Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 83 of 889 for:    "Depressive Disorder" [DISEASE] AND MADRS

A Fixed Dose Study of Adjunctive Treatment to Antidepressant Therapy for Adults With Major Depressive Disorder

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01173601
Recruitment Status : Completed
First Posted : August 2, 2010
Results First Posted : April 17, 2018
Last Update Posted : April 17, 2018
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Drug: LY2216684
Drug: Placebo
Drug: SSRI
Enrollment 1416
Recruitment Details  
Pre-assignment Details The first 3 weeks was a double-blind adjunctive placebo lead-in Confirmation Phase during which participants continued their SSRI with adjunctive placebo. If randomization criteria were met, participants were randomized to receive LY2216684 12 mg, 18 mg, or placebo. If criteria were not met, participants continued on placebo to maintain the blind.
Arm/Group Title Placebo + SSRI (Pre-Randomized Participants) 12 mg LY2216684 + SSRI (Randomized Participants) 18 mg LY2216684 + SSRI (Randomized Participants) Placebo + SSRI (Randomized Participants) Placebo + SSRI (Non-Randomized Participants)
Hide Arm/Group Description Placebo: Administered orally, once daily for 3 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI) LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a SSRI LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI Placebo: Administered orally, once daily for 8 weeks
Period Title: Confirmation (CF) Phase, 3 Weeks
Started 1416 0 0 0 0
Entered Discontinuation Phase 21 [1] 0 0 0 0
Completed 1328 [2] 0 0 0 0
Not Completed 88 0 0 0 0
Reason Not Completed
Adverse Event             23             0             0             0             0
Lack of Efficacy             9             0             0             0             0
Lost to Follow-up             7             0             0             0             0
Physician Decision             3             0             0             0             0
Protocol Violation             15             0             0             0             0
Withdrawal by Subject             25             0             0             0             0
Sponsor Decision             6             0             0             0             0
[1]
Participants who discontinued the CF Phase had the option to enter the DC phase.
[2]
Participants who completed the CF Phase entered the AT Phase.
Period Title: Adjunctive Treatment (AT) Phase, 8 Weeks
Started 0 231 230 240 627
Entered Taper Discontinuation Phase 0 100 [1] 107 [1] 0 0
Entered Abrupt Discontinuation Phase 0 100 [2] 108 [2] 221 [2] 586 [2]
Completed 0 196 197 210 559
Not Completed 0 35 33 30 68
Reason Not Completed
Adverse Event             0             10             15             7             14
Lack of Efficacy             0             10             6             8             9
Lost to Follow-up             0             3             0             2             9
Physician Decision             0             2             0             2             1
Protocol Violation             0             1             5             4             5
Withdrawal by Subject             0             9             7             5             24
Sponsor Decision             0             0             0             2             6
[1]
Participants who completed the AT Phase or discontinued early entered the taper DC Phase.
[2]
Participants who completed the AT Phase or discontinued early entered the abrupt DC Phase.
Arm/Group Title 12 mg LY2216684 + SSRI (Randomized Participants) 18 mg LY2216684 + SSRI (Randomized Participants) Placebo + SSRI (Randomized Participants) Placebo + SSRI (Non-Randomized Participants) Total
Hide Arm/Group Description LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI) LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI Total of all reporting groups
Overall Number of Baseline Participants 231 230 240 627 1328
Hide Baseline Analysis Population Description
Participants who completed the Confirmation Phase and were randomized to adjunctive LY2216684 or adjunctive placebo or who did not meet randomization criteria and continued on placebo to maintain the blind.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 231 participants 230 participants 240 participants 627 participants 1328 participants
44.95  (12.38) 46.06  (12.82) 44.38  (10.60) 44.73  (11.89) 44.94  (11.92)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 231 participants 230 participants 240 participants 627 participants 1328 participants
Female 145 149 155 451 900
Male 86 81 85 176 428
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 231 participants 230 participants 240 participants 627 participants 1328 participants
Hispanic or Latino 9 7 7 28 51
Not Hispanic or Latino 181 172 188 520 1061
Unknown or Not Reported 41 51 45 79 216
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 231 participants 230 participants 240 participants 627 participants 1328 participants
American Indian or Alaska Native 0 0 0 2 2
Asian 47 45 56 121 269
Native Hawaiian or Other Pacific Islander 0 0 0 0 0
Black or African American 14 14 19 65 112
White 164 170 164 429 927
More than one race 5 1 0 9 15
Unknown or Not Reported 1 0 1 1 3
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 231 participants 230 participants 240 participants 627 participants 1328 participants
United States 73 76 74 318 541
Poland 46 52 51 63 212
Ukraine 33 29 29 36 127
Russia 6 6 6 15 33
South Africa 10 9 10 44 73
Latvia 16 14 17 34 81
Japan 47 44 53 117 261
1.Primary Outcome
