Trial Outcomes & Findings for A Phase III Study of SM-13496 in Patients With Bipolar I Depression. (NCT NCT01986101)

NCT ID: NCT01986101

Last Updated: 2022-04-12

Results Overview

Montgomery-Asberg Depression Rating Scale (MADRS)is a clinician-rated assessment of a subject's level of depression. The MADRS total score ranges from a minimum of 0 to a maximum of 60. For the MADRS total score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome. The MADRS contains ten (10) items. The total score is computed as the sum of the scores for the 10 items.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 525 participants
• Primary outcome timeframe: Baseline to 6 weeks
• Results posted on: 2022-04-12

Participant Flow

Participant milestones

Measure	Placebo once daily orally Placebo: Placebo comparator	SM-13496 20 - 60 mg/Day once daily orally SM-13496: SM-13496 20mg for Days 1-7 and beginning Day 8 flexibly dosed 20-60mg/day for Weeks 2-6	SM-13496 80 - 120 mg/Day once daily orally SM-13496: SM-13496 20 mg/day for Days 1-2, 40 mg/day for Days 3-4, 60 mg/day for Days 5-6, 80 mg/day on Day 7 and beginning Day 8 flexibly dosed 80-120 mg/day for Weeks 2-6
Overall Study STARTED	172	184	169
Overall Study Intent-to-Treat Population	171	182	169
Overall Study Safety Population	172	184	169
Overall Study COMPLETED	139	157	137
Overall Study NOT COMPLETED	33	27	32

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

SDS total score was evaluated in most subjects.

Baseline characteristics by cohort

Measure	Placebo n=171 Participants once daily orally Placebo	SM-13496 20 - 60 mg/Day n=182 Participants once daily orally SM-13496 (lurasidone HCl): SM-13496 20 mg/day for Days 1-7 and beginning Day 8 flexibly dosed 20-60 mg/day for Weeks 2-6	SM-13496 80 - 120 mg/Day n=169 Participants once daily orally SM-13496 (lurasidone HCl): SM-13496 20 mg/day for Days 1-2, 40 mg/day for Days 3-4, 60 mg/day for Days 5-6, 80 mg/day on Day 7 and beginning Day 8 flexibly dosed 80-120 mg/day for Weeks 2-6	Total n=522 Participants Total of all reporting groups
Age, Continuous	41.3 years STANDARD_DEVIATION 12.64 • n=171 Participants	42.6 years STANDARD_DEVIATION 12.86 • n=182 Participants	43.2 years STANDARD_DEVIATION 12.78 • n=169 Participants	42.4 years STANDARD_DEVIATION 12.77 • n=522 Participants
Sex: Female, Male Female	94 Participants n=171 Participants	95 Participants n=182 Participants	88 Participants n=169 Participants	277 Participants n=522 Participants
Sex: Female, Male Male	77 Participants n=171 Participants	87 Participants n=182 Participants	81 Participants n=169 Participants	245 Participants n=522 Participants
Race/Ethnicity, Customized White	94 Participants n=171 Participants	105 Participants n=182 Participants	103 Participants n=169 Participants	302 Participants n=522 Participants
Race/Ethnicity, Customized Asian	77 Participants n=171 Participants	77 Participants n=182 Participants	66 Participants n=169 Participants	220 Participants n=522 Participants
Region of Enrollment Japan	60 Participants n=171 Participants	65 Participants n=182 Participants	53 Participants n=169 Participants	178 Participants n=522 Participants
Region of Enrollment Philippines	5 Participants n=171 Participants	3 Participants n=182 Participants	3 Participants n=169 Participants	11 Participants n=522 Participants
Region of Enrollment Taiwan	5 Participants n=171 Participants	3 Participants n=182 Participants	4 Participants n=169 Participants	12 Participants n=522 Participants
Region of Enrollment Ukraine	43 Participants n=171 Participants	43 Participants n=182 Participants	45 Participants n=169 Participants	131 Participants n=522 Participants
Region of Enrollment Malaysia	7 Participants n=171 Participants	6 Participants n=182 Participants	6 Participants n=169 Participants	19 Participants n=522 Participants
Region of Enrollment Slovakia	5 Participants n=171 Participants	7 Participants n=182 Participants	4 Participants n=169 Participants	16 Participants n=522 Participants
Region of Enrollment Lithuania	2 Participants n=171 Participants	4 Participants n=182 Participants	4 Participants n=169 Participants	10 Participants n=522 Participants
Region of Enrollment Russia	44 Participants n=171 Participants	51 Participants n=182 Participants	50 Participants n=169 Participants	145 Participants n=522 Participants
Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score	30.9 units on a scale STANDARD_DEVIATION 5.39 • n=171 Participants	30.6 units on a scale STANDARD_DEVIATION 5.57 • n=182 Participants	30.8 units on a scale STANDARD_DEVIATION 5.09 • n=169 Participants	30.8 units on a scale STANDARD_DEVIATION 5.35 • n=522 Participants
Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) Score (Depression)	4.60 units on a scale STANDARD_DEVIATION 0.690 • n=171 Participants	4.57 units on a scale STANDARD_DEVIATION 0.700 • n=182 Participants	4.58 units on a scale STANDARD_DEVIATION 0.603 • n=169 Participants	4.58 units on a scale STANDARD_DEVIATION 0.666 • n=522 Participants
Sheehan Disability Scale (SDS) total score	19.9 units on a scale STANDARD_DEVIATION 5.22 • n=141 Participants • SDS total score was evaluated in most subjects.	19.4 units on a scale STANDARD_DEVIATION 5.29 • n=154 Participants • SDS total score was evaluated in most subjects.	19.8 units on a scale STANDARD_DEVIATION 5.58 • n=127 Participants • SDS total score was evaluated in most subjects.	19.7 units on a scale STANDARD_DEVIATION 5.35 • n=422 Participants • SDS total score was evaluated in most subjects.

