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 NCT01180400)

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

295 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 between 2 September 2010 and 27 September 2011.

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

Participant milestones

Participant milestones
Measure	TC-5214 Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Placebo Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Study STARTED	147	148
Overall Study Received Treatment	147	146
Overall Study COMPLETED	122	121
Overall Study NOT COMPLETED	25	27

Reasons for withdrawal

Reasons for withdrawal
Measure	TC-5214 Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Placebo Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Overall Study Withdrawal by Subject	5	6
Overall Study Eligibility criteria not fulfilled	0	2
Overall Study Adverse Event	12	10
Overall Study Severe non-compliance to protocol	1	2
Overall Study Condition under investigation worsened	2	1
Overall Study Lack of Efficacy	2	0
Overall Study Study-specific withdrawal criteria	1	2
Overall Study Lost to Follow-up	2	3
Overall Study Other	0	1

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	TC-5214 n=147 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Placebo n=148 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID	Total n=295 Participants Total of all reporting groups
Age, Continuous	46.1 years STANDARD_DEVIATION 11.25 • n=99 Participants	43.4 years STANDARD_DEVIATION 11.31 • n=107 Participants	44.8 years STANDARD_DEVIATION 11.34 • n=206 Participants
Sex: Female, Male Female	94 Participants n=99 Participants	95 Participants n=107 Participants	189 Participants n=206 Participants
Sex: Female, Male Male	53 Participants n=99 Participants	53 Participants n=107 Participants	106 Participants n=206 Participants
Race/Ethnicity, Customized White	146 participants n=99 Participants	148 participants n=107 Participants	294 participants n=206 Participants
Race/Ethnicity, Customized Black or African American	0 participants n=99 Participants	0 participants n=107 Participants	0 participants n=206 Participants
Race/Ethnicity, Customized Asian	0 participants n=99 Participants	0 participants n=107 Participants	0 participants n=206 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
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=99 Participants	0 participants n=107 Participants	0 participants n=206 Participants
Race/Ethnicity, Customized Other	1 participants n=99 Participants	0 participants n=107 Participants	1 participants n=206 Participants
Hamilton Rating Scale for Depression-17 items (HAMD-17) total score at randomization	20.0 Scores on a scale STANDARD_DEVIATION 2.77 • n=99 Participants	20.5 Scores on a scale STANDARD_DEVIATION 3.41 • n=107 Participants	20.2 Scores on a scale STANDARD_DEVIATION 3.11 • n=206 Participants
Montgomery-Asberg Depression Rating Scale (MADRS) total score at randomization	24.3 Scores on a scale STANDARD_DEVIATION 4.92 • n=99 Participants	25.1 Scores on a scale STANDARD_DEVIATION 4.72 • n=107 Participants	24.7 Scores on a scale STANDARD_DEVIATION 4.82 • n=206 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.

Outcome measures

Outcome measures
Measure	TC-5214 n=145 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Placebo n=145 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Change in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Randomization to End of Treatment.	-11.7 units on a scale Standard Error 0.71	-11.6 units on a scale Standard Error 0.70

SECONDARY outcome

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

The percentage of patients with a ≥50% reduction from randomization (Week 8) in MADRS total score at end of treatment (Week 16) was calculated. 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	TC-5214 n=145 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Placebo n=145 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
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)	48.3 percentage of participants analyzed	49.0 percentage of participants analyzed

SECONDARY outcome

Timeframe: Week 16

The percentage of patients with a MADRS total score of ≤8 at end of treatment (Week 16) was calculated. 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	TC-5214 n=145 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Placebo n=145 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Remission in Depressive Symptoms of MDD, Defined as MADRS Total Score of ≤8 at End of Treatment (Week 16)	33.8 percentage of participants analyzed	26.9 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

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. 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	TC-5214 n=144 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Placebo n=144 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
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)	7.6 percentage of participants analyzed	6.3 percentage of participants analyzed

SECONDARY outcome

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

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. 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	TC-5214 n=138 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Placebo n=141 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)	14.5 percentage of patients analyzed	16.3 percentage of patients analyzed

SECONDARY outcome

Timeframe: Week 12, Week 14, Week 16

The percentage of patients with a MADRS total score of ≤8 at Week 12, Week 14, and end of treatment (Week 16)was calculated. 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	TC-5214 n=139 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Placebo n=142 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)	7.9 percentage of participants analyzed	9.2 percentage of participants analyzed

