Trial Outcomes & Findings for A Study of LY2216684 in Participants With Major Depression Disorder (NCT NCT01370499)

NCT ID: NCT01370499

Last Updated: 2018-10-25

Results Overview

Clinically significant events were defined as serious adverse events, regardless of causality. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 288 participants
• Primary outcome timeframe: Baseline through 52 weeks
• Results posted on: 2018-10-25

Participant Flow

This is an open-label study with 1 treatment (12 or 18 milligrams [mg] LY2216684 + SSRI). However, the data were analyzed by the participants' treatment group from 2 parent studies (Study LNBM: NCT01173601 or Study LNBQ: NCT01187407). In these prior, parent studies, participants were randomized to receive Placebo + SSRI or LY2216684 + SSRI.

Participant milestones

Measure	LY2216684 + SSRI (Placebo Prior Study) LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	LY2216684 + SSRI (LY2216684 Prior Study) LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI
Overall Study STARTED	195	93
Overall Study Entered Abrupt Discontinuation Phase	188	85
Overall Study Received at Least 1 Dose of Study Drug	195	92
Overall Study COMPLETED	84	49
Overall Study NOT COMPLETED	111	44

Reasons for withdrawal

Measure	LY2216684 + SSRI (Placebo Prior Study) LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)	LY2216684 + SSRI (LY2216684 Prior Study) LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI
Overall Study Adverse Event	38	12
Overall Study Lack of Efficacy	4	2
Overall Study Lost to Follow-up	2	1
Overall Study Physician Decision	3	3
Overall Study Protocol Violation	5	4
Overall Study Withdrawal by Subject	18	7
Overall Study Sponsor Decision	41	15

Baseline Characteristics

A Study of LY2216684 in Participants With Major Depression Disorder

Baseline characteristics by cohort

Measure	LY2216684 + SSRI (Placebo Prior Study) n=195 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI	LY2216684 + SSRI (LY2216684 Prior Study) n=93 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI	Total n=288 Participants Total of all reporting groups
Age, Continuous	39.28 years STANDARD_DEVIATION 9.41 • n=5 Participants	37.40 years STANDARD_DEVIATION 9.18 • n=7 Participants	38.68 years STANDARD_DEVIATION 9.36 • n=5 Participants
Sex: Female, Male Female	88 Participants n=5 Participants	45 Participants n=7 Participants	133 Participants n=5 Participants
Sex: Female, Male Male	107 Participants n=5 Participants	48 Participants n=7 Participants	155 Participants n=5 Participants
Race/Ethnicity, Customized Asian	195 Participants n=5 Participants	93 Participants n=7 Participants	288 Participants n=5 Participants
Region of Enrollment Japan	195 Participants n=5 Participants	93 Participants n=7 Participants	288 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline through 52 weeks

Population: All participants who took at least one dose of study medication and did not discontinue from the study for the reason 'Lost to follow-up' at the first post-baseline visit.

Clinically significant events were defined as serious adverse events, regardless of causality. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module.

Outcome measures

Measure	LY2216684 + SSRI (Placebo Prior Study) n=195 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI	LY2216684 + SSRI (LY2216684 Prior Study) n=92 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI
Number of Participants With Clinically Significant Events Subdural hygroma	1 Participants	0 Participants
Number of Participants With Clinically Significant Events Contusion	0 Participants	1 Participants
Number of Participants With Clinically Significant Events Hyperglycaemia	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline through 52 weeks

Population: All participants who took at least one dose of study medication and had a baseline and at least one post-baseline value.

The C-SSRS captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation was 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 was 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 was defined as treatment-emergent (TE) if not present at baseline. Percentage of participants was calculated by dividing the number of participants with suicide-related events by the total number of participants at risk, multiplied by 100%. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module.

Outcome measures

Measure	LY2216684 + SSRI (Placebo Prior Study) n=195 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI	LY2216684 + SSRI (LY2216684 Prior Study) n=92 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI
Percentage of Participants With Suicidal Behaviors and Ideations Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) TE of suicidal ideation	8.72 percentage of participants	8.70 percentage of participants
Percentage of Participants With Suicidal Behaviors and Ideations Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) Suicidal behavior	0.51 percentage of participants	0.00 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: All enrolled participants with a baseline and at least one post-baseline value.

The 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 to 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 mixed model repeated measures (MMRM) adjusting for pooled investigative site and visit, baseline score, and baseline score-by-visit interaction.

