Trial Outcomes & Findings for A Study to Assess the Efficacy and Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder (MDD) (NCT NCT01157078)
NCT ID: NCT01157078
Last Updated: 2014-04-11
Results Overview
A 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.
COMPLETED
PHASE3
319 participants
Randomization (Week 8) to end of treatment (Week 16)
2014-04-11
Participant Flow
This multicenter study was conducted in the United States and India between 22 June 2010 and 17 November 2011.
The study had an up to 21-day screening/washout period, and an 8-week prospective open-label antidepressant treatment (ADT) period to identify the target patient population of inadequate responders to ADT (\<50% reduction in HAMD-17 total score during the prospective open-label ADT period, a HAMD-17 total score of ≥16 and a CGI-S score ≥4).
Participant milestones
| Measure |
TC-5214
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
|---|---|---|
|
Overall Study
STARTED
|
159
|
160
|
|
Overall Study
Received Treatment
|
157
|
159
|
|
Overall Study
COMPLETED
|
124
|
124
|
|
Overall Study
NOT COMPLETED
|
35
|
36
|
Reasons for withdrawal
| Measure |
TC-5214
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
12
|
14
|
|
Overall Study
Eligibility criteria not fulfilled
|
2
|
0
|
|
Overall Study
Adverse Event
|
6
|
6
|
|
Overall Study
Severe non-compliance to protocol
|
2
|
4
|
|
Overall Study
Condition under investigation worsened
|
0
|
1
|
|
Overall Study
Lack of Efficacy
|
2
|
0
|
|
Overall Study
Study-specific withdrawal criteria
|
2
|
2
|
|
Overall Study
Lost to Follow-up
|
7
|
5
|
|
Overall Study
Other
|
2
|
4
|
Baseline Characteristics
A Study to Assess the Efficacy and Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder (MDD)
Baseline characteristics by cohort
| Measure |
TC-5214
n=159 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
n=160 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
Total
n=319 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
39.7 years
STANDARD_DEVIATION 11.37 • n=93 Participants
|
41.0 years
STANDARD_DEVIATION 11.53 • n=4 Participants
|
40.4 years
STANDARD_DEVIATION 11.45 • n=27 Participants
|
|
Sex: Female, Male
Female
|
101 Participants
n=93 Participants
|
99 Participants
n=4 Participants
|
200 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
58 Participants
n=93 Participants
|
61 Participants
n=4 Participants
|
119 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
White
|
99 participants
n=93 Participants
|
100 participants
n=4 Participants
|
199 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
11 participants
n=93 Participants
|
19 participants
n=4 Participants
|
30 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Asian
|
48 participants
n=93 Participants
|
37 participants
n=4 Participants
|
85 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or other Pacific Islander
|
0 participants
n=93 Participants
|
0 participants
n=4 Participants
|
0 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 participants
n=93 Participants
|
1 participants
n=4 Participants
|
1 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 participants
n=93 Participants
|
3 participants
n=4 Participants
|
4 participants
n=27 Participants
|
|
Hamilton Rating Scale for Depression-17 items (HAMD-17) total score at randomization
|
22.0 Scores on a scale
STANDARD_DEVIATION 4.13 • n=93 Participants
|
21.1 Scores on a scale
STANDARD_DEVIATION 3.81 • n=4 Participants
|
21.5 Scores on a scale
STANDARD_DEVIATION 3.98 • n=27 Participants
|
|
Montgomery-Asberg Depression Rating Scale (MADRS) total score at randomization
|
27.4 Scores on a scale
STANDARD_DEVIATION 5.58 • n=93 Participants
|
26.6 Scores on a scale
STANDARD_DEVIATION 5.63 • n=4 Participants
|
27.0 Scores on a scale
STANDARD_DEVIATION 5.61 • n=27 Participants
|
PRIMARY outcome
Timeframe: Randomization (Week 8) to end of treatment (Week 16)Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.
A 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.
Outcome measures
| Measure |
TC-5214
n=151 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
n=157 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
|---|---|---|
|
Change in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Randomization to End of Treatment.
|
-12.7 units on a scale
Standard Error 0.80
|
-11.7 units on a scale
Standard Error 0.80
|
SECONDARY outcome
Timeframe: Randomization (Week 8) to end of treatment (Week 16)Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.
The percentage of patients with a ≥50% reduction from randomization (Week 8) in MADRS total score at end of treatment (Week 16) was calculated. MADRS is 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.
