Bipolar Depression
Conditions
Keywords
Bipolar I, Depression
Brief summary
This clinical study is designed to test the hypothesis that lurasidone is effective, tolerable, and safe for the treatment of patients with bipolar I depression
Interventions
DRUGlurasidone
lurasidone 20 mg/day for Days 1-2, 40 mg/day for Days 3-4, 60 mg/day for Days 5-6 and 80 mg/day on Day 7 and 80-120 mg/day
DRUGPlacebo
Placebo Comparator
Sponsors
Sumitomo Pharma America, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subject is diagnosed with bipolar I disorder, most resent episode depressed * Subject must have a lifetime history of at least one bipolar manic or mixed episode
Exclusion criteria
* History of nonresponse to an adequate (6-week) trial of three or more antidepressants (with or without mood stabilizers) during the current episode * Subject has been hospitalized for a manic or mixed episode within 60 days prior to randomization * Imminent risk of suicide or injury to self, others, or property
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 | Montgomery-Asberg Depression Rating Scale (MADRS)is a clinician-rated assessment of a subject's level of depression. The MADRS total score ranges from a minimum of 0 to a maximum of 60. For the MADRS total score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome. The MADRS contains ten (10) items. The total score is computed as the sum of the scores for the 10 items. |
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 | Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) score (depression) is a clinician-rated assessment of a subject's level of depression. The CGI depression score ranges from a minimum of 0 to a maximum of 7. For the CGI depression score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome. |
| Mean Change From Baseline to Endpoint (Week 6) in: Sheehan Disability Scale (SDS) Total Score | Baseline to Week 6 | Sheehan Disability Scale (SDS) total score is a subject-rated assessment of a subject's level of depression. The SDS total score ranges from a minimum of 0 to a maximum of 30. For the SDS total score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome. The SDS contains three (3) items. The total score is computed as the sum of the scores for the 3 items. |
Countries
Czechia, France, India, Romania, Russia, South Africa, Ukraine, United States
Participant flow
Recruitment details
4/29/09 to 2/1/12
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo : Placebo Comparator | 162 |
| Lurasidone High Arm lurasidone : lurasidone 20 mg/day for Days 1-2, 40 mg/day for Days 3-4, 60 mg/day for Days 5-6 and 80 mg/day on Day 7 and 80-120 mg/day | 162 |
| Lurasidone Low Arm lurasidone : lurasidone 20 mg/day for Days 1-7, beginning day 8 flexibly dosed 20-60 mg/day | 161 |
| Total | 485 |
Baseline characteristics
| Characteristic | Placebo | Lurasidone High Arm | Lurasidone Low Arm | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 3 Participants | 3 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants | 3 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 159 Participants | 159 Participants | 155 Participants | 473 Participants |
| Age, Continuous | 41.2 years STANDARD_DEVIATION 12.45 | 42.0 years STANDARD_DEVIATION 12.35 | 41.3 years STANDARD_DEVIATION 12.31 | 41.5 years STANDARD_DEVIATION 12.35 |
| Region of Enrollment Czech Republic | 19 participants | 19 participants | 17 participants | 55 participants |
| Region of Enrollment France | 5 participants | 4 participants | 4 participants | 13 participants |
| Region of Enrollment India | 27 participants | 23 participants | 23 participants | 73 participants |
| Region of Enrollment Romania | 9 participants | 2 participants | 4 participants | 15 participants |
| Region of Enrollment Russian Federation | 10 participants | 10 participants | 11 participants | 31 participants |
| Region of Enrollment South Africa | 18 participants | 17 participants | 19 participants | 54 participants |
| Region of Enrollment Ukraine | 16 participants | 17 participants | 16 participants | 49 participants |
| Region of Enrollment United States | 58 participants | 70 participants | 67 participants | 195 participants |
| Sex: Female, Male Female | 87 Participants | 98 Participants | 91 Participants | 276 Participants |
| Sex: Female, Male Male | 75 Participants | 64 Participants | 70 Participants | 209 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 56 / 168 | 65 / 167 | 57 / 164 |
| serious Total, serious adverse events | 1 / 168 | 5 / 167 | 3 / 164 |
Outcome results
Primary
Mean Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Endpoint (Week 6)
Montgomery-Asberg Depression Rating Scale (MADRS)is a clinician-rated assessment of a subject's level of depression. The MADRS total score ranges from a minimum of 0 to a maximum of 60. For the MADRS total score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome. The MADRS contains ten (10) items. The total score is computed as the sum of the scores for the 10 items.
Time frame: Baseline to Week 6
Population: Intent-to-treat population is analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Endpoint (Week 6) | -10.7 units on a scale | Standard Error 0.83 |
| Lurasidone High Arm | Mean Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Endpoint (Week 6) | -15.4 units on a scale | Standard Error 0.83 |
| Lurasidone Low Arm | Mean Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Endpoint (Week 6) | -15.4 units on a scale | Standard Error 0.83 |
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed 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)
Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) score (depression) is a clinician-rated assessment of a subject's level of depression. The CGI depression score ranges from a minimum of 0 to a maximum of 7. For the CGI depression score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome.
Time frame: Baseline to Week 6
Population: Intent-to-treat population is analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline to Endpoint (Week 6) in: Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) Score (Depression) | -1.14 units on a scale | Standard Error 0.102 |
| Lurasidone High Arm | Mean Change From Baseline to Endpoint (Week 6) in: Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) Score (Depression) | -1.71 units on a scale | Standard Error 0.101 |
| Lurasidone Low Arm | Mean Change From Baseline to Endpoint (Week 6) in: Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) Score (Depression) | -1.83 units on a scale | Standard Error 0.102 |
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
Secondary
Mean Change From Baseline to Endpoint (Week 6) in: Sheehan Disability Scale (SDS) Total Score
Sheehan Disability Scale (SDS) total score is a subject-rated assessment of a subject's level of depression. The SDS total score ranges from a minimum of 0 to a maximum of 30. For the SDS total score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome. The SDS contains three (3) items. The total score is computed as the sum of the scores for the 3 items.
Time frame: Baseline to Week 6
Population: Intent-to-treat population is analyzed. Number of participants in table is not consistent with intent-to-treat population because: if one or more items are missing at a study visit, as can occur when a subject opts out of the work/school item because it does not apply, the authors of the scale recommend setting the total score to missing
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline to Endpoint (Week 6) in: Sheehan Disability Scale (SDS) Total Score | -6.3 units on a scale | Standard Error 0.77 |
| Lurasidone High Arm | Mean Change From Baseline to Endpoint (Week 6) in: Sheehan Disability Scale (SDS) Total Score | -9.8 units on a scale | Standard Error 0.73 |
| Lurasidone Low Arm | Mean Change From Baseline to Endpoint (Week 6) in: Sheehan Disability Scale (SDS) Total Score | -9.5 units on a scale | Standard Error 0.81 |
p-value: 0.003ANCOVA
p-value: <0.001ANCOVA