Bipolar Depression
Conditions
Keywords
Bipolar I Depression, Lurasidone, Latuda
Brief summary
Lurasidone HCI is a compound that is a candidate for the treatment of bipolar I depression. This clinical study is designed to test the hypothesis that Lurasidone in combination with either Lithium or Divalproex is effective among patients with bipolar I depression.
Interventions
DRUGLurasidone
Tablets 20-120 mg, PM dosing,daily for 6 weeks
DRUGPlacebo
Equivalent to Lurasidone dosing
Sponsors
Sumitomo Pharma America, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Provide written informed consent and is 18 to 75 years of age inclusive. 2. Meets DSM-IV-TR criteria for bipolar I disorder, most recent episode depressed (≥ 4 weeks and less than 12 months) without psychotic features. 3. Has a lifetime history of at least one bipolar manic or mixed manic episode. 4. Currently being treated with lithium or divalproex or willing to begin treatment with lithium or divalproex. 5. Not pregnant or nursing and is not planning pregnancy within the projected duration of the study. 6. Females of reproductive potential agree to remain abstinent or use adequate and reliable contraception throughout the study and for at least 30 days after 7. Good physical health on the basis of medical history, physical examination, and laboratory screening.
Exclusion criteria
1. Subject is considered by the investigator to be at imminent risk of suicide or injury to self, others, or property. 2. Any chronic organic disease of the CNS (other than Bipolar I Disorder). 3. Hospitalization for a manic or mixed episode within the past two months. 4. Used investigational compound within past 6 months. 5. Clinically significant history of alcohol or substance abuse within the past 3 months or alcohol or substance dependence within the past 12 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Endpoint (Week 6) | Baseline to week 6 | MADRS total score ranges from a minimum of 0 to a maximum of 60. Lower values represent a better score, higher values represent a worse score. Similarly, greater negative change from baseline represents improvement, and positive changes from baseline represent worsening. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to Endpoint (Week 6) in: Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) Score (Depression) | Baseline to week 6 | CGI-EP-S depression score ranges from a minimum of 0 to a maximum of 7. Lower values represent a better score, higher values represent a worse score. Similarly, greater negative change from baseline represents improvement, and positive changes from baseline represent worsening. |
| Mean Change From Baseline to Endpoint (Week 6) in: Sheehan Disability Scale (SDS) Total Score | Baseline to week 6 | SDS total score ranges from a minimum of 0 to a maximum of 30. Lower values represent a better score, higher values represent a worse score. Similarly, greater negative change from baseline represents improvement, and positive changes from baseline represent worsening. |
Countries
Canada, Colombia, Czechia, India, Japan, Lithuania, Peru, Slovakia, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lurasidone 20-120 mg Flexible Dose+Li/VPA | 176 |
| Placebo + Li/VPA | 166 |
| Total | 342 |
Baseline characteristics
| Characteristic | Lurasidone 20-120 mg Flexible Dose+Li/VPA | Placebo + Li/VPA | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 3 Participants | 0 Participants | 3 Participants |
| Age, Categorical >=65 years | 7 Participants | 5 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 166 Participants | 161 Participants | 327 Participants |
| Age Continuous | 43.1 years STANDARD_DEVIATION 11.9 | 44.1 years STANDARD_DEVIATION 11.99 | 43.6 years STANDARD_DEVIATION 11.94 |
| Region of Enrollment Canada | 9 participants | 8 participants | 17 participants |
| Region of Enrollment Colombia | 12 participants | 10 participants | 22 participants |
| Region of Enrollment Czech Republic | 9 participants | 8 participants | 17 participants |
| Region of Enrollment India | 20 participants | 22 participants | 42 participants |
| Region of Enrollment Japan | 5 participants | 4 participants | 9 participants |
| Region of Enrollment Lithuania | 10 participants | 9 participants | 19 participants |
| Region of Enrollment Peru | 6 participants | 7 participants | 13 participants |
| Region of Enrollment Slovakia | 17 participants | 21 participants | 38 participants |
| Region of Enrollment Ukraine | 17 participants | 14 participants | 31 participants |
| Region of Enrollment United States | 71 participants | 63 participants | 134 participants |
| Sex: Female, Male Female | 91 Participants | 93 Participants | 184 Participants |
| Sex: Female, Male Male | 85 Participants | 73 Participants | 158 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 79 / 177 | 63 / 171 |
| serious Total, serious adverse events | 5 / 177 | 3 / 171 |
Outcome results
Primary
Mean Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Endpoint (Week 6)
MADRS total score ranges from a minimum of 0 to a maximum of 60. Lower values represent a better score, higher values represent a worse score. Similarly, greater negative change from baseline represents improvement, and positive changes from baseline represent worsening.
Time frame: Baseline to week 6
Population: Full analysis set (intent-to-treat population)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lurasidone 20-120 mg Flexible Dose+Li/VPA | Mean Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Endpoint (Week 6) | -11.8 units on a scale | Standard Error 0.76 |
| Placebo + Li/VPA | Mean Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Endpoint (Week 6) | -10.4 units on a scale | Standard Error 0.79 |
Comparison: Null hypothesis (H0) assumes equal values between analysis groups in mean change from baseline in MADRS score, alternative hypothesis (HA) assumes unequal values between groups. Sample size determined by two-sample t-test. A mean difference of 3.25 units in change in MADRS score for the Lurasdone 20-120 mg arm over placebo with common standard deviation of 9 units was used. N=162 subjects per arm (total N=324) yields power of 90%. A 5% adjustment for drop-outs gives N=340, or N=170 per arm.p-value: 0.176Mixed Models Analysis
Secondary
Mean Change From Baseline to Endpoint (Week 6) in: Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) Score (Depression)
CGI-EP-S depression score ranges from a minimum of 0 to a maximum of 7. Lower values represent a better score, higher values represent a worse score. Similarly, greater negative change from baseline represents improvement, and positive changes from baseline represent worsening.
Time frame: Baseline to week 6
Population: Full analysis set (intent-to-treat population)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lurasidone 20-120 mg Flexible Dose+Li/VPA | Mean Change From Baseline to Endpoint (Week 6) in: Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) Score (Depression) | -1.36 units on a scale | Standard Error 0.099 |
| Placebo + Li/VPA | Mean Change From Baseline to Endpoint (Week 6) in: Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) Score (Depression) | -1.13 units on a scale | Standard Error 0.102 |
p-value: 0.095Mixed Models Analysis
Secondary
Mean Change From Baseline to Endpoint (Week 6) in: Sheehan Disability Scale (SDS) Total Score
SDS total score ranges from a minimum of 0 to a maximum of 30. Lower values represent a better score, higher values represent a worse score. Similarly, greater negative change from baseline represents improvement, and positive changes from baseline represent worsening.
Time frame: Baseline to week 6
Population: Full analysis set (intent-to-treat population)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lurasidone 20-120 mg Flexible Dose+Li/VPA | Mean Change From Baseline to Endpoint (Week 6) in: Sheehan Disability Scale (SDS) Total Score | -5.4 units on a scale | Standard Error 0.85 |
| Placebo + Li/VPA | Mean Change From Baseline to Endpoint (Week 6) in: Sheehan Disability Scale (SDS) Total Score | -5.4 units on a scale | Standard Error 0.74 |
p-value: 0.992ANCOVA