A Clinical Trial to Determine the Long-term Safety and Tolerability of an Investigational Drug in People With Major Depressive Episode Associated With Bipolar I Disorder (Bipolar I Depression).

Study Overview
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Brief Summary
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This is a clinical trial to determine the long-term safety and tolerability of an investigational drug in people with Major Depressive Episode Associated with Bipolar I Disorder (Bipolar I Depression). Participants in the study will receive the drug being studied. This study is accepting male and female participants between 18 and 65 years old who have completed Study SEP380-301. This study will be conducted in approximately 90 study centers worldwide. The treatment duration for this study is one (1) year.

Detailed Description
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This is a 12-month open-label safety extension study to evaluate the long-term safety, tolerability, and effectiveness of SEP-4199 CR 200-400 mg/day in the treatment of subjects with bipolar I depression who previously completed a lead-in study of SEP-4199 CR. The study will consist of a 12-month open-label flexible-dose treatment period, and a safety follow-up period. There are 15 scheduled visits, including a Baseline visit, 13 visits during the open-label treatment period, and 1 safety follow-up visit 7 (± 2) days after the last dose of study drug. If necessary, subjects may return to the clinic at anytime for an unscheduled visit

Official Title
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A 12-Month Open-label Extension Study to Evaluate the Long-term Safety, Tolerability, and Effectiveness of 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject provides written informed consent and is willing and able to comply with the protocol in the opinion of the Investigator. Subject has completed 6 weeks of double-blind treatment and all scheduled assessments from Visit 6/EOT (Day 42) of the lead-in study of SEP-4199 CR. Subject is medically appropriate for long-term open-label treatment with SEP-4199 CR in the opinion of the Investigator. Female subjects of childbearing potential must agree to use effective and reliable contraception throughout the study and for at least 30 days after the last dose of study drug has been taken. In the Investigator's judgment, the subject will adhere to this requirement. Male subjects agree to avoid fathering a child and to use effective methods of birth control throughout the study and until at least 90 days after the last study drug administration. Exclusion Criteria: Subject is at high risk of non-compliance in the opinion of the Investigator. Subject plans to initiate treatment with a prohibited psychotropic medication during the study. Subject plans to initiate treatment with transcranial magnetic stimulation (TMS), electroconvulsive therapy (ECT), vagus nerve stimulation (VNS), or deep brain stimulation (DBS) during the study. Subject experienced a moderate or severe hyperprolactinemia-related AESI in the lead-in study of SEP-4199 CR. Subject will require treatment with a drug that is associated with increases in QTc interval. Subject had any of the following at Visit 6/EOT (Day 42) of the lead-in study of SEP-4199 CR based on machine reading: increase in QTcF interval of ≥ 30 msec AND a QTcF interval ≥ 480 msec, from baseline of the lead-in study of SEP-4199 CR AND a QTCF interval ≥ 480msec increase in QTcF interval ≥ 60 msec, from baseline of the lead-in study of SEP-4199 CR QTcF interval ≥ 500 msec treatment-emergent clinically significant ECG abnormality. Subject is considered by the Investigator to be at imminent risk of suicide or injury to self or others, has a MADRS item 10 (suicidal ideation) score ≥ 4, or answers yes to suicidal ideation item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) on the C-SSRS assessment at Visit 6/EOT (Day 42) of the lead-in study of SEP-4199 CR. Female subject of childbearing potential, has a positive urine pregnancy test at Visit 6/EOT (Day 42) of the lead-in study of SEP-4199 CR or plans to become pregnant during the current study. Subject tests positive for any drug of abuse or cannabis at Visit 6/EOT (Day 42) of the lead-in study of SEP-4199 CR

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
Intervention Model: Single Group Assignment
Interventional Model Description: This is a 12-month open-label safety extension study to evaluate the long-term safety, tolerability, and effectiveness of SEP-4199 CR 200-400 mg/day in the treatment of subjects with bipolar I depression who previously completed a lead-in study of SEP-4199 CR. The study will consist of a 12-month open-label flexible-dose treatment period, and a safety follow-up period
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SEP-4199 CR<br>SEP-4199 CR either 200 mg (one 200 mg tablet) or 400 mg (two 200 mg tablets) once daily | Drug: SEP-4199 CR<br>* SEP-4199 CR either 200 mg (one 200 mg tablet) or 400 mg (two 200 mg tablets) once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of overall Adverse Events (AEs), Serious Adverse Events (AEs), and Adverse Events (AEs) leading to discontinuation |  | 52 Weeks | 

 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