A Phase III Study of SM-13496 in Patients With Bipolar I Depression.
Sponsor
Sumitomo Pharma Co., Ltd. (Industry)
Overall Status
Completed
CT.gov ID
NCT01986101
Collaborator
(none)
525
8
3
35.9
65.6
1.8
Study Details
Study Description
Brief Summary
The study evaluates the efficacy and safety of SM-13496 compared with placebo in patients with Bipolar I Depression.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
The primary objective is to compare the efficacy of SM-13496 (20-60 or 80-120 mg/day) monotherapy with that of placebo in patients with depressive symptoms associated with bipolar I disorder by assessing the change from baseline in the MADRS total score at Week 6.
Study Design
Study Type:
Interventional
Actual Enrollment
:
525 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study of SM-13496 for the Treatment of Bipolar I Depression.
Actual Study Start Date
:
Feb 19, 2014
Actual Primary Completion Date
:
Feb 1, 2017
Actual Study Completion Date
:
Feb 16, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo once daily orally |
Drug: Placebo
Placebo comparator
|
| Experimental: SM-13496 20 - 60 mg/day once daily orally |
Drug: SM-13496
SM-13496 20mg for Days 1-7 and beginning Day 8 flexibly dosed 20-60 mg/day for Weeks 2-6
Other Names:
|
| Experimental: SM-13496 80 - 120 mg/day once daily orally |
Drug: 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
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 6 [Baseline to 6 weeks]
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.
Secondary Outcome Measures
- Change From Baseline in the CGI-BP-S (Depression) Score at Week 6 [Baseline to 6 weeks]
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.
- Change From Baseline in the SDS Total Score at Week 6 (LOCF) [Baseline to 6 weeks]
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.
- Change From Baseline in the YMRS Total Score at Week 6 [Baseline to 6 weeks]
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.
- Change From Baseline in the HAM-A Total Score at Week 6 (LOCF) [Baseline to 6 weeks]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 74 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Patients who were fully informed of and understand the objectives, procedures, and possible benefits and risks of the study and who provided written voluntary consent to participate in the study.
-
Outpatients aged 18 through 74 years at the time of consent
-
Patients meets DSM-IV-TR criteria for bipolar I disorder, most recent episode depressed (≥ 4 weeks and less than 12 months) without psychotic features.
Exclusion Criteria:
-
Patients with imminent risk of suicide or injury to self, others, or property.
-
Patients who had been hospitalized because of a manic or mixed episode within 60 days prior to screening.
-
Patients who are otherwise considered ineligible for the study by the investigator.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Japan 76 sites | Tokyo | Japan | ||
| 2 | Lithuania 3 sites | Kaunas | Lithuania | ||
| 3 | Malaysia 5 sites | Kuala Lumpur | Malaysia | ||
| 4 | Philippines 4 sites | Manila | Philippines | ||
| 5 | Russia 19 sites | Moscow | Russian Federation | ||
| 6 | Slovakia 5 sites | Zilina | Slovakia | ||
| 7 | Taiwan 7 sites | Taipei | Taiwan | ||
| 8 | Ukraine 9 sites | Kiev | Ukraine |
Sponsors and Collaborators
- Sumitomo Pharma Co., Ltd.
Investigators
- Study Director: Director, Drug Development Division, Sumitomo Pharma Co., Ltd.
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Sumitomo Pharma Co., Ltd.
