A Study in Prevention of Re-emergence of Depression Symptoms

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01299272
• Collaborator: (none)
• Enrollment: 1,249
• Locations: 77
• Arms: 2
• Duration (Months): 30.1
• Patients Per Site: 16.2
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The primary objective of this study was to assess the maintenance of efficacy of LY2216684 compared with placebo as adjunctive therapy to selective serotonin reuptake inhibitors (SSRIs) as measured by the time-to-symptom reemergence among participants with major depressive disorder (MDD) who met randomization criteria with adjunctive LY2216684 during the stabilization period.

This trial consists of two distinct periods: an open-label treatment period, which consists of two parts, 8 weeks acute open-label with movement to 12 weeks open-label stabilization if participants are in remission at end of 8 weeks (open-label for 20 weeks total) followed by a randomized, double-blind, placebo-controlled period for 24 weeks.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: LY2216684; Drug: Placebo; Drug: SSRI	Phase 3

Detailed Description

In order to enter the Stabilization Open-label Period, participants must have met remission criteria, defined as a Montgomery-Asberg Depression Rating Scale (MADRS) total score ≤10 at Week 8. In order to enter the Double-blind Randomization Withdrawal Period, participants must have met randomization criteria, defined as a MADRS total score ≤10 at Weeks 18, 19, and 20.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1249 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: LY2216684 Compared to Placebo as Adjunctive Therapy to SSRI in the Prevention of Symptom Re-emergence in Major Depressive Disorder
• Study Start Date: May 1, 2011
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY2216684 + SSRI Acute Open-label (OL) Period: Participants received a starting dose of 12 milligrams (mg) LY2216684, administered orally, once daily for at least 2 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). Then, based on efficacy and tolerability, the dose could be increased to 18 mg (and decreased back to 12 mg) over the next 6 weeks. Stabilization OL Period: Participants meeting remission criteria continued on the same dose of LY2216684 for an additional 12 weeks. Participants who discontinued early during either OL Period were discontinued abruptly from LY2216684. Double-blind (DB) Randomized Withdrawal Period: At 20 weeks, participants meeting criteria for randomization continued their current dose of LY2216684 for another 24 weeks. Participants who completed this period or discontinued early were randomized to abrupt (placebo for 2 weeks) or tapered (12 mg LY2216684 for 4 days, 6 mg LY2216684 for 4 days, then placebo for 6 days) discontinuation of LY2216684.	Drug: LY2216684; Other Names: Edivoxetine ; Drug: SSRI; Participants should have been on their SSRI for at least 8 weeks prior and were to continue on their stable dose throughout the study.; Other Names: Selective Serotonin Reuptake Inhibitor
Placebo Comparator: Placebo + SSRI Acute Open-label (OL) Period: Participants received a starting dose of 12 milligrams (mg) LY2216684, administered orally, once daily for at least 2 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). Then, based on efficacy and tolerability, the dose could be increased to 18 mg (and decreased back to 12 mg) over the next 6 weeks. Stabilization OL Period: Participants meeting remission criteria continued on the same dose of LY2216684 for an additional 12 weeks. Participants who discontinued early during either OL Period were discontinued abruptly from LY2216684. Double-blind (DB) Randomized Withdrawal Period: At 20 weeks, participants meeting criteria for randomization were tapered from their LY2216684 dose to placebo following the regimen of 12 mg for 7 days, 6 mg for 7 days, and placebo for the remaining 22 weeks. Participants who completed this period or discontinued early continued to receive placebo for an additional 2 weeks	Drug: LY2216684; Other Names: Edivoxetine ; Drug: Placebo; Drug: SSRI; Participants should have been on their SSRI for at least 8 weeks prior and were to continue on their stable dose throughout the study.; Other Names: Selective Serotonin Reuptake Inhibitor

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Meet Criteria for Re-emergence of Depressive Symptoms Estimated by Kaplan-Meier Product Limit Method (Double-blind Randomized Withdrawal Period) [Randomization up to 44 weeks]

   Participants meeting any of the following criteria were determined as having major depressive disorder symptom re-emergence: 1) a Montgomery-Asberg Depression Rating Scale (MADRS) total score greater ≥14 or a Clinical Global Impressions of Severity (CGI-S) increase of 2 or more points from Week 18 at 2 consecutive visits or 2) discontinuation due to lack of efficacy/worsening of depression/suicidality. Time from randomization to the first visit at which the participant met the reemergence criteria was calculated. The percentage of participants who meet criteria was estimated using the Kaplan-Meier product limit method. The MADRS is a rating scale for severity of depressive mood symptoms and has a 10-item checklist with items rated on a scale of 0-6, for a total score range of 0 (low severity) to 60 (high severity). CGI-S measures severity of depression at the time of assessment compared with the start of treatment. Scores range from 1 (normal, not at all ill) to 7 (extremely ill).

Secondary Outcome Measures

1. Percentage of Participants With Re-emergence of Depressive Symptoms (Double-blind Randomized Withdrawal Period) [Week 44]

   Participants meeting any of the following criteria were determined as having major depressive disorder symptom re-emergence: 1) a Montgomery-Asberg Depression Rating Scale (MADRS) total score greater ≥14 or a Clinical Global Impressions of Severity (CGI-S) increase of 2 or more points from Week 18 at 2 consecutive visits or 2) discontinuation due to lack of efficacy/worsening of depression/suicidality. The percentage of participants with re-emergence of depressive symptoms was calculated by dividing the number of participants who meet any of the criteria by the total number of participants analyzed, multiplied by 100. The MADRS is a rating scale for severity of depressive mood symptoms and has a 10-item checklist with items rated on a scale of 0-6, for a total score range of 0 (low severity) to 60 (high severity). CGI-S measures severity of depression at the time of assessment compared with the start of treatment. Scores range from 1 (normal, not at all ill) to 7 (extremely ill).

2. Change From Randomization in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Item Scores at Week 44 (Double-blind Randomized Withdrawal Period) [Randomization, Week 44]

   Montgomery-Asberg Depression Rating Scale (MADRS) is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist (sadness [apparent], sadness [reported], inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which includes terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline MADRS total score (individual item score) and baseline MADRS total score (individual item score)-by-visit interaction.

3. Change From Randomization in the Hospital Anxiety and Depression Scale (HADS) Depression and Anxiety Subscale Scores at Week 44 (Double-blind Randomized Withdrawal Period) [Randomization, Week 44]

   The Hospital Anxiety and Depression Scale (HADS) is a 14-item questionnaire with 2 subscales: anxiety and depression. Each item is rated on a 4-point scale (0-3), giving maximum scores of 21 for anxiety and depression. Scores of 11 or more on either subscale are considered to be a 'significant' case of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7 represent 'normal'. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline subscale score and baseline subscale score-by-visit interaction.

4. Change From Randomization in the Clinical Global Impression of Severity (CGI-S) Scores at Week 44 (Double-blind Randomized Withdrawal Period) [Randomization, Week 44]

   The Clinical Global Impression of Severity (CGI-S) instrument is used to record the severity of mental illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline CGI-S score and baseline CGI-S score-by-visit interaction.

5. Change From Randomization in the Fatigue Associated With Depression (FAsD) Average Score, Experience Subscale Score, and Impact Subscale Score at Week 44 (Double-blind Randomized Withdrawal Period) [Randomization, Week 44]

   The FAsD is a 13-item participant-rated scale. Items 1-6 ask how often participants experience different aspects of fatigue with responses from 1 (never) to 5 (always). Items 7-13 ask how often fatigue impacts various aspects of the participant's lives with responses from 1 (not at all) to 5 (very much). The experience subscale score is derived by taking the mean of Items 1-6. The impact subscale score is derived by taking the mean of applicable Items 7-13. The average score is the mean of applicable Items 1-13. Item 12 applies only to participants with a spouse or significant other and Item 13 applies to participants who had a job or who went to school. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline score and baseline score-by-visit interaction.

