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A Study to Assess the Efficacy and Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder.

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ClinicalTrials.gov Identifier: NCT01197508
Recruitment Status : Completed
First Posted : September 9, 2010
Results First Posted : October 29, 2012
Last Update Posted : April 11, 2014
Sponsor:
Collaborator:
Targacept Inc.
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Drug: TC-5214
Drug: Placebo
Enrollment 696
Recruitment Details This multicenter study was conducted in Europe, South Africa, and Latin America between 1 September 2010 and 30 January 2012.
Pre-assignment Details 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).
Arm/Group Title 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214 Placebo
Hide Arm/Group Description Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Period Title: Overall Study
Started 174 174 174 174
Received Treatment 174 174 171 174
Completed 151 144 125 158
Not Completed 23 30 49 16
Reason Not Completed
Withdrawal by Subject             8             7             15             4
Eligiblity criteria not fulfilled             0             0             2             0
Adverse Event             10             13             23             3
Severe non-compliance to protocol             0             3             1             3
Condition under investigation worsened             1             1             1             1
Lack of Efficacy             1             2             2             1
Study-specific withdrawal criteria             0             0             1             2
Lost to Follow-up             1             1             2             0
Not specified             2             3             2             2
Arm/Group Title 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214 Placebo Total
Hide Arm/Group Description Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID Total of all reporting groups
Overall Number of Baseline Participants 174 174 174 174 696
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 174 participants 174 participants 174 participants 174 participants 696 participants
46.0  (10.66) 45.0  (11.72) 45.6  (10.72) 45.8  (11.75) 45.6  (11.21)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 174 participants 174 participants 174 participants 174 participants 696 participants
Female
127
  73.0%
125
  71.8%
117
  67.2%
129
  74.1%
498
  71.6%
Male
47
  27.0%
49
  28.2%
57
  32.8%
45
  25.9%
198
  28.4%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 174 participants 174 participants 174 participants 174 participants 696 participants
White 161 156 157 158 632
Black or African American 2 3 1 2 8
Asian 0 1 0 1 2
Native Hawaiian or other Pacific Islander 0 0 0 0 0
American Indian or Alaska Native 0 1 0 0 1
Other 11 13 16 13 53
Hamilton Rating Scale for Depression-17 items (HAMD-17) total score at randomization   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 174 participants 174 participants 174 participants 174 participants 696 participants
21.49  (3.587) 20.98  (3.182) 21.50  (3.674) 21.26  (3.614) 21.30  (3.517)
[1]
Measure Description: 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.
Montgomery-Asberg Depression Rating Scale (MADRS) total score at randomization   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 174 participants 174 participants 174 participants 174 participants 696 participants
24.69  (5.086) 24.67  (5.389) 25.03  (5.137) 24.11  (4.992) 24.62  (5.152)
[1]
Measure Description: 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.
1.Primary Outcome
Title Change in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Randomization to End of Treatment.
Hide Description 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.
Time Frame Randomization (Week 8) to end of treatment (Week 16)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 173 174 170 174
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-11.6  (0.65) -12.2  (0.66) -12.2  (0.69) -12.7  (0.65)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.1 mg BID TC-5214, Placebo
Comments Mixed model repeated measures (MMRM) includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization MADRS total score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments The adjusted p-value protects the overall family-wise error rate by taking into account the multiple comparisons between the TC-5214 doses for both the primary efficacy variable (MADRS) and the key secondary efficacy variable (SDS).
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 1.1
Confidence Interval (2-Sided) 95%
-0.53 to 2.79
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.84
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 mg BID TC-5214, Placebo
Comments Mixed model repeated measures (MMRM) includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization MADRS total score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-1.22 to 2.13
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.85
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg BID TC-5214, Placebo
Comments Mixed model repeated measures (MMRM) includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization MADRS total score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-1.21 to 2.22
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.88
Estimation Comments [Not Specified]
2.Secondary Outcome
Title 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)
Hide Description

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.

