Depressive Episodes, Bipolar I Depression
Conditions
Keywords
Depression, Depressive episode, Bipolar, Bipolar 1, Bipolar 1 depression
Brief summary
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
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
Interventions
DRUGSEP-4199 CR
SEP-4199 CR either 200 mg (one 200 mg tablet) or 400 mg (two 200 mg tablets) once daily
Sponsors
Sumitomo Pharma America, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open Label
Intervention 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
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Who Experienced Adverse Events in Study | 12 months | Incidence of adverse events |
| Number of Subjects Who Discontinued Due to Adverse Events | 12 months | Incidence of adverse events leading to discontinuation |
| Number of Subjects Who Experienced Serious Adverse Events in Study | 12 months | Incidence of Serious Adverse Events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery-Asberg Depression Rating Scale (MADRS) Total Score - Change From Baseline | 12 months | 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. |
| Clinical Global Impression Bipolar Version (CGI-BP-S) Depression Score - Change From Baseline | 12 months | 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). |
Countries
Bulgaria, Japan, United States
Participant flow
Pre-assignment details
The study will consist of a 12-month open-label flexible-dose treatment period, and a safety follow-up period.All subjects will initiate treatment with SEP-4199 CR 200 mg/day. Study medication dose may be increased to 400 mg/day is at the Month 1 visit, based on the Investigator's judgment. The dose may be decreased to a minimum of 200 mg/day at any time thereafter for tolerability.
Participants by arm
| Arm | Count |
|---|---|
| SEP-4199 CR SEP-4199 CR either 200 mg (one 200 mg tablet) or 400 mg (two 200 mg tablets) once daily | 64 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 11 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Other Early Termination Reason (Not Listed on CRF) | 36 |
| Overall Study | Withdrawal by Subject | 7 |
Baseline characteristics
| Characteristic | SEP-4199 CR |
|---|---|
| Age, Continuous | 44.8 Years STANDARD_DEVIATION 12.57 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 59 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 20 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 43 Participants |
| Sex: Female, Male Female | 40 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 64 |
| other Total, other adverse events | 39 / 64 |
| serious Total, serious adverse events | 3 / 64 |
Outcome results
Primary
Number of Subjects Who Discontinued Due to Adverse Events
Incidence of adverse events leading to discontinuation
Time frame: 12 months
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SEP-4199 CR | Number of Subjects Who Discontinued Due to Adverse Events | 9 Participants |
Primary
Number of Subjects Who Experienced Adverse Events in Study
Incidence of adverse events
Time frame: 12 months
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SEP-4199 CR | Number of Subjects Who Experienced Adverse Events in Study | 39 Participants |
Primary
Number of Subjects Who Experienced Serious Adverse Events in Study
Incidence of Serious Adverse Events
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SEP-4199 CR | Number of Subjects Who Experienced Serious Adverse Events in Study | 3 Participants |
Secondary
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).
Time frame: 12 months
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SEP-4199 CR | Clinical Global Impression Bipolar Version (CGI-BP-S) Depression Score - Change From Baseline | -0.8 score on a scale | Standard Deviation 1.34 |
Secondary
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.
Time frame: 12 months
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SEP-4199 CR | Montgomery-Asberg Depression Rating Scale (MADRS) Total Score - Change From Baseline | -6 score on a scale | Standard Deviation 12.54 |