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)

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

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

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

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=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	3 Participants n=483 Participants
Age, Categorical Between 18 and 65 years	112 Participants n=93 Participants	111 Participants n=4 Participants	113 Participants n=27 Participants	336 Participants n=483 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	2 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants
Age, Continuous	42 Years STANDARD_DEVIATION 11.65 • n=93 Participants	44.4 Years STANDARD_DEVIATION 12.72 • n=4 Participants	43.3 Years STANDARD_DEVIATION 12.10 • n=27 Participants	43.2 Years STANDARD_DEVIATION 12.17 • n=483 Participants
Sex: Female, Male Female	69 Participants n=93 Participants	76 Participants n=4 Participants	64 Participants n=27 Participants	209 Participants n=483 Participants
Sex: Female, Male Male	44 Participants n=93 Participants	38 Participants n=4 Participants	50 Participants n=27 Participants	132 Participants n=483 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=93 Participants	3 Participants n=4 Participants	2 Participants n=27 Participants	8 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	110 Participants n=93 Participants	109 Participants n=4 Participants	112 Participants n=27 Participants	331 Participants n=483 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	2 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants
Race (NIH/OMB) Asian	16 Participants n=93 Participants	16 Participants n=4 Participants	17 Participants n=27 Participants	49 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=93 Participants	2 Participants n=4 Participants	1 Participants n=27 Participants	4 Participants n=483 Participants
Race (NIH/OMB) Black or African American	6 Participants n=93 Participants	8 Participants n=4 Participants	8 Participants n=27 Participants	22 Participants n=483 Participants
Race (NIH/OMB) White	89 Participants n=93 Participants	87 Participants n=4 Participants	88 Participants n=27 Participants	264 Participants n=483 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Region of Enrollment Europe	83 Participants n=93 Participants	82 Participants n=4 Participants	84 Participants n=27 Participants	249 Participants n=483 Participants
Region of Enrollment Japan	16 Participants n=93 Participants	16 Participants n=4 Participants	17 Participants n=27 Participants	49 Participants n=483 Participants
Region of Enrollment United States	14 Participants n=93 Participants	16 Participants n=4 Participants	13 Participants n=27 Participants	43 Participants n=483 Participants
Age, Customized 18-64 years	113 Participants n=93 Participants	112 Participants n=4 Participants	114 Participants n=27 Participants	339 Participants n=483 Participants
Age, Customized >=65 years	0 Participants n=93 Participants	2 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants
Country Name Bulgaria	11 Participants n=93 Participants	10 Participants n=4 Participants	22 Participants n=27 Participants	43 Participants n=483 Participants
Country Name Japan	16 Participants n=93 Participants	16 Participants n=4 Participants	17 Participants n=27 Participants	49 Participants n=483 Participants
Country Name Poland	5 Participants n=93 Participants	1 Participants n=4 Participants	5 Participants n=27 Participants	11 Participants n=483 Participants
Country Name Russia	18 Participants n=93 Participants	20 Participants n=4 Participants	8 Participants n=27 Participants	46 Participants n=483 Participants
Country Name Serbia	19 Participants n=93 Participants	26 Participants n=4 Participants	18 Participants n=27 Participants	63 Participants n=483 Participants
Country Name Slovakia	8 Participants n=93 Participants	5 Participants n=4 Participants	6 Participants n=27 Participants	19 Participants n=483 Participants
Country Name Ukraine	22 Participants n=93 Participants	20 Participants n=4 Participants	25 Participants n=27 Participants	67 Participants n=483 Participants
Country Name United States	14 Participants n=93 Participants	16 Participants n=4 Participants	13 Participants n=27 Participants	43 Participants n=483 Participants
Baseline Weight (kg)	75.3 kg STANDARD_DEVIATION 14.47 • n=93 Participants	74.8 kg STANDARD_DEVIATION 16.19 • n=4 Participants	77.5 kg STANDARD_DEVIATION 16.59 • n=27 Participants	75.9 kg STANDARD_DEVIATION 15.78 • n=483 Participants
Baseline BMI (kg/m^2)	26.2 kg/m^2 STANDARD_DEVIATION 4.53 • n=93 Participants	26.6 kg/m^2 STANDARD_DEVIATION 4.91 • n=4 Participants	27 kg/m^2 STANDARD_DEVIATION 4.94 • n=27 Participants	26.6 kg/m^2 STANDARD_DEVIATION 4.79 • n=483 Participants
Baseline BMI Category < 18.5 kg/m^2	0 Participants n=93 Participants	3 Participants n=4 Participants	0 Participants n=27 Participants	3 Participants n=483 Participants
Baseline BMI Category 18.5 - <25.0 kg/m^2	51 Participants n=93 Participants	50 Participants n=4 Participants	45 Participants n=27 Participants	146 Participants n=483 Participants
Baseline BMI Category 25.0 - <30.0 kg/m^2	42 Participants n=93 Participants	33 Participants n=4 Participants	40 Participants n=27 Participants	115 Participants n=483 Participants
Baseline BMI Category >=30.0 kg/m^2	20 Participants n=93 Participants	28 Participants n=4 Participants	29 Participants n=27 Participants	77 Participants n=483 Participants
Baseline Montgomery-Asberg Depression Rating Scale( MADRS )Total Score	33.5 units on a scale STANDARD_DEVIATION 5.77 • n=93 Participants	33.8 units on a scale STANDARD_DEVIATION 5.63 • n=4 Participants	34.1 units on a scale STANDARD_DEVIATION 5.35 • n=27 Participants	33.8 units on a scale STANDARD_DEVIATION 5.58 • n=483 Participants
Baseline global severity assessed by the Clinical Global Impressions -Severity Depression Score	4.8 units on a scale STANDARD_DEVIATION 0.66 • n=93 Participants	4.8 units on a scale STANDARD_DEVIATION 0.65 • n=4 Participants	4.9 units on a scale STANDARD_DEVIATION 0.70 • n=27 Participants	4.8 units on a scale STANDARD_DEVIATION 0.67 • n=483 Participants

PRIMARY outcome

Timeframe: 6 Weeks

Population: ITT population, excluding subjects from Japan Region

Outcome measures

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 Weeks

Population: 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

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

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

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

CNS Medical Director

Sunovion Pharmaceuticals Inc.

Phone: 1-866-503-6351

Email: [email protected]

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