A Phase III Study of SM-13496 in Patients With Bipolar I Depression.

Study Overview
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Brief Summary
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The study evaluates the efficacy and safety of SM-13496 compared with placebo in patients with Bipolar I Depression.

Detailed Description
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The primary objective is to compare the efficacy of SM-13496 (20-60 or 80-120 mg/day) monotherapy with that of placebo in patients with depressive symptoms associated with bipolar I disorder by assessing the change from baseline in the MADRS total score at Week 6.

Official Title
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A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study of SM-13496 for the Treatment of Bipolar I Depression.

Conditions
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Bipolar Depression

Intervention / Treatment
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* Drug: Placebo
* Drug: SM-13496
* Drug: SM-13496


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who were fully informed of and understand the objectives, procedures, and possible benefits and risks of the study and who provided written voluntary consent to participate in the study. Outpatients aged 18 through 74 years at the time of consent Patients meets DSM-IV-TR criteria for bipolar I disorder, most recent episode depressed (≥ 4 weeks and less than 12 months) without psychotic features. Exclusion Criteria: Patients with imminent risk of suicide or injury to self, others, or property. Patients who had been hospitalized because of a manic or mixed episode within 60 days prior to screening. Patients who are otherwise considered ineligible for the study by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>once daily orally | Drug: Placebo<br>* Placebo comparator<br>|
| Experimental: SM-13496 20 - 60 mg/day<br>once daily orally | Drug: SM-13496<br>* SM-13496 20mg for Days 1-7 and beginning Day 8 flexibly dosed 20-60 mg/day for Weeks 2-6<br>* Other names: Lurasidone HCl;|
| Experimental: SM-13496 80 - 120 mg/day<br>once daily orally | Drug: SM-13496<br>* SM-13496 20 mg/day for Days 1-2, 40 mg/day for Days 3-4, 60 mg/day for Days 5-6, 80 mg/day on Day 7 and beginning Day 8 flexibly dosed 80-120 mg/day for Weeks 2-6<br>* Other names: Lurasidone HCl;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at 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. | Baseline to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the CGI-BP-S (Depression) Score at 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 1 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. | Baseline to 6 weeks | 
| Change From Baseline in the SDS Total Score at Week 6 (LOCF) | Sheehan Disability Scale (SDS) total score is a subject-rated assessment of a subject's level of functional impairment in work/school, social life and family life/home responsibilities. 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. | Baseline to 6 weeks | 
| Change From Baseline in the YMRS Total Score at Week 6 | YMRS (Young Mania Rating Scale) is a clinician-rated assessment of the severity of mania in subjects with a diagnosis of bipolar disorder. The YMRS total score ranges from a minimum of 0 to a maximum of 60. For the YMRS 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 YMRS contains eleven (11) items. The total score is computed as the sum of the scores for the 11 items. | Baseline to 6 weeks | 
| Change From Baseline in the HAM-A Total Score at Week 6 (LOCF) | The Hamilton Rating Scale for Anxiety (HAM-A) scale is a rating scale developed to quantify the severity of anxiety symptomatology. The HAM-A total score ranges from a minimum of 0 to a maximum of 56. For the HAM-A 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 HAM-A contains fourteen (14) items. The total score is computed as the sum of the scores for the 14 items. | Baseline to 6 weeks |