Title Change From Randomization to Week 8 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Hide Description The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS had a 10-item checklist. Items were 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 treatment, investigator, visit, baseline score, treatment-by-visit and baseline score-by-visit.
Time Frame Randomization, 8 weeks
Hide Outcome Measure Data
Hide 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 12 mg LY2216684 + SSRI 18 mg LY2216684 + SSRI Placebo + SSRI
Hide Arm/Group Description:
LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI
Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI
Overall Number of Participants Analyzed 230 230 240
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-8.47  (0.52) -8.70  (0.53) -7.77  (0.51)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 12 mg LY2216684 + SSRI, Placebo + SSRI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.338
Comments In order to test the primary outcome between each LY2216684 dose and placebo while controlling the overall Type I error at 0.05, the significance level was a priori partitioned equally between the 2 LY2216684 dose-placebo comparisons at 0.025.
Method Mixed Models Analysis
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 18 mg LY2216684 + SSRI, Placebo + SSRI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.201
Comments In order to test the primary outcome between each LY2216684 dose and placebo while controlling the overall Type I error at 0.05, the significance level was a priori partitioned equally between the 2 LY2216684 dose-placebo comparisons at 0.025.
Method Mixed Models Analysis
Comments [Not Specified]
2.Secondary Outcome
Title Change From Randomization to Week 8 in Sheehan Disability Scale (SDS) Global Functional Impairment Scale
Hide Description The SDS was completed by the participant and used to assess the effect of the participant's symptoms on their 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 Function Impairment Score is the sum of the 3 items, and scores ranged from 0 to 30 with higher values indicating 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 treatment, investigator, visit, baseline score, treatment-by-visit and baseline score-by-visit.
Time Frame Randomization, 8 weeks
Hide Outcome Measure Data
Hide 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 12 mg LY2216684 + SSRI 18 mg LY2216684 + SSRI Placebo + SSRI
Hide Arm/Group Description:
LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI
Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI
Overall Number of Participants Analyzed 224 222 236
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-5.36  (0.44) -5.27  (0.44) -4.47  (0.43)
3.Secondary Outcome
Title Change From Randomization to Week 8 in Fatigue Associated With Depression (FAsD) Impact Subscale Score
Hide Description 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 impact subscale score was derived by taking the mean of Items 7 through 13 (applicable items only). 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 treatment, investigator, visit, baseline subscale score, treatment-by-visit and baseline subscale score-by-visit.
Time Frame Randomization, 8 weeks
Hide Outcome Measure Data
Hide 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 12 mg LY2216684 + SSRI 18 mg LY2216684 + SSRI Placebo + SSRI
Hide Arm/Group Description:
LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI
Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI
Overall Number of Participants Analyzed 224 221 236
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.74  (0.06) -0.66  (0.06) -0.53  (0.06)
4.Secondary Outcome
Title Percentage of Participants Achieving a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of Less Than or Equal 10 up to Week 8
Hide Description A MADRS total score of less than or equal to 10 was defined as remission criteria. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS had a 10-item checklist. Items were 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). Percentage of participants was calculated by dividing the number of participants who meet criteria for remission by the total number of participants analyzed, multiplied by 100%.
Time Frame Randomization up to 8 weeks
Hide Outcome Measure Data
Hide 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 12 mg LY2216684 + SSRI 18 mg LY2216684 + SSRI Placebo + SSRI
Hide Arm/Group Description:
LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI
Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI
Overall Number of Participants Analyzed 230 230 240
Measure Type: Number
Unit of Measure: percentage of participants
27.83 26.96 26.67
5.Secondary Outcome
Title Percentage of Participants Achieving a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of Less Than or Equal 10 for at Least 2 Consecutive Measurements, Including the Participant's Last Measurement
Hide Description A MADRS total score of less than or equal to 10 for at least 2 consecutive measurements, including the participant's last measurement, was defined as remission criteria at last 2 consecutive visits. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS had a 10-item checklist. Items were 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). Percentage of participants was calculated by dividing the number of participants who meet criteria for remission at last 2 consecutive visits by the total number of participants analyzed, multiplied by 100%.
Time Frame Randomization up to 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with a baseline and at least one post-baseline value.
Arm/Group Title 12 mg LY2216684 + SSRI 18 mg LY2216684 + SSRI Placebo + SSRI
Hide Arm/Group Description:
LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI
Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI
Overall Number of Participants Analyzed 230 230 240
Measure Type: Number
Unit of Measure: percentage of participants
16.96 19.13 19.58
6.Secondary Outcome
Title Change From Randomization to Week 8 in Hospital and Anxiety and Depression Scale (HADS) Anxiety Subscale Score
Hide Description The HADS is a 14-item questionnaire with 2 subscales: anxiety and depression. Each item was rated on a 4-point scale (0-3), giving maximum scores of 21 for anxiety and depression 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 represent 'normal'. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline subscale score, treatment-by-visit, and baseline subscale score-by-visit.
Time Frame Randomization, 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with a baseline and at least one post-baseline value.
Arm/Group Title 12 mg LY2216684 + SSRI 18 mg LY2216684 + SSRI Placebo + SSRI
Hide Arm/Group Description:
LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI
Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI
Overall Number of Participants Analyzed 230 230 239
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.97  (0.22) -2.05  (0.22) -1.85  (0.22)
7.Secondary Outcome
Title Percentage of Participants Who Have a Greater Than or Equal to 50 Percent Improvement in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Randomization up to Week 8
Hide Description A greater than or equal to 50 percent improvement (that is, a decrease from baseline) in the MADRS total score was defined as response criteria. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS had a 10-item checklist. Items were 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). Percentage of participants was calculated by dividing the number of participants meeting response criteria at last visit by the total number of participants analyzed, multiplied by 100%.
Time Frame Randomization up to 8 weeks
Hide Outcome Measure Data
Hide 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 12 mg LY2216684 + SSRI 18 mg LY2216684 + SSRI Placebo + SSRI
Hide Arm/Group Description:
LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI
Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI
Overall Number of Participants Analyzed 230 230 240
Measure Type: Number
Unit of Measure: percentage of participants
30.43 34.35 27.08
8.Secondary Outcome
Title Change From Randomization to Week 8 in Hospital Anxiety and Depression Scale (HADS) Depression Subscale Score
Hide Description The HADS is a 14-item questionnaire with 2 subscales: anxiety and depression. Each item was rated on a 4-point scale (0-3), giving maximum scores of 21 for anxiety and depression 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 represent 'normal'. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline subscale score, treatment-by-visit and baseline subscale score-by-visit.
Time Frame Randomization, 8 weeks
Hide Outcome Measure Data
Hide 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 12 mg LY2216684 + SSRI 18 mg LY2216684 + SSRI Placebo + SSRI
Hide Arm/Group Description:
LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI
Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI
Overall Number of Participants Analyzed 230 230 239
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-3.19  (0.26) -3.38  (0.27) -2.76  (0.26)
9.Secondary Outcome
Title Change From Randomization to Week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) Individual Items
Hide Description The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS had 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 were 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 treatment, investigator, visit, baseline item score, treatment-by-visit and baseline item score-by-visit.
Time Frame Randomization, 8 weeks
Hide Outcome Measure Data
Hide 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 12 mg LY2216684 + SSRI 18 mg LY2216684 + SSRI Placebo + SSRI
Hide Arm/Group Description:
LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI
Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI
Overall Number of Participants Analyzed 230 230 240
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Apparent sadness -1.18  (0.08) -1.04  (0.08) -1.01  (0.08)
Reported sadness -1.21  (0.08) -1.20  (0.08) -1.00  (0.08)
Inner tension -0.71  (0.07) -0.74  (0.07) -0.65  (0.07)
Reduced sleep -0.97  (0.09) -0.94  (0.09) -0.83  (0.08)
Reduced appetite -0.82  (0.08) -0.74  (0.08) -0.75  (0.08)
Concentration difficulties -0.88  (0.08) -1.01  (0.08) -0.94  (0.08)
Lassitude -1.04  (0.08) -1.12  (0.08) -0.89  (0.08)
Inability to feel -1.05  (0.08) -1.07  (0.08) -0.90  (0.08)
Pessimistic thoughts -0.77  (0.07) -0.74  (0.07) -0.74  (0.07)
Suicidal thoughts -0.09  (0.03) -0.13  (0.03) -0.15  (0.03)
10.Secondary Outcome
Title Change From Randomization to Week 8 in Clinical Global Impressions of Severity (CGI-S)
Hide Description 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 treatment, investigator, visit, baseline score, treatment-by-visit and baseline score-by-visit.
Time Frame Randomization, 8 weeks
Hide Outcome Measure Data
Hide 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 12 mg LY2216684 + SSRI 18 mg LY2216684 + SSRI Placebo + SSRI
Hide Arm/Group Description:
LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI
Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI
Overall Number of Participants Analyzed 230 230 240
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.01  (0.07) -1.08  (0.07) -0.95  (0.07)
11.Secondary Outcome
Title Change From Randomization to Week 8 in Fatigue Associated With Depression (FAsD) Average Score and Experience Subscale Score