Outcome measures

Measure	LY2216684 + SSRI (Placebo Prior Study) n=195 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI	LY2216684 + SSRI (LY2216684 Prior Study) n=93 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI
Change From Baseline to 52 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Items MADRS total score	-4.33 units on a scale Standard Error 0.69	-6.63 units on a scale Standard Error 1.00
Change From Baseline to 52 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Items Apparent sadness	-0.36 units on a scale Standard Error 0.10	-1.01 units on a scale Standard Error 0.16
Change From Baseline to 52 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Items Reported sadness	-0.51 units on a scale Standard Error 0.12	-0.92 units on a scale Standard Error 0.20
Change From Baseline to 52 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Items Inner tension	-0.53 units on a scale Standard Error 0.10	-0.85 units on a scale Standard Error 0.18
Change From Baseline to 52 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Items Reduced sleep	-0.49 units on a scale Standard Error 0.12	-0.33 units on a scale Standard Error 0.19
Change From Baseline to 52 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Items Reduced appetite	-0.24 units on a scale Standard Error 0.08	-0.25 units on a scale Standard Error 0.16
Change From Baseline to 52 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Items Concentration difficulties	-0.72 units on a scale Standard Error 0.11	-1.12 units on a scale Standard Error 0.17
Change From Baseline to 52 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Items Lassitude	-0.71 units on a scale Standard Error 0.09	-0.78 units on a scale Standard Error 0.16
Change From Baseline to 52 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Items Inability to feel	-0.41 units on a scale Standard Error 0.11	-0.77 units on a scale Standard Error 0.14
Change From Baseline to 52 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Items Pessimistic thoughts	-0.31 units on a scale Standard Error 0.09	-0.63 units on a scale Standard Error 0.14
Change From Baseline to 52 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Items Suicidal thoughts	-0.19 units on a scale Standard Error 0.06	-0.25 units on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: All enrolled participants with a baseline and at least one post-baseline value.

Clinical Global Impression - 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 (among the most extremely ill participants). Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for pooled investigative site and visit, baseline score, and baseline score-by-visit interaction.

Outcome measures

Measure	LY2216684 + SSRI (Placebo Prior Study) n=195 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI	LY2216684 + SSRI (LY2216684 Prior Study) n=93 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI
Change From Baseline to 52 Week Endpoint in Clinical Global Impression - Severity (CGI-S)	-0.80 units on a scale Standard Error 0.10	-0.78 units on a scale Standard Error 0.13

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: All enrolled participants with a baseline and at least one post-baseline value.

The FAsD is a participant-rated scale with a total of 13 items. Six of the 13 items ask how often participants experience different aspects of fatigue with responses from 1 (never) to 5 (always). Seven of the 13 items 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 Score" was derived by taking the mean of Items 1 through 6, the "Impact Score" was derived by taking the mean of Items 7 through 13 (applicable items only), and the "Average Score" was the mean of Items 1 through 13 (derived by taking the mean of all applicable items for each participant). Item 12 applied only to participants with a spouse or significant other and Item 13 applied to participants who had a job or who went to school. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for pooled investigative site and visit, baseline score, and baseline score-by-visit interaction.

Outcome measures

Measure	LY2216684 + SSRI (Placebo Prior Study) n=183 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI	LY2216684 + SSRI (LY2216684 Prior Study) n=86 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI
Change From Baseline to 52 Week Endpoint in Fatigue Associated With Depression (FAsD) Average Score and Subscale Scores Average score	-0.32 units on a scale Standard Error 0.07	-0.18 units on a scale Standard Error 0.08
Change From Baseline to 52 Week Endpoint in Fatigue Associated With Depression (FAsD) Average Score and Subscale Scores Experience score	-0.28 units on a scale Standard Error 0.08	-0.15 units on a scale Standard Error 0.09
Change From Baseline to 52 Week Endpoint in Fatigue Associated With Depression (FAsD) Average Score and Subscale Scores Impact score	-0.34 units on a scale Standard Error 0.07	-0.19 units on a scale Standard Error 0.08

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: All enrolled participants with a baseline and at least one post-baseline value.

