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).

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)

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.

Study Overview

• Status: Terminated
• Conditions: Depressive Episodes, Bipolar I Depression
• Intervention / Treatment: Drug: SEP-4199 CR

Detailed 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. 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

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Kardzhali, Bulgaria, 6600
    • State Psychiatric Hospital - Kardzhali First Women Department Third Men Department
  • Plovdiv, Bulgaria, 4004
    • Medical Center Mentalcare OOD
  • Ruse, Bulgaria, 7003
    • Mental Health Center- Ruse EOOD Men Department for treatment of persons with acute psychotic disorders; Women Department for treatment of persons with acute psychotic disorders; Department "Daily stationary"
  • Sofia, Bulgaria, 1510
    • Medical Center Hera EOOD
  • Sofia, Bulgaria, 1113
    • Medical Center Sveti Naum EOOD
  • Sofia, Bulgaria, 1408
    • DCC St. Vrach and St. St. Kuzma and Damian OOD
  • Sofia, Bulgaria, 1680
    • Medical Center Intermedica OOD
  • Sofia, Bulgaria, 1000
    • Mental Health Center - Sofia EOOD
  • Tsarevo, Bulgaria, 9747
    • State Psychiatric Hospital - s. Tsarev brod First Department for Active Treatment - Men Second Department for Active Treatment - Men Women Department - Rehabilitation Sector Women Department - Acute Sector
  • Varna, Bulgaria, 9020
    • DCC Mladost-M Varna OOD
• Japan
  • Fukuoka-Ken
    • Fukuoka-Shi, Fukuoka-Ken, Japan, 810-0022
      • Shinseikai Kaku Mental Clinic
    • Fukuoka-shi, Fukuoka-Ken, Japan, 810-0004
      • Hiro Mental Clinic
    • Fukuoka-shi, Fukuoka-Ken, Japan, 810-0023
      • Mental Clinic Sakurazaka
    • Kitakyushu, Fukuoka-Ken, Japan, 802-0064
      • Hatakeyama Clinic
    • Kitakyushu-shi, Fukuoka-Ken, Japan, 800-0226
      • Someikai Kanagami Clinic
    • Kitakyushu-shi, Fukuoka-Ken, Japan, 802-0006
      • Kokura Mental Clinic
    • Kurume-shi, Fukuoka-Ken, Japan, 830-0033
      • Hirota Clinic
    • Omuta-shi, Fukuoka-Ken, Japan, 836-0004
      • Shiranui Hospital
  • Fukushima-Ken
    • Shirakawa-shi, Fukushima-Ken, Japan, 961-0021
      • Jisenkai Nanko Psychiatric Institute
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan, 006-8555
      • Teine Keijinkai Hospital
  • Hyogo-Ken
    • Kobe-shi, Hyogo-Ken, Japan, 651-0097
      • Tatsuta Clinic
  • Kagoshima-Ken
    • Kagoshima-shi, Kagoshima-Ken, Japan, 890-0069
      • Cerisier Heart Clinic
  • Kanagawa-Ken
    • Kawasaki, Kanagawa-Ken, Japan, 211-0004
      • Musashikosugi J Kokorono Clinic
    • Sagamihara-shi, Kanagawa-Ken, Japan, 252-0303
      • Yutaka Clinic
    • Yokohama-shi, Kanagawa-Ken, Japan, 225-0011
      • Azamino Mental Clinic
    • Yokohama-shi, Kanagawa-Ken, Japan, 231-0846
      • Yamatenomori Kokorono Clinic
  • Kumamoto-ken
    • Kumamoto-shi, Kumamoto-ken, Japan, 861-8002
      • Satokai Yuge Hospital
  • Okinawa-ken
    • Urasoe-shi, Okinawa-ken, Japan, 901-2102
      • Shiroma Clinic
  • Saga-Ken
    • Karatsu-shi, Saga-Ken, Japan, 847-0031
      • Rainbow & Sea Hospital
  • Tokyo-To
    • Bunkyō-Ku, Tokyo-To, Japan, 113-8431
      • Juntendo University Hospital
    • Meguro-ku, Tokyo-To, Japan, 152-0012
      • Senzoku Psychosomatic Clinic
    • Minato-Ku, Tokyo-To, Japan, 107-0062
      • Minami-Aoyama Antique Street Clinic
    • Nakano-ku, Tokyo-To, Japan, 164-0012
      • Heart Care Ginga Clinic
    • Setagaya-Ku, Tokyo-To, Japan, 154-0004
      • Sangenjaya Nakamura Mental Clinic
    • Setagaya-Ku, Tokyo-To, Japan, 154-0004
      • Sangenjaya Neurology- Psychosomatic Clinic
    • Shibuya-ku, Tokyo-To, Japan, 150-8935
      • Japanese Red Cross Medical Center
    • Shibuya-ku, Tokyo-To, Japan, 151-0053
      • Maynds Tower Mental Clinic
    • Shibuya-ku, Tokyo-To, Japan, 151-0053
      • Sangubashi Kokorono Clinic
    • Shinagawa-ku, Tokyo-To, Japan, 141-0021
      • Etoh Mental Clinic
    • Shinjuku-Ku, Tokyo-To, Japan, 162-0843
      • Himorogi Psychiatric Institute
    • Shinjuku-ku, Tokyo-To, Japan, 160-0023
      • Tamaki Clinic
    • Taito-ku, Tokyo-To, Japan, 110-0003
      • Uguisudani Mental Clinic
    • Toshima-ku, Tokyo-To, Japan, 170-0002
      • Ohwa Mental Clinic
    • Toshima-ku, Tokyo-To, Japan, 170-0011
      • Kitaikebukuro Kokoro No Clinic
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • University of Alabama at Birmingham Huntsville Regional Medical Campus
  • California
    • Anaheim, California, United States, 92805
      • Advanced Research Center, Inc.
    • Imperial, California, United States, 92251
      • Sun Valley Research Center
    • Riverside, California, United States, 92506
      • Clinical Innovations, Inc.
    • Torrance, California, United States, 90502
      • Collaborative Neuroscience Research, LLC
  • Florida
    • Gainesville, Florida, United States, 32607
      • Sarkis Clinical Trials
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions, Inc.
    • Miami, Florida, United States, 33122
      • Premier Clinical Research Institute, Inc
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions, Inc.
  • Georgia
    • Atlanta, Georgia, United States, 30338
      • Atlanta Behavioral Research, LLC
    • Marietta, Georgia, United States, 30060
      • Psych Atlanta, P.C.
  • Illinois
    • Warrenville, Illinois, United States, 60555
      • AMR Conventions Research
  • Missouri
    • Saint Charles, Missouri, United States, 63304
      • St. Charles Psychiatric Associates / Midwest Research Group
  • Nebraska
    • Lincoln, Nebraska, United States, 68526
      • Alivation Research, LLC
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08002
      • Center For Emotional Fitness
  • New York
    • Rochester, New York, United States, 14618
      • Finger Lakes Clinical Research
    • Staten Island, New York, United States, 10312
      • Richmond Behavioral Associates ERG Clinical Research - New York PLLC
  • North Carolina
    • Charlotte, North Carolina, United States, 28211
      • New Hope Clinical Research
  • Ohio
    • Avon Lake, Ohio, United States, 44012
      • Quest Therapeutics of Avon Lake
    • North Canton, Ohio, United States, 44720
      • Neuro-Behavioral Clinical Research, Inc
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Sooner Clinical Research
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104
      • Lehigh Center for Clinical Research, LLC
  • Texas
    • Austin, Texas, United States, 78754
      • Community Clinical Research, Inc.
    • Houston, Texas, United States, 77054
      • UTHealth Science Center at Houston
    • The Woodlands, Texas, United States, 77381
      • Family Psychiatry of The Woodlands

