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 NCT01153347)

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

2409 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 the US and India between 15 June 2010 and 31 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	0.5 mg BID TC-5214 Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 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	160	160	160	161
Overall Study Received Treatment	160	158	158	160
Overall Study COMPLETED	127	116	110	129
Overall Study NOT COMPLETED	33	44	50	32

Reasons for withdrawal

Reasons for withdrawal
Measure	0.5 mg BID TC-5214 Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 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	7	7	7	7
Overall Study Eligibility criteria not fulfilled	0	1	2	1
Overall Study Adverse Event	3	9	21	7
Overall Study Severe non-compliance to protocol	6	7	4	3
Overall Study Condition under investigation worsened	1	1	0	0
Overall Study Lack of Efficacy	2	2	0	4
Overall Study Study-specific withdrawal criteria	4	3	1	2
Overall Study Lost to Follow-up	4	9	11	8
Overall Study Other	5	5	4	0
Overall Study Death	1	0	0	0

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	0.5 mg BID TC-5214 n=160 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 n=160 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 mg BID	4 mg BID TC-5214 n=160 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID	Placebo n=161 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID	Total n=641 Participants Total of all reporting groups
Age, Continuous	40.6 years STANDARD_DEVIATION 11.78 • n=5 Participants	42.1 years STANDARD_DEVIATION 11.77 • n=7 Participants	42.1 years STANDARD_DEVIATION 11.35 • n=5 Participants	43.2 years STANDARD_DEVIATION 11.92 • n=4 Participants	42.0 years STANDARD_DEVIATION 11.72 • n=21 Participants
Sex: Female, Male Female	85 Participants n=5 Participants	91 Participants n=7 Participants	93 Participants n=5 Participants	96 Participants n=4 Participants	365 Participants n=21 Participants
Sex: Female, Male Male	75 Participants n=5 Participants	69 Participants n=7 Participants	67 Participants n=5 Participants	65 Participants n=4 Participants	276 Participants n=21 Participants
Race/Ethnicity, Customized White	87 participants n=5 Participants	100 participants n=7 Participants	91 participants n=5 Participants	103 participants n=4 Participants	381 participants n=21 Participants
Race/Ethnicity, Customized Black or African American	20 participants n=5 Participants	23 participants n=7 Participants	27 participants n=5 Participants	14 participants n=4 Participants	84 participants n=21 Participants
Race/Ethnicity, Customized Asian	50 participants n=5 Participants	35 participants n=7 Participants	40 participants n=5 Participants	42 participants n=4 Participants	167 participants n=21 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	1 participants n=21 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Race/Ethnicity, Customized Other	3 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	1 participants n=4 Participants	7 participants n=21 Participants
Hamilton Rating Scale for Depression-17 items (HAMD-17) total score at randomization	22.3 Scores on a scale STANDARD_DEVIATION 3.98 • n=5 Participants	21.5 Scores on a scale STANDARD_DEVIATION 3.74 • n=7 Participants	22.0 Scores on a scale STANDARD_DEVIATION 4.07 • n=5 Participants	22.1 Scores on a scale STANDARD_DEVIATION 4.08 • n=4 Participants	22.0 Scores on a scale STANDARD_DEVIATION 3.97 • n=21 Participants
Montgomery-Asberg Depression Rating Scale (MADRS) total score at randomization	26.86 Scores on a scale STANDARD_DEVIATION 6.331 • n=5 Participants	26.37 Scores on a scale STANDARD_DEVIATION 6.036 • n=7 Participants	27.06 Scores on a scale STANDARD_DEVIATION 5.854 • n=5 Participants	26.70 Scores on a scale STANDARD_DEVIATION 6.809 • n=4 Participants	26.75 Scores on a scale STANDARD_DEVIATION 6.261 • n=21 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	0.5 mg BID TC-5214 n=155 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 n=156 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 mg BID	4 mg BID TC-5214 n=152 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 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Randomization to End of Treatment.	-12.1 units on a scale Standard Error 0.81	-11.8 units on a scale Standard Error 0.83	-11.3 units on a scale Standard Error 0.84	-11.2 units on a scale Standard Error 0.80