6. Change From Randomization in the Sheehan Disability Scale (SDS) Items at Week 44 (Double-blind Randomized Withdrawal Period) [Randomization, Week 44]

   The Sheehan Disability Scale (SDS) is completed by the participant and used to assess the effect of the participant's symptoms on their work (work/school impairment score), social life (social life/leisure activities impairment score), and family life (family life/home responsibilities impairment score). Each item is measured on a 0 (not at all) to 10 (extremely) point scale with higher values indicating greater disruption. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline score and baseline score-by-visit interaction

7. Change From Randomization in the EuroQol Questionnaire-5 Dimension (EQ-5D) Index Scores, Visual Analog Scale up to Week 44 (Double-blind Randomized Withdrawal Period) [Randomization, up to Week 44]

   The EQ-5D, a health-related, quality-of-life instrument, contains 2 parts: a health status profile and a visual analog scale (VAS). The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a 3-level scale (no problem, some problems, and major problems). These dimensions are converted into weighted health-state index scores according to United States (US) and United Kingdom (UK) population-based algorithms. The US and UK based index scores range from -0.11 to 1.0 (where a score of 1.0 indicates perfect health) and from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension), respectively. The VAS consists of participants rating their current health state from 0 (worst imaginable health state) to 100 (best imaginable health). Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) model with main effects of treatment, country, and baseline score.

8. Number of Participants With Treatment-emergent Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) (Double-blind Randomized Withdrawal Period) [Randomization through Week 44]

   The Columbia-Suicide Severity Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation is defined as a "yes" answer to any 1 of 5 suicidal ideation questions, which includes a wish to be dead and 4 different categories of active suicidal ideation. Suicidal behavior is defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation and behavior are defined as treatment-emergent (TE) if not present during the period up through randomization. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module.

9. Change From Randomization in the Arizona Sexual Experiences (ASEX) Questionnaire at Week 44 (Double-blind Randomized Withdrawal Period) [Randomization, Week 44]

   Arizona Sexual Experiences (ASEX) Questionnaire is a 5-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. Each item is rated from 1 (extremely) to 6 (no/never). Possible total scores ranged from 5 to 30, with the higher scores indicating more sexual dysfunction. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline ASEX total score and baseline ASEX total score-by-visit interaction.

10. Change From Randomization in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) Total Score at Week 44 (Double-blind Randomized Withdrawal Period) [Randomization, Week 44]

    Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) is a 7-item participant-rated questionnaire pertaining to a participant's cognitive and physical well-being. It assesses motivation, wakefulness, energy, focus, recall, word-finding difficulty, and mental acuity. Each item is scored on a 6-point scale ranging from 1 (greater than normal) to 6 (totally absent). Total score is reported and ranges from 7 to 42, with higher scores indicating greater impairment. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline CPFQ total score and baseline CPFQ total score-by-visit interaction.

11. Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Item Scores up to Week 8 (Acute Open-label Period) [Baseline, up to Week 8]

    Montgomery-Asberg Depression Rating Scale (MADRS) is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist (sadness [apparent], sadness [reported], inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).

12. Change From Week 8 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Item Scores up to Week 20 (Stabilization Open-label Period) [Week 8, up to Week 20]

    Montgomery-Asberg Depression Rating Scale (MADRS) is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist (sadness [apparent], sadness [reported], inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).

13. Change From Baseline in the Hospital Anxiety and Depression Scale (HADS) Depression and Anxiety Subscale Scores up to Week 8 (Acute Open-label Period) [Baseline, up to Week 8]

    The Hospital Anxiety and Depression Scale (HADS) is a 14-item questionnaire with 2 subscales: anxiety and depression. Each item is rated on a 4-point scale (0-3), giving maximum scores of 21 for anxiety and depression. Scores of 11 or more on either subscale were considered to be a 'significant' case of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7 represent 'normal'.

14. Change From Week 8 in the Hospital Anxiety and Depression Scale (HADS) Depression and Anxiety Subscale Scores up to Week 20 (Stabilization Open-label Period) [Week 8, up to Week 20]

    The Hospital Anxiety and Depression Scale (HADS) is a 14-item questionnaire with 2 subscales: anxiety and depression. Each item is rated on a 4-point scale (0-3), giving maximum scores of 21 for anxiety and depression. Scores of 11 or more on either subscale are considered to be a 'significant' case of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7 represent 'normal'.

15. Change From Baseline in the Clinical Global Impression of Severity (CGI-S) Scores up to Week 8 (Acute Open-label Period) [Baseline, up to Week 8]

    The Clinical Global Impression of Severity (CGI-S) instrument is used to record the severity of mental illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants).

16. Change From Week 8 in the Clinical Global Impression of Severity (CGI-S) Scores up to Week 20 (Stabilization Open-label Period) [Week 8, up to Week 20]

    The Clinical Global Impression of Severity (CGI-S) instrument is used to record the severity of mental illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants).

17. Change From Baseline in the Fatigue Associated With Depression (FAsD) Average Score, Experience Subscale Score, and Impact Subscale Score up to Week 8 (Acute Open-label Period) [Baseline, up to Week 8]

    The Fatigue Associated With Depression (FAsD) is a 13-item participant-rated scale. Items 1-6 ask how often participants experience different aspects of fatigue with responses from 1 (never) to 5 (always). Items 7-13 ask how often fatigue impacts various aspects of the participant's lives with responses from 1 (not at all) to 5 (very much). The experience subscale score is derived by taking the mean of Items 1-6. The impact subscale score is derived by taking the mean of applicable Items 7-13. The average score is the mean of applicable Items 1-13. Item 12 applies only to participants with a spouse or significant other and Item 13 applies to participants who had a job or who went to school.

18. Change From Week 8 in the Fatigue Associated With Depression (FAsD) Average Score, Experience Subscale Score, and Impact Subscale Score up to Week 20 (Stabilization Open-label Period) [Week 8, up to Week 20]

    The Fatigue Associated with Depression (FAsD) is a 13-item participant-rated scale. Items 1-6 ask how often participants experience different aspects of fatigue with responses from 1 (never) to 5 (always). Items 7-13 ask how often fatigue impacts various aspects of the participant's lives with responses from 1 (not at all) to 5 (very much). The experience subscale score is derived by taking the mean of Items 1-6. The impact subscale score is derived by taking the mean of applicable Items 7-13. The average score is the mean of applicable Items 1-13. Item 12 applies only to participants with a spouse or significant other and Item 13 applies to participants who had a job or who went to school.

19. Change From Baseline in the Sheehan Disability Scale (SDS) Items up to Week 8 (Acute Open-label Period) [Baseline, up to Week 8]

    The Sheehan Disability Scale (SDS) is completed by the participant and used to assess the effect of the participant's symptoms on their work (work/school impairment score), social life (social life/leisure activities impairment score), and family life (family life/home responsibilities impairment score). Each item is measured on a 0 (not at all) to 10 (extremely) point scale with higher values indicating greater disruption.

20. Change From Week 8 in the Sheehan Disability Scale (SDS) Items up to Week 20 (Stabilization Open-label Period) [Week 8, up to Week 20]

    The Sheehan Disability Scale (SDS) is completed by the participant and used to assess the effect of the participant's symptoms on their work (work/school impairment score), social life (social life/leisure activities impairment score), and family life (family life/home responsibilities impairment score). Each item is measured on a 0 (not at all) to 10 (extremely) point scale with higher values indicating greater disruption.

21. Change From Baseline in the EuroQol Questionnaire-5 Dimension (EQ-5D) Index Scores, Visual Analog Scale up to Week 20 (Open-label Period) [Baseline, up to Week 20]

    The EQ-5D, a health-related, quality-of-life instrument, contains 2 parts: a health status profile and a visual analog scale (VAS). The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a 3-level scale (no problem, some problems, and major problems). These dimensions are converted into weighted health-state index scores according to United States (US) and United Kingdom (UK) population-based algorithms. The US and UK based index scores range from -0.11 to 1.0 (where a score of 1.0 indicates perfect health) and from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension), respectively. The VAS consists of participants rating their current health state from 0 (worst imaginable health state) to 100 (best imaginable health).