Time Frame Randomization (Week 8) to end of treatment (Week 16)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 173 174 170 174
Measure Type: Number
Unit of Measure: percentage of participants analyzed
48.6 51.1 41.2 54.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.1 mg BID TC-5214, Placebo
Comments Logistic regression model including treatment and pooled center as fixed effects and the randomization MADRS total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.144
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.45 to 1.12
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.17
Estimation Comments TC-5214 is the numerator in the OR, OR>1 represents a result in favor of TC-5214.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 mg BID TC-5214, Placebo
Comments Logistic regression model including treatment and pooled center as fixed effects and the randomization MADRS total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.203
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.47 to 1.17
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.17
Estimation Comments TC-5214 is the numerator in the OR, OR>1 represents a result in favor of TC-5214.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg BID TC-5214, Placebo
Comments Logistic regression model including treatment and pooled center as fixed effects and the randomization MADRS total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.52
Confidence Interval (2-Sided) 95%
0.32 to 0.82
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.12
Estimation Comments TC-5214 is the numerator in the OR, OR>1 represents a result in favor of TC-5214.
3.Secondary Outcome
Title Remission in Depressive Symptoms of MDD, Defined as MADRS Total Score of ≤8 at End of Treatment (Week 16)
Hide Description

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.

Time Frame Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 173 174 170 174
Measure Type: Number
Unit of Measure: percentage of participants analyzed
37.0 35.1 30.0 39.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.1 mg BID TC-5214, Placebo
Comments Logistic regression model including treatment and pooled center as fixed effects and the randomization MADRS total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.636
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.54 to 1.45
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.22
Estimation Comments TC-5214 is the numerator in the OR, OR>1 represents a result in favor of TC-5214.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 mg BID TC-5214, Placebo
Comments Logistic regression model including treatment and pooled center as fixed effects and the randomization MADRS total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.215
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.44 to 1.20
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.19
Estimation Comments TC-5214 is the numerator in the OR, OR>1 represents a result in favor of TC-5214.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg BID TC-5214, Placebo
Comments Logistic regression model including treatment and pooled center as fixed effects and the randomization MADRS total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.034
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
0.35 to 0.96
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.15
Estimation Comments TC-5214 is the numerator in the OR, OR>1 represents a result in favor of TC-5214.
4.Secondary Outcome
Title 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)
Hide Description

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.

Time Frame Randomization (Week 8) to end of treatment (Week 16); Week 10, Week 12, Week 14, and Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 173 173 166 173
Measure Type: Number
Unit of Measure: percentage of participants analyzed
7.5 8.1 9.6 9.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.1 mg BID TC-5214, Placebo
Comments Logistic regression model including treatment and pooled center as fixed effects and the randomization MADRS total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.711
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.36 to 1.99
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.37
Estimation Comments TC-5214 is the numerator in the OR, OR>1 represents a result in favor of TC-5214.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 mg BID TC-5214, Placebo
Comments Logistic regression model including treatment and pooled center as fixed effects and the randomization MADRS total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.594
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.34 to 1.85
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.34
Estimation Comments TC-5214 is the numerator in the OR, OR>1 represents a result in favor of TC-5214.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg BID TC-5214, Placebo
Comments Logistic regression model including treatment and pooled center as fixed effects and the randomization MADRS total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.749
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.15
Confidence Interval (2-Sided) 95%
0.50 to 2.65
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.49
Estimation Comments TC-5214 is the numerator in the OR, OR>1 represents a result in favor of TC-5214.
5.Secondary Outcome
Title 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)
Hide Description

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.