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	0.5 mg BID TC-5214 n=155 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 n=156 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 mg BID	4 mg BID TC-5214 n=152 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
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)	43.9 percentage of participants analyzed	39.7 percentage of participants analyzed	38.8 percentage of participants analyzed	42.7 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	0.5 mg BID TC-5214 n=155 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 n=156 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 mg BID	4 mg BID TC-5214 n=152 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
Remission in Depressive Symptoms of MDD, Defined as MADRS Total Score of ≤8 at End of Treatment (Week 16)	29.0 percentage of participants analyzed	26.9 percentage of participants analyzed	23.7 percentage of participants analyzed	29.9 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	0.5 mg BID TC-5214 n=148 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 n=153 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 mg BID	4 mg BID TC-5214 n=145 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID	Placebo n=153 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Early and Sustained Response, Defined as a ≥50% Reduction From Randomization (Week 8) in MADRS Total Score and a MADRS Total Score of ≤12 at Week 10, Week 12, Week 14, and End of Treatment (Week 16)	8.8 percentage of participants analyzed	7.8 percentage of participants analyzed	8.3 percentage of participants analyzed	8.5 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	0.5 mg BID TC-5214 n=145 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 n=150 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 mg BID	4 mg BID TC-5214 n=143 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID	Placebo n=151 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)	15.9 percentage of patients analyzed	18.7 percentage of patients analyzed	14.0 percentage of patients analyzed	15.9 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	0.5 mg BID TC-5214 n=146 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 n=150 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 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=152 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)	10.3 percentage of participants analyzed	12.7 percentage of participants analyzed	7.6 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	0.5 mg BID TC-5214 n=147 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 n=144 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 mg BID	4 mg BID TC-5214 n=142 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID	Placebo n=150 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	-10.1 units on a scale Standard Error 0.79	-9.7 units on a scale Standard Error 0.79	-9.5 units on a scale Standard Error 0.79	-9.1 units on a scale Standard Error 0.78

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	0.5 mg BID TC-5214 n=155 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 n=156 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 mg BID	4 mg BID TC-5214 n=152 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 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)	-1.3 units on a scale Standard Error 0.10	-1.3 units on a scale Standard Error 0.11	-1.2 units on a scale Standard Error 0.11	-1.2 units on a scale Standard Error 0.10

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	0.5 mg BID TC-5214 n=155 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 n=156 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 mg BID	4 mg BID TC-5214 n=152 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
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)	48.4 percentage of participants analyzed	49.4 percentage of participants analyzed	37.5 percentage of participants analyzed	47.8 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, the total score can range from 0 to 56. Higher HAM-A scores indicate higher levels of anxiety.

Outcome measures

Outcome measures
Measure	0.5 mg BID TC-5214 n=147 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 n=144 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 mg BID	4 mg BID TC-5214 n=142 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID	Placebo n=150 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)	-7.07 units on a scale Standard Error 0.648	-6.46 units on a scale Standard Error 0.652	-6.75 units on a scale Standard Error 0.655	-6.24 units on a scale Standard Error 0.641

SECONDARY outcome

Timeframe: Randomization (Week 8) to Week 9

Outcome measures

Outcome measures
Measure	0.5 mg BID TC-5214 n=152 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 n=150 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 mg BID	4 mg BID TC-5214 n=146 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID	Placebo n=152 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	-4.0 units on a scale Standard Error 0.52	-5.1 units on a scale Standard Error 0.52	-4.0 units on a scale Standard Error 0.52	-5.0 units on a scale Standard Error 0.52

