Trial Outcomes & Findings for A Study to Assess the Efficacy and Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder. (NCT NCT01197508)

NCT ID: NCT01197508

Last Updated: 2014-04-11

Results Overview

A 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

696 participants

Primary outcome timeframe

Randomization (Week 8) to end of treatment (Week 16)

Results posted on

2014-04-11

Participant Flow

This multicenter study was conducted in Europe, South Africa, and Latin America between 1 September 2010 and 30 January 2012.

The study had an up to 21-day screening/washout period, and an 8-week prospective open-label antidepressant treatment (ADT) period to identify the target patient population of inadequate responders to ADT (\<50% reduction in HAMD-17 total score during the prospective open-label ADT period, a HAMD-17 total score of ≥16 and a CGI-S score ≥4).

Participant milestones

Participant milestones
Measure
0.1 mg BID TC-5214
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Study
STARTED
174
174
174
174
Overall Study
Received Treatment
174
174
171
174
Overall Study
COMPLETED
151
144
125
158
Overall Study
NOT COMPLETED
23
30
49
16

Reasons for withdrawal

Reasons for withdrawal
Measure
0.1 mg BID TC-5214
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Study
Withdrawal by Subject
8
7
15
4
Overall Study
Eligiblity criteria not fulfilled
0
0
2
0
Overall Study
Adverse Event
10
13
23
3
Overall Study
Severe non-compliance to protocol
0
3
1
3
Overall Study
Condition under investigation worsened
1
1
1
1
Overall Study
Lack of Efficacy
1
2
2
1
Overall Study
Study-specific withdrawal criteria
0
0
1
2
Overall Study
Lost to Follow-up
1
1
2
0
Overall Study
Other
2
3
2
2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
0.1 mg BID TC-5214
n=174 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
n=174 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
n=174 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo
n=174 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Total
n=696 Participants
Total of all reporting groups
Age, Continuous
46.0 years
STANDARD_DEVIATION 10.66 • n=99 Participants
45.0 years
STANDARD_DEVIATION 11.72 • n=107 Participants
45.6 years
STANDARD_DEVIATION 10.72 • n=206 Participants
45.8 years
STANDARD_DEVIATION 11.75 • n=7 Participants
45.6 years
STANDARD_DEVIATION 11.21 • n=31 Participants
Sex: Female, Male
Female
127 Participants
n=99 Participants
125 Participants
n=107 Participants
117 Participants
n=206 Participants
129 Participants
n=7 Participants
498 Participants
n=31 Participants
Sex: Female, Male
Male
47 Participants
n=99 Participants
49 Participants
n=107 Participants
57 Participants
n=206 Participants
45 Participants
n=7 Participants
198 Participants
n=31 Participants
Race/Ethnicity, Customized
White
161 participants
n=99 Participants
156 participants
n=107 Participants
157 participants
n=206 Participants
158 participants
n=7 Participants
632 participants
n=31 Participants
Race/Ethnicity, Customized
Black or African American
2 participants
n=99 Participants
3 participants
n=107 Participants
1 participants
n=206 Participants
2 participants
n=7 Participants
8 participants
n=31 Participants
Race/Ethnicity, Customized
Asian
0 participants
n=99 Participants
1 participants
n=107 Participants
0 participants
n=206 Participants
1 participants
n=7 Participants
2 participants
n=31 Participants
Race/Ethnicity, Customized
Native Hawaiian or other Pacific Islander
0 participants
n=99 Participants
0 participants
n=107 Participants
0 participants
n=206 Participants
0 participants
n=7 Participants
0 participants
n=31 Participants
Race/Ethnicity, Customized
American Indian or Alaska Native
0 participants
n=99 Participants
1 participants
n=107 Participants
0 participants
n=206 Participants
0 participants
n=7 Participants
1 participants
n=31 Participants
Race/Ethnicity, Customized
Other
11 participants
n=99 Participants
13 participants
n=107 Participants
16 participants
n=206 Participants
13 participants
n=7 Participants
53 participants
n=31 Participants
Hamilton Rating Scale for Depression-17 items (HAMD-17) total score at randomization
21.49 Scores on a scale
STANDARD_DEVIATION 3.587 • n=99 Participants
20.98 Scores on a scale
STANDARD_DEVIATION 3.182 • n=107 Participants
21.50 Scores on a scale
STANDARD_DEVIATION 3.674 • n=206 Participants
21.26 Scores on a scale
STANDARD_DEVIATION 3.614 • n=7 Participants
21.30 Scores on a scale
STANDARD_DEVIATION 3.517 • n=31 Participants
Montgomery-Asberg Depression Rating Scale (MADRS) total score at randomization
24.69 Scores on a scale
STANDARD_DEVIATION 5.086 • n=99 Participants
24.67 Scores on a scale
STANDARD_DEVIATION 5.389 • n=107 Participants
25.03 Scores on a scale
STANDARD_DEVIATION 5.137 • n=206 Participants
24.11 Scores on a scale
STANDARD_DEVIATION 4.992 • n=7 Participants
24.62 Scores on a scale
STANDARD_DEVIATION 5.152 • n=31 Participants