ClinicalTrials.gov Identifier:
NCT01986101
Other Study ID Numbers:
- D1002001
- JapicCTI-132318
- 2013-003038-34
First Posted:
Nov 18, 2013
Last Update Posted:
Apr 12, 2022
Last Verified:
Apr 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Placebo | SM-13496 20 - 60 mg/Day | SM-13496 80 - 120 mg/Day |
|---|---|---|---|
| Arm/Group Description | once daily orally Placebo: Placebo comparator | 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 | 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 |
| Period Title: Overall Study | |||
| STARTED | 172 | 184 | 169 |
| Intent-to-Treat Population | 171 | 182 | 169 |
| Safety Population | 172 | 184 | 169 |
| COMPLETED | 139 | 157 | 137 |
| NOT COMPLETED | 33 | 27 | 32 |
Baseline Characteristics
| Arm/Group Title | Placebo | SM-13496 20 - 60 mg/Day | SM-13496 80 - 120 mg/Day | Total |
|---|---|---|---|---|
| Arm/Group Description | once daily orally Placebo | 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 | 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 of all reporting groups |
| Overall Participants | 171 | 182 | 169 | 522 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
41.3
(12.64)
|
42.6
(12.86)
|
43.2
(12.78)
|
42.4
(12.77)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
94
55%
|
95
52.2%
|
88
52.1%
|
277
53.1%
|
| Male |
77
45%
|
87
47.8%
|
81
47.9%
|
245
46.9%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| White |
94
55%
|
105
57.7%
|
103
60.9%
|
302
57.9%
|
| Asian |
77
45%
|
77
42.3%
|
66
39.1%
|
220
42.1%
|
| Region of Enrollment (Count of Participants) | ||||
| Japan |
60
35.1%
|
65
35.7%
|
53
31.4%
|
178
34.1%
|
| Philippines |
5
2.9%
|
3
1.6%
|
3
1.8%
|
11
2.1%
|
| Taiwan |
5
2.9%
|
3
1.6%
|
4
2.4%
|
12
2.3%
|
| Ukraine |
43
25.1%
|
43
23.6%
|
45
26.6%
|
131
25.1%
|
| Malaysia |
7
4.1%
|
6
3.3%
|
6
3.6%
|
19
3.6%
|
| Slovakia |
5
2.9%
|
7
3.8%
|
4
2.4%
|
16
3.1%
|
| Lithuania |
2
1.2%
|
4
2.2%
|
4
2.4%
|
10
1.9%
|
| Russia |
44
25.7%
|
51
28%
|
50
29.6%
|
145
27.8%
|
| Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score (units on a scale) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [units on a scale] |
30.9
(5.39)
|
30.6
(5.57)
|
30.8
(5.09)
|
30.8
(5.35)
|
| Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) Score (Depression) (units on a scale) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [units on a scale] |
4.60
(0.690)
|
4.57
(0.700)
|
4.58
(0.603)
|
4.58
(0.666)
|
| Sheehan Disability Scale (SDS) total score (units on a scale) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [units on a scale] |
19.9
(5.22)
|
19.4
(5.29)
|
19.8
(5.58)
|
19.7
(5.35)
|
Outcome Measures
| Title | Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 6 |
|---|---|
| Description | 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. |
| Time Frame | Baseline to 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-treat population is analyzed. |
| Arm/Group Title | Placebo | SM-13496 20 - 60 mg/Day | SM-13496 80 - 120 mg/Day |
|---|---|---|---|
| Arm/Group Description | once daily orally Placebo: Placebo comparator | 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 | 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 |
| Measure Participants | 171 | 182 | 169 |
| Least Squares Mean (Standard Error) [units on a scale] |
-10.6
(0.72)
|
-13.6
(0.69)
|
-12.6
(0.73)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, SM-13496 20 - 60 mg/Day |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.007 |
| Comments | Hochberg-adjusted | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -2.9 | |
| Confidence Interval |
(2-Sided) 95% -4.9 to -1.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.00 |
|
| Estimation Comments | A negative difference in least square mean change from baseline between SM-13496 group and placebo indicates a greater improvement in the SM-13496 group over the placebo group. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, SM-13496 80 - 120 mg/Day |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.057 |
| Comments | Hochberg-adjusted. | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -2.0 | |
| Confidence Interval |
(2-Sided) 95% -4.0 to 0.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.03 |
|
| Estimation Comments | A negative difference in least square mean change from baseline between SM-13496 group and placebo indicates a greater improvement in the SM-13496 group over the placebo group. | |
| Title | Change From Baseline in the CGI-BP-S (Depression) Score at Week 6 |
|---|---|
| Description | 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. |
| Time Frame | Baseline to 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-treat population is analyzed. |