The Hospital Anxiety and Depression Scale (HADS) is a 14-item questionnaire with 2 subscales: anxiety and depression. The anxiety subscale score is the sum of the 7 odd-numbered items and depression subscale score is the sum of the 7 even-numbered items, giving maximum scores of 21 for each subscale. 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, 'normal'. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for pooled investigative site and visit, baseline score, and baseline score-by-visit interaction.

Outcome measures

Measure	LY2216684 + SSRI (Placebo Prior Study) n=189 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI	LY2216684 + SSRI (LY2216684 Prior Study) n=87 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI
Change From Baseline to 52 Week Endpoint in Hospital Anxiety and Depression Scale (HADS) Depression and Anxiety Subscale Scores Depression	-1.95 units on a scale Standard Error 0.34	-1.24 units on a scale Standard Error 0.44
Change From Baseline to 52 Week Endpoint in Hospital Anxiety and Depression Scale (HADS) Depression and Anxiety Subscale Scores Anxiety	-1.46 units on a scale Standard Error 0.28	-0.55 units on a scale Standard Error 0.38

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: All enrolled participants with a baseline and at least one post-baseline value.

The SDS Global Functional Impairment Score (total score) and subscores were completed by the participant and were used to assess the effect of the participant's symptoms on his or her work (Item 1), social (Item 2), and family life (Item 3). Each item is measured on a 0 (not at all) to 10 (extremely) point scale with higher values indicating greater disruption. The Global Functional Impairment Score is the sum of the 3 items, and scores ranged from 0 to 30 with high values indicating greater disruption in the participant's work life (work/school impairment score), social life (social life/leisure activities impairment score), and family life (family life/home responsibilities impairment score). Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for pooled investigative site and visit, baseline score, and baseline score-by-visit interaction.

Outcome measures

Measure	LY2216684 + SSRI (Placebo Prior Study) n=177 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI	LY2216684 + SSRI (LY2216684 Prior Study) n=81 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI
Change From Baseline to 52 Week Endpoint in Sheehan Disability Scale (SDS) Total Score and Subscale Scores Global functional impairment score	-3.11 units on a scale Standard Error 0.63	-2.37 units on a scale Standard Error 0.70
Change From Baseline to 52 Week Endpoint in Sheehan Disability Scale (SDS) Total Score and Subscale Scores Work impairment score	-0.98 units on a scale Standard Error 0.29	-1.42 units on a scale Standard Error 0.42
Change From Baseline to 52 Week Endpoint in Sheehan Disability Scale (SDS) Total Score and Subscale Scores Social life impairment score	-1.01 units on a scale Standard Error 0.21	-0.66 units on a scale Standard Error 0.25
Change From Baseline to 52 Week Endpoint in Sheehan Disability Scale (SDS) Total Score and Subscale Scores Family life impairment score	-1.10 units on a scale Standard Error 0.20	-0.55 units on a scale Standard Error 0.24

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: All enrolled participants with a baseline and at least one post-baseline value.

The 5Q-5D Visual Analog Scale is a generic, multidimensional, health-related, quality-of-life instrument. Overall health state score is self-reported using a visual analogue scale, marked on a scale of 0 to 100 with 0 representing worst imaginable health state and 100 representing best imaginable health state. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for pooled investigative site and visit, baseline score, and baseline score-by-visit interaction.

Outcome measures

Measure	LY2216684 + SSRI (Placebo Prior Study) n=177 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI	LY2216684 + SSRI (LY2216684 Prior Study) n=81 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI
Change From Baseline to 52 Week Endpoint in EuroQol Questionnaire - 5 Dimension (EQ-5D)	9.445 units on a scale Standard Error 1.846	9.989 units on a scale Standard Error 2.288

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: All enrolled participants with a baseline and at least one post-baseline value.

The Q-LES-Q-SF is a self-administered 16-item questionnaire measuring degree of enjoyment and satisfaction experienced in various areas of daily life during the past week on a 5-point Likert scale (1=very poor and 5=very good). The total possible scores range from 16 to 80. Higher scores indicate higher levels of enjoyment/satisfaction. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for pooled investigative site and visit, baseline score, and baseline score-by-visit interaction.

Outcome measures

Measure	LY2216684 + SSRI (Placebo Prior Study) n=177 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI	LY2216684 + SSRI (LY2216684 Prior Study) n=81 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI
Change From Baseline to 52 Week Endpoint in Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF)	6.28 units on a scale Standard Error 1.30	5.19 units on a scale Standard Error 1.58

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: All participants who took at least one dose of study medication and had a baseline and at least one post-baseline value.