Hide Description 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 subscale score was derived by taking the mean of Items 1 through 6, 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 treatment, investigator, visit, baseline score, treatment-by-visit and baseline score-by-visit.
Time Frame Randomization, 8 weeks
Hide Outcome Measure Data
Hide 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 12 mg LY2216684 + SSRI 18 mg LY2216684 + SSRI Placebo + SSRI
Hide Arm/Group Description:
LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI
Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI
Overall Number of Participants Analyzed 224 221 236
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Average score -0.69  (0.05) -0.67  (0.05) -0.57  (0.05)
Experience score -0.66  (0.06) -0.67  (0.06) -0.60  (0.05)
12.Secondary Outcome
Title Change From Randomization to Week 8 in Sheehan Disability Scale (SDS) Items
Hide Description The Sheehan Disability Scale (SDS) was 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 mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline item score, treatment-by-visit, and baseline item score-by-visit.
Time Frame Randomization, 8 weeks
Hide Outcome Measure Data
Hide 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 12 mg LY2216684 + SSRI 18 mg LY2216684 + SSRI Placebo + SSRI
Hide Arm/Group Description:
LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI
Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI
Overall Number of Participants Analyzed 224 222 236
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Work impairment score Number Analyzed 149 participants 145 participants 167 participants
-1.77  (0.19) -1.74  (0.20) -1.44  (0.19)
Social life impairment score Number Analyzed 224 participants 222 participants 236 participants
-1.85  (0.16) -1.81  (0.16) -1.64  (0.16)
Family life impairment score Number Analyzed 224 participants 222 participants 236 participants
-1.72  (0.16) -1.71  (0.16) -1.43  (0.15)
13.Secondary Outcome
Title Change From Randomization to Week 8 in the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF)
Hide Description The Q-LES-Q-SF is a self-administered 16-item questionnaire that measures 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 raw score is the sum of items 1 to 14 and ranges from 14 to 70. The raw scores are converted to and expressed as the percentage of the maximum possible score. Higher scores indicate higher levels of enjoyment/satisfaction. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit and baseline score-by-visit.
Time Frame Randomization, 8 weeks
Hide Outcome Measure Data
Hide 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 12 mg LY2216684 + SSRI 18 mg LY2216684 + SSRI Placebo + SSRI
Hide Arm/Group Description:
LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI
Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI
Overall Number of Participants Analyzed 224 222 236
Least Squares Mean (Standard Error)
Unit of Measure: percentage of maximum possible score
10.51  (0.98) 9.93  (0.98) 8.47  (0.95)
14.Secondary Outcome
Title Change From Randomization to Week 8 in the EuroQol Questionnaire-5 Dimension (EQ-5D)
Hide Description The EQ-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 the 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 treatment, investigator, visit, baseline score, treatment-by-visit and baseline score-by-visit.
Time Frame Randomization, 8 weeks
Hide Outcome Measure Data
Hide 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 12 mg LY2216684 + SSRI 18 mg LY2216684 + SSRI Placebo + SSRI
Hide Arm/Group Description:
LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI
Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI
Overall Number of Participants Analyzed 224 222 236
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
12.201  (1.218) 12.762  (1.225) 9.756  (1.188)
15.Secondary Outcome
Title Percentage of Treatment Emergent (TE) Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
Hide Description The C-SSRS captured 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 and behavior are defined as TE if not present at baseline. Percentage of participants was calculated by dividing the number of participants with suicide-related TE 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.
Time Frame Randomization through 8 weeks
Hide Outcome Measure Data
Hide 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 12 mg LY2216684 + SSRI 18 mg LY2216684 + SSRI Placebo + SSRI
Hide Arm/Group Description:
LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI
Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI
Overall Number of Participants Analyzed 230 230 240
Measure Type: Number
Unit of Measure: percentage of participants
TE of suicidal ideation Number Analyzed 230 participants 230 participants 240 participants
3.91 3.91 3.33
TE of suicidal behavior Number Analyzed 209 participants 214 participants 226 participants
0.00 0.47 0.44
16.Secondary Outcome
Title Change From Randomization to Week 8 in Arizona Sexual Experiences (ASEX) Scale
Hide Description The ASEX scale was used to assess sexual functioning in both males and females. The ASEX total score for the male and female version was 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 treatment, investigator, visit, baseline score, treatment-by-visit and baseline score-by-visit.
Time Frame Randomization, 8 weeks
Hide Outcome Measure Data
Hide 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 12 mg LY2216684 + SSRI 18 mg LY2216684 + SSRI Placebo + SSRI
Hide Arm/Group Description:
LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI
Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI
Overall Number of Participants Analyzed 222 220 233
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.32  (0.26) -1.27  (0.26) -0.79  (0.25)