22. Number of Participants With Treatment-emergent Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) (Open-label Period) [Baseline through Week 20]

    The Columbia-Suicide Severity Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation is defined as a "yes" answer to any 1 of 5 suicidal ideation questions, which included a wish to be dead and 4 different categories of active suicidal ideation. Suicidal behavior is defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation and behavior are defined as treatment-emergent (TE) if not present at baseline. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module.

23. Change From Baseline in the Arizona Sexual Experiences (ASEX) Questionnaire up to Week 20 (Open-label Period) [Baseline, up to Week 20]

    Arizona Sexual Experiences (ASEX) Questionnaire is a 5-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. Each item is rated from 1 (extremely) to 6 (no/never). Possible total scores ranged from 5 to 30, with the higher scores indicating more sexual dysfunction.

24. Change From Baseline in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) Total Score at Week 20 (Open-label Period) [Baseline, up to Week 20]

    Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) is a 7-item participant-rated questionnaire pertaining to a participant's cognitive and physical well-being. It assesses motivation, wakefulness, energy, focus, recall, word-finding difficulty, and mental acuity. Each item is scored on a 6-point scale ranging from 1 (greater than normal) to 6 (totally absent). Total score is reported and ranges from 7 to 42, with higher scores indicating greater impairment.

25. Change From Randomization in Blood Pressure at Week 44 (Double-blind Randomized Withdrawal Period) [Randomization, Week 44]

    Blood pressure measurements were taken 3 times at each visit in a sitting position. The average of the 3 values was used for analysis. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline and baseline-by-visit interaction.

26. Change From Baseline in Blood Pressure up to Week 20 (Open-label Period) [Baseline, up to Week 20]

    Blood pressure measurements were taken 3 times at each visit in a sitting position. The average of the 3 values was used for analysis.

27. Change From Randomization in Pulse Rate at Week 44 (Double-blind Randomized Withdrawal Period) [Randomization, Week 44]

    Pulse rate measurements were collected when the participant was in a sitting position. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline and baseline-by-visit interaction.

28. Change From Baseline in Pulse Rate up to Week 20 (Open-label Period) [Baseline, up to Week 20]

    Pulse measurements were collected when the participant was in a sitting position.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Outpatients with clinical diagnosis of Major Depressive Disorder (MDD)

• Using a reliable method of birth control

• Are taking a selective serotonin reuptake inhibitor (SSRI) approved for MDD treatment within the participant's country and the SSRI prescribed, including dose, should be consistent with labeling guidelines within the participating country

• Have a partial response to SSRI treatment

• Meet inclusion scores on pre-defined psychiatric scales to assess diagnosis of depression, disease severity, and response to SSRI treatment

• Reliable and able to keep all scheduled appointments

• Have had at least 1 previous episode of MDD prior to the current episode within the past 5 years

Exclusion Criteria:

• Have had or currently have any additional ongoing Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) Axis 1 condition other than major depression within 1 year of screening

• Have a current or any previous diagnosis of a bipolar disorder, schizophrenia, or other psychotic disorder

• Have a history of substance abuse and/or dependence within the past 1 year (drug categories defined by DSM-IV-TR), not including caffeine and nicotine.

• Have a DSM-IV-TR Axis II disorder that, in the judgment of the investigator, would interfere with compliance with protocol

• Have any diagnosed medical condition which could be exacerbated by noradrenergic agents, including unstable hypertension, unstable heart disease, tachycardia, tachyarrhythmia, narrow-angle glaucoma, or history of urinary hesitation or retention

• Have initiated or discontinued hormone therapy (including birth control or thyroid hormone) within the previous 3 months prior to enrollment

• Have a lifetime history of vagal nerve stimulation (VNS), transcranial magnetic stimulation (TMS), or psychosurgery

• Have received electroconvulsive therapy (ECT) in the past year

• Have a serious or unstable medical condition

• Have a history of seizure disorders

• Have initiated psychotherapy, change in intensity of psychotherapy or other nondrug therapies (such as acupuncture or hypnosis) within 6 weeks prior to enrollment or any time during the study

• Participants who, in the opinion of the investigator, are judged to be at serious risk for harm to self or others

• Are pregnant or breastfeeding

• Meet criteria for treatment-resistant depression

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Redlands	California	United States	92374
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Sherman Oaks	California	United States	91403
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Wildomar	California	United States	92595
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Coral Gables	Florida	United States	33145
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Gainesville	Florida	United States	32607
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Atlanta	Georgia	United States	30338
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Libertyville	Illinois	United States	60048
8	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lafayette	Indiana	United States	47905
9	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Terre Haute	Indiana	United States	47802
10	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Prairie Village	Kansas	United States	66206
11	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Boston	Massachusetts	United States	02131
12	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Las Vegas	Nevada	United States	89104
13	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Cherry Hill	New Jersey	United States	08002
14	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Albuquerque	New Mexico	United States	87109
15	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Brooklyn	New York	United States	11214
16	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	New York	New York	United States	10021
17	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Rochester	New York	United States	14618
18	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Staten Island	New York	United States	10312
19	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Charlotte	North Carolina	United States	28211
20	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Greensboro	North Carolina	United States	27408
21	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Cincinnati	Ohio	United States	45219
22	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Oklahoma City	Oklahoma	United States	73109
23	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Philadelphia	Pennsylvania	United States	19139
24	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Austin	Texas	United States	78756
25	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Clinton	Utah	United States	84015
26	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Spokane	Washington	United States	99204
27	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Middleton	Wisconsin	United States	53562
28	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Buenos Aires		Argentina	C1058AAJ
29	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Córdoba		Argentina	X5009BIN
30	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	La Plata		Argentina	1900
31	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Heusden-Zolder		Belgium	3550
32	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Split		Croatia	21000
33	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Zagreb		Croatia	10000
34	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Arcachon		France	33120
35	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Caen		France	14000
36	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Dole		France	39100
37	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Douai		France	59500
38	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Elancourt		France	78990
39	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fains		France	55000
40	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Toulon		France	83000
41	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Toulouse		France	31000
42	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Dresden		Germany	01307
43	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hamburg		Germany	22143
44	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hannover		Germany	30159
45	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Oranienburg		Germany	16515
46	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Haidari		Greece	12462
47	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Thessaloniki		Greece	56429
48	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tripoli		Greece	22100
49	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Camaiore-Viareggio		Italy	55043
50	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Catania		Italy	95125
51	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Colleferro		Italy	00034
52	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ferrara		Italy	44100
53	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Siena		Italy	53100
54	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Gwangju		Korea, Republic of	501-757
55	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Seoul		Korea, Republic of	137-040
56	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fracc. Bosques Del Prado Norte		Mexico	20217
57	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Guadalajara		Mexico	45170
58	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ponce		Puerto Rico	00731-7779
59	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	San Juan		Puerto Rico	00927
60	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bucharest		Romania	041914
61	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Focsani		Romania	620165
62	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Targu Mures		Romania	540139
63	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Moscow		Russian Federation	115522
64	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Saint Petersburg		Russian Federation	190121
65	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Smolensk		Russian Federation	214019
66	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Stavropol		Russian Federation	355038
67	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tomsk		Russian Federation	634014
68	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Banska Bystrica		Slovakia	97409
69	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bratislava		Slovakia	81107
70	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Svidnik		Slovakia	08901
71	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Zvolen		Slovakia	96001
72	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Madrid		Spain	28029
73	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Palma De Mallorca		Spain	07013
74	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Salamanca		Spain	37003
75	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Sevilla		Spain	41700
76	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Adapazari		Turkey	200130
77	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Diyarbakir		Turkey	21280

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01299272
• Other Study ID Numbers: 11317; H9P-MC-LNBN
• First Posted: Feb 18, 2011
• Last Update Posted: Apr 17, 2018
• Last Verified: Mar 1, 2018

• Additional relevant MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major; Serotonin; Serotonin Uptake Inhibitors

Study Results

Participant Flow

Pre-assignment Detail	All enrolled participants entered the Acute Open-label (OL) Period. At Week 8, if remission criteria were met, participants entered the Stabilization OL Period. At Week 20, if randomization criteria were met, participants entered the 24-week Double-blind Randomized Withdrawal Period. Those who discontinued early entered the Discontinuation Period.