PRIMARY outcome

Timeframe: Randomization (Week 8) to end of treatment (Week 16)

Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.

A 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.

Outcome measures

Outcome measures
Measure
0.1 mg BID TC-5214
n=173 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
n=174 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
n=170 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo
n=174 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Change in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Randomization to End of Treatment.
-11.6 units on a scale
Standard Error 0.65
-12.2 units on a scale
Standard Error 0.66
-12.2 units on a scale
Standard Error 0.69
-12.7 units on a scale
Standard Error 0.65

SECONDARY outcome

Timeframe: Randomization (Week 8) to end of treatment (Week 16)

Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.

The percentage of patients with a ≥50% reduction from randomization (Week 8) in MADRS total score at end of treatment (Week 16) was calculated. MADRS is 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.

Outcome measures

Outcome measures
Measure
0.1 mg BID TC-5214
n=173 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
n=174 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
n=170 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo
n=174 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Response in Depressive Symptoms of Major Depressive Disorder (MDD), Defined as a ≥50% Reduction From Randomization (Week 8) in MADRS Total Score at End of Treatment (Week 16)
48.6 percentage of participants analyzed
51.1 percentage of participants analyzed
41.2 percentage of participants analyzed
54.0 percentage of participants analyzed

SECONDARY outcome

Timeframe: Week 16

Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.

The percentage of patients with a MADRS total score of ≤8 at end of treatment (Week 16) was calculated. MADRS is 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.

Outcome measures

Outcome measures
Measure
0.1 mg BID TC-5214
n=173 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
n=174 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
n=170 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo
n=174 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Remission in Depressive Symptoms of MDD, Defined as MADRS Total Score of ≤8 at End of Treatment (Week 16)
37.0 percentage of participants analyzed
35.1 percentage of participants analyzed
30.0 percentage of participants analyzed
39.1 percentage of participants analyzed

SECONDARY outcome

Timeframe: Randomization (Week 8) to end of treatment (Week 16); Week 10, Week 12, Week 14, and Week 16

Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.

The percentage of patients with a ≥50% reduction from randomization (Week 8) in MADRS total score and a MADRS total score of ≤12 at Week 10, Week 12, Week 14, and end of treatment (Week 16) was calculated. MADRS is 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.

Outcome measures

Outcome measures
Measure
0.1 mg BID TC-5214
n=173 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
n=173 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
n=166 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo
n=173 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Early and Sustained Response, Defined as a ≥50% Reduction From Randomization (Week 8) in MADRS Total Score and a MADRS Total Score of ≤12 at Week 10, Week 12, Week 14, and End of Treatment (Week 16)
7.5 percentage of participants analyzed
8.1 percentage of participants analyzed
9.6 percentage of participants analyzed
9.2 percentage of participants analyzed

SECONDARY outcome

Timeframe: Randomization (Week 8) to end of treatment (Week 16); Week 12, Week 14, and Week 16

Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.

The percentage of patients with a ≥50% reduction from randomization (Week 8) in MADRS total score and a MADRS total score of ≤12 at Week 12, Week 14, and end of treatment (Week 16) was calculated. MADRS is 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.

