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A Safety Study in Participants 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: NCT01155661
Recruitment Status : Completed
First Posted : July 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 Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Depressive Disorder, Major
Interventions Drug: LY2216684 (edivoxetine)
Drug: SSRI
Enrollment 608
Recruitment Details  
Pre-assignment Details There was a 54 week LY2216684 treatment Open-label Phase followed by 1 week Discontinuation Phase after abrupt discontinuation of treatment.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description LY2216684 (edivoxetine): 12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI)
Period Title: Overall Study
Started 608
Completed 328
Not Completed 280
Reason Not Completed
Adverse Event             101
Death             1
Lack of Efficacy             32
Lost to Follow-up             22
Physician Decision             3
Protocol Violation             35
Withdrawal by Subject             73
Sponsor Decision             13
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description LY2216684 (edivoxetine): 12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI)
Overall Number of Baseline Participants 608
Hide Baseline Analysis Population Description
All enrolled participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 608 participants
47.54  (12.97)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 608 participants
Female 455
Male 153
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 608 participants
Hispanic or Latino 214
Not Hispanic or Latino 320
Unknown or Not Reported 74
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 608 participants
American Indian or Alaska Native 14
Asian 5
Native Hawaiian or Other Pacific Islander 0
Black or African American 59
White 521
More than one race 9
Unknown or Not Reported 0
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 608 participants
United States 300
Mexico 110
Brazil 82
Chile 50
Lithuania 38
Netherlands 19
Spain 9
1.Primary Outcome
Title The Number of Participants Experiencing Clinically Significant Effects
Hide Description

A clinically significant effect was defined as a serious adverse event, regardless of causality.

A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Event module.