Outcome measures
| Measure |
TC-5214
n=151 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
n=157 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
|---|---|---|
|
Response in Depressive Symptoms of Major Depressive Disorder (MDD), Defined as a ≥50% Reduction From Randomization (Week 8) in MADRS Total Score at End of Treatment (Week 16)
|
42.0 percentage of participants analyzed
|
47.0 percentage of participants analyzed
|
SECONDARY outcome
Timeframe: Week 16Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.
The percentage of patients with a MADRS total score of ≤8 at end of treatment (Week 16) was calculated. MADRS is 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.
Outcome measures
| Measure |
TC-5214
n=151 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
n=157 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
|---|---|---|
|
Remission in Depressive Symptoms of MDD, Defined as MADRS Total Score of ≤8 at End of Treatment (Week 16)
|
30.5 percentage of participants analyzed
|
24.2 percentage of participants analyzed
|
SECONDARY outcome
Timeframe: Randomization (Week 8) to end of treatment (Week 16); Week 10, Week 12, Week 14, and Week 16Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.
The percentage of patients with a ≥50% reduction from randomization (Week 8) in MADRS total score and a MADRS total score of ≤12 at Week 10, Week 12, Week 14, and end of treatment (Week 16) was calculated. MADRS is 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.
Outcome measures
| Measure |
TC-5214
n=150 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
n=153 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
|---|---|---|
|
Early and Sustained Response, Defined as a ≥50% Reduction From Randomization (Week 8) in MADRS Total Score and a MADRS Total Score of ≤12 at Week 10, Week 12, Week 14, and End of Treatment (Week 16)
|
6.0 percentage of participants analyzed
|
3.9 percentage of participants analyzed
|
SECONDARY outcome
Timeframe: Randomization (Week 8) to end of treatment (Week 16); Week 12, Week 14, and Week 16Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.
The percentage of patients with a ≥50% reduction from randomization (Week 8) in MADRS total score and a MADRS total score of ≤12 at Week 12, Week 14, and end of treatment (Week 16) was calculated. MADRS is 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.
Outcome measures
| Measure |
TC-5214
n=148 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
n=152 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
|---|---|---|
|
Sustained Response, Defined as a ≥50% Reduction From Randomization (Week 8) in MADRS Total Score and a MADRS Total Score of ≤12 at Week 12, Week 14, and End of Treatment (Week 16)
|
14.2 percentage of patients analyzed
|
11.8 percentage of patients analyzed
|
SECONDARY outcome
Timeframe: Week 12, Week 14, Week 16Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.
The percentage of patients with a MADRS total score of ≤8 at Week 12, Week 14, and end of treatment (Week 16)was calculated. MADRS is 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.
Outcome measures
| Measure |
TC-5214
n=148 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
n=153 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
|---|---|---|
|
Sustained Remission, Defined as a MADRS Total Score of ≤8 at Week 12, Week 14, and End of Treatment (Week 16)
|
9.5 percentage of participants analyzed
|
6.5 percentage of participants analyzed
|
SECONDARY outcome
Timeframe: Randomization (Week 8) to end of treatment (Week 16)Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.
A 17-item, clinician-rated scale that assesses depressive symptoms. The HAMD-17 consists of 17 symptoms, each of which is rated from 0 to 2 or 0 to 4, where 0 is none/absent. The HAMD-17 total score is calculated as the sum of the 17 individual symptom scores; the total score can range from 0 to 52. Higher HAMD-17 scores indicate more severe depression.
Outcome measures
| Measure |
TC-5214
n=139 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
n=145 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
|---|---|---|
|
Change in Depressive Symptoms From Randomization (Week 8) to End of Treatment (Week 16) as Measured by Hamilton Rating Scale for Depression-17 Items (HAMD-17) Total Score
|
-9.7 units on a scale
Standard Error 0.96
|
-9.3 units on a scale
Standard Error 0.96
|
SECONDARY outcome
Timeframe: Randomization (Week 8) to end of treatment (Week 16)Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.
A 3-part, clinician-administered scale that rates the improvement or worsening of the patient's illness from randomization (baseline). Each item is scored on a 1 to 7 scale. Higher CGI-S scores indicate greater illness severity.
Outcome measures
| Measure |
TC-5214
n=151 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
n=157 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
|---|---|---|
|
Change in the Clinician-rated Global Outcome of Severity as Measured by the Clinical Global Impression-Severity (CGI-S) Score From Randomization (Week 8) to End of Treatment (Week 16)
|
-1.4 units on a scale
Standard Error 0.11
|
-1.3 units on a scale
Standard Error 0.11
|
SECONDARY outcome
Timeframe: Randomization (Week 8) to end of treatment (Week 16)Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.