SECONDARY outcome

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

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	TC-5214 n=135 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Placebo n=139 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Change in Depressive Symptoms From Randomization (Week 8) to End of Treatment (Week 16) as Measured by Hamilton Rating Scale for Depression-17 Items (HAMD-17) Total Score	-9.4 units on a scale Standard Error 0.56	-9.8 units on a scale Standard Error 0.55

SECONDARY outcome

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

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	TC-5214 n=145 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Placebo n=145 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Change in 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)	-1.6 units on a scale Standard Error 0.11	-1.6 units on a scale Standard Error 0.11

SECONDARY outcome

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

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	TC-5214 n=145 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Placebo n=145 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
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)	64.8 percentage of participants analyzed	65.5 percentage of participants analyzed

SECONDARY outcome

Timeframe: Randomization (Week 8) to Week 9

Outcome measures

Outcome measures
Measure	TC-5214 n=145 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Placebo n=141 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 0.47	-3.1 units on a scale Standard Error 0.46

SECONDARY outcome

Timeframe: Randomization (Week 8) to Week 10

Outcome measures

Outcome measures
Measure	TC-5214 n=143 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Placebo n=140 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	-4.9 units on a scale Standard Error 0.56	-5.4 units on a scale Standard Error 0.56

SECONDARY outcome

Timeframe: Randomization (Week 8) to Week 12

Outcome measures

Outcome measures
Measure	TC-5214 n=135 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Placebo n=133 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	-7.2 units on a scale Standard Error 0.62	-8.2 units on a scale Standard Error 0.62

SECONDARY outcome

Timeframe: Randomization (Week 8) to Week 14

Outcome measures

Outcome measures
Measure	TC-5214 n=126 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Placebo n=132 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	-9.1 units on a scale Standard Error 0.68	-10.3 units on a scale Standard Error 0.67

SECONDARY outcome

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

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	TC-5214 n=138 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Placebo n=142 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	-5.79 units on a scale Standard Error 0.548	-5.75 units on a scale Standard Error 0.536

SECONDARY outcome

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

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	TC-5214 n=115 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Placebo n=120 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	-2.2 units on a scale Standard Error 0.25	-1.8 units on a scale Standard Error 0.24

SECONDARY outcome

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

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	TC-5214 n=138 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Placebo n=142 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	-2.0 units on a scale Standard Error 0.19	-1.9 units on a scale Standard Error 0.19

SECONDARY outcome

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

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	TC-5214 n=138 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Placebo n=142 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	-1.9 units on a scale Standard Error 0.20	-2.0 units on a scale Standard Error 0.19

SECONDARY outcome

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

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	TC-5214 n=137 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Placebo n=142 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	11.22 units on a scale Standard Error 1.246	11.07 units on a scale Standard Error 1.217

SECONDARY outcome

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

The Q-LES-Q-SF (Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form) measures the patient's satisfaction with medication and overall quality of life. The 15th item queries respondents' satisfaction with the medication they are taking, rated on a 1 to 4 scale, score 0 indicates that no medication was taken. Higher scores are indicative of greater satisfaction.

Outcome measures

Outcome measures
Measure	TC-5214 n=131 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Placebo n=133 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	0.3 units on a scale Standard Error 0.08	0.4 units on a scale Standard Error 0.07

SECONDARY outcome

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

The Q-LES-Q-SF (Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form) measures the patient's satisfaction with medication and overall quality of life. The 16th item is a global rating of overall life satisfaction and contentment, rated on a 1 to 5 scale. Higher scores are indicative of greater satisfaction.

Outcome measures

Outcome measures
Measure	TC-5214 n=138 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Placebo n=142 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

SECONDARY outcome

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

A self-assessment questionnaire that provides 2 measures of health status. The EQ-5D index score is a weighted linear combination over 5 dimensions of health status. The score for each of the 5 dimensions can range from 1 to 3, and an equation is used to calculate the EQ-5D index score. The EQ-5D index score can range from possible negative values (minimum -0.415) to a maximum of 1.0. The EQ-VAS is a visual analog scale with a range of 0 to 100. For both variables, a higher score indicates a better health state.

