Trial Outcomes & Findings for A Clinical Study to Test the Effectiveness of an Investigational Drug to Treat People That Have Major Depressive Episodes When They Have Bipolar 1 Depression (NCT NCT03543410)
NCT ID: NCT03543410
Last Updated: 2023-05-18
Results Overview
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
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
344 participants
Primary outcome timeframe
6 Weeks
Results posted on
2023-05-18
Participant Flow
A total 344 subjects were randomized in this study. Three subjects, who were randomized but never received any dose of study medication, were not included in the reporting.
Participant milestones
| Measure |
SEP-4199 200 mg
SEP-4199 200 mg/day (supplied in two 100mg tablets)
|
SEP-4199 400 mg
SEP-4199 400 mg/day (supplied in two 200mg tablets)
|
Placebo
Placebo (supplied in two tablets/day)
|
|---|---|---|---|
|
Overall Study
STARTED
|
113
|
114
|
114
|
|
Overall Study
COMPLETED
|
92
|
101
|
99
|
|
Overall Study
NOT COMPLETED
|
21
|
13
|
15
|
Reasons for withdrawal
| Measure |
SEP-4199 200 mg
SEP-4199 200 mg/day (supplied in two 100mg tablets)
|
SEP-4199 400 mg
SEP-4199 400 mg/day (supplied in two 200mg tablets)
|
Placebo
Placebo (supplied in two tablets/day)
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
10
|
8
|
2
|
|
Overall Study
Lack of Efficacy
|
0
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
5
|
2
|
8
|
|
Overall Study
Protocol Violation
|
0
|
1
|
0
|
|
Overall Study
Due to COVID-19
|
4
|
0
|
2
|
|
Overall Study
NON-COMPLIANCE WITH STUDY DRUG
|
0
|
0
|
2
|
|
Overall Study
Not Due to COVID-19
|
2
|
0
|
1
|
Baseline Characteristics
A Clinical Study to Test the Effectiveness of an Investigational Drug to Treat People That Have Major Depressive Episodes When They Have Bipolar 1 Depression
Baseline characteristics by cohort
| Measure |
SEP-4199 200 mg
n=113 Participants
SEP-4199 200 mg/day (supplied in two 100mg tablets)
|
SEP-4199 400 mg
n=114 Participants
SEP-4199 400 mg/day (supplied in two 200mg tablets)
|
Placebo
n=114 Participants
Placebo (supplied in two tablets/day)
|
Total
n=341 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
3 Participants
n=7 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
112 Participants
n=99 Participants
|
111 Participants
n=107 Participants
|
113 Participants
n=206 Participants
|
336 Participants
n=7 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
|
Age, Continuous
|
42 Years
STANDARD_DEVIATION 11.65 • n=99 Participants
|
44.4 Years
STANDARD_DEVIATION 12.72 • n=107 Participants
|
43.3 Years
STANDARD_DEVIATION 12.10 • n=206 Participants
|
43.2 Years
STANDARD_DEVIATION 12.17 • n=7 Participants
|
|
Sex: Female, Male
Female
|
69 Participants
n=99 Participants
|
76 Participants
n=107 Participants
|
64 Participants
n=206 Participants
|
209 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
44 Participants
n=99 Participants
|
38 Participants
n=107 Participants
|
50 Participants
n=206 Participants
|
132 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
8 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
110 Participants
n=99 Participants
|
109 Participants
n=107 Participants
|
112 Participants
n=206 Participants
|
331 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Asian
|
16 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
17 Participants
n=206 Participants
|
49 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
4 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Black or African American
|
6 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
22 Participants
n=7 Participants
|
|
Race (NIH/OMB)
White
|
89 Participants
n=99 Participants
|
87 Participants
n=107 Participants
|
88 Participants
n=206 Participants
|
264 Participants
n=7 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Region of Enrollment
Europe
|
83 Participants
n=99 Participants
|
82 Participants
n=107 Participants
|
84 Participants
n=206 Participants
|
249 Participants
n=7 Participants
|
|
Region of Enrollment
Japan
|
16 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
17 Participants
n=206 Participants
|
49 Participants
n=7 Participants
|
|
Region of Enrollment
United States
|