Outcome measures

Outcome measures
Measure
0.1 mg BID TC-5214
n=170 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
n=171 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
n=163 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo
n=173 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Sustained Response, Defined as a ≥50% Reduction From Randomization (Week 8) in MADRS Total Score and a MADRS Total Score of ≤12 at Week 12, Week 14, and End of Treatment (Week 16)
14.7 percentage of patients analyzed
19.3 percentage of patients analyzed
15.3 percentage of patients analyzed
23.7 percentage of patients analyzed

SECONDARY outcome

Timeframe: Week 12, Week 14, Week 16

Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.

The percentage of patients with a MADRS total score of ≤8 at Week 12, Week 14, and end of treatment (Week 16)was calculated. MADRS is 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.

Outcome measures

Outcome measures
Measure
0.1 mg BID TC-5214
n=170 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
n=172 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
n=163 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo
n=173 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Sustained Remission, Defined as a MADRS Total Score of ≤8 at Week 12, Week 14, and End of Treatment (Week 16)
10.6 percentage of participants analyzed
10.5 percentage of participants analyzed
8.0 percentage of participants analyzed
12.1 percentage of participants analyzed

SECONDARY outcome

Timeframe: Randomization (Week 8) to end of treatment (Week 16)

Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.

A 17-item, clinician-rated scale that assesses depressive symptoms. The HAMD-17 consists of 17 symptoms, each of which is rated from 0 to 2 or 0 to 4, where 0 is none/absent. The HAMD-17 total score is calculated as the sum of the 17 individual symptom scores; the total score can range from 0 to 52. Higher HAMD-17 scores indicate more severe depression.

Outcome measures

Outcome measures
Measure
0.1 mg BID TC-5214
n=165 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
n=161 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
n=162 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo
n=170 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Change in Depressive Symptoms From Randomization (Week 8) to End of Treatment (Week 16) as Measured by Hamilton Rating Scale for Depression-17 Items (HAMD-17) Total Score
-10.07 units on a scale
Standard Error 0.597
-10.21 units on a scale
Standard Error 0.603
-9.07 units on a scale
Standard Error 0.597
-11.16 units on a scale
Standard Error 0.592

SECONDARY outcome

Timeframe: Randomization (Week 8) to end of treatment (Week 16)

Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.

A 3-part, clinician-administered scale that rates the improvement or worsening of the patient's illness from randomization (baseline). Each item is scored on a 1 to 7 scale. Higher CGI-S scores indicate greater illness severity.

Outcome measures

Outcome measures
Measure
0.1 mg BID TC-5214
n=173 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
n=174 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
n=170 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo
n=174 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Change in the Clinician-rated Global Outcome of Severity as Measured by the Clinical Global Impression-Severity (CGI-S) Score From Randomization (Week 8) to End of Treatment (Week 16)
-1.5 units on a scale
Standard Error 0.09
-1.6 units on a scale
Standard Error 0.09
-1.7 units on a scale
Standard Error 0.10
-1.7 units on a scale
Standard Error 0.09

SECONDARY outcome

Timeframe: Randomization (Week 8) to end of treatment (Week 16)

Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.

A 3-part, clinician-administered scale that rates the improvement or worsening of the patient's illness from randomization (baseline). Each item is scored on a 1 to 7 scale. CGI-I scores \>4 indicate worsening, while scores \<4 indicate improvement.

Outcome measures

Outcome measures
Measure
0.1 mg BID TC-5214
n=173 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
n=174 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
n=170 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo
n=174 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Response in the Clinical Global Impression-Improvement (CGI-I) Defined as CGI-I Rating of "Very Much Improved" or "Much Improved" From Randomization (Week 8) to End of Treatment (Week 16)
59.5 percentage of participants analyzed
62.1 percentage of participants analyzed
58.8 percentage of participants analyzed
67.8 percentage of participants analyzed

SECONDARY outcome

Timeframe: Randomization (Week 8) to end of treatment (Week 16)

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.

Outcome measures

Outcome measures
Measure
0.1 mg BID TC-5214
n=166 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
n=161 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
n=161 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo
n=170 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Change in Hamilton Anxiety Scale (HAM-A) Total Score From Randomization (Week 8) to End of Treatment (Week 16)
-8.5 units on a scale
Standard Error 0.58
-8.6 units on a scale
Standard Error 0.59
-8.1 units on a scale
Standard Error 0.58
-9.3 units on a scale
Standard Error 0.58

SECONDARY outcome

Timeframe: Randomization (Week 8) to Week 9

Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.