Time Frame Randomization (Week 8) to end of treatment (Week 16); Week 12, Week 14, and Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 170 171 163 173
Measure Type: Number
Unit of Measure: percentage of patients analyzed
14.7 19.3 15.3 23.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.1 mg BID TC-5214, Placebo
Comments Logistic regression model including treatment and pooled center as fixed effects and the randomization MADRS total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.037
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.52
Confidence Interval (2-Sided) 95%
0.28 to 0.96
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.16
Estimation Comments TC-5214 is the numerator in the OR, OR>1 represents a result in favor of TC-5214.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 mg BID TC-5214, Placebo
Comments Logistic regression model including treatment and pooled center as fixed effects and the randomization MADRS total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.222
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
0.38 to 1.25
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.21
Estimation Comments TC-5214 is the numerator in the OR, OR>1 represents a result in favor of TC-5214.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg BID TC-5214, Placebo
Comments Logistic regression model including treatment and pooled center as fixed effects and the randomization MADRS total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.042
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.52
Confidence Interval (2-Sided) 95%
0.28 to 0.98
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.17
Estimation Comments TC-5214 is the numerator in the OR, OR>1 represents a result in favor of TC-5214.
6.Secondary Outcome
Title Sustained Remission, Defined as a MADRS Total Score of ≤8 at Week 12, Week 14, and End of Treatment (Week 16)
Hide Description

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.

Time Frame Week 12, Week 14, Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 170 172 163 173
Measure Type: Number
Unit of Measure: percentage of participants analyzed
10.6 10.5 8.0 12.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.1 mg BID TC-5214, Placebo
Comments Logistic regression model including treatment and pooled center as fixed effects and the randomization MADRS total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.913
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.48 to 2.27
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.41
Estimation Comments TC-5214 is the numerator in the OR, OR>1 represents a result in favor of TC-5214.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 mg BID TC-5214, Placebo
Comments Logistic regression model including treatment and pooled center as fixed effects and the randomization MADRS total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.841
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.42 to 2.01
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.37
Estimation Comments TC-5214 is the numerator in the OR, OR>1 represents a result in favor of TC-5214.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg BID TC-5214, Placebo
Comments Logistic regression model including treatment and pooled center as fixed effects and the randomization MADRS total score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.239
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.26 to 1.39
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.26
Estimation Comments TC-5214 is the numerator in the OR, OR>1 represents a result in favor of TC-5214.
7.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Randomization (Week 8) to end of treatment (Week 16)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 165 161 162 170
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-10.07  (0.597) -10.21  (0.603) -9.07  (0.597) -11.16  (0.592)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.1 mg BID TC-5214, Placebo
Comments Analysis of covariance (ANCOVA) with randomization HAMD-17 total score as covariate, treatment as a fixed effect and pooled center as a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.120
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 1.10
Confidence Interval (2-Sided) 95%
-0.288 to 2.481
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.705
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 mg BID TC-5214, Placebo
Comments Analysis of covariance (ANCOVA) with randomization HAMD-17 total score as covariate, treatment as a fixed effect and pooled center as a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.184
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
-0.452 to 2.354
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.715
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg BID TC-5214, Placebo
Comments Analysis of covariance (ANCOVA) with randomization HAMD-17 total score as covariate, treatment as a fixed effect and pooled center as a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 2.09
Confidence Interval (2-Sided) 95%
0.692 to 3.484
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.711
Estimation Comments [Not Specified]
8.Secondary Outcome
Title 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)
Hide Description 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.
Time Frame Randomization (Week 8) to end of treatment (Week 16)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 173 174 170 174
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.5  (0.09) -1.6  (0.09) -1.7  (0.10) -1.7  (0.09)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.1 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit, and treatment by visit interaction as explanatory variables and the randomization CGI-S total score as a covariate. Treatment, visit, and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.131
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.2
Confidence Interval 95%
-0.05 to 0.42
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.12
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit, and treatment by visit interaction as explanatory variables and the randomization CGI-S total score as a covariate. Treatment, visit, and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.551
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.17 to 0.31
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.12
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit, and treatment by visit interaction as explanatory variables and the randomization CGI-S total score as a covariate. Treatment, visit, and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.645
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.19 to 0.30
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.12
Estimation Comments [Not Specified]
9.Secondary Outcome
Title 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)
Hide Description 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.