17.Secondary Outcome
Title Change From Randomization to Week 8 in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ)
Hide Description 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 was 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 treatment, investigator, visit, baseline score, treatment-by-visit and baseline score-by-visit.
Time Frame Randomization, 8 weeks
Hide Outcome Measure Data
Hide 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 12 mg LY2216684 + SSRI 18 mg LY2216684 + SSRI Placebo + SSRI
Hide Arm/Group Description:
LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI
Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI
Overall Number of Participants Analyzed 224 222 236
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-4.70  (0.37) -4.41  (0.38) -3.79  (0.36)
18.Secondary Outcome
Title The Percentage of Participants Experiencing Treatment-Emergent Adverse Events as a Function of CYP2D6 Phenotype
Hide Description Treatment-emergent adverse events (TEAEs) were events that first occurred or worsened during the treatment phase. CYP2D6 functional phenotype was classified as poor metabolizer (PM) or non-poor metabolizer (non-PM). The percentage of participants who reported the TEAE is presented for each phenotype classification. Only TEAEs for which there was a statistically significant treatment-by-SSRI therapy interaction were included: tinnitus and influenza. A summary of serious and other non-serious adverse events regardless of causality is located in the Report of Adverse Events module.
Time Frame Through 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients who do not discontinue from the study for the reason 'Lost to follow-up' at the first post-baseline visit.
Arm/Group Title 12 mg LY2216684 + SSRI 18 mg LY2216684 + SSRI Placebo + SSRI
Hide Arm/Group Description:
LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI
Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI
Overall Number of Participants Analyzed 144 140 157
Measure Type: Number
Unit of Measure: percentage of participants
Tinnitus non-PM Number Analyzed 144 participants 140 participants 157 participants
0.00 0.00 1.27
Tinnitus PM Number Analyzed 77 participants 83 participants 76 participants
0.00 3.61 0.00
Influenza non-PM Number Analyzed 144 participants 140 participants 157 participants
1.39 0.00 0.64
Influenza PM Number Analyzed 77 participants 83 participants 76 participants
0.00 2.41 0.00
19.Secondary Outcome
Title Change From Randomization to Week 8 in Blood Pressure (BP)
Hide Description Blood pressure (BP) measurements were collected when the participant was in a sitting position. Three measurements of sitting BP 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 treatment, investigator, visit, baseline value, treatment-by-visit and baseline value-by-visit.
Time Frame Randomization, 8 weeks
Hide Outcome Measure Data
Hide 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 12 mg LY2216684 + SSRI 18 mg LY2216684 + SSRI Placebo + SSRI
Hide Arm/Group Description:
LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI
Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI
Overall Number of Participants Analyzed 230 230 240
Least Squares Mean (Standard Error)
Unit of Measure: millimeters of mercury (mmHg)
Sitting systolic BP 2.11  (0.57) 3.18  (0.57) 0.02  (0.55)
Sitting diastolic BP 3.57  (0.43) 4.00  (0.43) 0.66  (0.42)
20.Secondary Outcome
Title Change From Randomization to Week 8 in Pulse Rate
Hide Description 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 treatment, investigator, visit, baseline value, treatment-by-visit and baseline value-by-visit.
Time Frame Randomization, 8 weeks
Hide Outcome Measure Data
Hide 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 12 mg LY2216684 + SSRI 18 mg LY2216684 + SSRI Placebo + SSRI
Hide Arm/Group Description:
LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI
Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI
Overall Number of Participants Analyzed 230 230 240
Least Squares Mean (Standard Error)
Unit of Measure: beats per minute (bpm)
8.66  (0.64) 9.12  (0.64) -1.41  (0.62)
21.Secondary Outcome
Title Pharmacokinetics: Plasma Concentrations of LY2216684
Hide Description A validated bioanalytical assay was used to determine plasma LY2216684 concentrations.
Time Frame 1 week, 4 weeks, and 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants exposed to LY2216684 with evaluable plasma concentration values. Samples with concentrations below the lower quantification limit (BQL) of the assay were treated as missing values for the analysis and samples with incomplete dosing information were not included in the pharmacokinetics assessment.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
LY2216684: fixed doses of 12 milligrams (mg) administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI) or 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI
Overall Number of Participants Analyzed 442
Mean (Standard Deviation)
Unit of Measure: nanograms per milliliter (ng/mL)
12 mg dose Number Analyzed 427 participants
37.8  (20.7)
18 mg dose Number Analyzed 202 participants
55.3  (30.4)
Time Frame Adverse event data was collected over the 3-week double blind adjunctive placebo lead-in confirmation phase, the 8 week double-blind placebo-controlled adjunctive active treatment phase, and the 2-week discontinuation (DC) phase.
Adverse Event Reporting Description During the 2-week DC phase, participants who received LY2216684 were randomly assigned to either abrupt DC or tapered DC over the 2-week period. Participants who had received placebo either during the adjunctive treatment phase or the lead-in confirmation phase remained on placebo during the 2-week DC phase.
 