SECONDARY outcome

Timeframe: Randomization (Week 8) to Week 10

Outcome measures

Outcome measures
Measure	0.5 mg BID TC-5214 n=150 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 n=146 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 mg BID	4 mg BID TC-5214 n=139 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID	Placebo n=148 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Change in MADRS Total Score From Randomization (Week 8) to Week 10	-6.3 units on a scale Standard Error 0.60	-6.9 units on a scale Standard Error 0.60	-7.3 units on a scale Standard Error 0.61	-7.1 units on a scale Standard Error 0.60

SECONDARY outcome

Timeframe: Randomization (Week 8) to Week 12

Outcome measures

Outcome measures
Measure	0.5 mg BID TC-5214 n=142 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 n=135 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 mg BID	4 mg BID TC-5214 n=128 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID	Placebo n=145 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	-9.4 units on a scale Standard Error 0.70	-9.4 units on a scale Standard Error 0.71	-8.9 units on a scale Standard Error 0.73	-8.5 units on a scale Standard Error 0.70

SECONDARY outcome

Timeframe: Randomization (Week 8) to Week 14

Outcome measures

Outcome measures
Measure	0.5 mg BID TC-5214 n=140 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 n=127 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 mg BID	4 mg BID TC-5214 n=119 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID	Placebo n=134 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Change in MADRS Total Score From Randomization (Week 8) to Week 14	-11.0 units on a scale Standard Error 0.74	-11.3 units on a scale Standard Error 0.76	-10.6 units on a scale Standard Error 0.77	-10.7 units on a scale Standard Error 0.74

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	0.5 mg BID TC-5214 n=152 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 n=148 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 mg BID	4 mg BID TC-5214 n=149 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID	Placebo n=153 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	-5.53 units on a scale Standard Error 0.631	-5.45 units on a scale Standard Error 0.643	-4.53 units on a scale Standard Error 0.651	-4.93 units on a scale Standard Error 0.627

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	0.5 mg BID TC-5214 n=132 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 n=123 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 mg BID	4 mg BID TC-5214 n=134 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	-1.7 units on a scale Standard Error 0.21	-1.8 units on a scale Standard Error 0.22	-1.7 units on a scale Standard Error 0.21	-1.7 units on a scale Standard Error 0.21

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	0.5 mg BID TC-5214 n=152 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 n=148 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 mg BID	4 mg BID TC-5214 n=149 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID	Placebo n=153 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Change in Functional Impairment From Randomization (Week 8) to End of Treatment (Week 16) as Measured by SDS Social Life Domain Score	-1.9 units on a scale Standard Error 0.22	-1.9 units on a scale Standard Error 0.23	-1.6 units on a scale Standard Error 0.23	-1.9 units on a scale Standard Error 0.22

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	0.5 mg BID TC-5214 n=152 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 n=148 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 mg BID	4 mg BID TC-5214 n=149 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID	Placebo n=153 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 0.22	-1.8 units on a scale Standard Error 0.23	-1.6 units on a scale Standard Error 0.23	-1.6 units on a scale Standard Error 0.22

SECONDARY outcome

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

The Q-LES-Q-SF 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	0.5 mg BID TC-5214 n=152 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 n=148 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 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=151 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Change in Overall Quality of Life and Satisfaction From Randomization (Week 8) to End of Treatment (Week 16) by Assessing the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) % Maximum Total Score	12.81 units on a scale Standard Error 1.470	11.42 units on a scale Standard Error 1.483	8.83 units on a scale Standard Error 1.499	10.71 units on a scale Standard Error 1.467

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	0.5 mg BID TC-5214 n=142 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 n=136 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 mg BID	4 mg BID TC-5214 n=124 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID	Placebo n=138 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 0.08	0.2 units on a scale Standard Error 0.08	0.4 units on a scale Standard Error 0.08

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	0.5 mg BID TC-5214 n=152 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 n=148 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 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=151 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	0.6 units on a scale Standard Error 0.08	0.5 units on a scale Standard Error 0.08	0.4 units on a scale Standard Error 0.08	0.5 units on a scale Standard Error 0.08