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SEP-4199 CR; SEP-4199 CR either 200 mg (one 200 mg tablet) or 400 mg (two 200 mg tablets) once daily during open-label flexible-dose treatment period.	Drug: SEP-4199 CR; SEP-4199 CR either 200 mg (one 200 mg tablet) or 400 mg (two 200 mg tablets) once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Who Experienced Adverse Events in Study	Incidence of adverse events	12 months
Number of Subjects Who Discontinued Due to Adverse Events	Incidence of adverse events leading to discontinuation	12 months
Number of Subjects Who Experienced Serious Adverse Events in Study	Incidence of Serious Adverse Events	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montgomery-Asberg Depression Rating Scale (MADRS) Total Score - Change From Baseline	Open Label (OL) Month 12 (LOCF) is defined as the last non-missing post-OL Baseline measurement up to and including the OL Month 12 measurement and within 9 days post the last dose of open-label extension study medication. The 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 and total score range is of 0 to 60 with higher scores indicating increased depressive symptoms.Individual items are then summed to determine total score.	12 months
Clinical Global Impression Bipolar Version (CGI-BP-S) Depression Score - Change From Baseline	Open Label (OL) Month 12 (LOCF) is defined as the last non-missing post-OL Baseline measurement up to and including the OL Month 12 measurement and within 9 days post the last dose of open-label extension study medication.The Clinical Global Impression Bipolar Version (CGI-BP-S) scale is a 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. Depression Score is one the individual item on CGI-BP-S Scale.The CGI-BP-S depression score takes one of the following values: 1 (normal, not at all ill), 2 (borderline mentally ill), 3 (mildly ill), 4 (moderately ill), 5 (markedly ill), 6 (severely ill), 7 (among the most extremely ill patients).	12 months

Collaborators and Investigators

• Sponsor: Sumitomo Pharma America, Inc.
• Investigators: Study Chair: CNS Medical Director, Sumitomo Pharma America, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2022
• Primary Completion (Actual): November 17, 2023
• Study Completion (Actual): November 17, 2023

Study Registration Dates

• First Submitted: January 27, 2022
• First Submitted That Met QC Criteria: January 27, 2022
• First Posted (Actual): February 7, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 20, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Depression, Depressive episode, Bipolar, Bipolar 1, Bipolar 1 depression
• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Depression; Depressive Disorder
• Other Study ID Numbers: SEP380-303; 2021-002108-11 (EudraCT Number); jRCT2031220302 (Registry Identifier: Japan Registry for Clinical Trials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study may be made available upon request via theVivli Center for Global Clinical Reserach Data site
• IPD Sharing Time Frame: IPD will be made available upon request within 12 months of posting the study results on ct.gov.
• IPD Sharing Access Criteria: 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No