Arm/Group Title Placebo + SSRI (Pre-randomized) CF Phase 12 mg LY2216684 + SSRI (Randomized) AT Phase 18 mg LY2216684 + SSRI (Randomized) AT Phase Placebo + SSRI (Randomized) AT Phase Placebo + SSRI (Non-randomized) AT Phase Placebo + SSRI (Pre-randomized) Discontinuation Phase 12 mg LY2216684 + SSRI (Abrupt Discontinuation Phase) 12 mg LY2216684 + SSRI (Taper Discontinuation Phase) 18 mg LY2216684 + SSRI (Abrupt Discontinuation Phase) 18 mg LY2216684 + SSRI (Taper Discontinuation Phase) Placebo + SSRI (Randomized) Discontinuation Phase Placebo + SSRI (Non-randomized) Discontinuation Phase
Hide Arm/Group Description

Placebo: Administered orally, once daily for 3 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 Confirmation (CF) Phase.

LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a SSRI, during the adjunctive treatment phase.

Includes randomized participants who did not discontinue for the reason 'Lost to Follow-up' at the first post-randomization visit during the Adjunctive Treatment (AT) Phase.

LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI, during the adjunctive treatment phase.

Includes randomized participants who did not discontinue for the reason 'Lost to Follow-up' at the first post-randomization visit during the Adjunctive Treatment (AT) Phase.

Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI, during the adjunctive treatment phase

Includes randomized participants who did not discontinue for the reason 'Lost to Follow-up' at the first post-randomization visit during the Adjunctive Treatment (AT) Phase.

Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI, during the adjunctive treatment phase.

Includes all non-randomized participants who did not discontinue for the reason 'Lost to Follow-up' at the first post-randomization visit during the Adjunctive Treatment (AT) Phase.

Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI, during the adjunctive treatment phase.

Includes all enrolled participants who abruptly discontinued placebo after early withdrawal during the Confirmation (CF) Phase and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation (DC) Phase visit.

LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a SSRI

Includes all randomized participants who 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: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a SSRI

Includes all randomized participants who tapered discontinuation of 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: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI, during the adjunctive treatment phase

Includes all randomized participants who 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: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI, during the adjunctive treatment phase

Includes all randomized participants who tapered discontinuation of 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.

Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI, during the adjunctive treatment phase.

Includes all randomized participants who discontinued placebo 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.

Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI, during the adjunctive treatment phase.

Includes all non-randomized participants who discontinued placebo 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.