A 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.

Outcome measures

Outcome measures
Measure
0.1 mg BID TC-5214
n=167 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
n=162 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
n=164 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo
n=168 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Change in MADRS Total Score From Randomization (Week 8) to Week 9
-3.0 units on a scale
Standard Error 0.42
-3.0 units on a scale
Standard Error 0.43
-2.6 units on a scale
Standard Error 0.42
-3.2 units on a scale
Standard Error 0.42

SECONDARY outcome

Timeframe: Randomization (Week 8) to Week 10

Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.

A 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.

Outcome measures

Outcome measures
Measure
0.1 mg BID TC-5214
n=170 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
n=166 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
n=157 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo
n=171 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Change in MADRS Total Score From Randomization (Week 8) to Week 10
-4.8 units on a scale
Standard Error 0.50
-5.9 units on a scale
Standard Error 0.50
-5.0 units on a scale
Standard Error 0.51
-6.0 units on a scale
Standard Error 0.50

SECONDARY outcome

Timeframe: Randomization (Week 8) to Week 12

Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.

A 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.

Outcome measures

Outcome measures
Measure
0.1 mg BID TC-5214
n=163 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
n=157 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
n=144 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo
n=166 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Change in MADRS Total Score From Randomization (Week 8) to Week 12
-8.1 units on a scale
Standard Error 0.55
-8.5 units on a scale
Standard Error 0.56
-7.8 units on a scale
Standard Error 0.57
-8.7 units on a scale
Standard Error 0.55

SECONDARY outcome

Timeframe: Randomization (Week 8) to Week 14

Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.

A 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.

Outcome measures

Outcome measures
Measure
0.1 mg BID TC-5214
n=159 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
n=149 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
n=131 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo
n=164 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Change in MADRS Total Score From Randomization (Week 8) to Week 14
-9.5 units on a scale
Standard Error 0.59
-10.6 units on a scale
Standard Error 0.60
-9.6 units on a scale
Standard Error 0.62
-11.0 units on a scale
Standard Error 0.59

SECONDARY outcome

Timeframe: Randomization (Week 8) to end of treatment (Week 16)

Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.

Sheehan Disability Scale (SDS) is 5-item, self-administered scale that measures the extent a patient is impaired by their disease. Higher scores indicate more severe impairment. The SDS total score is calculated as the sum of the score for the 3 inter-correlated domains (school/work, social life, and family life/home responsibilities) and ranges from 0 (unimpaired) to 30 (highly impaired).

Outcome measures

Outcome measures
Measure
0.1 mg BID TC-5214
n=171 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
n=168 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
n=163 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo
n=172 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Change in Functional Impairment From Randomization (Week 8) to End of Treatment (Week 16) as Measured by the Sheehan Disability Scale (SDS) Total Score
-6.08 units on a scale
Standard Error 0.561
-6.34 units on a scale
Standard Error 0.569
-6.21 units on a scale
Standard Error 0.592
-7.06 units on a scale
Standard Error 0.556

SECONDARY outcome

Timeframe: Randomization (Week 8) to end of treatment (Week 16)

Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.

A 5-item, self-administered scale that measures the extent a patient is impaired by their disease. Higher scores indicate more severe impairment. The 3 inter-correlated domains are school/work, social life, and family life/home responsibilities. The numerical rating for the work/school domain score is 0- 10, where 10 is considered to be 'highly impaired'.

Outcome measures

Outcome measures
Measure
0.1 mg BID TC-5214
n=141 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
n=140 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
n=126 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo
n=137 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Change in Functional Impairment From Randomization (Week 8) to End of Treatment (Week 16) as Measured by SDS Work/School Domain Score
-2.0 units on a scale
Standard Error 0.21
-1.8 units on a scale
Standard Error 0.22
-1.9 units on a scale
Standard Error 0.24
-2.1 units on a scale
Standard Error 0.22

SECONDARY outcome

Timeframe: Randomization (Week 8) to end of treatment (Week 16)

Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.

A 5-item, self-administered scale that measures the extent a patient is impaired by their disease. Higher scores indicate more severe impairment. The 3 inter-correlated domains are school/work, social life, and family life/home responsibilities. The numerical rating for the SDS social life domain score is 0- 10, where 10 is considered to be 'highly impaired'.