PRIMARY outcome

Timeframe: Baseline to 6 weeks

Population: Intention-to-treat population is analyzed.

Montgomery-Asberg Depression Rating Scale (MADRS)is a clinician-rated assessment of a subject's level of depression.

The MADRS total score ranges from a minimum of 0 to a maximum of 60. For the MADRS total score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome.

The MADRS contains ten (10) items. The total score is computed as the sum of the scores for the 10 items.

Outcome measures

Measure	Placebo n=171 Participants once daily orally Placebo: Placebo comparator	SM-13496 20 - 60 mg/Day n=182 Participants once daily orally SM-13496: SM-13496 20 mg/day for Days 1-7 and beginning Day 8 flexibly dosed 20-60 mg/day for Weeks 2-6	SM-13496 80 - 120 mg/Day n=169 Participants once daily orally SM-13496: SM-13496 20 mg/day for Days 1-2, 40 mg/day for Days 3-4, 60 mg/day for Days 5-6, 80 mg/day on Day 7 and beginning Day 8 flexibly dosed 80-120 mg/day for Weeks 2-6
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 6	-10.6 units on a scale Standard Error 0.72	-13.6 units on a scale Standard Error 0.69	-12.6 units on a scale Standard Error 0.73

SECONDARY outcome

Timeframe: Baseline to 6 weeks

Population: Intention-to-treat population is analyzed.

Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) score (depression) is a clinician-rated assessment of a subject's level of depression.

The CGI depression score ranges from a minimum of 1 to a maximum of 7. For the CGI depression score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome.

Outcome measures

Measure	Placebo n=171 Participants once daily orally Placebo: Placebo comparator	SM-13496 20 - 60 mg/Day n=182 Participants once daily orally SM-13496: SM-13496 20 mg/day for Days 1-7 and beginning Day 8 flexibly dosed 20-60 mg/day for Weeks 2-6	SM-13496 80 - 120 mg/Day n=169 Participants once daily orally SM-13496: SM-13496 20 mg/day for Days 1-2, 40 mg/day for Days 3-4, 60 mg/day for Days 5-6, 80 mg/day on Day 7 and beginning Day 8 flexibly dosed 80-120 mg/day for Weeks 2-6
Change From Baseline in the CGI-BP-S (Depression) Score at Week 6	-1.11 units on a scale Standard Error 0.092	-1.51 units on a scale Standard Error 0.088	-1.41 units on a scale Standard Error 0.093

SECONDARY outcome

Timeframe: Baseline to 6 weeks

Population: Intention-to-Treat Population is analyzed. Values were missing for some subjects.

Sheehan Disability Scale (SDS) total score is a subject-rated assessment of a subject's level of functional impairment in work/school, social life and family life/home responsibilities.

The SDS total score ranges from a minimum of 0 to a maximum of 30. For the SDS total score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome.

The SDS contains three (3) items. The total score is computed as the sum of the scores for the 3 items.