Arm/Group Title	LY2216684 + SSRI (Acute Open-label Period)	LY2216684 + SSRI (Stabilization Open-label Period)	LY2216684 + SSRI (Double-blind Randomized Withdrawal Period)	Placebo + SSRI (Double-blind Randomized Withdrawal Period)
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI).	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD for an additional 12 weeks.	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Period Title: Acute Open-label (OL) Period
STARTED	1249	0	0	0
Entered Discontinuation (DC) Period	271	0	0	0
COMPLETED	835	0	0	0
NOT COMPLETED	414	0	0	0
Period Title: Acute Open-label (OL) Period
STARTED	0	835	0	0
Entered Discontinuation (DC) Period	0	164	0	0
COMPLETED	0	586	0	0
NOT COMPLETED	0	249	0	0
Period Title: Acute Open-label (OL) Period
STARTED	0	0	294	292
Entered Taper Discontinuation Period	0	0	129	0
Entered Abrupt Discontinuation Period	0	0	132	268
COMPLETED	0	0	224	234
NOT COMPLETED	0	0	70	58

Baseline Characteristics

Arm/Group Title	All Enrolled Participants
Arm/Group Description	All enrolled participants started on a flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for an additional 12 weeks. At 20 weeks, participants meeting criteria for randomization either 1) continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks or 2) were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Overall Participants	1249
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.4 (12.54)
Sex: Female, Male (Count of Participants)
Female	917 73.4%
Male	332 26.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	50 4%
Asian	21 1.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	99 7.9%
White	1066 85.3%
More than one race	13 1%
Unknown or Not Reported	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	254 20.3%
Not Hispanic or Latino	622 49.8%
Unknown or Not Reported	373 29.9%
Region of Enrollment (Count of Participants)
United States	535 42.8%
Slovakia	65 5.2%
Greece	43 3.4%
Spain	43 3.4%
Turkey	30 2.4%
Russia	96 7.7%
Italy	44 3.5%
France	61 4.9%
Mexico	63 5%
Puerto Rico	77 6.2%
Argentina	62 5%
Belgium	11 0.9%
Croatia	9 0.7%
Romania	19 1.5%
Germany	73 5.8%
South Korea	18 1.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Meet Criteria for Re-emergence of Depressive Symptoms Estimated by Kaplan-Meier Product Limit Method (Double-blind Randomized Withdrawal Period)
Description	Participants meeting any of the following criteria were determined as having major depressive disorder symptom re-emergence: 1) a Montgomery-Asberg Depression Rating Scale (MADRS) total score greater ≥14 or a Clinical Global Impressions of Severity (CGI-S) increase of 2 or more points from Week 18 at 2 consecutive visits or 2) discontinuation due to lack of efficacy/worsening of depression/suicidality. Time from randomization to the first visit at which the participant met the reemergence criteria was calculated. The percentage of participants who meet criteria was estimated using the Kaplan-Meier product limit method. The MADRS is a rating scale for severity of depressive mood symptoms and has a 10-item checklist with items rated on a scale of 0-6, for a total score range of 0 (low severity) to 60 (high severity). CGI-S measures severity of depression at the time of assessment compared with the start of treatment. Scores range from 1 (normal, not at all ill) to 7 (extremely ill).
Time Frame	Randomization up to 44 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Measure Participants	294	292
Number [percentage of participants]	10.43 0.8%	8.24 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY2216684 + SSRI, Placebo + SSRI
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.485
	Comments
	Method	Log Rank
	Comments

2. Secondary Outcome

Title	Percentage of Participants With Re-emergence of Depressive Symptoms (Double-blind Randomized Withdrawal Period)
Description	Participants meeting any of the following criteria were determined as having major depressive disorder symptom re-emergence: 1) a Montgomery-Asberg Depression Rating Scale (MADRS) total score greater ≥14 or a Clinical Global Impressions of Severity (CGI-S) increase of 2 or more points from Week 18 at 2 consecutive visits or 2) discontinuation due to lack of efficacy/worsening of depression/suicidality. The percentage of participants with re-emergence of depressive symptoms was calculated by dividing the number of participants who meet any of the criteria by the total number of participants analyzed, multiplied by 100. The MADRS is a rating scale for severity of depressive mood symptoms and has a 10-item checklist with items rated on a scale of 0-6, for a total score range of 0 (low severity) to 60 (high severity). CGI-S measures severity of depression at the time of assessment compared with the start of treatment. Scores range from 1 (normal, not at all ill) to 7 (extremely ill).
Time Frame	Week 44

Outcome Measure Data

Analysis Population Description

All randomized participants.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Measure Participants	294	292
Number [percentage of participants]	9.9 0.8%	8.2 NaN

3. Secondary Outcome

Title	Change From Randomization in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Item Scores at Week 44 (Double-blind Randomized Withdrawal Period)
Description	Montgomery-Asberg Depression Rating Scale (MADRS) is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist (sadness [apparent], sadness [reported], inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which includes terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline MADRS total score (individual item score) and baseline MADRS total score (individual item score)-by-visit interaction.
Time Frame	Randomization, Week 44

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Measure Participants	290	292
MADRS Total Score	0.40 (0.33)	0.34 (0.33)
Item 1: Apparent Sadness	0.09 (0.05)	0.08 (0.05)
Item 2: Reported Sadness	0.09 (0.06)	0.05 (0.06)
Item 3: Inner Tension	0.06 (0.07)	0.14 (0.06)
Item 4: Reduced Sleep	-0.02 (0.07)	-0.06 (0.07)
Item 5: Reduced Appetite	0.00 (0.04)	-0.00 (0.04)
Item 6: Concentration Difficulties	0.07 (0.06)	0.08 (0.06)
Item 7: Lassitude	0.02 (0.06)	0.07 (0.06)
Item 8: Inability to Feel	-0.00 (0.05)	-0.05 (0.05)
Item 9: Pessimistic Thoughts	-0.01 (0.05)	-0.02 (0.04)
Item 10: Suicidal Thoughts	0.02 (0.02)	0.01 (0.02)

4. Secondary Outcome

Title	Change From Randomization in the Hospital Anxiety and Depression Scale (HADS) Depression and Anxiety Subscale Scores at Week 44 (Double-blind Randomized Withdrawal Period)
Description	The Hospital Anxiety and Depression Scale (HADS) is a 14-item questionnaire with 2 subscales: anxiety and depression. Each item is rated on a 4-point scale (0-3), giving maximum scores of 21 for anxiety and depression. Scores of 11 or more on either subscale are considered to be a 'significant' case of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7 represent 'normal'. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline subscale score and baseline subscale score-by-visit interaction.
Time Frame	Randomization, Week 44

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Measure Participants	286	285
HADS Anxiety Subscale Score	-0.00 (0.22)	0.15 (0.22)
HADS Depression Subscale Score	-0.18 (0.23)	0.15 (0.23)

5. Secondary Outcome

Title	Change From Randomization in the Clinical Global Impression of Severity (CGI-S) Scores at Week 44 (Double-blind Randomized Withdrawal Period)
Description	The Clinical Global Impression of Severity (CGI-S) instrument is used to record the severity of mental illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline CGI-S score and baseline CGI-S score-by-visit interaction.
Time Frame	Randomization, Week 44

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Measure Participants	290	292
Least Squares Mean (Standard Error) [units on a scale]	0.01 (0.05)	-0.00 (0.05)

6. Secondary Outcome

Title	Change From Randomization in the Fatigue Associated With Depression (FAsD) Average Score, Experience Subscale Score, and Impact Subscale Score at Week 44 (Double-blind Randomized Withdrawal Period)
Description	The FAsD is a 13-item participant-rated scale. Items 1-6 ask how often participants experience different aspects of fatigue with responses from 1 (never) to 5 (always). Items 7-13 ask how often fatigue impacts various aspects of the participant's lives with responses from 1 (not at all) to 5 (very much). The experience subscale score is derived by taking the mean of Items 1-6. The impact subscale score is derived by taking the mean of applicable Items 7-13. The average score is the mean of applicable Items 1-13. Item 12 applies only to participants with a spouse or significant other and Item 13 applies to participants who had a job or who went to school. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline score and baseline score-by-visit interaction.
Time Frame	Randomization, Week 44