Outcome measures

Outcome measures
Measure
0.1 mg BID TC-5214
n=171 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
n=168 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
n=163 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo
n=172 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Change in Functional Impairment From Randomization (Week 8) to End of Treatment (Week 16) as Measured by SDS Social Life Domain Score
-2.1 units on a scale
Standard Error 0.20
-2.2 units on a scale
Standard Error 0.20
-2.2 units on a scale
Standard Error 0.21
-2.4 units on a scale
Standard Error 0.20

SECONDARY outcome

Timeframe: Randomization (Week 8) to end of treatment (Week 16)

Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.

A 5-item, self-administered scale that measures the extent a patient is impaired by their disease. Higher scores indicate more severe impairment. The 3 inter-correlated domains are school/work, social life, and family life/home responsibilities. The numerical rating for the SDS family life/home responsibilities domain score is 0- 10, where 10 is considered to be 'highly impaired'.

Outcome measures

Outcome measures
Measure
0.1 mg BID TC-5214
n=171 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
n=168 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
n=163 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo
n=172 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Change in Functional Impairment From Randomization (Week 8) to End of Treatment (Week 16) as Measured by SDS Family Life/Home Responsibilities Domain Score
-2.0 units on a scale
Standard Error 0.20
-2.1 units on a scale
Standard Error 0.20
-2.0 units on a scale
Standard Error 0.21
-2.3 units on a scale
Standard Error 0.20

SECONDARY outcome

Timeframe: Randomization (Week 8) to end of treatment (Week 16)

Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.

The Q-LES-Q-SF (Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form) total score is derived by summing item scores 1 to 14. Higher scores are indicative of greater enjoyment or satisfaction in each domain. The Q-LES-Q-SF % maximum total score is calculated as 100% × (Q-LES-Q-SF total score - 14) / 56, and can range from 0% to 100%.

Outcome measures

Outcome measures
Measure
0.1 mg BID TC-5214
n=171 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
n=166 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
n=162 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo
n=172 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Change in Overall Quality of Life and Satisfaction From Randomization (Week 8) to End of Treatment (Week 16) by Assessing the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) % Maximum Total Score
13.08 units on a scale
Standard Error 1.388
13.24 units on a scale
Standard Error 1.402
11.84 units on a scale
Standard Error 1.409
14.55 units on a scale
Standard Error 1.391

SECONDARY outcome

Timeframe: Randomization (Week 8) to end of treatment (Week 16)

Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.

The Q-LES-Q-SF (Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form) measures the patient's satisfaction with medication and overall quality of life. The 15th item queries respondents' satisfaction with the medication they are taking. Higher scores are indicative of greater enjoyment or satisfaction in each domain.

Outcome measures

Outcome measures
Measure
0.1 mg BID TC-5214
n=153 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
n=154 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
n=151 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo
n=157 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Change From Randomization (Week 8) to End of Treatment (Week 16) in Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q LES-Q-SF) Item 15
0.6 units on a scale
Standard Error 0.08
0.7 units on a scale
Standard Error 0.08
0.5 units on a scale
Standard Error 0.08
0.7 units on a scale
Standard Error 0.08

SECONDARY outcome

Timeframe: Randomization (Week 8) to end of treatment (Week 16)

Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.

The Q-LES-Q-SF (Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form) measures the patient's satisfaction with medication and overall quality of life. The 16th item is a global rating of overall life satisfaction and contentment. Higher scores are indicative of greater enjoyment or satisfaction in each domain.

Outcome measures

Outcome measures
Measure
0.1 mg BID TC-5214
n=170 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
n=166 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
n=162 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo
n=172 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Change From Randomization (Week 8) to End of Treatment (Week 16) in Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q LES-Q-SF) Item 16
0.7 units on a scale
Standard Error 0.08
0.7 units on a scale
Standard Error 0.08
0.6 units on a scale
Standard Error 0.08
0.8 units on a scale
Standard Error 0.08

SECONDARY outcome

Timeframe: Randomization (Week 8) to end of treatment (Week 16)

Population: Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214 or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.

A self-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.