SECONDARY outcome

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

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	0.5 mg BID TC-5214 n=152 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 n=147 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 mg BID	4 mg BID TC-5214 n=147 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID	Placebo n=153 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	0.114 units on a scale Standard Error 0.0169	0.107 units on a scale Standard Error 0.0173	0.106 units on a scale Standard Error 0.0176	0.120 units on a scale Standard Error 0.0168
Change in EuroQol - 5 Dimensions (EQ-5D) From Randomization (Week 8) to End of Treatment (Week 16) EQ-5D VAS score	13.4 units on a scale Standard Error 1.69	12.9 units on a scale Standard Error 1.73	10.3 units on a scale Standard Error 1.76	11.5 units on a scale Standard Error 1.68

SECONDARY outcome

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

A self-administered scale to be used by clinical subjects to rate suffering over the past week with regard to irritability symptoms. The total SIS score is the sum of 7 items, and ranges from 0 to 70. Each item is assessed on an 11- point scale where 0=not at all, 1-3=mildly, 4-6=moderately, 7-9=markedly, and 10=extremely. The SIS also records the number of days impaired by irritability.

Outcome measures

Outcome measures
Measure	0.5 mg BID TC-5214 n=152 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 n=148 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 mg BID	4 mg BID TC-5214 n=149 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID	Placebo n=153 Participants Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Change in Irritability Symptoms as Measured by the Sheehan Irritability Scale (SIS) Total Score From Randomization (Week 8) to End of Treatment (Week 16)	-10.2 units on a scale Standard Error 1.46	-10.1 units on a scale Standard Error 1.49	-8.3 units on a scale Standard Error 1.50	-8.8 units on a scale Standard Error 1.46

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 76 other events

Deaths: 0 deaths

0.5 mg BID TC-5214

Serious events: 2 serious events

Other events: 80 other events

Deaths: 0 deaths

2 mg BID TC-5214

Serious events: 0 serious events

Other events: 88 other events

Deaths: 0 deaths

4 mg BID TC-5214

Serious events: 5 serious events

Other events: 99 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=160 participants at risk Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo	0.5 mg BID TC-5214 n=160 participants at risk Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 n=158 participants at risk Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 mg BID	4 mg BID TC-5214 n=158 participants at risk Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
General disorders Non-Cardiac Chest Pain	0.62% 1/160 • Number of events 1	0.00% 0/160	0.00% 0/158	0.00% 0/158
Infections and infestations Upper Respiratory Tract Infection	0.00% 0/160	0.00% 0/160	0.00% 0/158	0.63% 1/158 • Number of events 1
Injury, poisoning and procedural complications Clavicle Fracture	0.00% 0/160	0.00% 0/160	0.00% 0/158	0.63% 1/158 • Number of events 1
Injury, poisoning and procedural complications Rib Fracture	0.00% 0/160	0.00% 0/160	0.00% 0/158	0.63% 1/158 • Number of events 1
Injury, poisoning and procedural complications Scapula Fracture	0.00% 0/160	0.00% 0/160	0.00% 0/158	0.63% 1/158 • Number of events 1
Nervous system disorders Convulsion	0.00% 0/160	0.00% 0/160	0.00% 0/158	0.63% 1/158 • Number of events 1
Psychiatric disorders Major Depression	0.00% 0/160	0.62% 1/160 • Number of events 1	0.00% 0/158	0.63% 1/158 • Number of events 1
Psychiatric disorders Suicidal Ideation	0.00% 0/160	0.62% 1/160 • Number of events 1	0.00% 0/158	0.00% 0/158
Renal and urinary disorders Obstructive Uropathy	0.00% 0/160	0.00% 0/160	0.00% 0/158	0.63% 1/158 • Number of events 1
Renal and urinary disorders Renal Failure Acute	0.00% 0/160	0.00% 0/160	0.00% 0/158	0.63% 1/158 • Number of events 1
Reproductive system and breast disorders Benign Prostatic Hyperplasia	0.00% 0/160	0.00% 0/160	0.00% 0/158	0.63% 1/158 • Number of events 1
Reproductive system and breast disorders Endometriosis	0.62% 1/160 • Number of events 1	0.00% 0/160	0.00% 0/158	0.00% 0/158
Respiratory, thoracic and mediastinal disorders Pulmonary Fibrosis	0.00% 0/160	0.62% 1/160 • Number of events 1	0.00% 0/158	0.00% 0/158

