Bipolar Depression
Conditions
Keywords
Bipolar I, Latuda, Lurasidone
Brief summary
This clinical study is designed to test the hypothesis that lurasidone is effective, tolerable, and safe when added to treatment with lithium or Divalproex for the treatment of patients with bipolar I depression.
Interventions
DRUGlurasidone + (lithium or divalproex)
lurasidone 20 mg/day for Days 1-2-3, 40 mg/day for Days 4-5-6, and 60 mg/day on Day 7.
DRUGPlacebo + (lithium or divalproex)
20 mg/day for Days 1-2-3, 40 mg/day for Days 4-5-6, and 60 mg/day on Day 7
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 * Subject must be taking lithium or divalproex at least 28 days prior to screening
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, 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 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 | Baselin Week 6 | STS 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
Czechia, France, Germany, India, Poland, Romania, Russia, South Africa, Ukraine, United States
Participant flow
Recruitment details
5/11/2009 - 1/9/2012
Participants by arm
| Arm | Count |
|---|---|
| Lurasidone lurasidone + (lithium or divalproex) : lurasidone 20 mg/day for Days 1-2-3, 40 mg/day for Days 4-5-6, and 60 mg/day on Day 7. | 179 |
| Placebo Placebo + (lithium or divalproex) : 20 mg/day for Days 1-2-3, 40 mg/day for Days 4-5-6, and 60 mg/day on Day 7 | 161 |
| Total | 340 |
Baseline characteristics
| Characteristic | Lurasidone | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 1 Participants | 5 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 178 Participants | 155 Participants | 333 Participants |
| Age, Continuous | 41.0 years STANDARD_DEVIATION 11.53 | 42.6 years STANDARD_DEVIATION 11.75 | 41.7 years STANDARD_DEVIATION 11.65 |
| Region of Enrollment Czech Republic | 27 participants | 21 participants | 48 participants |
| Region of Enrollment France | 8 participants | 8 participants | 16 participants |
| Region of Enrollment Germany | 2 participants | 4 participants | 6 participants |
| Region of Enrollment India | 43 participants | 37 participants | 80 participants |
| Region of Enrollment Poland | 9 participants | 6 participants | 15 participants |
| Region of Enrollment Romania | 2 participants | 3 participants | 5 participants |
| Region of Enrollment Russian Federation | 9 participants | 10 participants | 19 participants |
| Region of Enrollment South Africa | 10 participants | 8 participants | 18 participants |
| Region of Enrollment Ukraine | 11 participants | 12 participants | 23 participants |
| Region of Enrollment United States | 58 participants | 52 participants | 110 participants |
| Sex: Female, Male Female | 86 Participants | 76 Participants | 162 Participants |
| Sex: Female, Male Male | 93 Participants | 85 Participants | 178 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 73 / 183 | 51 / 163 |
| serious Total, serious adverse events | 2 / 183 | 2 / 163 |
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, Week 6
Population: Full analysis set (intent-to-treat population)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lurasidone | Mean Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Endpoint (Week 6) | -17.1 units on a scale | Standard Error 0.87 |
| Placebo | Mean Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Endpoint (Week 6) | -13.5 units on a scale | Standard Error 0.91 |
p-value: 0.005Mixed 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 Week 6
Population: Full analyis set (intent-to-treat population)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lurasidone | Mean Change From Baseline to Endpoint (Week 6) in: Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) Score (Depression) | -1.96 units on a scale | Standard Error 0.104 |
| Placebo | Mean Change From Baseline to Endpoint (Week 6) in: Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) Score (Depression) | -1.51 units on a scale | Standard Error 0.109 |
p-value: 0.003Mixed Models Analysis
Secondary
Mean Change From Baseline to Endpoint (Week 6) in: Sheehan Disability Scale (SDS) Total Score
STS 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: Baselin Week 6
Population: Full analysis set (intent-to-treat population)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lurasidone | Mean Change From Baseline to Endpoint (Week 6) in: Sheehan Disability Scale (SDS) Total Score | -9.5 units on a scale | Standard Deviation 0.78 |
| Placebo | Mean Change From Baseline to Endpoint (Week 6) in: Sheehan Disability Scale (SDS) Total Score | -7.0 units on a scale | Standard Deviation 0.81 |
p-value: 0.012ANCOVA