A 3-part, clinician-administered scale that rates the improvement or worsening of the patient's illness from randomization (baseline). Each item is scored on a 1 to 7 scale. CGI-I scores \>4 indicate worsening, while scores \<4 indicate improvement.
Outcome measures
| Measure |
TC-5214
n=151 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
n=157 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
|---|---|---|
|
Response in the Clinical Global Impression-Improvement (CGI-I) Defined as CGI-I Rating of "Very Much Improved" or "Much Improved" From Randomization (Week 8) to End of Treatment (Week 16)
|
56.3 percentage of participants analyzed
|
51.0 percentage of participants analyzed
|
SECONDARY outcome
Timeframe: Randomization (Week 8) to Week 9Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.
A 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms. MADRS is 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.
Outcome measures
| Measure |
TC-5214
n=142 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
n=151 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
|---|---|---|
|
Change in MADRS Total Score From Randomization (Week 8) to Week 9
|
-3.6 units on a scale
Standard Error 0.45
|
-3.8 units on a scale
Standard Error 0.45
|
SECONDARY outcome
Timeframe: Randomization (Week 8) to Week 10Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.
A 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.
Outcome measures
| Measure |
TC-5214
n=147 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
n=146 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
|---|---|---|
|
Change in MADRS Total Score From Randomization (Week 8) to Week 10
|
-6.1 units on a scale
Standard Error 0.60
|
-6.8 units on a scale
Standard Error 0.60
|
SECONDARY outcome
Timeframe: Randomization (Week 8) to Week 12Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.
A 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.
Outcome measures
| Measure |
TC-5214
n=139 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
n=144 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
|---|---|---|
|
Change in MADRS Total Score From Randomization (Week 8) to Week 12
|
-8.7 units on a scale
Standard Error 0.68
|
-8.0 units on a scale
Standard Error 0.67
|
SECONDARY outcome
Timeframe: Randomization (Week 8) to Week 14Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.
A 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.
Outcome measures
| Measure |
TC-5214
n=133 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
n=136 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
|---|---|---|
|
Change in MADRS Total Score From Randomization (Week 8) to Week 14
|
-11.1 units on a scale
Standard Error 0.72
|
-10.5 units on a scale
Standard Error 0.72
|
SECONDARY outcome
Timeframe: Randomization (Week 8) to end of treatment (Week 16)Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.
Sheehan Disability Scale (SDS) is 5-item, self-administered scale that measures the extent a patient is impaired by their disease. Higher scores indicate more severe impairment. The SDS total score is calculated as the sum of the score for the 3 inter-correlated domains (school/work, social life, and family life/home responsibilities) and ranges from 0 (unimpaired) to 30 (highly impaired).
Outcome measures
| Measure |
TC-5214
n=143 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
n=151 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
|---|---|---|
|
Change in Functional Impairment From Randomization (Week 8) to End of Treatment (Week 16) as Measured by the Sheehan Disability Scale (SDS) Total Score
|
-6.09 units on a scale
Standard Error 0.696
|
-5.47 units on a scale
Standard Error 0.700
|
SECONDARY outcome
Timeframe: Randomization (Week 8) to end of treatment (Week 16)Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.
A 5-item, self-administered scale that measures the extent a patient is impaired by their disease. Higher scores indicate more severe impairment. The 3 inter-correlated domains are school/work, social life, and family life/home responsibilities. The numerical rating for the work/school domain score is 0- 10, where 10 is considered to be 'highly impaired'.
Outcome measures
| Measure |
TC-5214
n=124 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
n=134 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
|---|---|---|
|
Change in Functional Impairment From Randomization (Week 8) to End of Treatment (Week 16) as Measured by SDS Work/School Domain Score
|
-2.0 units on a scale
Standard Error 0.24
|
-1.7 units on a scale
Standard Error 0.24
|
SECONDARY outcome
Timeframe: Randomization (Week 8) to end of treatment (Week 16)Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.
A 5-item, self-administered scale that measures the extent a patient is impaired by their disease. Higher scores indicate more severe impairment. The 3 inter-correlated domains are school/work, social life, and family life/home responsibilities. The numerical rating for the SDS social life domain score is 0- 10, where 10 is considered to be 'highly impaired'.
