Company decided not to move forward with further accrual.

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.

IPD for this study may be made available upon request via the Vivli Center for Global Clinical Research Data Site

IPD will be made available upon request within 12 months of posting the study results on ct.gov.

Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Double Blind