A Clinical Study of an Investigational Drug for the Treatment of Major Depressive Episode Associated With Bipolar I Disorder.

Study Overview
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Brief Summary
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A clinical trial to study the efficacy and safety of an investigational drug in people with major depressive episodes associated with with Bipolar I disorder (bipolar I depression) Participants in the study will either receive the drug being studied or a placebo. The study will be conducted in approximately 90 sites in North America, Europe, Latin America and Japan. It will be have both male and female participants ages 18-65. Participation in the study will be approximately 10 weeks.

Detailed Description
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This study is a randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the efficacy, safety, and tolerability of treatment with SEP-4199 CR at fixed doses of 200 mg/day or 400 mg/day compared with placebo for the treatment of major depressive episode associated with bipolar I disorder (bipolar I depression). The study is projected to randomize approximately 522 subjects inNorth America, Japan, Europe and Latin America, to SEP-4199 CR 200 mg/day, SEP-4199 CR 400 mg/day, and placebo treatment groups in a 1:1:1 ratio

Official Title
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A Multi-region, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Evaluating SEP-4199 Controlled Release (CR) for the Treatment of Major Depressive Episode Associated With Bipolar I Disorder (Bipolar I Depression)

Conditions
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Depressive Episodes, Bipolar I Depression

Intervention / Treatment
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* Drug: SEP-4199 CR 200 mg
* Drug: SEP-4199 CR 400 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion Criteria (not all inclusive): 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 65 years of age, inclusive, at the time of informed consent. Subject meets DSM-5 criteria, based on the SCID-5-CT, for bipolar I disorder, current episode depressed with or without rapid cycling disease course (≥ 4 episodes of mood disturbance but < 8 episodes in the previous 12 months) with or without psychotic features. Subject's current major depressive episode is ≥ 4 weeks and less than 12 months in duration at Screening. Subject has a MADRS total score ≥ 22 at both Screening and Baseline. Subject has a CGI-BP-S depression score ≥ 4 at both Screening and Baseline. Subject has a YMRS total score ≤ 12 at both Screening and Baseline. Subject is in good physical health, based on medical history, physical examination, neurological examination, vital signs, ECGs, and results of clinical laboratory tests (hematology, chemistry, and urinalysis). Exclusion Criteria: Exclusion Criteria (not all inclusive): Subject currently has any DSM-5 defined psychiatric diagnosis other than bipolar I disorder that was the primary focus of treatment, or is currently being treated with concomitant medication Subject has a lifetime history of, or symptoms consistent with, schizophrenia, schizoaffective disorder, or a major psychiatric diagnosis other than bipolar I disorder that is judged to pose risk to the study scientific objectives Subject has a history of non-response to an adequate (6-week) trial of 3 or more antidepressants (with or without mood stabilizers) during the current major depressive episode. Subject has any clinically significant unstable medical condition or any clinically significant chronic disease that would pose a risk to the subject or that might confound the results of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Interventional Model Description: Randomized, Double-Blind, Placebo-Controlled, Parallel-Group
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SEP-4199 CR 200 mg<br>SEP-4199 CR 200 mg/day | Drug: SEP-4199 CR 200 mg<br>* SEP-4199 CR 200 mg Tablet (supplied in one 200mg tablet and one placebo tablet)<br>|
| Experimental: SEP-4199 CR 400 mg<br>SEP-4199 CR 400 mg/day | Drug: SEP-4199 CR 400 mg<br>* SEP-4199 CR 400 mg tablet (supplied in two 200mg tablets)<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo tablet (supplied in two tablets)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) total score | The Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician-rated assessment of the subject's level of depression. The measure contains 10 items that measure apparent and reported sadness, inner tension, reduced sleep and appetite, difficulty concentrating, lassitude, inability to feel, and pessimistic and suicidal thoughts. Each item is scored in a range of 0 to 6 points, with higher scores indicating increased depressive symptoms. | Baseline and Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Week 6 in Clinical Global Impressions-Severity: Bipolar Version (CGI-BP-S) depression score | Clinical Global Impressions - Severity: Bipolar Version (CGI-BP-S) is clinician-rated assessment of the subject's current illness state on a 7-point scale, where a higher score is associated with greater illness severity. | Baseline and Week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression, Depressive episode, Bipolar, Bipolar 1, Bipolar 1 depression