Outcome measures

Measure	Placebo n=128 Participants once daily orally Placebo: Placebo comparator	SM-13496 20 - 60 mg/Day n=147 Participants once daily orally SM-13496: SM-13496 20 mg/day for Days 1-7 and beginning Day 8 flexibly dosed 20-60 mg/day for Weeks 2-6	SM-13496 80 - 120 mg/Day n=124 Participants once daily orally SM-13496: SM-13496 20 mg/day for Days 1-2, 40 mg/day for Days 3-4, 60 mg/day for Days 5-6, 80 mg/day on Day 7 and beginning Day 8 flexibly dosed 80-120 mg/day for Weeks 2-6
Change From Baseline in the SDS Total Score at Week 6 (LOCF)	-5.7 units on a scale Standard Error 0.66	-7.6 units on a scale Standard Error 0.62	-6.8 units on a scale Standard Error 0.67

SECONDARY outcome

Timeframe: Baseline to 6 weeks

Population: Intention-to-Treat Population is analyzed.

YMRS (Young Mania Rating Scale) is a clinician-rated assessment of the severity of mania in subjects with a diagnosis of bipolar disorder.

The YMRS total score ranges from a minimum of 0 to a maximum of 60. For the YMRS total score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome.

The YMRS contains eleven (11) items. The total score is computed as the sum of the scores for the 11 items.

Outcome measures

Measure	Placebo n=171 Participants once daily orally Placebo: Placebo comparator	SM-13496 20 - 60 mg/Day n=182 Participants once daily orally SM-13496: SM-13496 20 mg/day for Days 1-7 and beginning Day 8 flexibly dosed 20-60 mg/day for Weeks 2-6	SM-13496 80 - 120 mg/Day n=169 Participants once daily orally SM-13496: SM-13496 20 mg/day for Days 1-2, 40 mg/day for Days 3-4, 60 mg/day for Days 5-6, 80 mg/day on Day 7 and beginning Day 8 flexibly dosed 80-120 mg/day for Weeks 2-6
Change From Baseline in the YMRS Total Score at Week 6	-0.51 units on a scale Standard Error 0.190	-0.98 units on a scale Standard Error 0.180	-0.99 units on a scale Standard Error 0.191

SECONDARY outcome

Timeframe: Baseline to 6 weeks

Population: Intention-to-treat population is analyzed. Values were missing for some subjects.

The Hamilton Rating Scale for Anxiety (HAM-A) scale is a rating scale developed to quantify the severity of anxiety symptomatology.

The HAM-A total score ranges from a minimum of 0 to a maximum of 56. For the HAM-A total score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome.

The HAM-A contains fourteen (14) items. The total score is computed as the sum of the scores for the 14 items.

Outcome measures

Measure	Placebo n=164 Participants once daily orally Placebo: Placebo comparator	SM-13496 20 - 60 mg/Day n=179 Participants once daily orally SM-13496: SM-13496 20 mg/day for Days 1-7 and beginning Day 8 flexibly dosed 20-60 mg/day for Weeks 2-6	SM-13496 80 - 120 mg/Day n=167 Participants once daily orally SM-13496: SM-13496 20 mg/day for Days 1-2, 40 mg/day for Days 3-4, 60 mg/day for Days 5-6, 80 mg/day on Day 7 and beginning Day 8 flexibly dosed 80-120 mg/day for Weeks 2-6
Change From Baseline in the HAM-A Total Score at Week 6 (LOCF)	-5.7 units on a scale Standard Error 0.51	-7.4 units on a scale Standard Error 0.49	-6.4 units on a scale Standard Error 0.50