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Measure Participants	286	286
FAsD Experience Subscale Score	-0.05 (0.05)	0.05 (0.05)
FAsD Impact Subscale Score	-0.06 (0.05)	-0.01 (0.05)
FAsD Average Score	-0.05 (0.05)	0.02 (0.05)

7. Secondary Outcome

Title	Change From Randomization in the Sheehan Disability Scale (SDS) Items at Week 44 (Double-blind Randomized Withdrawal Period)
Description	The Sheehan Disability Scale (SDS) is completed by the participant and used to assess the effect of the participant's symptoms on their work (work/school impairment score), social life (social life/leisure activities impairment score), and family life (family life/home responsibilities impairment score). Each item is measured on a 0 (not at all) to 10 (extremely) point scale with higher values indicating greater disruption. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline score and baseline score-by-visit interaction
Time Frame	Randomization, Week 44

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Measure Participants	289	289
Work Impairment Score	-0.24 (0.17)	0.02 (0.17)
Social Life Impairment Score	-0.17 (0.14)	-0.15 (0.14)
Family Life Impairment Score	-0.26 (0.14)	-0.08 (0.14)

8. Secondary Outcome

Title	Change From Randomization in the EuroQol Questionnaire-5 Dimension (EQ-5D) Index Scores, Visual Analog Scale up to Week 44 (Double-blind Randomized Withdrawal Period)
Description	The EQ-5D, a health-related, quality-of-life instrument, contains 2 parts: a health status profile and a visual analog scale (VAS). The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a 3-level scale (no problem, some problems, and major problems). These dimensions are converted into weighted health-state index scores according to United States (US) and United Kingdom (UK) population-based algorithms. The US and UK based index scores range from -0.11 to 1.0 (where a score of 1.0 indicates perfect health) and from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension), respectively. The VAS consists of participants rating their current health state from 0 (worst imaginable health state) to 100 (best imaginable health). Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) model with main effects of treatment, country, and baseline score.
Time Frame	Randomization, up to Week 44

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value. Last observation carried forward (LOCF) methodology was used.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Measure Participants	278	285
EQ-5D US	0.01 (0.01)	0.01 (0.01)
EQ-5D UK	0.01 (0.02)	0.01 (0.02)
VAS	1.87 (1.39)	0.61 (1.39)

9. Secondary Outcome

Title	Number of Participants With Treatment-emergent Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) (Double-blind Randomized Withdrawal Period)
Description	The Columbia-Suicide Severity Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation is defined as a "yes" answer to any 1 of 5 suicidal ideation questions, which includes a wish to be dead and 4 different categories of active suicidal ideation. Suicidal behavior is defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation and behavior are defined as treatment-emergent (TE) if not present during the period up through randomization. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module.
Time Frame	Randomization through Week 44

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Measure Participants	291	292
TE Suicidal Ideation	5 0.4%	4 NaN
TE Suicidal Behavior	1 0.1%	0 NaN

10. Secondary Outcome

Title	Change From Randomization in the Arizona Sexual Experiences (ASEX) Questionnaire at Week 44 (Double-blind Randomized Withdrawal Period)
Description	Arizona Sexual Experiences (ASEX) Questionnaire is a 5-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. Each item is rated from 1 (extremely) to 6 (no/never). Possible total scores ranged from 5 to 30, with the higher scores indicating more sexual dysfunction. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline ASEX total score and baseline ASEX total score-by-visit interaction.
Time Frame	Randomization, Week 44

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Measure Participants	280	277
Least Squares Mean (Standard Error) [units on a scale]	-0.39 (0.33)	-0.08 (0.33)

11. Secondary Outcome

Title	Change From Randomization in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) Total Score at Week 44 (Double-blind Randomized Withdrawal Period)
Description	Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) is a 7-item participant-rated questionnaire pertaining to a participant's cognitive and physical well-being. It assesses motivation, wakefulness, energy, focus, recall, word-finding difficulty, and mental acuity. Each item is scored on a 6-point scale ranging from 1 (greater than normal) to 6 (totally absent). Total score is reported and ranges from 7 to 42, with higher scores indicating greater impairment. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline CPFQ total score and baseline CPFQ total score-by-visit interaction.
Time Frame	Randomization, Week 44

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Measure Participants	286	286
Least Squares Mean (Standard Error) [units on a scale]	-0.27 (0.31)	-0.05 (0.31)

12. Secondary Outcome

Title	Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Item Scores up to Week 8 (Acute Open-label Period)
Description	Montgomery-Asberg Depression Rating Scale (MADRS) is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist (sadness [apparent], sadness [reported], inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
Time Frame	Baseline, up to Week 8

Outcome Measure Data

Analysis Population Description

All participants who have non-missing values at baseline and at least one post-baseline value. Last observation carried forward (LOCF) methodology was used.

Arm/Group Title	LY2216684 + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI).
Measure Participants	1214
MADRS Total Score	-13.21 (8.30)
Item 1: Apparent Sadness	-1.82 (1.37)
Item 2: Reported Sadness	-1.86 (1.39)
Item 3: Inner Tension	-1.24 (1.37)
Item 4: Reduced Sleep	-1.29 (1.57)
Item 5: Reduced Appetite	-0.65 (1.47)
Item 6: Concentration Difficulties	-1.49 (1.43)
Item 7: Lassitude	-1.74 (1.44)
Item 8: Inability to Feel	-1.65 (1.42)
Item 9: Pessimistic Thoughts	-1.23 (1.28)
Item 10: Suicidal Thoughts	-0.24 (0.70)

13. Secondary Outcome

Title	Change From Week 8 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Item Scores up to Week 20 (Stabilization Open-label Period)
Description	Montgomery-Asberg Depression Rating Scale (MADRS) is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist (sadness [apparent], sadness [reported], inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
Time Frame	Week 8, up to Week 20

Outcome Measure Data

Analysis Population Description

All participants who have non-missing values at Week 8 and at least one post-Week 8 value. Last observation carried forward (LOCF) methodology was used.

Arm/Group Title	LY2216684 + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD for 12 weeks.
Measure Participants	812
MADRS Total Score	-0.38 (6.09)
Item 1: Apparent Sadness	-0.01 (1.01)
Item 2: Reported Sadness	-0.08 (1.15)
Item 3: Inner Tension	-0.05 (1.18)
Item 4: Reduced Sleep	-0.12 (1.28)
Item 5: Reduced Appetite	0.00 (0.89)
Item 6: Concentration Difficulties	-0.06 (1.19)
Item 7: Lassitude	0.02 (1.19)
Item 8: Inability to Feel	-0.09 (1.08)
Item 9: Pessimistic Thoughts	-0.04 (0.87)
Item 10: Suicidal Thoughts	0.03 (0.47)

14. Secondary Outcome

Title	Change From Baseline in the Hospital Anxiety and Depression Scale (HADS) Depression and Anxiety Subscale Scores up to Week 8 (Acute Open-label Period)
Description	The Hospital Anxiety and Depression Scale (HADS) is a 14-item questionnaire with 2 subscales: anxiety and depression. Each item is rated on a 4-point scale (0-3), giving maximum scores of 21 for anxiety and depression. Scores of 11 or more on either subscale were considered to be a 'significant' case of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7 represent 'normal'.
Time Frame	Baseline, up to Week 8

Outcome Measure Data

Analysis Population Description

All participants who have non-missing values at baseline and at least one post-baseline value. Last observation carried forward (LOCF) methodology was used.