Time Frame Randomization (Week 8) to end of treatment (Week 16)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 173 174 170 174
Measure Type: Number
Unit of Measure: percentage of participants analyzed
59.5 62.1 58.8 67.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.1 mg BID TC-5214, Placebo
Comments Logistic regression model including treatment and pooled center as fixed effects and the randomization Clinical Global Impression Severity (CGI-S) as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.046
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
0.38 to 0.99
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.15
Estimation Comments TC-5214 is the numerator in the OR, OR>1 represents a result in favor of TC-5214.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 mg BID TC-5214, Placebo
Comments Logistic regression model including treatment and pooled center as fixed effects and the randomization Clinical Global Impression Severity (CGI-S) as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.051
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
0.38 to 1.00
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.15
Estimation Comments TC-5214 is the numerator in the OR, OR>1 represents a result in favor of TC-5214.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg BID TC-5214, Placebo
Comments Logistic regression model including treatment and pooled center as fixed effects and the randomization Clinical Global Impression Severity (CGI-S) as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.040
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.60
Confidence Interval (2-Sided) 95%
0.37 to 0.98
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.15
Estimation Comments TC-5214 is the numerator in the OR, OR>1 represents a result in favor of TC-5214.
10.Secondary Outcome
Title Change in Hamilton Anxiety Scale (HAM-A) Total Score From Randomization (Week 8) to End of Treatment (Week 16)
Hide Description A 14-item clinician-administered scale for the evaluation of anxiety symptoms. Each HAM-A item is rated on a 0 to 4 scale. Higher HAM-A scores indicate higher levels of anxiety.
Time Frame Randomization (Week 8) to end of treatment (Week 16)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 166 161 161 170
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-8.5  (0.58) -8.6  (0.59) -8.1  (0.58) -9.3  (0.58)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.1 mg BID TC-5214, Placebo
Comments An analysis of covariance (ANCOVA) with randomization HAM-A total score as covariate, treatment as a fixed effect and pooled center as a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.273
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
-0.58 to 2.03
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.66
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 mg BID TC-5214, Placebo
Comments An analysis of covariance (ANCOVA) with randomization HAM-A total score as covariate, treatment as a fixed effect and pooled center as a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.315
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
-0.65 to 2.00
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.67
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg BID TC-5214, Placebo
Comments An analysis of covariance (ANCOVA) with randomization HAM-A total score as covariate, treatment as a fixed effect and pooled center as a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.078
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 1.2
Confidence Interval (2-Sided) 95%
-0.13 to 2.51
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.67
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change in MADRS Total Score From Randomization (Week 8) to Week 9
Hide Description 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.
Time Frame Randomization (Week 8) to Week 9
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 167 162 164 168
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-3.0  (0.42) -3.0  (0.43) -2.6  (0.42) -3.2  (0.42)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.1 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization MADRS total score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.590
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.68 to 1.19
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.47
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization MADRS total score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.679
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.74 to 1.14
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.48
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization MADRS total score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.215
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.6
Confidence Interval (2-Sided) 95%
-0.35 to 1.53
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.48
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Change in MADRS Total Score From Randomization (Week 8) to Week 10
Hide Description 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.
Time Frame Randomization (Week 8) to Week 10
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 170 166 157 171
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-4.8  (0.50) -5.9  (0.50) -5.0  (0.51) -6.0  (0.50)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.1 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization MADRS total score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.052
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 1.2
Confidence Interval (2-Sided) 95%
-0.01 to 2.38
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.61
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization MADRS total score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.874
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-1.11 to 1.30
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.61
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization MADRS total score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.099
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 1.0
Confidence Interval (2-Sided) 95%
-0.19 to 2.24
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.62
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Change in MADRS Total Score From Randomization (Week 8) to Week 12
Hide Description 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.
Time Frame Randomization (Week 8) to Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 163 157 144 166
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-8.1  (0.55) -8.5  (0.56) -7.8  (0.57) -8.7  (0.55)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.1 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization MADRS total score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.394
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.6
Confidence Interval (2-Sided) 95%
-0.77 to 1.95
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.69
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization MADRS total score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.712
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-1.11 to 1.63
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.70
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization MADRS total score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.167
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 1.0
Confidence Interval (2-Sided) 95%
-0.41 to 2.38
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.71
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Change in MADRS Total Score From Randomization (Week 8) to Week 14
Hide Description 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.