All-Cause Mortality
Placebo + SSRI (Pre-randomized) CF Phase 12 mg LY2216684 + SSRI (Randomized) AT Phase 18 mg LY2216684 + SSRI (Randomized) AT Phase Placebo + SSRI (Randomized) AT Phase Placebo + SSRI (Non-randomized) AT Phase Placebo + SSRI (Pre-randomized) Discontinuation Phase 12 mg LY2216684 + SSRI (Abrupt Discontinuation Phase) 12 mg LY2216684 + SSRI (Taper Discontinuation Phase) 18 mg LY2216684 + SSRI (Abrupt Discontinuation Phase) 18 mg LY2216684 + SSRI (Taper Discontinuation Phase) Placebo + SSRI (Randomized) Discontinuation Phase Placebo + SSRI (Non-randomized) Discontinuation Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo + SSRI (Pre-randomized) CF Phase 12 mg LY2216684 + SSRI (Randomized) AT Phase 18 mg LY2216684 + SSRI (Randomized) AT Phase Placebo + SSRI (Randomized) AT Phase Placebo + SSRI (Non-randomized) AT Phase Placebo + SSRI (Pre-randomized) Discontinuation Phase 12 mg LY2216684 + SSRI (Abrupt Discontinuation Phase) 12 mg LY2216684 + SSRI (Taper Discontinuation Phase) 18 mg LY2216684 + SSRI (Abrupt Discontinuation Phase) 18 mg LY2216684 + SSRI (Taper Discontinuation Phase) Placebo + SSRI (Randomized) Discontinuation Phase Placebo + SSRI (Non-randomized) Discontinuation Phase
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 Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/1413 (0.14%)      3/231 (1.30%)      2/230 (0.87%)      1/240 (0.42%)      5/627 (0.80%)      1/20 (5.00%)      1/108 (0.93%)      1/100 (1.00%)      0/108 (0.00%)      1/107 (0.93%)      0/221 (0.00%)      1/585 (0.17%)    
Gastrointestinal disorders                         
Gastritis  1  0/1413 (0.00%)  0 1/231 (0.43%)  1 0/230 (0.00%)  0 0/240 (0.00%)  0 0/627 (0.00%)  0 0/20 (0.00%)  0 0/108 (0.00%)  0 0/100 (0.00%)  0 0/108 (0.00%)  0 0/107 (0.00%)  0 0/221 (0.00%)  0 0/585 (0.00%)  0
Oesophageal achalasia  1  1/1413 (0.07%)  1 1/231 (0.43%)  1 0/230 (0.00%)  0 0/240 (0.00%)  0 0/627 (0.00%)  0 0/20 (0.00%)  0 1/108 (0.93%)  1 0/100 (0.00%)  0 0/108 (0.00%)  0 0/107 (0.00%)  0 0/221 (0.00%)  0 0/585 (0.00%)  0
Hepatobiliary disorders                         
Cholecystitis  1  0/1413 (0.00%)  0 0/231 (0.00%)  0 0/230 (0.00%)  0 0/240 (0.00%)  0 0/627 (0.00%)  0 0/20 (0.00%)  0 0/108 (0.00%)  0 1/100 (1.00%)  1 0/108 (0.00%)  0 0/107 (0.00%)  0 0/221 (0.00%)  0 0/585 (0.00%)  0
Cholelithiasis  1  0/1413 (0.00%)  0 0/231 (0.00%)  0 0/230 (0.00%)  0 0/240 (0.00%)  0 1/627 (0.16%)  1 0/20 (0.00%)  0 0/108 (0.00%)  0 0/100 (0.00%)  0 0/108 (0.00%)  0 0/107 (0.00%)  0 0/221 (0.00%)  0 0/585 (0.00%)  0
Infections and infestations                         
Sialoadenitis  1  0/1413 (0.00%)  0 0/231 (0.00%)  0 0/230 (0.00%)  0 0/240 (0.00%)  0 1/627 (0.16%)  1 0/20 (0.00%)  0 0/108 (0.00%)  0 0/100 (0.00%)  0 0/108 (0.00%)  0 0/107 (0.00%)  0 0/221 (0.00%)  0 0/585 (0.00%)  0
Investigations                         
Blood pressure increased  1  0/1413 (0.00%)  0 0/231 (0.00%)  0 0/230 (0.00%)  0 0/240 (0.00%)  0 1/627 (0.16%)  1 0/20 (0.00%)  0 0/108 (0.00%)  0 0/100 (0.00%)  0 0/108 (0.00%)  0 0/107 (0.00%)  0 0/221 (0.00%)  0 0/585 (0.00%)  0
Electrocardiogram qt prolonged  1  0/1413 (0.00%)  0 0/231 (0.00%)  0 0/230 (0.00%)  0 0/240 (0.00%)  0 1/627 (0.16%)  1 0/20 (0.00%)  0 0/108 (0.00%)  0 0/100 (0.00%)  0 0/108 (0.00%)  0 0/107 (0.00%)  0 0/221 (0.00%)  0 0/585 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                         
Colon cancer metastatic  1  0/1413 (0.00%)  0 0/231 (0.00%)  0 0/230 (0.00%)  0 0/240 (0.00%)  0 1/627 (0.16%)  1 0/20 (0.00%)  0 0/108 (0.00%)  0 0/100 (0.00%)  0 0/108 (0.00%)  0 0/107 (0.00%)  0 0/221 (0.00%)  0 1/585 (0.17%)  1
Oesophageal carcinoma  1  1/1413 (0.07%)  1 0/231 (0.00%)  0 0/230 (0.00%)  0 0/240 (0.00%)  0 0/627 (0.00%)  0 1/20 (5.00%)  1 0/108 (0.00%)  0 0/100 (0.00%)  0 0/108 (0.00%)  0 0/107 (0.00%)  0 0/221 (0.00%)  0 0/585 (0.00%)  0
Psychiatric disorders                         
Depression  1  0/1413 (0.00%)  0 0/231 (0.00%)  0 1/230 (0.43%)  1 0/240 (0.00%)  0 0/627 (0.00%)  0 0/20 (0.00%)  0 0/108 (0.00%)  0 0/100 (0.00%)  0 0/108 (0.00%)  0 0/107 (0.00%)  0 0/221 (0.00%)  0 0/585 (0.00%)  0