The 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 scores ranged from 7 to 42. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for pooled investigative site and visit, baseline score, and baseline score-by-visit interaction.

Outcome measures

Measure	LY2216684 + SSRI (Placebo Prior Study) n=183 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI	LY2216684 + SSRI (LY2216684 Prior Study) n=86 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI
Change From Baseline to 52 Week Endpoint in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ)	-4.02 units on a scale Standard Error 0.54	-2.53 units on a scale Standard Error 0.75

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: All participants who took at least one dose of study medication and had a baseline and at least one post-baseline value.

The Arizona Sexual Experiences (ASEX) scale is used to assess sexual functioning in both males and females. The ASEX total score for the male and female version is calculated as the sum of the responses (rated from 1 [extremely] to 6 [no/never]) to the 5 items of the ASEX scale. Total scores ranged from 5 to 30, with higher scores indicating greater sexual dysfunction. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for pooled investigative site and visit, baseline score, and baseline score-by-visit interaction.

Outcome measures

Measure	LY2216684 + SSRI (Placebo Prior Study) n=183 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI	LY2216684 + SSRI (LY2216684 Prior Study) n=85 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI
Change From Baseline to 52 Week Endpoint in Arizona Sexual Experiences (ASEX) Scale	-0.65 units on a scale Standard Error 0.39	-0.40 units on a scale Standard Error 0.55

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: All participants who took at least one dose of study medication and had a baseline and at least one post-baseline value.

Blood pressure measurements were collected when the participant was in a sitting position. Three measurements of sitting blood pressure collected at approximately 1-minute intervals at every visit were averaged and used as the value for the visit. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for pooled investigative site and visit, baseline score, and baseline score-by-visit interaction.

Outcome measures

Measure	LY2216684 + SSRI (Placebo Prior Study) n=195 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI	LY2216684 + SSRI (LY2216684 Prior Study) n=92 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI
Change From Baseline to 52 Week Endpoint in Blood Pressure Sitting systolic blood pressure	6.66 millimeters of mercury (mmHg) Standard Error 0.93	3.68 millimeters of mercury (mmHg) Standard Error 1.28
Change From Baseline to 52 Week Endpoint in Blood Pressure Sitting diastolic blood pressure	7.55 millimeters of mercury (mmHg) Standard Error 0.83	6.34 millimeters of mercury (mmHg) Standard Error 1.03

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: All participants who took at least one dose of study medication and had a baseline and at least one post-baseline value.

Pulse measurements were collected when the participant was in a sitting position. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for pooled investigative site and visit, baseline score, and baseline score-by-visit interaction.

Outcome measures

Measure	LY2216684 + SSRI (Placebo Prior Study) n=195 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI	LY2216684 + SSRI (LY2216684 Prior Study) n=92 Participants LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to an SSRI
Change From Baseline to 52 Week Endpoint in Pulse Rate	17.00 beats per minute (bpm) Standard Error 1.24	10.98 beats per minute (bpm) Standard Error 1.49

Adverse Events

LY2216684 + SSRI (Placebo Prior Study)

Serious events: 1 serious events

Other events: 158 other events

Deaths: 0 deaths

LY2216684 + SSRI (LY2216684 Prior Study)

Serious events: 2 serious events

Other events: 67 other events

Deaths: 0 deaths

LY2216684 + SSRI (Placebo Prior Study) DC Phase

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

LY2216684 + SSRI (LY2216684 Prior Study) DC Phase

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	LY2216684 + SSRI (Placebo Prior Study) n=195 participants at risk LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI) Includes all randomized participants who received at least 1 dose of study drug.	LY2216684 + SSRI (LY2216684 Prior Study) n=92 participants at risk LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI) Includes all randomized participants who received at least 1 dose of study drug.	LY2216684 + SSRI (Placebo Prior Study) DC Phase n=188 participants at risk No study drug was administered. Participants were to maintain their selective serotonin reuptake inhibitor (SSRI) treatment at a stable dose for 1 week. Includes all randomized participants who received at least 1 dose of study drug and abruptly discontinued LY2216684 either at the end of the study or after early withdrawal from the study and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation (DC) Phase visit.	LY2216684 + SSRI (LY2216684 Prior Study) DC Phase n=84 participants at risk No study drug was administered. Participants were to maintain their SSRI treatment at a stable dose for 1 week. Includes all participants who received at least 1 dose of study drug and abruptly discontinued LY2216684 either at the end of the study or after early withdrawal from the study and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation (DC) Phase visit.
Injury, poisoning and procedural complications Contusion	0.00% 0/195	1.1% 1/92 • Number of events 1	0.00% 0/188	0.00% 0/84
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/195	1.1% 1/92 • Number of events 1	0.00% 0/188	0.00% 0/84
Nervous system disorders Subdural hygroma	0.51% 1/195 • Number of events 1	0.00% 0/92	0.00% 0/188	0.00% 0/84