Time Frame Randomization (Week 8) to Week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 159 149 131 164
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-9.5  (0.59) -10.6  (0.60) -9.6  (0.62) -11.0  (0.59)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.1 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization MADRS total score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.046
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 1.5
Confidence Interval (2-Sided) 95%
0.02 to 2.95
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.75
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization MADRS total score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.681
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-1.17 to 1.79
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.75
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization MADRS total score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.087
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
-0.19 to 2.84
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.77
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Change in Functional Impairment From Randomization (Week 8) to End of Treatment (Week 16) as Measured by the Sheehan Disability Scale (SDS) Total Score
Hide Description 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).
Time Frame Randomization (Week 8) to end of treatment (Week 16)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 171 168 163 172
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-6.08  (0.561) -6.34  (0.569) -6.21  (0.592) -7.06  (0.556)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.1 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit, and treatment by visit interaction as explanatory variables and the randomization SDS total score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments The adjusted p-value protects the overall family-wise error rate by taking into account the multiple comparisons between the TC-5214 doses for both the primary efficacy variable (MADRS) and the key secondary efficacy variable (SDS).
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
-0.464 to 2.427
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.736
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit, and treatment by visit interaction as explanatory variables and the randomization SDS total score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments The adjusted p-value protects the overall family-wise error rate by taking into account the multiple comparisons between the TC-5214 doses for both the primary efficacy variable (MADRS) and the key secondary efficacy variable (SDS).
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.72
Confidence Interval (2-Sided) 95%
-0.740 to 2.188
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.746
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit, and treatment by visit interaction as explanatory variables and the randomization SDS total score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments The adjusted p-value protects the overall family-wise error rate by taking into account the multiple comparisons between the TC-5214 doses for both the primary efficacy variable (MADRS) and the key secondary efficacy variable (SDS).
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
-0.649 to 2.346
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.762
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Change in Functional Impairment From Randomization (Week 8) to End of Treatment (Week 16) as Measured by SDS Work/School Domain Score
Hide Description 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'.
Time Frame Randomization (Week 8) to end of treatment (Week 16)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 141 140 126 137
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.0  (0.21) -1.8  (0.22) -1.9  (0.24) -2.1  (0.22)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.1 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization SDS work/school domain score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.914
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.54 to 0.61
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.29
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization SDS work/school domain score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.446
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.36 to 0.81
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.30
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization SDS work/school domain score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.656
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.47 to 0.75
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.31
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Change in Functional Impairment From Randomization (Week 8) to End of Treatment (Week 16) as Measured by SDS Social Life Domain Score
Hide Description 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'.
Time Frame Randomization (Week 8) to end of treatment (Week 16)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 171 168 163 172
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.1  (0.20) -2.2  (0.20) -2.2  (0.21) -2.4  (0.20)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.1 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization SDS social life domain score. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.248
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.21 to 0.82
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.26
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization SDS social life domain score. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.498
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.34 to 0.70
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.27
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization SDS social life domain score. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.441
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.32 to 0.74
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.27
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Change in Functional Impairment From Randomization (Week 8) to End of Treatment (Week 16) as Measured by SDS Family Life/Home Responsibilities Domain Score
Hide Description 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'.
Time Frame Randomization (Week 8) to end of treatment (Week 16)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 171 168 163 172
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.0  (0.20) -2.1  (0.20) -2.0  (0.21) -2.3  (0.20)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.1 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization SDS family life/home responsibilities domain score. Treatment, visit and treatment by visit interaction are effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.174
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.16 to 0.87
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.26
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization SDS family life/home responsibilities domain score. Treatment, visit and treatment by visit interaction are effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.402
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.30 to 0.74
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.27
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization SDS family life/home responsibilities domain score. Treatment, visit and treatment by visit interaction are effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.197
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.18 to 0.88
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.27
Estimation Comments [Not Specified]
19.Secondary Outcome
Title 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
Hide Description 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%.
