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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 (MDD)

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ClinicalTrials.gov Identifier: NCT01157078
Recruitment Status : Completed
First Posted : July 5, 2010
Results First Posted : November 20, 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
Conditions Major Depressive Disorder
Depression
Interventions Drug: TC-5214
Drug: Placebo
Enrollment 319
Recruitment Details This multicenter study was conducted in the United States and India between 22 June 2010 and 17 November 2011.
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 TC-5214 Placebo
Hide Arm/Group Description Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Period Title: Overall Study
Started 159 160
Received Treatment 157 159
Completed 124 124
Not Completed 35 36
Reason Not Completed
Withdrawal by Subject             12             14
Eligibility criteria not fulfilled             2             0
Adverse Event             6             6
Severe non-compliance to protocol             2             4
Condition under investigation worsened             0             1
Lack of Efficacy             2             0
Study-specific withdrawal criteria             2             2
Lost to Follow-up             7             5
Not specified             2             4
Arm/Group Title TC-5214 Placebo Total
Hide Arm/Group Description Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID Total of all reporting groups
Overall Number of Baseline Participants 159 160 319
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 159 participants 160 participants 319 participants
39.7  (11.37) 41.0  (11.53) 40.4  (11.45)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 159 participants 160 participants 319 participants
Female
101
  63.5%
99
  61.9%
200
  62.7%
Male
58
  36.5%
61
  38.1%
119
  37.3%
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 159 participants 160 participants 319 participants
White 99 100 199
Black or African American 11 19 30
Asian 48 37 85
Native Hawaiian or other Pacific Islander 0 0 0
American Indian or Alaska Native 0 1 1
Other 1 3 4
[1]
Measure Description: Race
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 159 participants 160 participants 319 participants
22.0  (4.13) 21.1  (3.81) 21.5  (3.98)
[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 159 participants 160 participants 319 participants
27.4  (5.58) 26.6  (5.63) 27.0  (5.61)
[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)
Hide 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 TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 151 157
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-12.7  (0.80) -11.7  (0.80)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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 0.349
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 -1.0
Confidence Interval (2-Sided) 95%
-3.14 to 1.11
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.08
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)
Hide 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 TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 151 157
Measure Type: Number
Unit of Measure: percentage of participants analyzed
42.0 47.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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 0.444
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.20
Confidence Interval (2-Sided) 95%
0.75 to 1.92
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.29
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
Hide 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 TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 151 157
Measure Type: Number
Unit of Measure: percentage of participants analyzed
30.5 24.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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 0.130
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.52
Confidence Interval (2-Sided) 95%
0.88 to 2.61
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.42
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
Hide 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 TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 150 153
Measure Type: Number
Unit of Measure: percentage of participants analyzed
6.0 3.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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 0.307
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.75
Confidence Interval (2-Sided) 95%
0.60 to 5.14
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.96
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
Hide 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 TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 148 152
Measure Type: Number
Unit of Measure: percentage of patients analyzed
14.2 11.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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 0.313
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.44
Confidence Interval (2-Sided) 95%
0.71 to 2.94
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.52
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
Hide 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 TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 148 153
Measure Type: Number
Unit of Measure: percentage of participants analyzed
9.5 6.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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 0.201
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.77
Confidence Interval (2-Sided) 95%
0.74 to 4.24
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.79
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)
Hide 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 TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 139 145
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-9.7  (0.96) -9.3  (0.96)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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 0.552
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-2.10 to 1.12
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.82
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)
Hide 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 TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 151 157
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.4  (0.11) -1.3  (0.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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 0.803
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.0
Confidence Interval 95%
-0.31 to 0.24
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.14
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)
Hide 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 TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 151 157
Measure Type: Number
Unit of Measure: percentage of participants analyzed
56.3 51.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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 0.440
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.20
Confidence Interval (2-Sided) 95%
0.75 to 1.91
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.28
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 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.

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 Week 9
Hide 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 TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 142 151
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-3.6  (0.45) -3.8  (0.45)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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 0.768
Comments Analysis for change in MADRS total score from randomization to Week 9.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.91 to 1.23
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.55
Estimation Comments [Not Specified]
11.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
Hide 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 TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 147 146
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-6.1  (0.60) -6.8  (0.60)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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 0.373
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
-0.84 to 2.24
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.78
Estimation Comments [Not Specified]
12.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
Hide 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 TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 139 144
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-8.7  (0.68) -8.0  (0.67)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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 0.435
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-2.47 to 1.07
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.90
Estimation Comments [Not Specified]
13.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
Hide 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 TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 133 136
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-11.1  (0.72) -10.5  (0.72)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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 0.501
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-2.56 to 1.25
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.97
Estimation Comments [Not Specified]
14.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)
Hide 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 TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 143 151
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-6.09  (0.696) -5.47  (0.700)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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 0.424
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 -0.62
Confidence Interval (2-Sided) 95%
-2.134 to 0.901
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.771
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 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)
Hide 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 TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 124 134
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.0  (0.24) -1.7  (0.24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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 0.214
Comments Analysis for change in SDS work/school domain 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 -0.4
Confidence Interval (2-Sided) 95%
-0.96 to 0.22
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.30
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 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)
Hide 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 TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 143 151
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.9  (0.24) -1.9  (0.24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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 0.931
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.59 to 0.54
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.29
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 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)
Hide 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 TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 143 151
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.1  (0.28) -2.0  (0.28)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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 0.755
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.60 to 0.44
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.26
Estimation Comments [Not Specified]
18.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)
Hide 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 TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 141 148
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
12.47  (1.736) 11.65  (1.738)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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 0.646
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
-2.699 to 4.346
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.789
Estimation Comments [Not Specified]
19.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, rated on a 1 to 4 scale, score 0 indicates that no medication was taken. Higher scores are indicative of greater satisfaction.