Other adverse events

Other adverse events
Measure	Placebo n=160 participants at risk Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo	0.5 mg BID TC-5214 n=160 participants at risk Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID	2 mg BID TC-5214 n=158 participants at risk Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 mg BID	4 mg BID TC-5214 n=158 participants at risk Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Eye disorders Vision Blurred	0.00% 0/160	0.62% 1/160 • Number of events 1	1.9% 3/158 • Number of events 3	3.8% 6/158 • Number of events 7
Gastrointestinal disorders Constipation	4.4% 7/160 • Number of events 8	7.5% 12/160 • Number of events 13	15.8% 25/158 • Number of events 28	28.5% 45/158 • Number of events 48
Gastrointestinal disorders Nausea	6.2% 10/160 • Number of events 11	4.4% 7/160 • Number of events 7	8.2% 13/158 • Number of events 13	6.3% 10/158 • Number of events 11
Gastrointestinal disorders Dry Mouth	1.2% 2/160 • Number of events 3	3.8% 6/160 • Number of events 6	7.0% 11/158 • Number of events 11	7.0% 11/158 • Number of events 11
Gastrointestinal disorders Diarrhoea	6.2% 10/160 • Number of events 10	6.2% 10/160 • Number of events 11	5.1% 8/158 • Number of events 8	6.3% 10/158 • Number of events 11
Gastrointestinal disorders Abdominal Distension	0.62% 1/160 • Number of events 1	1.2% 2/160 • Number of events 2	3.2% 5/158 • Number of events 5	1.9% 3/158 • Number of events 3
Gastrointestinal disorders Vomiting	3.1% 5/160 • Number of events 5	0.62% 1/160 • Number of events 1	3.2% 5/158 • Number of events 6	2.5% 4/158 • Number of events 4
Gastrointestinal disorders Dyspepsia	0.62% 1/160 • Number of events 1	2.5% 4/160 • Number of events 5	1.3% 2/158 • Number of events 2	1.9% 3/158 • Number of events 3
Gastrointestinal disorders Flatulence	0.00% 0/160	1.2% 2/160 • Number of events 2	2.5% 4/158 • Number of events 4	1.9% 3/158 • Number of events 3
General disorders Fatigue	3.8% 6/160 • Number of events 6	1.2% 2/160 • Number of events 2	2.5% 4/158 • Number of events 4	4.4% 7/158 • Number of events 8
General disorders Pyrexia	0.62% 1/160 • Number of events 2	3.1% 5/160 • Number of events 5	0.63% 1/158 • Number of events 1	0.00% 0/158
General disorders Asthenia	0.00% 0/160	0.62% 1/160 • Number of events 1	0.63% 1/158 • Number of events 1	2.5% 4/158 • Number of events 4
General disorders Pain	1.9% 3/160 • Number of events 3	2.5% 4/160 • Number of events 4	0.63% 1/158 • Number of events 2	1.9% 3/158 • Number of events 3
Infections and infestations Nasopharyngitis	4.4% 7/160 • Number of events 7	3.8% 6/160 • Number of events 6	4.4% 7/158 • Number of events 8	3.2% 5/158 • Number of events 5
Infections and infestations Bronchitis	3.8% 6/160 • Number of events 6	0.00% 0/160	0.00% 0/158	2.5% 4/158 • Number of events 4
Infections and infestations Upper Respiratory Tract Infection	3.8% 6/160 • Number of events 6	1.2% 2/160 • Number of events 2	3.8% 6/158 • Number of events 6	1.9% 3/158 • Number of events 3
Infections and infestations Sinusitis	2.5% 4/160 • Number of events 5	1.2% 2/160 • Number of events 2	1.9% 3/158 • Number of events 3	0.00% 0/158