Time Frame Randomization (Week 8) to end of treatment (Week 16)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 171 166 162 172
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
13.08  (1.388) 13.24  (1.402) 11.84  (1.409) 14.55  (1.391)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.1 mg BID TC-5214, Placebo
Comments ANCOVA with randomization Q-LES-Q-SF % maximum total score as covariate, treatment as a fixed effect and pooled center as a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.371
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -1.47
Confidence Interval (2-Sided) 95%
-4.697 to 1.756
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.643
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 mg BID TC-5214, Placebo
Comments ANCOVA with randomization Q-LES-Q-SF % maximum total score as covariate, treatment as a fixed effect and pooled center as a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.432
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -1.32
Confidence Interval (2-Sided) 95%
-4.597 to 1.967
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.672
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg BID TC-5214, Placebo
Comments ANCOVA with randomization Q-LES-Q-SF % maximum total score as covariate, treatment as a fixed effect and pooled center as a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.105
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -2.71
Confidence Interval (2-Sided) 95%
-5.992 to 0.573
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.672
Estimation Comments [Not Specified]
20.Secondary Outcome
Title 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
Hide Description 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. Higher scores are indicative of greater enjoyment or satisfaction in each domain.
Time Frame Randomization (Week 8) to end of treatment (Week 16)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 153 154 151 157
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.6  (0.08) 0.7  (0.08) 0.5  (0.08) 0.7  (0.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.1 mg BID TC-5214, Placebo
Comments An analysis of covariance (ANCOVA) with randomization Q-LES-Q-SF item 15 score as covariate, treatment as a fixed effect and pooled center as a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.312
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.29 to 0.09
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.10
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 mg BID TC-5214, Placebo
Comments An analysis of covariance (ANCOVA) with randomization Q-LES-Q-SF item 15 score as covariate, treatment as a fixed effect and pooled center as a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.885
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.18 to 0.21
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.10
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg BID TC-5214, Placebo
Comments An analysis of covariance (ANCOVA) with randomization Q-LES-Q-SF item 15 score as covariate, treatment as a fixed effect and pooled center as a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.067
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.37 to 0.01
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.10
Estimation Comments [Not Specified]
21.Secondary Outcome
Title 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
Hide Description 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. Higher scores are indicative of greater enjoyment or satisfaction in each domain.
Time Frame Randomization (Week 8) to end of treatment (Week 16)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 170 166 162 172
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.7  (0.08) 0.7  (0.08) 0.6  (0.08) 0.8  (0.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.1 mg BID TC-5214, Placebo
Comments An analysis of covariance (ANCOVA) with randomization Q-LES-Q-SF item 16 as a fixed effect and pooled center as a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.152
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.33 to 0.05
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.10
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 mg BID TC-5214, Placebo
Comments An analysis of covariance (ANCOVA) with randomization Q-LES-Q-SF item 16 as a fixed effect and pooled center as a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.078
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.37 to 0.02
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.10
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg BID TC-5214, Placebo
Comments An analysis of covariance (ANCOVA) with randomization Q-LES-Q-SF item 16 as a fixed effect and pooled center as a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.033
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.41 to -0.02
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.10
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Change in EuroQol - 5 Dimensions (EQ-5D) From Randomization (Week 8) to End of Treatment (Week 16)
Hide Description 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 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.