14 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
43 Participants
n=7 Participants
|
|
Age, Customized
18-64 years
|
113 Participants
n=99 Participants
|
112 Participants
n=107 Participants
|
114 Participants
n=206 Participants
|
339 Participants
n=7 Participants
|
|
Age, Customized
>=65 years
|
0 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
|
Country Name
Bulgaria
|
11 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
22 Participants
n=206 Participants
|
43 Participants
n=7 Participants
|
|
Country Name
Japan
|
16 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
17 Participants
n=206 Participants
|
49 Participants
n=7 Participants
|
|
Country Name
Poland
|
5 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
11 Participants
n=7 Participants
|
|
Country Name
Russia
|
18 Participants
n=99 Participants
|
20 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
46 Participants
n=7 Participants
|
|
Country Name
Serbia
|
19 Participants
n=99 Participants
|
26 Participants
n=107 Participants
|
18 Participants
n=206 Participants
|
63 Participants
n=7 Participants
|
|
Country Name
Slovakia
|
8 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
19 Participants
n=7 Participants
|
|
Country Name
Ukraine
|
22 Participants
n=99 Participants
|
20 Participants
n=107 Participants
|
25 Participants
n=206 Participants
|
67 Participants
n=7 Participants
|
|
Country Name
United States
|
14 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
43 Participants
n=7 Participants
|
|
Baseline Weight (kg)
|
75.3 kg
STANDARD_DEVIATION 14.47 • n=99 Participants
|
74.8 kg
STANDARD_DEVIATION 16.19 • n=107 Participants
|
77.5 kg
STANDARD_DEVIATION 16.59 • n=206 Participants
|
75.9 kg
STANDARD_DEVIATION 15.78 • n=7 Participants
|
|
Baseline BMI (kg/m^2)
|
26.2 kg/m^2
STANDARD_DEVIATION 4.53 • n=99 Participants
|
26.6 kg/m^2
STANDARD_DEVIATION 4.91 • n=107 Participants
|
27 kg/m^2
STANDARD_DEVIATION 4.94 • n=206 Participants
|
26.6 kg/m^2
STANDARD_DEVIATION 4.79 • n=7 Participants
|
|
Baseline BMI Category
< 18.5 kg/m^2
|
0 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
3 Participants
n=7 Participants
|
|
Baseline BMI Category
18.5 - <25.0 kg/m^2
|
51 Participants
n=99 Participants
|
50 Participants
n=107 Participants
|
45 Participants
n=206 Participants
|
146 Participants
n=7 Participants
|
|
Baseline BMI Category
25.0 - <30.0 kg/m^2
|
42 Participants
n=99 Participants
|
33 Participants
n=107 Participants
|
40 Participants
n=206 Participants
|
115 Participants
n=7 Participants
|
|
Baseline BMI Category
>=30.0 kg/m^2
|
20 Participants
n=99 Participants
|
28 Participants
n=107 Participants
|
29 Participants
n=206 Participants
|
77 Participants
n=7 Participants
|
|
Baseline Montgomery-Asberg Depression Rating Scale( MADRS )Total Score
|
33.5 units on a scale
STANDARD_DEVIATION 5.77 • n=99 Participants
|
33.8 units on a scale
STANDARD_DEVIATION 5.63 • n=107 Participants
|
34.1 units on a scale
STANDARD_DEVIATION 5.35 • n=206 Participants
|
33.8 units on a scale
STANDARD_DEVIATION 5.58 • n=7 Participants
|
|
Baseline global severity assessed by the Clinical Global Impressions -Severity Depression Score
|
4.8 units on a scale
STANDARD_DEVIATION 0.66 • n=99 Participants
|
4.8 units on a scale
STANDARD_DEVIATION 0.65 • n=107 Participants
|
4.9 units on a scale
STANDARD_DEVIATION 0.70 • n=206 Participants
|
4.8 units on a scale
STANDARD_DEVIATION 0.67 • n=7 Participants
|
PRIMARY outcome
Timeframe: 6 WeeksPopulation: ITT population, excluding subjects from Japan Region
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
Outcome measures
| Measure |
SEP-4199 200 mg
n=96 Participants
SEP-4199 200 mg/day (supplied in two 100mg tablets)
|
SEP-4199 400 mg
n=97 Participants
SEP-4199 400 mg/day (supplied in two 200mg tablets)
|
Placebo
n=96 Participants
Placebo (supplied in two tablets/day)
|
|---|---|---|---|
|
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 6
|
-19.485 units on a scale
Standard Error 1.226
|
-19.324 units on a scale
Standard Error 1.182
|
-16.196 units on a scale
Standard Error 1.231
|
SECONDARY outcome
Timeframe: 6 WeeksPopulation: ITT population, excluding subjects from Japan Region
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.