Suicidal ideation  1  0/1413 (0.00%)  0 1/231 (0.43%)  1 0/230 (0.00%)  0 0/240 (0.00%)  0 0/627 (0.00%)  0 0/20 (0.00%)  0 0/108 (0.00%)  0 0/100 (0.00%)  0 0/108 (0.00%)  0 0/107 (0.00%)  0 0/221 (0.00%)  0 0/585 (0.00%)  0
Suicide attempt  1  0/1413 (0.00%)  0 0/231 (0.00%)  0 0/230 (0.00%)  0 1/240 (0.42%)  1 0/627 (0.00%)  0 0/20 (0.00%)  0 0/108 (0.00%)  0 0/100 (0.00%)  0 0/108 (0.00%)  0 0/107 (0.00%)  0 0/221 (0.00%)  0 0/585 (0.00%)  0
Vascular disorders                         
Arteriosclerosis  1  0/1413 (0.00%)  0 0/231 (0.00%)  0 1/230 (0.43%)  1 0/240 (0.00%)  0 0/627 (0.00%)  0 0/20 (0.00%)  0 0/108 (0.00%)  0 0/100 (0.00%)  0 0/108 (0.00%)  0 1/107 (0.93%)  1 0/221 (0.00%)  0 0/585 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo + SSRI (Pre-randomized) CF Phase 12 mg LY2216684 + SSRI (Randomized) AT Phase 18 mg LY2216684 + SSRI (Randomized) AT Phase Placebo + SSRI (Randomized) AT Phase Placebo + SSRI (Non-randomized) AT Phase Placebo + SSRI (Pre-randomized) Discontinuation Phase 12 mg LY2216684 + SSRI (Abrupt Discontinuation Phase) 12 mg LY2216684 + SSRI (Taper Discontinuation Phase) 18 mg LY2216684 + SSRI (Abrupt Discontinuation Phase) 18 mg LY2216684 + SSRI (Taper Discontinuation Phase) Placebo + SSRI (Randomized) Discontinuation Phase Placebo + SSRI (Non-randomized) Discontinuation Phase
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 Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   240/1413 (16.99%)      71/231 (30.74%)      73/230 (31.74%)      36/240 (15.00%)      100/627 (15.95%)      3/20 (15.00%)      17/108 (15.74%)      15/100 (15.00%)      18/108 (16.67%)      19/107 (17.76%)      39/221 (17.65%)      106/585 (18.12%)    
Cardiac disorders                         
Tachycardia  1  4/1413 (0.28%)  4 16/231 (6.93%)  16 23/230 (10.00%)  24 0/240 (0.00%)  0 3/627 (0.48%)  4 0/20 (0.00%)  0 0/108 (0.00%)  0 0/100 (0.00%)  0 0/108 (0.00%)  0 1/107 (0.93%)  1 0/221 (0.00%)  0 0/585 (0.00%)  0
Gastrointestinal disorders                         
Nausea  1  55/1413 (3.89%)  57 11/231 (4.76%)  11 17/230 (7.39%)  21 1/240 (0.42%)  1 13/627 (2.07%)  13 0/20 (0.00%)  0 2/108 (1.85%)  2 1/100 (1.00%)  1 5/108 (4.63%)  7 6/107 (5.61%)  6 4/221 (1.81%)  4 19/585 (3.25%)  21
Infections and infestations                         
Nasopharyngitis  1  43/1413 (3.04%)  45 18/231 (7.79%)  18 10/230 (4.35%)  10 15/240 (6.25%)  15 34/627 (5.42%)  37 0/20 (0.00%)  0 3/108 (2.78%)  3 2/100 (2.00%)  2 3/108 (2.78%)  3 2/107 (1.87%)  2 11/221 (4.98%)  11 10/585 (1.71%)  10
Nervous system disorders                         
Dizziness  1  45/1413 (3.18%)  48 8/231 (3.46%)  9 12/230 (5.22%)  13 5/240 (2.08%)  10 13/627 (2.07%)  16 0/20 (0.00%)  0 3/108 (2.78%)  3 5/100 (5.00%)  5 3/108 (2.78%)  4 8/107 (7.48%)  11 7/221 (3.17%)  9 34/585 (5.81%)  42
Headache  1  116/1413 (8.21%)  136 22/231 (9.52%)  28 18/230 (7.83%)  18 14/240 (5.83%)  16 39/627 (6.22%)  47 3/20 (15.00%)  3 13/108 (12.04%)  29 7/100 (7.00%)  9 10/108 (9.26%)  14 10/107 (9.35%)  18 26/221 (11.76%)  36 69/585 (11.79%)  108
Reproductive system and breast disorders                         
Erectile dysfunction  1  3/447 (0.67%)  3 2/86 (2.33%)  2 1/81 (1.23%)  1 0/85 (0.00%)  0 2/176 (1.14%)  2 1/6 (16.67%)  1 0/37 (0.00%)  0 0/41 (0.00%)  0 0/38 (0.00%)  0 0/37 (0.00%)  0 0/81 (0.00%)  0 0/168 (0.00%)  0
Skin and subcutaneous tissue disorders                         
Hyperhidrosis  1  17/1413 (1.20%)  17 19/231 (8.23%)  20 16/230 (6.96%)  16 2/240 (0.83%)  2 6/627 (0.96%)  6 0/20 (0.00%)  0 0/108 (0.00%)  0 1/100 (1.00%)  1 1/108 (0.93%)  3 4/107 (3.74%)  7 1/221 (0.45%)  1 3/585 (0.51%)  3
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01173601     History of Changes
Other Study ID Numbers: 11316
H9P-MC-LNBM ( Other Identifier: Eli Lilly and Company )
First Submitted: July 29, 2010
First Posted: August 2, 2010
Results First Submitted: February 17, 2018
Results First Posted: April 17, 2018
Last Update Posted: April 17, 2018