Depressive Episodes, Bipolar I Depression
Conditions
Keywords
Depression, Depressive episode, Bipolar, Bipolar 1, Bipolar 1 depression
Brief summary
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.
Detailed description
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
Interventions
DRUGSEP-4199 CR 200 mg
SEP-4199 CR 200 mg Tablet (supplied in one 200mg tablet and one placebo tablet)
DRUGSEP-4199 CR 400 mg
SEP-4199 CR 400 mg tablet (supplied in two 200mg tablets)
DRUGPlacebo
Placebo tablet (supplied in two tablets)
Sponsors
Sumitomo Pharma America, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double Blind
Intervention model description
Randomized, Double-Blind, Placebo-Controlled, Parallel-Group
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 6 | 6 Weeks | Montgomery-Asberg Depression Rating Scale (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 ranging from 0 to 6. The MADRS total score ranges from 0 to 60, with higher scores indicating increased depressive symptoms |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Global Severity Assessed by the Clinical Global Impressions Severity: Bipolar Version (CGI-BP-S) Score (Depression) at Week 6 | 6 Weeks | Clinical Global Impressions Severity: Bipolar Version (CGI-BP-S) score (depression) is a single value, clinician-rated assessment of illness severity, and 7-point scale with range from 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 subjects. A higher score is associated with greater illness severity. |
Countries
Bulgaria, Canada, Japan, Romania, Slovakia, United States
Participant flow
Pre-assignment details
All participants had to go through at least 3 days or 5 half-lives antipsychotic medication washout.In total 83 Participants are Randomized in the trial, however one of the participant is randomized in error and was discontinued from study before taking any IP, So this subject is not considered in analysis population. Hence we have difference of 1 subject in Enrollment Number.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo: Placebo tablet (supplied in two tablets) | 27 |
| SEP-4199 CR 200 mg SEP-4199 CR 200 mg: SEP-4199 CR 200 mg Tablet (supplied in one 200mg tablet and one placebo tablet) | 27 |
| SEP-4199 CR 400 mg SEP-4199 CR 400 mg: SEP-4199 CR 400 mg tablet (supplied in two 200mg tablets) | 28 |
| Total | 82 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 2 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Other Study Discontinuation Reason | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | SEP-4199 CR 200 mg | SEP-4199 CR 400 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 43.9 Years STANDARD_DEVIATION 11.34 | 46.7 Years STANDARD_DEVIATION 11.67 | 42.8 Years STANDARD_DEVIATION 12.53 | 44.5 Years STANDARD_DEVIATION 11.83 |
| Baseline Clinical Global Impressions - Severity: Bipolar Version (CGI-BP-S) score (depression) | 5 units on a scale STANDARD_DEVIATION 0.65 | 5 units on a scale STANDARD_DEVIATION 0.68 | 4.9 units on a scale STANDARD_DEVIATION 0.69 | 5 units on a scale STANDARD_DEVIATION 0.66 |
| Baseline Montgomery-Asberg Depression Rating Scale( MADRS )Total Score | 36.6 units on a scale STANDARD_DEVIATION 5.64 | 37.5 units on a scale STANDARD_DEVIATION 6.22 | 37.6 units on a scale STANDARD_DEVIATION 4.92 | 37.2 units on a scale STANDARD_DEVIATION 5.55 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 9 Participants | 10 Participants | 29 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 18 Participants | 16 Participants | 50 Participants |
| Region of Enrollment Bulgaria | 11 Participants | 12 Participants | 11 Participants | 34 Participants |
| Region of Enrollment Japan | 10 Participants | 9 Participants | 10 Participants | 29 Participants |
| Region of Enrollment Romania | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United States | 6 Participants | 5 Participants | 7 Participants | 18 Participants |
| Sex: Female, Male Female | 18 Participants | 17 Participants | 17 Participants | 52 Participants |
| Sex: Female, Male Male | 9 Participants | 10 Participants | 11 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 27 | 0 / 28 |
| other Total, other adverse events | 7 / 27 | 1 / 27 | 6 / 28 |
| serious Total, serious adverse events | 0 / 27 | 0 / 27 | 0 / 28 |
Outcome results
Primary
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 6
Montgomery-Asberg Depression Rating Scale (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 ranging from 0 to 6. The MADRS total score ranges from 0 to 60, with higher scores indicating increased depressive symptoms
Time frame: 6 Weeks
Population: ITT population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 6 | -10.33 units on a scale | Standard Error 2.004 |
| SEP-4199 CR 200 mg | Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 6 | -14.27 units on a scale | Standard Error 2.055 |
| SEP-4199 CR 400 mg | Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 6 | -16.67 units on a scale | Standard Error 2.014 |
p-value: 0.171895% CI: [-9.64, 1.75]Mixed Models Analysis
p-value: 0.028695% CI: [-11.99, -0.68]Mixed Models Analysis
Secondary
Change From Baseline in Global Severity Assessed by the Clinical Global Impressions Severity: Bipolar Version (CGI-BP-S) Score (Depression) at Week 6
Clinical Global Impressions Severity: Bipolar Version (CGI-BP-S) score (depression) is a single value, clinician-rated assessment of illness severity, and 7-point scale with range from 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 subjects. A higher score is associated with greater illness severity.
Time frame: 6 Weeks
Population: ITT population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Global Severity Assessed by the Clinical Global Impressions Severity: Bipolar Version (CGI-BP-S) Score (Depression) at Week 6 | -1.16 units on a scale | Standard Error 0.214 |
| SEP-4199 CR 200 mg | Change From Baseline in Global Severity Assessed by the Clinical Global Impressions Severity: Bipolar Version (CGI-BP-S) Score (Depression) at Week 6 | -1.26 units on a scale | Standard Error 0.222 |
| SEP-4199 CR 400 mg | Change From Baseline in Global Severity Assessed by the Clinical Global Impressions Severity: Bipolar Version (CGI-BP-S) Score (Depression) at Week 6 | -1.46 units on a scale | Standard Error 0.217 |
p-value: 0.731495% CI: [-0.72, 0.51]Mixed Models Analysis
p-value: 0.316995% CI: [-0.91, 0.3]Mixed Models Analysis