Arm/Group Title	LY2216684 + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI).
Measure Participants	1199
HADS Anxiety Subscale Score	-3.02 (3.92)
HADS Depression Subscale Score	-3.98 (4.41)

15. Secondary Outcome

Title	Change From Week 8 in the Hospital Anxiety and Depression Scale (HADS) Depression and Anxiety Subscale Scores up to Week 20 (Stabilization Open-label Period)
Description	The Hospital Anxiety and Depression Scale (HADS) is a 14-item questionnaire with 2 subscales: anxiety and depression. Each item is rated on a 4-point scale (0-3), giving maximum scores of 21 for anxiety and depression. Scores of 11 or more on either subscale are considered to be a 'significant' case of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7 represent 'normal'.
Time Frame	Week 8, up to Week 20

Outcome Measure Data

Analysis Population Description

All participants who have non-missing values at Week 8 and at least one post-Week 8 value. Last observation carried forward (LOCF) methodology was used.

Arm/Group Title	LY2216684 + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD for 12 weeks.
Measure Participants	781
HADS Anxiety Subscale Score	-0.77 (3.73)
HADS Depression Subscale Score	-0.74 (3.57)

16. Secondary Outcome

Title	Change From Baseline in the Clinical Global Impression of Severity (CGI-S) Scores up to Week 8 (Acute Open-label Period)
Description	The Clinical Global Impression of Severity (CGI-S) instrument is used to record the severity of mental illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants).
Time Frame	Baseline, up to Week 8

Outcome Measure Data

Analysis Population Description

All participants who have non-missing values at baseline and at least one post-baseline value. Last observation carried forward (LOCF) methodology was used.

Arm/Group Title	LY2216684 + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI).
Measure Participants	1214
Mean (Standard Deviation) [units on a scale]	-1.51 (1.17)

17. Secondary Outcome

Title	Change From Week 8 in the Clinical Global Impression of Severity (CGI-S) Scores up to Week 20 (Stabilization Open-label Period)
Description	The Clinical Global Impression of Severity (CGI-S) instrument is used to record the severity of mental illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants).
Time Frame	Week 8, up to Week 20

Outcome Measure Data

Analysis Population Description

All participants who have non-missing values at Week 8 and at least one post-Week 8 value. Last observation carried forward (LOCF) methodology was used.

Arm/Group Title	LY2216684 + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD for 12 weeks.
Measure Participants	812
Mean (Standard Deviation) [units on a scale]	-0.25 (0.95)

18. Secondary Outcome

Title	Change From Baseline in the Fatigue Associated With Depression (FAsD) Average Score, Experience Subscale Score, and Impact Subscale Score up to Week 8 (Acute Open-label Period)
Description	The Fatigue Associated With Depression (FAsD) is a 13-item participant-rated scale. Items 1-6 ask how often participants experience different aspects of fatigue with responses from 1 (never) to 5 (always). Items 7-13 ask how often fatigue impacts various aspects of the participant's lives with responses from 1 (not at all) to 5 (very much). The experience subscale score is derived by taking the mean of Items 1-6. The impact subscale score is derived by taking the mean of applicable Items 7-13. The average score is the mean of applicable Items 1-13. Item 12 applies only to participants with a spouse or significant other and Item 13 applies to participants who had a job or who went to school.
Time Frame	Baseline, up to Week 8

Outcome Measure Data

Analysis Population Description

All participants who have non-missing values at baseline and at least one post-baseline value. Last observation carried forward (LOCF) methodology was used.

Arm/Group Title	LY2216684 + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI).
Measure Participants	1166
FAsD Experience Subscale Score	-0.82 (0.99)
FAsD Impact Subscale Score	-0.88 (1.03)
FAsD Average Score	-0.85 (0.93)

19. Secondary Outcome

Title	Change From Week 8 in the Fatigue Associated With Depression (FAsD) Average Score, Experience Subscale Score, and Impact Subscale Score up to Week 20 (Stabilization Open-label Period)
Description	The Fatigue Associated with Depression (FAsD) is a 13-item participant-rated scale. Items 1-6 ask how often participants experience different aspects of fatigue with responses from 1 (never) to 5 (always). Items 7-13 ask how often fatigue impacts various aspects of the participant's lives with responses from 1 (not at all) to 5 (very much). The experience subscale score is derived by taking the mean of Items 1-6. The impact subscale score is derived by taking the mean of applicable Items 7-13. The average score is the mean of applicable Items 1-13. Item 12 applies only to participants with a spouse or significant other and Item 13 applies to participants who had a job or who went to school.
Time Frame	Week 8, up to Week 20

Outcome Measure Data

Analysis Population Description

All participants who have non-missing values at Week 8 and at least one post-Week 8 value. Last observation carried forward (LOCF) methodology was used.

Arm/Group Title	LY2216684 + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD for 12 weeks.
Measure Participants	781
FAsD Experience Subscale Score	-0.22 (0.93)
FAsD Impact Subscale Score	-0.15 (0.87)
FAsD Average Score	-0.19 (0.84)

20. Secondary Outcome

Title	Change From Baseline in the Sheehan Disability Scale (SDS) Items up to Week 8 (Acute Open-label Period)
Description	The Sheehan Disability Scale (SDS) is completed by the participant and used to assess the effect of the participant's symptoms on their work (work/school impairment score), social life (social life/leisure activities impairment score), and family life (family life/home responsibilities impairment score). Each item is measured on a 0 (not at all) to 10 (extremely) point scale with higher values indicating greater disruption.
Time Frame	Baseline, up to Week 8

Outcome Measure Data

Analysis Population Description

All participants who have non-missing values at baseline and at least one post-baseline value. Last observation carried forward (LOCF) methodology was used.

Arm/Group Title	LY2216684 + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI).
Measure Participants	1197
Work Impairment Score	-2.17 (2.65)
Social Life Impairment Score	-2.38 (2.85)
Family Life Impairment Score	-2.16 (2.81)

21. Secondary Outcome

Title	Change From Week 8 in the Sheehan Disability Scale (SDS) Items up to Week 20 (Stabilization Open-label Period)
Description	The Sheehan Disability Scale (SDS) is completed by the participant and used to assess the effect of the participant's symptoms on their work (work/school impairment score), social life (social life/leisure activities impairment score), and family life (family life/home responsibilities impairment score). Each item is measured on a 0 (not at all) to 10 (extremely) point scale with higher values indicating greater disruption.
Time Frame	Week 8, up to Week 20

Outcome Measure Data

Analysis Population Description

All participants who have non-missing values at Week 8 and at least one post-Week 8 value. Last observation carried forward (LOCF) methodology was used.

Arm/Group Title	LY2216684 + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD for 12 weeks.
Measure Participants	781
Work Impairment Score	-0.58 (2.61)
Social Life Impairment Score	-0.47 (2.54)
Family Life Impairment Score	-0.50 (2.50)

22. Secondary Outcome

Title	Change From Baseline in the EuroQol Questionnaire-5 Dimension (EQ-5D) Index Scores, Visual Analog Scale up to Week 20 (Open-label Period)
Description	The EQ-5D, a health-related, quality-of-life instrument, contains 2 parts: a health status profile and a visual analog scale (VAS). The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a 3-level scale (no problem, some problems, and major problems). These dimensions are converted into weighted health-state index scores according to United States (US) and United Kingdom (UK) population-based algorithms. The US and UK based index scores range from -0.11 to 1.0 (where a score of 1.0 indicates perfect health) and from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension), respectively. The VAS consists of participants rating their current health state from 0 (worst imaginable health state) to 100 (best imaginable health).
Time Frame	Baseline, up to Week 20

Outcome Measure Data

Analysis Population Description

All participants who have non-missing values at baseline and at least one post-baseline value. Last observation carried forward (LOCF) methodology was used.

Arm/Group Title	LY2216684 + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD for 12 weeks.
Measure Participants	779
EQ-5D US	0.15 (0.19)
EQ-5D UK	0.21 (0.29)
VAS	18.07 (22.15)

23. Secondary Outcome

Title	Number of Participants With Treatment-emergent Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) (Open-label Period)
Description	The Columbia-Suicide Severity Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation is defined as a "yes" answer to any 1 of 5 suicidal ideation questions, which included a wish to be dead and 4 different categories of active suicidal ideation. Suicidal behavior is defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation and behavior are defined as treatment-emergent (TE) if not present at baseline. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module.
Time Frame	Baseline through Week 20

Outcome Measure Data

Analysis Population Description

All participants who have non-missing values at baseline and at least one post-baseline value.