Time Frame Randomization (Week 8) to end of treatment (Week 16)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 171 168 163 172
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
EQ-5D index score 0.128  (0.0147) 0.139  (0.0149) 0.133  (0.0155) 0.139  (0.0146)
EQ-5D VAS score 16.4  (1.52) 17.0  (1.54) 15.9  (1.61) 18.7  (1.51)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.1 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization EQ-5D total score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.543
Comments Analysis for change in EQ-5D index score from randomization (Week 8) to end of treatment (Week 16)
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -0.011
Confidence Interval (2-Sided) 95%
-0.0465 to 0.0245
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0181
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization EQ-5D total score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.998
Comments Analysis for change in EQ-5D index score from randomization (Week 8) to end of treatment (Week 16)
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.000
Confidence Interval (2-Sided) 95%
-0.0360 to 0.0361
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0183
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization EQ-5D total score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.743
Comments Analysis for change in EQ-5D index score from randomization (Week 8) to end of treatment (Week 16)
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -0.006
Confidence Interval (2-Sided) 95%
-0.0432 to 0.0308
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0188
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 0.1 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization EQ-5D VAS total score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.244
Comments Analysis of change in EQ-5D VAS score from randomization (Week 8) to end of treatment (Week 16)
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -2.3
Confidence Interval (2-Sided) 95%
-6.10 to 1.56
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.95
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection 1 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization EQ-5D VAS total score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.389
Comments Analysis of change in EQ-5D VAS score from randomization (Week 8) to end of treatment (Week 16)
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -1.7
Confidence Interval (2-Sided) 95%
-5.59 to 2.18
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.98
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection 4 mg BID TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit and treatment by visit interaction as explanatory variables and the randomization EQ-5D VAS total score as a covariate. Treatment, visit and treatment by visit interaction are fixed effects in the model; pooled center is a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.165
Comments Analysis of change in EQ-5D VAS score from randomization (Week 8) to end of treatment (Week 16)
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -2.8
Confidence Interval (2-Sided) 95%
-6.79 to 1.16
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.02
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214
Hide Arm/Group Description Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
All-Cause Mortality
Placebo 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/174 (1.15%)      2/174 (1.15%)      4/174 (2.30%)      2/171 (1.17%)    
Gastrointestinal disorders         
Food Poisoning  1  0/174 (0.00%)  0 0/174 (0.00%)  0 1/174 (0.57%)  1 0/171 (0.00%)  0
Infections and infestations         
Pneumonia  1  0/174 (0.00%)  0 0/174 (0.00%)  0 1/174 (0.57%)  1 0/171 (0.00%)  0
Urinary Tract Infection  1  0/174 (0.00%)  0 0/174 (0.00%)  0 1/174 (0.57%)  1 0/171 (0.00%)  0
Injury, poisoning and procedural complications         