Outcome measures

Outcome measures
Measure
0.1 mg BID TC-5214
n=171 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
n=168 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
n=163 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo
n=172 Participants
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Change in EuroQol - 5 Dimensions (EQ-5D) From Randomization (Week 8) to End of Treatment (Week 16)
EQ-5D index score
0.128 units on a scale
Standard Error 0.0147
0.139 units on a scale
Standard Error 0.0149
0.133 units on a scale
Standard Error 0.0155
0.139 units on a scale
Standard Error 0.0146
Change in EuroQol - 5 Dimensions (EQ-5D) From Randomization (Week 8) to End of Treatment (Week 16)
EQ-5D VAS score
16.4 units on a scale
Standard Error 1.52
17.0 units on a scale
Standard Error 1.54
15.9 units on a scale
Standard Error 1.61
18.7 units on a scale
Standard Error 1.51

Adverse Events

Placebo

Serious events: 2 serious events
Other events: 64 other events
Deaths: 0 deaths

0.1 mg BID TC-5214

Serious events: 2 serious events
Other events: 68 other events
Deaths: 0 deaths

1 mg BID TC-5214

Serious events: 4 serious events
Other events: 72 other events
Deaths: 0 deaths

4 mg BID TC-5214

Serious events: 2 serious events
Other events: 94 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Placebo
n=174 participants at risk
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo
0.1 mg BID TC-5214
n=174 participants at risk
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
n=174 participants at risk
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
n=171 participants at risk
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Gastrointestinal disorders
Food Poisoning
0.00%
0/174
0.00%
0/174
0.57%
1/174 • Number of events 1
0.00%
0/171
Infections and infestations
Pneumonia
0.00%
0/174
0.00%
0/174
0.57%
1/174 • Number of events 1
0.00%
0/171
Infections and infestations
Urinary Tract Infection
0.00%
0/174
0.00%
0/174
0.57%
1/174 • Number of events 1
0.00%
0/171
Injury, poisoning and procedural complications
Toxicity To Various Agents
0.00%
0/174
0.57%
1/174 • Number of events 1
0.00%
0/174
0.00%
0/171
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix Carcinoma
0.57%
1/174 • Number of events 1
0.00%
0/174
0.00%
0/174
0.00%
0/171
Pregnancy, puerperium and perinatal conditions
Abortion Spontaneous
0.57%
1/174 • Number of events 1
0.00%
0/174
0.00%
0/174
0.00%
0/171
Psychiatric disorders
Depression
0.00%
0/174
0.00%
0/174
0.57%
1/174 • Number of events 1
0.00%
0/171
Psychiatric disorders
Suicidal Ideation
0.00%
0/174
0.00%
0/174
0.00%
0/174
1.2%
2/171 • Number of events 2
Psychiatric disorders
Suicide Attempt
0.00%
0/174
1.1%
2/174 • Number of events 2
0.57%
1/174 • Number of events 1
0.58%
1/171 • Number of events 1