Arm/Group Title	LY2216684 + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD for 12 weeks.
Measure Participants	1216
TE Suicidal Ideation	66 5.3%
TE Suicidal Behavior	5 0.4%

24. Secondary Outcome

Title	Change From Baseline in the Arizona Sexual Experiences (ASEX) Questionnaire up to Week 20 (Open-label Period)
Description	Arizona Sexual Experiences (ASEX) Questionnaire is a 5-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. Each item is rated from 1 (extremely) to 6 (no/never). Possible total scores ranged from 5 to 30, with the higher scores indicating more sexual dysfunction.
Time Frame	Baseline, up to Week 20

Outcome Measure Data

Analysis Population Description

All participants who have non-missing values at baseline and at least one post-baseline value. Last observation carried forward (LOCF) methodology was used.

Arm/Group Title	LY2216684 + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD for 12 weeks.
Measure Participants	1115
Mean (Standard Deviation) [units on a scale]	-1.78 (4.98)

25. Secondary Outcome

Title	Change From Baseline in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) Total Score at Week 20 (Open-label Period)
Description	Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) is a 7-item participant-rated questionnaire pertaining to a participant's cognitive and physical well-being. It assesses motivation, wakefulness, energy, focus, recall, word-finding difficulty, and mental acuity. Each item is scored on a 6-point scale ranging from 1 (greater than normal) to 6 (totally absent). Total score is reported and ranges from 7 to 42, with higher scores indicating greater impairment.
Time Frame	Baseline, up to Week 20

Outcome Measure Data

Analysis Population Description

All participants who have non-missing values at baseline and at least one post-baseline value. Last observation carried forward (LOCF) methodology was used.

Arm/Group Title	LY2216684 + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD for 12 weeks.
Measure Participants	1167
Mean (Standard Deviation) [units on a scale]	-6.68 (7.03)

26. Secondary Outcome

Title	Change From Randomization in Blood Pressure at Week 44 (Double-blind Randomized Withdrawal Period)
Description	Blood pressure measurements were taken 3 times at each visit in a sitting position. The average of the 3 values was used for analysis. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline and baseline-by-visit interaction.
Time Frame	Randomization, Week 44

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Measure Participants	291	292
Systolic blood pressure	-0.20 (0.75)	-4.19 (0.75)
Diastolic blood pressure	0.24 (0.55)	-4.18 (0.55)

27. Secondary Outcome

Title	Change From Baseline in Blood Pressure up to Week 20 (Open-label Period)
Description	Blood pressure measurements were taken 3 times at each visit in a sitting position. The average of the 3 values was used for analysis.
Time Frame	Baseline, up to Week 20

Outcome Measure Data

Analysis Population Description

All participants who have non-missing values at baseline and at least one post-baseline value. Last observation carried forward (LOCF) methodology was used.

Arm/Group Title	LY2216684 + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD for 12 weeks.
Measure Participants	1214
Systolic blood pressure	2.30 (11.95)
Diastolic blood pressure	2.81 (8.63)

28. Secondary Outcome

Title	Change From Randomization in Pulse Rate at Week 44 (Double-blind Randomized Withdrawal Period)
Description	Pulse rate measurements were collected when the participant was in a sitting position. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline and baseline-by-visit interaction.
Time Frame	Randomization, Week 44

Outcome Measure Data

Analysis Population Description

All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

Arm/Group Title	LY2216684 + SSRI	Placebo + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.
Measure Participants	291	292
Least Squares Mean (Standard Error) [beats per minute (bpm)]	-2.54 (0.74)	-10.76 (0.74)

29. Secondary Outcome

Title	Change From Baseline in Pulse Rate up to Week 20 (Open-label Period)
Description	Pulse measurements were collected when the participant was in a sitting position.
Time Frame	Baseline, up to Week 20

Outcome Measure Data

Analysis Population Description

All participants who have non-missing values at baseline and at least one post-baseline value. Last observation carried forward (LOCF) methodology was used.

Arm/Group Title	LY2216684 + SSRI
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD for 12 weeks.
Measure Participants	1214
Mean (Standard Deviation) [beats per minute (bpm)]	10.80 (12.47)