Time Frame Randomization (Week 8) to end of treatment (Week 16)
Hide 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 TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 123 126
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.2  (0.08) 0.3  (0.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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 0.446
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.31 to 0.14
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.12
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 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, rated on a 1 to 5 scale. Higher scores are indicative of greater satisfaction.

Time Frame Randomization (Week 8) to end of treatment (Week 16)
Hide 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 TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 140 148
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.7  (0.08) 0.5  (0.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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 0.178
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.06 to 0.33
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.10
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Change in Irritability Symptoms as Measured by the Sheehan Irritability Scale (SIS) Total Score From Randomization (Week 8) to End of Treatment (Week 16)
Hide Description A self-administered scale to be used by clinical subjects to rate suffering over the past week with regard to irritability symptoms. The total SIS score is the sum of 7 items, and ranges from 0 to 70. Each item is assessed on an 11-point scale where 0=not at all, 1-3=mildly, 4-6=moderately, 7-9=markedly, and 10=extremely. The SIS also records the number of days impaired by irritability.
Time Frame Randomization (Week 8) to end of treatment (Week 16)
Hide 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 TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 144 151
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-12.6  (1.96) -11.5  (1.97)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TC-5214, Placebo
Comments MMRM model includes treatment, pooled center, visit, and treatment by visit interaction as explanatory variables and the randomization SIS 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 0.515
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-4.22 to 2.12
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.61
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 (minimum -0.415) to a maximum of 1.0. The EQ-VAS is a visual analog scale with a range of 0 to 100. For both variables, a higher score indicates a better health state.
Time Frame Randomization (Week 8) to end of treatment (Week 16)
Hide 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 TC-5214 Placebo
Hide Arm/Group Description:
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Number of Participants Analyzed 144 151
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
EQ-5D index score 0.113  (0.0199) 0.089  (0.0199)
EQ-5D VAS score 13.3  (2.03) 11.6  (2.03)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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 0.298
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 0.024
Confidence Interval (2-Sided) 95%
-0.0209 to 0.0680
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0226
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 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 0.484
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 1.6
Confidence Interval (2-Sided) 95%
-2.98 to 6.26
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.34
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title TC-5214 Placebo
Hide Arm/Group Description Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
All-Cause Mortality
TC-5214 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
TC-5214 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/157 (0.64%)      0/159 (0.00%)    
Nervous system disorders     
Headache  1  1/157 (0.64%)  1 0/159 (0.00%)  0
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%
TC-5214 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   80/157 (50.96%)      77/159 (48.43%)    
Gastrointestinal disorders     
Constipation  1  19/157 (12.10%)  19 10/159 (6.29%)  12
Nausea  1  12/157 (7.64%)  13 6/159 (3.77%)  6
Dry Mouth  1  7/157 (4.46%)  7 6/159 (3.77%)  6
Diarrhoea  1  15/157 (9.55%)  18 10/159 (6.29%)  10
Vomiting  1  4/157 (2.55%)  4 3/159 (1.89%)  3
General disorders     
Fatigue  1  9/157 (5.73%)  9 7/159 (4.40%)  7
Infections and infestations     
Nasopharyngitis  1  3/157 (1.91%)  3 6/159 (3.77%)  8
Upper respiratory tract infection  1  8/157 (5.10%)  9 5/159 (3.14%)  5
Investigations     
Weight increased  1  5/157 (3.18%)  5 3/159 (1.89%)  3
Musculoskeletal and connective tissue disorders     
Musculoskeletal stiffness  1  1/157 (0.64%)  1 4/159 (2.52%)  5
Nervous system disorders     
Headache  1  19/157 (12.10%)  22 17/159 (10.69%)  17
Dizziness  1  7/157 (4.46%)  9 13/159 (8.18%)  18
Somnolence  1  7/157 (4.46%)  7 8/159 (5.03%)  8
Tremor  1  0/157 (0.00%)  0 4/159 (2.52%)  5
Dizziness postural  1  2/157 (1.27%)  2 5/159 (3.14%)  7
Psychiatric disorders     
Insomnia  1  5/157 (3.18%)  5 10/159 (6.29%)  12
Anxiety  1  4/157 (2.55%)  4 2/159 (1.26%)  2
Abnormal dreams  1  6/157 (3.82%)  6 8/159 (5.03%)  8
Agitation  1  2/157 (1.27%)  2 4/159 (2.52%)  5
Nightmare  1  2/157 (1.27%)  2 4/159 (2.52%)  4
Skin and subcutaneous tissue disorders     
Hyperhidrosis  1  3/157 (1.91%)  3 4/159 (2.52%)  4
Vascular disorders     
Orthostatic Hypotension  1  6/157 (3.82%)  7 5/159 (3.14%)  10
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
Layout table for Results Point of Contact information
Name/Title: Gerard Lynch
Organization: AstraZeneca
EMail: aztrial_results_posting@astrazeneca.com
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01157078     History of Changes
Other Study ID Numbers: D4130C00002
First Submitted: June 24, 2010
First Posted: July 5, 2010
Results First Submitted: June 26, 2012
Results First Posted: November 20, 2012
Last Update Posted: April 11, 2014