intent to treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lurasidone | Mean Change From Baseline to Week 6 in the Young Mania Rating Scale (YMRS) Total Score | -7.0 units on a scale | Standard Error 0.35 |
| Placebo | Mean Change From Baseline to Week 6 in the Young Mania Rating Scale (YMRS) Total Score | -4.9 units on a scale | Standard Error 0.37 |
p-value: <0.000195% CI: [-3.1, -1.1]Mixed Models Analysis
Secondary
Percentage of Subjects Who Achieve a Remission, Defined as a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of ≤ 12 at Week 6 (LOCF)
Time frame: Baseline to Week 6
Population: Intent to treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lurasidone | Percentage of Subjects Who Achieve a Remission, Defined as a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of ≤ 12 at Week 6 (LOCF) | 49.1 percentage of subjects |
| Placebo | Percentage of Subjects Who Achieve a Remission, Defined as a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of ≤ 12 at Week 6 (LOCF) | 23.0 percentage of subjects |
p-value: <0.000195% CI: [2.105, 8.663]Regression, Logistic
Secondary
Percentage of Subjects Who Achieve a Response, Defined as ≥ 50% Reduction From Baseline on the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 6 (LOCF).
Time frame: Baseline to Week 6
Population: Intent to treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lurasidone | Percentage of Subjects Who Achieve a Response, Defined as ≥ 50% Reduction From Baseline on the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 6 (LOCF). | 64.8 percentage of subjects |
| Placebo | Percentage of Subjects Who Achieve a Response, Defined as ≥ 50% Reduction From Baseline on the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 6 (LOCF). | 30.0 percentage of subjects |
p-value: <0.000195% CI: [3.251, 13.459]Regression, Logistic