Other adverse events

Other adverse events
Measure
Placebo
n=174 participants at risk
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo
0.1 mg BID TC-5214
n=174 participants at risk
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214
n=174 participants at risk
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
4 mg BID TC-5214
n=171 participants at risk
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Ear and labyrinth disorders
Vertigo
0.00%
0/174
0.57%
1/174 • Number of events 1
1.1%
2/174 • Number of events 2
3.5%
6/171 • Number of events 6
Gastrointestinal disorders
Constipation
6.3%
11/174 • Number of events 11
7.5%
13/174 • Number of events 13
7.5%
13/174 • Number of events 14
19.9%
34/171 • Number of events 35
Gastrointestinal disorders
Dry Mouth
1.7%
3/174 • Number of events 4
2.9%
5/174 • Number of events 5
2.9%
5/174 • Number of events 5
10.5%
18/171 • Number of events 18
Gastrointestinal disorders
Diarrhoea
6.9%
12/174 • Number of events 13
0.57%
1/174 • Number of events 1
1.7%
3/174 • Number of events 4
1.8%
3/171 • Number of events 4
Gastrointestinal disorders
Nausea
5.2%
9/174 • Number of events 10
4.0%
7/174 • Number of events 8
3.4%
6/174 • Number of events 7
6.4%
11/171 • Number of events 11
Gastrointestinal disorders
Vomiting
1.7%
3/174 • Number of events 3
0.57%
1/174 • Number of events 1
1.1%
2/174 • Number of events 2
2.9%
5/171 • Number of events 5
Gastrointestinal disorders
Abdominal Pain Upper
2.3%
4/174 • Number of events 4
0.57%
1/174 • Number of events 1
2.3%
4/174 • Number of events 5
2.3%
4/171 • Number of events 4
General disorders
Fatigue
2.3%
4/174 • Number of events 4
3.4%
6/174 • Number of events 6
5.7%
10/174 • Number of events 10
5.3%
9/171 • Number of events 9
Infections and infestations
Influenza
4.6%
8/174 • Number of events 8
1.1%
2/174 • Number of events 2
3.4%
6/174 • Number of events 6
2.9%
5/171 • Number of events 5
Infections and infestations
Nasopharyngitis
2.9%
5/174 • Number of events 5
1.7%
3/174 • Number of events 4
0.57%
1/174 • Number of events 1
0.00%
0/171
Infections and infestations
Urinary Tract Infection
0.00%
0/174
1.1%
2/174 • Number of events 2
0.57%
1/174 • Number of events 2
2.9%
5/171 • Number of events 6
Infections and infestations
Alanine Aminotransferase Increased
0.00%
0/174
0.57%
1/174 • Number of events 1
2.3%
4/174 • Number of events 4
1.2%
2/171 • Number of events 3
Metabolism and nutrition disorders
Increased Appetite
0.00%
0/174
0.57%
1/174 • Number of events 1
2.3%
4/174 • Number of events 4
0.00%
0/171
Nervous system disorders
Headache
13.2%
23/174 • Number of events 27
12.6%
22/174 • Number of events 27
13.8%
24/174 • Number of events 41
9.9%
17/171 • Number of events 17
Nervous system disorders
Dizziness
4.0%
7/174 • Number of events 9
5.2%
9/174 • Number of events 9
7.5%
13/174 • Number of events 13
7.6%
13/171 • Number of events 14
Nervous system disorders
Somnolence
2.9%
5/174 • Number of events 5
2.9%
5/174 • Number of events 5
4.0%
7/174 • Number of events 7
5.3%
9/171 • Number of events 10
Nervous system disorders
Dysgeusia
0.00%
0/174
0.57%
1/174 • Number of events 1
0.57%
1/174 • Number of events 1
2.3%
4/171 • Number of events 4
Psychiatric disorders
Insomnia
0.57%
1/174 • Number of events 1
3.4%
6/174 • Number of events 6
5.2%
9/174 • Number of events 11
4.1%
7/171 • Number of events 8
Psychiatric disorders
Agitation
2.3%
4/174 • Number of events 4
1.7%
3/174 • Number of events 3
1.7%
3/174 • Number of events 3
2.9%
5/171 • Number of events 5
Psychiatric disorders
Nervousness
0.00%
0/174
0.00%
0/174
2.3%
4/174 • Number of events 4
0.58%
1/171 • Number of events 1
Psychiatric disorders
Nightmare
1.1%
2/174 • Number of events 2
2.3%
4/174 • Number of events 4
0.57%
1/174 • Number of events 1
2.3%
4/171 • Number of events 4
Skin and subcutaneous tissue disorders
Hyperhidrosis
0.57%
1/174 • Number of events 1
2.9%
5/174 • Number of events 5
2.3%
4/174 • Number of events 4
4.1%
7/171 • Number of events 9
Skin and subcutaneous tissue disorders
Pruritus
2.3%
4/174 • Number of events 5
0.00%
0/174
0.00%
0/174
0.00%
0/171
Vascular disorders
Orthostatic Hypotension
0.57%
1/174 • Number of events 1
0.57%
1/174 • Number of events 1
0.00%
0/174
4.7%
8/171 • Number of events 11
Vascular disorders
Hypotension
0.00%
0/174
0.57%
1/174 • Number of events 1
0.00%
0/174
3.5%
6/171 • Number of events 6
Vascular disorders
Hypertension
1.1%
2/174 • Number of events 2
1.1%
2/174 • Number of events 3
1.7%
3/174 • Number of events 3
2.3%
4/171 • Number of events 4

Additional Information

Gerard Lynch

AstraZeneca

Results disclosure agreements

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

Restriction type: GT60