Outcome measures
| Measure |
TC-5214
n=143 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
n=151 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
|---|---|---|
|
Change in Functional Impairment From Randomization (Week 8) to End of Treatment (Week 16) as Measured by SDS Social Life Domain Score
|
-1.9 units on a scale
Standard Error 0.24
|
-1.9 units on a scale
Standard Error 0.24
|
SECONDARY outcome
Timeframe: Randomization (Week 8) to end of treatment (Week 16)Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.
A 5-item, self-administered scale that measures the extent a patient is impaired by their disease. Higher scores indicate more severe impairment. The 3 inter-correlated domains are school/work, social life, and family life/home responsibilities. The numerical rating for the SDS family life/home responsibilities domain score is 0- 10, where 10 is considered to be 'highly impaired'.
Outcome measures
| Measure |
TC-5214
n=143 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
n=151 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
|---|---|---|
|
Change in Functional Impairment From Randomization (Week 8) to End of Treatment (Week 16) as Measured by SDS Family Life/Home Responsibilities Domain Score
|
-2.1 units on a scale
Standard Error 0.28
|
-2.0 units on a scale
Standard Error 0.28
|
SECONDARY outcome
Timeframe: Randomization (Week 8) to end of treatment (Week 16)Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.
The Q-LES-Q-SF (Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form)total score is derived by summing item scores 1 to 14. Higher scores are indicative of greater enjoyment or satisfaction in each domain. The Q-LES-Q-SF % maximum total score is calculated as 100% × (Q-LES-Q-SF total score - 14) / 56, and can range from 0% to 100%.
Outcome measures
| Measure |
TC-5214
n=141 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
n=148 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
|---|---|---|
|
Change in Overall Quality of Life and Satisfaction From Randomization (Week 8) to End of Treatment (Week 16) by Assessing the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) % Maximum Total Score
|
12.47 units on a scale
Standard Error 1.736
|
11.65 units on a scale
Standard Error 1.738
|
SECONDARY outcome
Timeframe: Randomization (Week 8) to end of treatment (Week 16)Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.
The Q-LES-Q-SF (Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form) measures the patient's satisfaction with medication and overall quality of life. The 15th item queries respondents' satisfaction with the medication they are taking, rated on a 1 to 4 scale, score 0 indicates that no medication was taken. Higher scores are indicative of greater satisfaction.
Outcome measures
| Measure |
TC-5214
n=123 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
n=126 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
|---|---|---|
|
Change From Randomization (Week 8) to End of Treatment (Week 16) in Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q LES-Q-SF) Item 15
|
0.2 units on a scale
Standard Error 0.08
|
0.3 units on a scale
Standard Error 0.08
|
SECONDARY outcome
Timeframe: Randomization (Week 8) to end of treatment (Week 16)Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.
The Q-LES-Q-SF (Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form) measures the patient's satisfaction with medication and overall quality of life. The 16th item is a global rating of overall life satisfaction and contentment, rated on a 1 to 5 scale. Higher scores are indicative of greater satisfaction.
Outcome measures
| Measure |
TC-5214
n=140 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
n=148 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
|---|---|---|
|
Change From Randomization (Week 8) to End of Treatment (Week 16) in Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q LES-Q-SF) Item 16
|
0.7 units on a scale
Standard Error 0.08
|
0.5 units on a scale
Standard Error 0.08
|
SECONDARY outcome
Timeframe: Randomization (Week 8) to end of treatment (Week 16)Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.
A self-administered scale to be used by clinical subjects to rate suffering over the past week with regard to irritability symptoms. The total SIS score is the sum of 7 items, and ranges from 0 to 70. Each item is assessed on an 11-point scale where 0=not at all, 1-3=mildly, 4-6=moderately, 7-9=markedly, and 10=extremely. The SIS also records the number of days impaired by irritability.
Outcome measures
| Measure |
TC-5214
n=144 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
n=151 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
|---|---|---|
|
Change in Irritability Symptoms as Measured by the Sheehan Irritability Scale (SIS) Total Score From Randomization (Week 8) to End of Treatment (Week 16)
|
-12.6 units on a scale
Standard Error 1.96
|
-11.5 units on a scale
Standard Error 1.97
|
SECONDARY outcome
Timeframe: Randomization (Week 8) to end of treatment (Week 16)Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.