Toxicity To Various Agents  1  0/174 (0.00%)  0 1/174 (0.57%)  1 0/174 (0.00%)  0 0/171 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Cervix Carcinoma  1  1/174 (0.57%)  1 0/174 (0.00%)  0 0/174 (0.00%)  0 0/171 (0.00%)  0
Pregnancy, puerperium and perinatal conditions         
Abortion Spontaneous  1  1/174 (0.57%)  1 0/174 (0.00%)  0 0/174 (0.00%)  0 0/171 (0.00%)  0
Psychiatric disorders         
Depression  1  0/174 (0.00%)  0 0/174 (0.00%)  0 1/174 (0.57%)  1 0/171 (0.00%)  0
Suicidal Ideation  1  0/174 (0.00%)  0 0/174 (0.00%)  0 0/174 (0.00%)  0 2/171 (1.17%)  2
Suicide Attempt  1  0/174 (0.00%)  0 2/174 (1.15%)  2 1/174 (0.57%)  1 1/171 (0.58%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Placebo 0.1 mg BID TC-5214 1 mg BID TC-5214 4 mg BID TC-5214
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   64/174 (36.78%)      68/174 (39.08%)      72/174 (41.38%)      94/171 (54.97%)    
Ear and labyrinth disorders         
Vertigo  1  0/174 (0.00%)  0 1/174 (0.57%)  1 2/174 (1.15%)  2 6/171 (3.51%)  6
Gastrointestinal disorders         
Constipation  1  11/174 (6.32%)  11 13/174 (7.47%)  13 13/174 (7.47%)  14 34/171 (19.88%)  35
Dry Mouth  1  3/174 (1.72%)  4 5/174 (2.87%)  5 5/174 (2.87%)  5 18/171 (10.53%)  18
Diarrhoea  1  12/174 (6.90%)  13 1/174 (0.57%)  1 3/174 (1.72%)  4 3/171 (1.75%)  4
Nausea  1  9/174 (5.17%)  10 7/174 (4.02%)  8 6/174 (3.45%)  7 11/171 (6.43%)  11
Vomiting  1  3/174 (1.72%)  3 1/174 (0.57%)  1 2/174 (1.15%)  2 5/171 (2.92%)  5
Abdominal Pain Upper  1  4/174 (2.30%)  4 1/174 (0.57%)  1 4/174 (2.30%)  5 4/171 (2.34%)  4
General disorders         
Fatigue  1  4/174 (2.30%)  4 6/174 (3.45%)  6 10/174 (5.75%)  10 9/171 (5.26%)  9
Infections and infestations         
Influenza  1  8/174 (4.60%)  8 2/174 (1.15%)  2 6/174 (3.45%)  6 5/171 (2.92%)  5
Nasopharyngitis  1  5/174 (2.87%)  5 3/174 (1.72%)  4 1/174 (0.57%)  1 0/171 (0.00%)  0
Urinary Tract Infection  1  0/174 (0.00%)  0 2/174 (1.15%)  2 1/174 (0.57%)  2 5/171 (2.92%)  6
Alanine Aminotransferase Increased  1  0/174 (0.00%)  0 1/174 (0.57%)  1 4/174 (2.30%)  4 2/171 (1.17%)  3
Metabolism and nutrition disorders         
Increased Appetite  1  0/174 (0.00%)  0 1/174 (0.57%)  1 4/174 (2.30%)  4 0/171 (0.00%)  0
Nervous system disorders         
Headache  1  23/174 (13.22%)  27 22/174 (12.64%)  27 24/174 (13.79%)  41 17/171 (9.94%)  17
Dizziness  1  7/174 (4.02%)  9 9/174 (5.17%)  9 13/174 (7.47%)  13 13/171 (7.60%)  14
Somnolence  1  5/174 (2.87%)  5 5/174 (2.87%)  5 7/174 (4.02%)  7 9/171 (5.26%)  10
Dysgeusia  1  0/174 (0.00%)  0 1/174 (0.57%)  1 1/174 (0.57%)  1 4/171 (2.34%)  4
Psychiatric disorders         
Insomnia  1  1/174 (0.57%)  1 6/174 (3.45%)  6 9/174 (5.17%)  11 7/171 (4.09%)  8
Agitation  1  4/174 (2.30%)  4 3/174 (1.72%)  3 3/174 (1.72%)  3 5/171 (2.92%)  5
Nervousness  1  0/174 (0.00%)  0 0/174 (0.00%)  0 4/174 (2.30%)  4 1/171 (0.58%)  1
Nightmare  1  2/174 (1.15%)  2 4/174 (2.30%)  4 1/174 (0.57%)  1 4/171 (2.34%)  4
Skin and subcutaneous tissue disorders         
Hyperhidrosis  1  1/174 (0.57%)  1 5/174 (2.87%)  5 4/174 (2.30%)  4 7/171 (4.09%)  9
Pruritus  1  4/174 (2.30%)  5 0/174 (0.00%)  0 0/174 (0.00%)  0 0/171 (0.00%)  0
Vascular disorders         
Orthostatic Hypotension  1  1/174 (0.57%)  1 1/174 (0.57%)  1 0/174 (0.00%)  0 8/171 (4.68%)  11
Hypotension  1  0/174 (0.00%)  0 1/174 (0.57%)  1 0/174 (0.00%)  0 6/171 (3.51%)  6
Hypertension  1  2/174 (1.15%)  2 2/174 (1.15%)  3 3/174 (1.72%)  3 4/171 (2.34%)  4
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
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: Gerard Lynch
Organization: AstraZeneca
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01197508     History of Changes
Other Study ID Numbers: D4130C00005
First Submitted: September 8, 2010
First Posted: September 9, 2010
Results First Submitted: June 26, 2012
Results First Posted: October 29, 2012
Last Update Posted: April 11, 2014