Adverse Events

Placebo

Serious events: 5 serious events

Other events: 44 other events

Deaths: 0 deaths

SM-13496 20 - 60 mg/Day

Serious events: 2 serious events

Other events: 49 other events

Deaths: 0 deaths

SM-13496 80 - 120 mg/Day

Serious events: 4 serious events

Other events: 75 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=172 participants at risk once daily orally Placebo	SM-13496 20 - 60 mg/Day n=184 participants at risk once daily orally SM-13496 (lurasidone HCl): SM-13496 20 mg/day for Days 1-7 and beginning Day 8 flexibly dosed 20-60 mg/day for Weeks 2-6	SM-13496 80 - 120 mg/Day n=169 participants at risk once daily orally SM-13496 (lurasidone HCl): SM-13496 20 mg/day for Days 1-2, 40 mg/day for Days 3-4, 60 mg/day for Days 5-6, 80 mg/day on Day 7 and beginning Day 8 flexibly dosed 80-120 mg/day for Weeks 2-6
Cardiac disorders Acute myocardial infarction	0.58% 1/172 • Number of events 1 • 6 weeks Safety population is analyzed.	0.00% 0/184 • 6 weeks Safety population is analyzed.	0.00% 0/169 • 6 weeks Safety population is analyzed.
Gastrointestinal disorders Abdominal pain	0.58% 1/172 • Number of events 1 • 6 weeks Safety population is analyzed.	0.00% 0/184 • 6 weeks Safety population is analyzed.	0.00% 0/169 • 6 weeks Safety population is analyzed.
General disorders Disease progression	0.58% 1/172 • Number of events 1 • 6 weeks Safety population is analyzed.	0.00% 0/184 • 6 weeks Safety population is analyzed.	0.59% 1/169 • Number of events 1 • 6 weeks Safety population is analyzed.
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/172 • 6 weeks Safety population is analyzed.	0.00% 0/184 • 6 weeks Safety population is analyzed.	0.59% 1/169 • Number of events 1 • 6 weeks Safety population is analyzed.
Psychiatric disorders Bipolar I disorder	0.58% 1/172 • Number of events 1 • 6 weeks Safety population is analyzed.	0.00% 0/184 • 6 weeks Safety population is analyzed.	0.00% 0/169 • 6 weeks Safety population is analyzed.
Psychiatric disorders Mania	0.58% 1/172 • Number of events 1 • 6 weeks Safety population is analyzed.	0.54% 1/184 • Number of events 1 • 6 weeks Safety population is analyzed.	0.00% 0/169 • 6 weeks Safety population is analyzed.
Psychiatric disorders Panic attack	0.00% 0/172 • 6 weeks Safety population is analyzed.	0.00% 0/184 • 6 weeks Safety population is analyzed.	0.59% 1/169 • Number of events 1 • 6 weeks Safety population is analyzed.
Psychiatric disorders Suicidal ideation	0.00% 0/172 • 6 weeks Safety population is analyzed.	0.54% 1/184 • Number of events 1 • 6 weeks Safety population is analyzed.	0.00% 0/169 • 6 weeks Safety population is analyzed.
Psychiatric disorders Suicide attempt	0.00% 0/172 • 6 weeks Safety population is analyzed.	0.00% 0/184 • 6 weeks Safety population is analyzed.	0.59% 1/169 • Number of events 1 • 6 weeks Safety population is analyzed.

Other adverse events

Measure	Placebo n=172 participants at risk once daily orally Placebo	SM-13496 20 - 60 mg/Day n=184 participants at risk once daily orally SM-13496 (lurasidone HCl): SM-13496 20 mg/day for Days 1-7 and beginning Day 8 flexibly dosed 20-60 mg/day for Weeks 2-6	SM-13496 80 - 120 mg/Day n=169 participants at risk once daily orally SM-13496 (lurasidone HCl): SM-13496 20 mg/day for Days 1-2, 40 mg/day for Days 3-4, 60 mg/day for Days 5-6, 80 mg/day on Day 7 and beginning Day 8 flexibly dosed 80-120 mg/day for Weeks 2-6
Gastrointestinal disorders Nausea	5.8% 10/172 • Number of events 13 • 6 weeks Safety population is analyzed.	6.5% 12/184 • Number of events 13 • 6 weeks Safety population is analyzed.	11.8% 20/169 • Number of events 23 • 6 weeks Safety population is analyzed.
Infections and infestations Nasopharyngitis	4.7% 8/172 • Number of events 8 • 6 weeks Safety population is analyzed.	5.4% 10/184 • Number of events 10 • 6 weeks Safety population is analyzed.	3.6% 6/169 • Number of events 6 • 6 weeks Safety population is analyzed.
Nervous system disorders Akathisia	6.4% 11/172 • Number of events 12 • 6 weeks Safety population is analyzed.	13.0% 24/184 • Number of events 27 • 6 weeks Safety population is analyzed.	23.7% 40/169 • Number of events 46 • 6 weeks Safety population is analyzed.
Nervous system disorders Headache	8.7% 15/172 • Number of events 22 • 6 weeks Safety population is analyzed.	2.7% 5/184 • Number of events 7 • 6 weeks Safety population is analyzed.	5.3% 9/169 • Number of events 11 • 6 weeks Safety population is analyzed.
Nervous system disorders Parkinsonism	2.3% 4/172 • Number of events 7 • 6 weeks Safety population is analyzed.	2.2% 4/184 • Number of events 4 • 6 weeks Safety population is analyzed.	5.9% 10/169 • Number of events 19 • 6 weeks Safety population is analyzed.
Nervous system disorders Somnolence	4.1% 7/172 • Number of events 8 • 6 weeks Safety population is analyzed.	3.8% 7/184 • Number of events 7 • 6 weeks Safety population is analyzed.	6.5% 11/169 • Number of events 12 • 6 weeks Safety population is analyzed.

Additional Information

Clinical Research

Sumitomo Dainippon Pharmaceutical

Phone: +81-3-5159-2519

Email: cc@ds-pharma.co.jp

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place