Adverse Events

Arm/Group Title	LY2216684 + SSRI (Acute Open-label Period)		LY2216684 + SSRI (Stabilization Open-label Period)		LY2216684 + SSRI (Double-blind Randomized Withdrawal Period)		Placebo + SSRI (Double-blind Randomized Withdrawal Period)		LY2216684 + SSRI (Randomized Tapered Discontinuation Period)		LY2216684 + SSRI (Randomized Abrupt Discontinuation Period)		Placebo + SSRI (Abrupt Discontinuation Period)		LY2216684 + SSRI (Nonrandomized Abrupt Discontinuation Period)
Arm/Group Description	Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). Includes all enrolled participants who did not discontinue for the reason 'Lost to Follow-up' at the first post-baseline visit during the Acute Open-label Period.		Same, stable dose of LY2216684 as in the Acute Open-label Period, orally, once daily (QD) for 12 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). Includes all participants who completed the Acute Open-label Period and did not discontinue for the reason 'Lost to Follow-up' at the first post-baseline visit during the Stabilization Open-label Period.		Same, stable dose of LY2216684 as in the Stabilization Open-label Period, orally, once daily (QD) for 24 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). Includes randomized participants who did not discontinue for the reason 'Lost to Follow-up' at the first post-randomization visit during the Double-blind Randomized Withdrawal Period.		Placebo, orally, once daily (QD) for 24 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). Includes randomized participants who did not discontinue for the reason 'Lost to Follow-up' at the first post-randomization visit during the Double-blind Randomized Withdrawal Period.		12 milligrams (mg) LY2216684 for 4 days, 6 mg LY2216684 for 4 days, then placebo for 6 days, orally, once daily (QD), adjunctive to a selective serotonin reuptake inhibitor (SSRI). Includes all randomized participants who tapered discontinuation of LY2216684 after completion of or early withdrawal from the Double-blind Randomized Withdrawal Period and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation Period visit.		Placebo, orally, once daily (QD) for 2 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). Includes all randomized participants who abruptly discontinued LY2216684 after completion of or early withdrawal from the Double-blind Randomized Withdrawal Period and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation Period visit.		Placebo, orally, once daily (QD) for 2 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). Includes all randomized participants who discontinued placebo after completion of or early withdrawal from the Double-blind Randomized Withdrawal Period and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation Period visit.		Placebo, orally, once daily (QD) for 2 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). Includes all non-randomized participants who discontinued early from either Open-label Period and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation Period visit.
All Cause Mortality
	LY2216684 + SSRI (Acute Open-label Period)		LY2216684 + SSRI (Stabilization Open-label Period)		LY2216684 + SSRI (Double-blind Randomized Withdrawal Period)		Placebo + SSRI (Double-blind Randomized Withdrawal Period)		LY2216684 + SSRI (Randomized Tapered Discontinuation Period)		LY2216684 + SSRI (Randomized Abrupt Discontinuation Period)		Placebo + SSRI (Abrupt Discontinuation Period)		LY2216684 + SSRI (Nonrandomized Abrupt Discontinuation Period)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	LY2216684 + SSRI (Acute Open-label Period)		LY2216684 + SSRI (Stabilization Open-label Period)		LY2216684 + SSRI (Double-blind Randomized Withdrawal Period)		Placebo + SSRI (Double-blind Randomized Withdrawal Period)		LY2216684 + SSRI (Randomized Tapered Discontinuation Period)		LY2216684 + SSRI (Randomized Abrupt Discontinuation Period)		Placebo + SSRI (Abrupt Discontinuation Period)		LY2216684 + SSRI (Nonrandomized Abrupt Discontinuation Period)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/1244 (1.5%)		15/831 (1.8%)		2/294 (0.7%)		6/292 (2.1%)		2/128 (1.6%)		0/132 (0%)		2/267 (0.7%)		8/434 (1.8%)
Cardiac disorders
Myocardial infarction	1/1244 (0.1%)	1	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Tachycardia	1/1244 (0.1%)	1	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Ventricular extrasystoles	0/1244 (0%)	0	1/831 (0.1%)	1	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Gastrointestinal disorders
Abdominal pain upper	1/1244 (0.1%)	1	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Colitis ischaemic	0/1244 (0%)	0	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	1/434 (0.2%)	1
Intestinal obstruction	0/1244 (0%)	0	1/831 (0.1%)	1	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Nausea	3/1244 (0.2%)	3	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Oesophageal spasm	1/1244 (0.1%)	1	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Vomiting	3/1244 (0.2%)	3	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
General disorders
Chest pain	0/1244 (0%)	0	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	1/434 (0.2%)	1
Infections and infestations
Diverticulitis	1/1244 (0.1%)	1	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Gastroenteritis	1/1244 (0.1%)	1	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Pneumonia	0/1244 (0%)	0	1/831 (0.1%)	1	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Injury, poisoning and procedural complications
Intentional overdose	1/1244 (0.1%)	1	1/831 (0.1%)	1	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Poisoning	0/1244 (0%)	0	1/831 (0.1%)	1	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Road traffic accident	0/1244 (0%)	0	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	1/434 (0.2%)	1
Tendon rupture	0/1244 (0%)	0	0/831 (0%)	0	1/294 (0.3%)	1	0/292 (0%)	0	1/128 (0.8%)	1	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Investigations
Blood creatine phosphokinase increased	1/1244 (0.1%)	1	1/831 (0.1%)	1	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Blood glucose increased	1/1244 (0.1%)	1	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/1244 (0.1%)	1	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	1/434 (0.2%)	1
Ketosis	1/1244 (0.1%)	1	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/1244 (0%)	0	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	1/434 (0.2%)	1
Intervertebral disc disorder	1/1244 (0.1%)	1	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	1/434 (0.2%)	1
Osteoarthritis	1/1244 (0.1%)	1	1/831 (0.1%)	1	0/294 (0%)	0	1/292 (0.3%)	1	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Angiomyolipoma	0/1244 (0%)	0	0/831 (0%)	0	0/294 (0%)	0	1/292 (0.3%)	1	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Breast cancer	1/1244 (0.1%)	1	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	1/434 (0.2%)	1
Cholesteatoma	1/1244 (0.1%)	1	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	1/434 (0.2%)	1
Metastases to liver	1/1244 (0.1%)	1	1/831 (0.1%)	1	0/294 (0%)	0	1/292 (0.3%)	1	0/128 (0%)	0	0/132 (0%)	0	1/267 (0.4%)	1	0/434 (0%)	0
Nervous system disorders
Convulsion	1/1244 (0.1%)	1	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Dizziness	0/1244 (0%)	0	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	1/434 (0.2%)	1
Encephalopathy	1/1244 (0.1%)	1	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Headache	0/1244 (0%)	0	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	1/434 (0.2%)	1
Hypoaesthesia	1/1244 (0.1%)	1	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Syncope	1/1244 (0.1%)	1	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	1/434 (0.2%)	1
Pregnancy, puerperium and perinatal conditions
Abortion	0/914 (0%)	0	1/641 (0.2%)	1	0/223 (0%)	0	0/226 (0%)	0	0/95 (0%)	0	0/105 (0%)	0	0/212 (0%)	0	0/307 (0%)	0
Blighted ovum	1/914 (0.1%)	1	0/641 (0%)	0	0/223 (0%)	0	0/226 (0%)	0	0/95 (0%)	0	0/105 (0%)	0	0/212 (0%)	0	1/307 (0.3%)	1
Psychiatric disorders
Alcohol abuse	0/1244 (0%)	0	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	1/434 (0.2%)	1
Depression	0/1244 (0%)	0	1/831 (0.1%)	1	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	1/434 (0.2%)	1
Major depression	0/1244 (0%)	0	0/831 (0%)	0	0/294 (0%)	0	1/292 (0.3%)	1	1/128 (0.8%)	1	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Self injurious behaviour	1/1244 (0.1%)	1	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Suicidal behaviour	0/1244 (0%)	0	1/831 (0.1%)	2	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Suicidal ideation	0/1244 (0%)	0	1/831 (0.1%)	1	0/294 (0%)	0	1/292 (0.3%)	1	0/128 (0%)	0	0/132 (0%)	0	1/267 (0.4%)	1	0/434 (0%)	0
Suicide attempt	1/1244 (0.1%)	1	2/831 (0.2%)	2	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Renal and urinary disorders
Nephrolithiasis	1/1244 (0.1%)	1	1/831 (0.1%)	1	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Reproductive system and breast disorders
Vaginal polyp	0/914 (0%)	0	1/641 (0.2%)	1	1/223 (0.4%)	1	0/226 (0%)	0	0/95 (0%)	0	0/105 (0%)	0	0/212 (0%)	0	0/307 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/1244 (0%)	0	0/831 (0%)	0	0/294 (0%)	0	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	1/434 (0.2%)	1
Surgical and medical procedures
Hysterectomy	0/914 (0%)	0	1/641 (0.2%)	1	0/223 (0%)	0	0/226 (0%)	0	0/95 (0%)	0	0/105 (0%)	0	0/212 (0%)	0	0/307 (0%)	0
Vascular disorders
Hypertension	2/1244 (0.2%)	2	0/831 (0%)	0	0/294 (0%)	0	1/292 (0.3%)	1	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Other (Not Including Serious) Adverse Events
	LY2216684 + SSRI (Acute Open-label Period)		LY2216684 + SSRI (Stabilization Open-label Period)		LY2216684 + SSRI (Double-blind Randomized Withdrawal Period)		Placebo + SSRI (Double-blind Randomized Withdrawal Period)		LY2216684 + SSRI (Randomized Tapered Discontinuation Period)		LY2216684 + SSRI (Randomized Abrupt Discontinuation Period)		Placebo + SSRI (Abrupt Discontinuation Period)		LY2216684 + SSRI (Nonrandomized Abrupt Discontinuation Period)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	505/1244 (40.6%)		112/831 (13.5%)		37/294 (12.6%)		21/292 (7.2%)		9/128 (7%)		4/132 (3%)		16/267 (6%)		32/434 (7.4%)
Gastrointestinal disorders
Constipation	132/1244 (10.6%)	134	14/831 (1.7%)	14	4/294 (1.4%)	5	2/292 (0.7%)	2	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	0/434 (0%)	0
Dry mouth	80/1244 (6.4%)	81	10/831 (1.2%)	10	3/294 (1%)	3	0/292 (0%)	0	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	1/434 (0.2%)	1
Nausea	147/1244 (11.8%)	155	18/831 (2.2%)	21	7/294 (2.4%)	7	5/292 (1.7%)	5	3/128 (2.3%)	3	1/132 (0.8%)	1	5/267 (1.9%)	6	8/434 (1.8%)	10
Nervous system disorders
Dizziness	83/1244 (6.7%)	86	8/831 (1%)	8	3/294 (1%)	3	4/292 (1.4%)	4	1/128 (0.8%)	1	1/132 (0.8%)	1	4/267 (1.5%)	4	4/434 (0.9%)	4
Headache	111/1244 (8.9%)	128	53/831 (6.4%)	54	18/294 (6.1%)	24	13/292 (4.5%)	13	7/128 (5.5%)	10	4/132 (3%)	5	11/267 (4.1%)	16	24/434 (5.5%)	30
Skin and subcutaneous tissue disorders
Hyperhidrosis	215/1244 (17.3%)	228	23/831 (2.8%)	24	8/294 (2.7%)	8	1/292 (0.3%)	1	0/128 (0%)	0	0/132 (0%)	0	0/267 (0%)	0	5/434 (1.2%)	5

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.