Outcome measures

Outcome measures
Measure	TC-5214 n=138 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Placebo n=142 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	0.109 units on a scale Standard Error 0.0154	0.120 units on a scale Standard Error 0.0150
Change in EuroQol - 5 Dimensions (EQ-5D) From Randomization (Week 8) to End of Treatment (Week 16) EQ-5D VAS score	13.6 units on a scale Standard Error 1.59	14.0 units on a scale Standard Error 1.54

Adverse Events

TC-5214

Serious events: 1 serious events

Other events: 83 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 65 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	TC-5214 n=147 participants at risk Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Placebo n=146 participants at risk Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine Cancer	0.68% 1/147 • Number of events 1	0.00% 0/146
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.00% 0/147	0.68% 1/146 • Number of events 1
Injury, poisoning and procedural complications Fracture	0.00% 0/147	0.68% 1/146 • Number of events 1

Other adverse events

Other adverse events
Measure	TC-5214 n=147 participants at risk Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Placebo n=146 participants at risk Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Nervous system disorders Headache	17.7% 26/147 • Number of events 35	13.7% 20/146 • Number of events 32
Gastrointestinal disorders Constipation	12.9% 19/147 • Number of events 24	2.7% 4/146 • Number of events 4
Gastrointestinal disorders Nausea	9.5% 14/147 • Number of events 19	5.5% 8/146 • Number of events 12
Gastrointestinal disorders Dry Mouth	6.1% 9/147 • Number of events 10	4.1% 6/146 • Number of events 6
Vascular disorders Orthostatic Hypotension	6.8% 10/147 • Number of events 23	10.3% 15/146 • Number of events 41
Nervous system disorders Dizziness	5.4% 8/147 • Number of events 10	4.1% 6/146 • Number of events 6
Nervous system disorders Somnolence	5.4% 8/147 • Number of events 11	2.7% 4/146 • Number of events 5
Gastrointestinal disorders Diarrhoea	4.8% 7/147 • Number of events 7	5.5% 8/146 • Number of events 8
General disorders Fatigue	4.8% 7/147 • Number of events 7	5.5% 8/146 • Number of events 8
Vascular disorders Hypertension	3.4% 5/147 • Number of events 7	0.68% 1/146 • Number of events 1
Infections and infestations Sinusitis	2.7% 4/147 • Number of events 4	0.00% 0/146
Ear and labyrinth disorders Vertigo	2.7% 4/147 • Number of events 4	1.4% 2/146 • Number of events 2
General disorders Asthenia	2.7% 4/147 • Number of events 6	0.68% 1/146 • Number of events 1
Musculoskeletal and connective tissue disorders Back Pain	2.7% 4/147 • Number of events 4	2.1% 3/146 • Number of events 3
Skin and subcutaneous tissue disorders Hyperhidrosis	2.0% 3/147 • Number of events 3	3.4% 5/146 • Number of events 6
Infections and infestations Nasopharyngitis	3.4% 5/147 • Number of events 5	1.4% 2/146 • Number of events 2
Metabolism and nutrition disorders Increased Appetite	1.4% 2/147 • Number of events 2	2.1% 3/146 • Number of events 3
Infections and infestations Influenza	2.7% 4/147 • Number of events 4	2.1% 3/146 • Number of events 3
Nervous system disorders Sedation	1.4% 2/147 • Number of events 2	2.1% 3/146 • Number of events 4
Nervous system disorders Tremor	1.4% 2/147 • Number of events 2	2.1% 3/146 • Number of events 3
Investigations Aspartate Aminotransferase Increased	0.68% 1/147 • Number of events 1	2.1% 3/146 • Number of events 3
Psychiatric disorders Insomnia	2.0% 3/147 • Number of events 3	3.4% 5/146 • Number of events 5
Infections and infestations Pharyngitis	0.00% 0/147	2.1% 3/146 • Number of events 3
Eye disorders Vision blurred	2.0% 3/147 • Number of events 3	0.68% 1/146 • Number of events 1
Gastrointestinal disorders Abdominal distention	2.0% 3/147 • Number of events 3	1.4% 2/146 • Number of events 2
Gastrointestinal disorders Abdominal pain upper	2.0% 3/147 • Number of events 3	0.00% 0/146
Nervous system disorders Dizziness postural	2.0% 3/147 • Number of events 3	0.68% 1/146 • Number of events 4
Psychiatric disorders Anxiety	1.4% 2/147 • Number of events 2	2.1% 3/146 • Number of events 3

Additional Information

Gerard Lynch

AstraZeneca

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60