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

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)

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.

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

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.