Infections and infestations Aspartate Aminotransferase Increased	0.62% 1/160 • Number of events 1	0.62% 1/160 • Number of events 1	2.5% 4/158 • Number of events 4	0.00% 0/158
Metabolism and nutrition disorders Increased Appetite	0.62% 1/160 • Number of events 1	0.62% 1/160 • Number of events 1	2.5% 4/158 • Number of events 4	1.3% 2/158 • Number of events 2
Musculoskeletal and connective tissue disorders Back Pain	2.5% 4/160 • Number of events 4	1.2% 2/160 • Number of events 2	1.3% 2/158 • Number of events 2	0.63% 1/158 • Number of events 1
Musculoskeletal and connective tissue disorders Muscle Spasms	1.2% 2/160 • Number of events 2	0.00% 0/160	0.63% 1/158 • Number of events 1	2.5% 4/158 • Number of events 4
Musculoskeletal and connective tissue disorders Muscle Tightness	0.00% 0/160	0.62% 1/160 • Number of events 1	0.00% 0/158	2.5% 4/158 • Number of events 4
Musculoskeletal and connective tissue disorders Myalgia	1.9% 3/160 • Number of events 3	2.5% 4/160 • Number of events 4	1.9% 3/158 • Number of events 3	1.3% 2/158 • Number of events 2
Nervous system disorders Headache	13.8% 22/160 • Number of events 25	8.8% 14/160 • Number of events 19	9.5% 15/158 • Number of events 17	8.2% 13/158 • Number of events 14
Nervous system disorders Dizziness	1.9% 3/160 • Number of events 3	6.9% 11/160 • Number of events 11	5.1% 8/158 • Number of events 8	8.9% 14/158 • Number of events 14
Nervous system disorders Somnolence	3.1% 5/160 • Number of events 5	3.8% 6/160 • Number of events 6	2.5% 4/158 • Number of events 4	5.1% 8/158 • Number of events 8
Nervous system disorders Dizziness Postural	1.2% 2/160 • Number of events 2	0.62% 1/160 • Number of events 1	1.9% 3/158 • Number of events 5	3.2% 5/158 • Number of events 7
Nervous system disorders Akathisia	2.5% 4/160 • Number of events 4	0.00% 0/160	1.9% 3/158 • Number of events 3	0.63% 1/158 • Number of events 1
Psychiatric disorders Insomnia	5.6% 9/160 • Number of events 10	5.0% 8/160 • Number of events 8	5.1% 8/158 • Number of events 8	3.8% 6/158 • Number of events 7
Psychiatric disorders Abnormal Dreams	1.9% 3/160 • Number of events 3	1.2% 2/160 • Number of events 2	3.8% 6/158 • Number of events 6	1.3% 2/158 • Number of events 2
Psychiatric disorders Agitation	2.5% 4/160 • Number of events 4	3.1% 5/160 • Number of events 5	2.5% 4/158 • Number of events 4	1.3% 2/158 • Number of events 2
Psychiatric disorders Anxiety	0.62% 1/160 • Number of events 1	1.9% 3/160 • Number of events 3	2.5% 4/158 • Number of events 4	1.3% 2/158 • Number of events 2
Renal and urinary disorders Pollakiuria	0.00% 0/160	0.62% 1/160 • Number of events 1	0.00% 0/158	3.2% 5/158 • Number of events 5
Vascular disorders Orthostatic Hypotension	1.2% 2/160 • Number of events 3	0.62% 1/160 • Number of events 1	0.63% 1/158 • Number of events 5	3.2% 5/158 • Number of events 5
Vascular disorders Hypertension	2.5% 4/160 • Number of events 4	1.9% 3/160 • Number of events 3	0.63% 1/158 • Number of events 1	0.63% 1/158 • Number of events 1

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