A self-assessment questionnaire that provides 2 measures of health status. The EQ-5D index score is a weighted linear combination over 5 dimensions of health status. The score for each of the 5 dimensions can range from 1 to 3, and an equation is used to calculate the EQ-5D index score. The EQ-5D index score can range from possible negative values (minimum -0.415) to a maximum of 1.0. The EQ-VAS is a visual analog scale with a range of 0 to 100. For both variables, a higher score indicates a better health state.
Outcome measures
| Measure |
TC-5214
n=144 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
n=151 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
|---|---|---|
|
Change in EuroQol - 5 Dimensions (EQ-5D) From Randomization (Week 8) to End of Treatment (Week 16)
EQ-5D index score
|
0.113 units on a scale
Standard Error 0.0199
|
0.089 units on a scale
Standard Error 0.0199
|
|
Change in EuroQol - 5 Dimensions (EQ-5D) From Randomization (Week 8) to End of Treatment (Week 16)
EQ-5D VAS score
|
13.3 units on a scale
Standard Error 2.03
|
11.6 units on a scale
Standard Error 2.03
|
Adverse Events
TC-5214
Placebo
Serious adverse events
| Measure |
TC-5214
n=157 participants at risk
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
n=159 participants at risk
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
|---|---|---|
|
Nervous system disorders
Headache
|
0.64%
1/157 • Number of events 1
|
0.00%
0/159
|
Other adverse events
| Measure |
TC-5214
n=157 participants at risk
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
|
Placebo
n=159 participants at risk
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
|
|---|---|---|
|
Nervous system disorders
Headache
|
12.1%
19/157 • Number of events 22
|
10.7%
17/159 • Number of events 17
|
|
Gastrointestinal disorders
Constipation
|
12.1%
19/157 • Number of events 19
|
6.3%
10/159 • Number of events 12
|
|
Gastrointestinal disorders
Nausea
|
7.6%
12/157 • Number of events 13
|
3.8%
6/159 • Number of events 6
|
|
Gastrointestinal disorders
Dry Mouth
|
4.5%
7/157 • Number of events 7
|
3.8%
6/159 • Number of events 6
|
|
Vascular disorders
Orthostatic Hypotension
|
3.8%
6/157 • Number of events 7
|
3.1%
5/159 • Number of events 10
|
|
Nervous system disorders
Dizziness
|
4.5%
7/157 • Number of events 9
|
8.2%
13/159 • Number of events 18
|
|
Nervous system disorders
Somnolence
|
4.5%
7/157 • Number of events 7
|
5.0%
8/159 • Number of events 8
|
|
Gastrointestinal disorders
Diarrhoea
|
9.6%
15/157 • Number of events 18
|
6.3%
10/159 • Number of events 10
|
|
General disorders
Fatigue
|
5.7%
9/157 • Number of events 9
|
4.4%
7/159 • Number of events 7
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
1.9%
3/157 • Number of events 3
|
2.5%
4/159 • Number of events 4
|
|
Infections and infestations
Nasopharyngitis
|
1.9%
3/157 • Number of events 3
|
3.8%
6/159 • Number of events 8
|
|
Nervous system disorders
Tremor
|
0.00%
0/157
|
2.5%
4/159 • Number of events 5
|
|
Psychiatric disorders
Insomnia
|
3.2%
5/157 • Number of events 5
|
6.3%
10/159 • Number of events 12
|
|
Nervous system disorders
Dizziness postural
|
1.3%
2/157 • Number of events 2
|
3.1%
5/159 • Number of events 7
|
|
Psychiatric disorders
Anxiety
|
2.5%
4/157 • Number of events 4
|
1.3%
2/159 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
2.5%
4/157 • Number of events 4
|
1.9%
3/159 • Number of events 3
|
|
Infections and infestations
Upper respiratory tract infection
|
5.1%
8/157 • Number of events 9
|
3.1%
5/159 • Number of events 5
|
|
Investigations
Weight increased
|
3.2%
5/157 • Number of events 5
|
1.9%
3/159 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
0.64%
1/157 • Number of events 1
|
2.5%
4/159 • Number of events 5
|
|
Psychiatric disorders
Abnormal dreams
|
3.8%
6/157 • Number of events 6
|
5.0%
8/159 • Number of events 8
|
|
Psychiatric disorders
Agitation
|
1.3%
2/157 • Number of events 2
|
2.5%
4/159 • Number of events 5
|
|
Psychiatric disorders
Nightmare
|
1.3%
2/157 • Number of events 2
|
2.5%
4/159 • Number of events 4
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60