| Arm/Group Title | Placebo | SM-13496 20 - 60 mg/Day | SM-13496 80 - 120 mg/Day |
|---|---|---|---|
| Arm/Group Description | once daily orally Placebo: Placebo comparator | 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 | 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 |
| Measure Participants | 171 | 182 | 169 |
| Least Squares Mean (Standard Error) [units on a scale] |
-1.11
(0.092)
|
-1.51
(0.088)
|
-1.41
(0.093)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, SM-13496 20 - 60 mg/Day |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.40 | |
| Confidence Interval |
(2-Sided) 95% -0.65 to -0.15 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.127 |
|
| Estimation Comments | A negative difference in least square mean change from baseline between SM-13496 group and placebo indicates a greater improvement in the SM-13496 group over the placebo group. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, SM-13496 80 - 120 mg/Day |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.019 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.31 | |
| Confidence Interval |
(2-Sided) 95% -0.56 to -0.05 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.130 |
|
| Estimation Comments | A negative difference in least square mean change from baseline between SM-13496 group and placebo indicates a greater improvement in SM-13496 group over the placebo group. | |
| Title | Change From Baseline in the SDS Total Score at Week 6 (LOCF) |
|---|---|
| Description | 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. |
| Time Frame | Baseline to 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-Treat Population is analyzed. Values were missing for some subjects. |
| Arm/Group Title | Placebo | SM-13496 20 - 60 mg/Day | SM-13496 80 - 120 mg/Day |
|---|---|---|---|
| Arm/Group Description | once daily orally Placebo: Placebo comparator | 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 | 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 |
| Measure Participants | 128 | 147 | 124 |
| Least Squares Mean (Standard Error) [units on a scale] |
-5.7
(0.66)
|
-7.6
(0.62)
|
-6.8
(0.67)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, SM-13496 20 - 60 mg/Day |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.037 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.8 | |
| Confidence Interval |
(2-Sided) 95% -3.6 to -0.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.89 |
|
| Estimation Comments | A negative difference in least square mean change from baseline between SM-13496 group and placebo indicates a greater improvement in the SM-13496 group over the placebo group. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, SM-13496 80 - 120 mg/Day |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.223 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.1 | |
| Confidence Interval |
(2-Sided) 95% -2.9 to 0.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.92 |
|
| Estimation Comments | A negative difference in least square mean change from baseline between SM-13496 group and placebo indicates a greater improvement in the SM-13496 group over the placebo group. | |
| Title | Change From Baseline in the YMRS Total Score at Week 6 |
|---|---|
| Description | 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. |
| Time Frame | Baseline to 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-Treat Population is analyzed. |
| Arm/Group Title | Placebo | SM-13496 20 - 60 mg/Day | SM-13496 80 - 120 mg/Day |
|---|---|---|---|
| Arm/Group Description | once daily orally Placebo: Placebo comparator | 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 | 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 |
| Measure Participants | 171 | 182 | 169 |
| Least Squares Mean (Standard Error) [units on a scale] |
-0.51
(0.190)
|
-0.98
(0.180)
|
-0.99
(0.191)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, SM-13496 20 - 60 mg/Day |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.076 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.47 | |
| Confidence Interval |
(2-Sided) 95% -0.98 to 0.05 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.262 |
|
| Estimation Comments | A negative difference in least square mean change from baseline between SM-13496 group and placebo indicates a greater improvement in the SM-13496 group over the placebo group. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, SM-13496 80 - 120 mg/Day |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.075 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.48 | |
| Confidence Interval |
(2-Sided) 95% -1.01 to 0.05 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.269 |
|