Other adverse events

Measure	LY2216684 + SSRI (Placebo Prior Study) n=195 participants at risk LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI) Includes all randomized participants who received at least 1 dose of study drug.	LY2216684 + SSRI (LY2216684 Prior Study) n=92 participants at risk LY2216684: 12 mg or 18 mg, administered orally, once daily for 52 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI) Includes all randomized participants who received at least 1 dose of study drug.	LY2216684 + SSRI (Placebo Prior Study) DC Phase n=188 participants at risk No study drug was administered. Participants were to maintain their selective serotonin reuptake inhibitor (SSRI) treatment at a stable dose for 1 week. Includes all randomized participants who received at least 1 dose of study drug and abruptly discontinued LY2216684 either at the end of the study or after early withdrawal from the study and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation (DC) Phase visit.	LY2216684 + SSRI (LY2216684 Prior Study) DC Phase n=84 participants at risk No study drug was administered. Participants were to maintain their SSRI treatment at a stable dose for 1 week. Includes all participants who received at least 1 dose of study drug and abruptly discontinued LY2216684 either at the end of the study or after early withdrawal from the study and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation (DC) Phase visit.
Musculoskeletal and connective tissue disorders Back pain	2.1% 4/195 • Number of events 4	6.5% 6/92 • Number of events 7	0.00% 0/188	0.00% 0/84
Nervous system disorders Dizziness	10.8% 21/195 • Number of events 28	4.3% 4/92 • Number of events 4	0.53% 1/188 • Number of events 1	0.00% 0/84
Nervous system disorders Headache	8.7% 17/195 • Number of events 45	7.6% 7/92 • Number of events 8	1.1% 2/188 • Number of events 2	1.2% 1/84 • Number of events 1
Renal and urinary disorders Urinary hesitation	7.2% 14/195 • Number of events 14	0.00% 0/92	0.00% 0/188	0.00% 0/84
Renal and urinary disorders Urinary retention	5.1% 10/195 • Number of events 10	4.3% 4/92 • Number of events 4	0.00% 0/188	0.00% 0/84
Skin and subcutaneous tissue disorders Hyperhidrosis	16.9% 33/195 • Number of events 33	17.4% 16/92 • Number of events 16	0.00% 0/188	0.00% 0/84
Cardiac disorders Palpitations	18.5% 36/195 • Number of events 38	13.0% 12/92 • Number of events 12	1.1% 2/188 • Number of events 2	1.2% 1/84 • Number of events 1
Cardiac disorders Tachycardia	31.8% 62/195 • Number of events 77	18.5% 17/92 • Number of events 20	0.00% 0/188	0.00% 0/84
Gastrointestinal disorders Constipation	9.7% 19/195 • Number of events 20	7.6% 7/92 • Number of events 7	0.00% 0/188	0.00% 0/84
Gastrointestinal disorders Nausea	13.3% 26/195 • Number of events 29	8.7% 8/92 • Number of events 10	0.00% 0/188	1.2% 1/84 • Number of events 1
Gastrointestinal disorders Vomiting	7.2% 14/195 • Number of events 14	3.3% 3/92 • Number of events 4	0.00% 0/188	0.00% 0/84
Infections and infestations Nasopharyngitis	28.7% 56/195 • Number of events 94	31.5% 29/92 • Number of events 39	1.6% 3/188 • Number of events 3	0.00% 0/84
Investigations Blood pressure increased	5.6% 11/195 • Number of events 11	0.00% 0/92	0.53% 1/188 • Number of events 1	1.2% 1/84 • Number of events 1
Investigations Heart rate increased	12.8% 25/195 • Number of events 31	7.6% 7/92 • Number of events 11	0.00% 0/188	0.00% 0/84

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

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

Restriction type: GT60