Outcome measures
| Measure |
SEP-4199 200 mg
n=96 Participants
SEP-4199 200 mg/day (supplied in two 100mg tablets)
|
SEP-4199 400 mg
n=97 Participants
SEP-4199 400 mg/day (supplied in two 200mg tablets)
|
Placebo
n=96 Participants
Placebo (supplied in two tablets/day)
|
|---|---|---|---|
|
Change From Baseline in Global Severity Assessed by the Clinical Global Impressions - Severity: Bipolar Version (CGI-BP-S) Score (Depression) at Week 6
|
-2.020 units on a scale
Standard Error 0.144
|
-1.958 units on a scale
Standard Error 0.138
|
-1.739 units on a scale
Standard Error 0.144
|
Adverse Events
SEP-4199 200 mg
Serious events: 1 serious events
Other events: 21 other events
Deaths: 0 deaths
SEP-4199 400 mg
Serious events: 0 serious events
Other events: 23 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 29 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
SEP-4199 200 mg
n=113 participants at risk
SEP-4199 200 mg/day (supplied in two 100mg tablets)
|
SEP-4199 400 mg
n=114 participants at risk
SEP-4199 400 mg/day (supplied in two 200mg tablets)
|
Placebo
n=114 participants at risk
Placebo (supplied in two tablets/day)
|
|---|---|---|---|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.00%
0/113 • Up to 7 weeks
Adverse events were untoward medical occurrences that occurred on or after the first dose of study medication.
|
0.00%
0/114 • Up to 7 weeks
Adverse events were untoward medical occurrences that occurred on or after the first dose of study medication.
|
0.88%
1/114 • Number of events 1 • Up to 7 weeks
Adverse events were untoward medical occurrences that occurred on or after the first dose of study medication.
|
|
Nervous system disorders
Ischaemic stroke
|
0.88%
1/113 • Number of events 1 • Up to 7 weeks
Adverse events were untoward medical occurrences that occurred on or after the first dose of study medication.
|
0.00%
0/114 • Up to 7 weeks
Adverse events were untoward medical occurrences that occurred on or after the first dose of study medication.
|
0.00%
0/114 • Up to 7 weeks
Adverse events were untoward medical occurrences that occurred on or after the first dose of study medication.
|
Other adverse events
| Measure |
SEP-4199 200 mg
n=113 participants at risk
SEP-4199 200 mg/day (supplied in two 100mg tablets)
|
SEP-4199 400 mg
n=114 participants at risk
SEP-4199 400 mg/day (supplied in two 200mg tablets)
|
Placebo
n=114 participants at risk
Placebo (supplied in two tablets/day)
|
|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
3.5%
4/113 • Number of events 4 • Up to 7 weeks
Adverse events were untoward medical occurrences that occurred on or after the first dose of study medication.
|
3.5%
4/114 • Number of events 4 • Up to 7 weeks
Adverse events were untoward medical occurrences that occurred on or after the first dose of study medication.
|
5.3%
6/114 • Number of events 6 • Up to 7 weeks
Adverse events were untoward medical occurrences that occurred on or after the first dose of study medication.
|
|
Investigations
Electrocardiogram QT prolonged
|
0.00%
0/113 • Up to 7 weeks
Adverse events were untoward medical occurrences that occurred on or after the first dose of study medication.
|
7.9%
9/114 • Number of events 9 • Up to 7 weeks
Adverse events were untoward medical occurrences that occurred on or after the first dose of study medication.
|
0.00%
0/114 • Up to 7 weeks
Adverse events were untoward medical occurrences that occurred on or after the first dose of study medication.
|
|
Nervous system disorders
Headache
|
9.7%
11/113 • Number of events 12 • Up to 7 weeks
Adverse events were untoward medical occurrences that occurred on or after the first dose of study medication.
|
2.6%
3/114 • Number of events 3 • Up to 7 weeks
Adverse events were untoward medical occurrences that occurred on or after the first dose of study medication.
|
11.4%
13/114 • Number of events 16 • Up to 7 weeks
Adverse events were untoward medical occurrences that occurred on or after the first dose of study medication.
|
|
Psychiatric disorders
Anxiety
|
0.88%
1/113 • Number of events 2 • Up to 7 weeks
Adverse events were untoward medical occurrences that occurred on or after the first dose of study medication.
|
1.8%
2/114 • Number of events 5 • Up to 7 weeks
Adverse events were untoward medical occurrences that occurred on or after the first dose of study medication.
|
6.1%
7/114 • Number of events 7 • Up to 7 weeks
Adverse events were untoward medical occurrences that occurred on or after the first dose of study medication.
|
|
Psychiatric disorders
Insomnia
|
4.4%
5/113 • Number of events 6 • Up to 7 weeks
Adverse events were untoward medical occurrences that occurred on or after the first dose of study medication.
|
4.4%
5/114 • Number of events 6 • Up to 7 weeks
Adverse events were untoward medical occurrences that occurred on or after the first dose of study medication.
|
6.1%
7/114 • Number of events 9 • Up to 7 weeks
Adverse events were untoward medical occurrences that occurred on or after the first dose of study medication.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee In the event the Study is part of a multi-center study, the first publication of the results of the Study shall be made in conjunction with the results of other participating study sites as a multi-center publication; provided however, if a multi-center publication is not forthcoming within twenty-four (24) months following completion of the Study at all sites, Institution and Investigator shall be free to publish.
- Publication restrictions are in place
Restriction type: OTHER