| Estimation Comments | A negative difference in least square mean change from baseline between SM-13496 group and placebo indicates a greater improvement in the SM-13496 group over the placebo group. | |
| Title | Change From Baseline in the HAM-A Total Score at Week 6 (LOCF) |
|---|---|
| Description | 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. |
| Time Frame | Baseline to 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-treat population is analyzed. Values were missing for some subjects. |
| Arm/Group Title | Placebo | SM-13496 20 - 60 mg/Day | SM-13496 80 - 120 mg/Day |
|---|---|---|---|
| Arm/Group Description | once daily orally Placebo | 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 | 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 |
| Measure Participants | 164 | 179 | 167 |
| Least Squares Mean (Standard Error) [units on a scale] |
-5.7
(0.51)
|
-7.4
(0.49)
|
-6.4
(0.50)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, SM-13496 20 - 60 mg/Day |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.016 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.7 | |
| Confidence Interval |
(2-Sided) 95% -3.1 to -0.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.70 |
|
| Estimation Comments | A negative difference in least square mean change from baseline between SM-13496 group and placebo indicates a greater improvement in the SM-13496 group over the placebo group. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, SM-13496 80 - 120 mg/Day |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.294 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.7 | |
| Confidence Interval |
(2-Sided) 95% -2.1 to 0.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.71 |
|
| Estimation Comments | A negative difference in least square mean change from baseline between SM-13496 group and placebo indicates a greater improvement in the SM-13496 group over the placebo group. | |
Adverse Events
| Time Frame | 6 weeks | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Safety population is analyzed. | |||||
| Arm/Group Title | Placebo | SM-13496 20 - 60 mg/Day | SM-13496 80 - 120 mg/Day | |||
| Arm/Group Description | once daily orally Placebo | 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 | 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 | |||
All Cause Mortality |
||||||
| Placebo | SM-13496 20 - 60 mg/Day | SM-13496 80 - 120 mg/Day | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/172 (0%) | 0/184 (0%) | 0/169 (0%) | |||
Serious Adverse Events |
||||||
| Placebo | SM-13496 20 - 60 mg/Day | SM-13496 80 - 120 mg/Day | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/172 (2.9%) | 2/184 (1.1%) | 4/169 (2.4%) | |||
| Cardiac disorders | ||||||
| Acute myocardial infarction | 1/172 (0.6%) | 1 | 0/184 (0%) | 0 | 0/169 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Abdominal pain | 1/172 (0.6%) | 1 | 0/184 (0%) | 0 | 0/169 (0%) | 0 |
| General disorders | ||||||
| Disease progression | 1/172 (0.6%) | 1 | 0/184 (0%) | 0 | 1/169 (0.6%) | 1 |
| Injury, poisoning and procedural complications | ||||||
| Tendon rupture | 0/172 (0%) | 0 | 0/184 (0%) | 0 | 1/169 (0.6%) | 1 |
| Psychiatric disorders | ||||||
| Bipolar I disorder | 1/172 (0.6%) | 1 | 0/184 (0%) | 0 | 0/169 (0%) | 0 |
| Mania | 1/172 (0.6%) | 1 | 1/184 (0.5%) | 1 | 0/169 (0%) | 0 |
| Panic attack | 0/172 (0%) | 0 | 0/184 (0%) | 0 | 1/169 (0.6%) | 1 |
| Suicidal ideation | 0/172 (0%) | 0 | 1/184 (0.5%) | 1 | 0/169 (0%) | 0 |
| Suicide attempt | 0/172 (0%) | 0 | 0/184 (0%) | 0 | 1/169 (0.6%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||
| Placebo | SM-13496 20 - 60 mg/Day | SM-13496 80 - 120 mg/Day | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 44/172 (25.6%) | 49/184 (26.6%) | 75/169 (44.4%) | |||
| Gastrointestinal disorders | ||||||
| Nausea | 10/172 (5.8%) | 13 | 12/184 (6.5%) | 13 | 20/169 (11.8%) | 23 |
| Infections and infestations | ||||||
| Nasopharyngitis | 8/172 (4.7%) | 8 | 10/184 (5.4%) | 10 | 6/169 (3.6%) | 6 |
| Nervous system disorders | ||||||
| Akathisia | 11/172 (6.4%) | 12 | 24/184 (13%) | 27 | 40/169 (23.7%) | 46 |
| Headache | 15/172 (8.7%) | 22 | 5/184 (2.7%) | 7 | 9/169 (5.3%) | 11 |
| Parkinsonism | 4/172 (2.3%) | 7 | 4/184 (2.2%) | 4 | 10/169 (5.9%) | 19 |
| Somnolence | 7/172 (4.1%) | 8 | 7/184 (3.8%) | 7 | 11/169 (6.5%) | 12 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Clinical Research |
|---|---|
| Organization | Sumitomo Dainippon Pharmaceutical |
| Phone | +81-3-5159-2519 |
| cc@ds-pharma.co.jp |
Responsible Party:
Sumitomo Pharma Co., Ltd.
ClinicalTrials.gov Identifier:
NCT01986101
Other Study ID Numbers:
- D1002001
- JapicCTI-132318
- 2013-003038-34
First Posted:
Nov 18, 2013
Last Update Posted:
Apr 12, 2022
Last Verified:
Apr 1, 2022