Time Frame Baseline through 54 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who did not discontinue from the study for the reason 'Lost to follow-up' at the first post-baseline visit.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
LY2216684 (edivoxetine): 12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI)
Overall Number of Participants Analyzed 600
Measure Type: Number
Unit of Measure: participants
13
2.Secondary Outcome
Title Percent of Participants With Suicidal Ideation and Behavior Based on the 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.
Time Frame Baseline through Week 54
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants with a baseline and at least one post-baseline C-SSRS value.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
LY2216684 (edivoxetine): 12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI)
Overall Number of Participants Analyzed 589
Measure Type: Number
Unit of Measure: percentage of participants
Suicidal Ideation 11.71
Suicidal Behavior 0.17
3.Secondary Outcome
Title Change From Baseline to 54 Week Endpoint in the 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 investigator, visit, baseline score, and baseline-by-visit.
Time Frame Baseline, Week 54
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants with a baseline and at least one post-baseline ASEX total score value.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
LY2216684 (edivoxetine): 12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI)
Overall Number of Participants Analyzed 537
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.28  (0.25)
4.Secondary Outcome
Title Change From Baseline to 54 Week Endpoint 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 investigator, visit, baseline score, and baseline-by-visit.
Time Frame Baseline, Week 54
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants with a baseline and at least one post-baseline CPFQ total score value.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
LY2216684 (edivoxetine): 12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI)
Overall Number of Participants Analyzed 541
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-8.64  (0.30)
5.Secondary Outcome
Title Change From Baseline to 54 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Items
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 investigator, visit, baseline score, and baseline-by-visit.
Time Frame Baseline, Week 54
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants with a baseline and at least one post-baseline MADRS individual item and total score value.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
LY2216684 (edivoxetine): 12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI)
Overall Number of Participants Analyzed 589
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
MADRS Item 1: Apparent Sadness -2.17  (0.05)
MADRS Item 2: Reported Sadness -2.38  (0.06)
MADRS Item 3: Inner Tension -1.56  (0.06)
MADRS Item 4: Reduced Sleep -1.97  (0.07)
MADRS Item 5: Reduced Appetite -1.08  (0.04)
MADRS Item 6: Concentration Difficulties -1.88  (0.06)
MADRS Item 7: Lassitude -2.18  (0.06)
MADRS Item 8: Inability to Feel -2.22  (0.06)
MADRS Item 9: Pessimistic Thoughts -1.52  (0.05)
MADRS Item 10: Suicidal Thoughts -0.26  (0.02)
MADRS Total Score -16.97  (0.41)
6.Secondary Outcome
Title Change From Baseline to 54 Week Endpoint in Hospital Anxiety and Depression Scale (HADS) Depression Subscale Score
Hide 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 subscales. 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, 'normal.' Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for investigator, visit, baseline score, and baseline-by-visit.
Time Frame Baseline, Week 54
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants with a baseline and at least one post-baseline Hospital Anxiety and Depression Scale (HADS) depression subscale value.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
LY2216684 (edivoxetine): 12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI)
Overall Number of Participants Analyzed 588
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-6.32  (0.21)
7.Secondary Outcome
Title Change From Baseline to 54 Week Endpoint in Clinical Global Impression - Severity (CGI-S)
Hide Description 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 investigator, visit, baseline score, and baseline-by-visit.
Time Frame Baseline, Week 54
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants with a baseline and at least one post-baseline Clinical Global Impression - Severity (CGI-S) value.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
LY2216684 (edivoxetine): 12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI)
Overall Number of Participants Analyzed 589
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.17  (0.06)
8.Secondary Outcome
Title Change From Baseline to 54 Week Endpoint in Fatigue Associated With Depression (FAsD) Average Score and Subscale Scores
Hide Description The Fatigue Associated with Depression (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 investigator, visit, baseline score, and baseline-by-visit.
Time Frame Baseline, Week 54
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants with a baseline and at least one post-baseline Fatigue Associated with Depression (FAsD) average score and subscale score.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
LY2216684 (edivoxetine): 12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI)
Overall Number of Participants Analyzed 541
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
FAsD Experience Score -1.25  (0.05)
FAsD Impact Score -1.37  (0.05)
FAsD Average Score -1.30  (0.05)
9.Secondary Outcome
Title Probability of Meeting the Response Criteria for Depressive Symptoms at Week 54 Endpoint
Hide Description Response criteria was defined as at least a 50% decrease from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total score. 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). This analysis models the probability of response at each visit, and the estimated probabilities were adjusted for visit and the baseline MADRS total score.
Time Frame Baseline, Week 54
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants with a baseline and at least one post-baseline Montgomery-Asberg Depression Rating Scale (MADRS) total score value.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
LY2216684 (edivoxetine): 12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI)
Overall Number of Participants Analyzed 589
Measure Type: Number
Unit of Measure: Probability of response
0.772
10.Secondary Outcome
Title Probability of Meeting the Remission Criteria for Depressive Symptoms at Week 54 Endpoint
Hide Description Remission criteria was defined as a Montgomery-Asberg Depression Rating Scale (MADRS) total score of <= 10. 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). This analysis models the probability of remission at each visit, and the estimated probabilities were adjusted for visit and the baseline MADRS total score.
Time Frame Baseline, Week 54
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants with a baseline and at least one post-baseline Montgomery-Asberg Depression Rating Scale (MADRS) total score value.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
LY2216684 (edivoxetine): 12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI)
Overall Number of Participants Analyzed 589
Measure Type: Number
Unit of Measure: Probability of remission
0.758
11.Secondary Outcome
Title Percentage of Participants Who Meet Response Criteria of Depressive Symptoms by Week 8
Hide Description Response criteria was defined as at least a 50% decrease from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total score. 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). The Kaplan-Meier product limit method of time to first response was calculated. In the calculation, participants who did not meet response criteria were considered as right-censored observations. The estimated percentage of participants who met response criteria by Week 8 from the Kaplan-Meier method is presented.
Time Frame Baseline, Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants with a baseline and at least one post-baseline Montgomery-Asberg Depression Rating Scale (MADRS) total score value.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
LY2216684 (edivoxetine): 12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI)
Overall Number of Participants Analyzed 589
Measure Type: Number
Unit of Measure: percentage of participants
59.2
12.Secondary Outcome
Title Change From Baseline to 54 Week Endpoint in Hospital Anxiety and Depression Scale (HADS) Anxiety Subscale Score
Hide Description The Hospital Anxiety and Depression Scale (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, 'normal.' Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for investigator, visit, baseline score, and baseline-by-visit.
Time Frame Baseline, Week 54
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants with a baseline and at least one post-baseline Hospital Anxiety and Depression Scale (HADS) anxiety subscale value.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
LY2216684 (edivoxetine): 12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI)
Overall Number of Participants Analyzed 588
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-4.57  (0.18)
13.Secondary Outcome
Title Change From Baseline to 54 Week Endpoint in Sheehan Disability Scale (SDS) Total Score and Subscores
Hide Description The Sheehan Disability Scale (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 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 Functional Impairment Score is the sum of the 3 items, and scores ranged from 0 to 30 with higher values indicating greater disruption in the participant's work life (work/school impairment [imp] score), social life (social life/leisure activities impairment [imp] score), and family life (family life/home responsibilities impairment [imp] score). Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for investigator, visit, baseline score, and baseline-by-visit.
Time Frame Baseline, Week 54
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants with a baseline and at least one post-baseline Sheehan Disability Scale (SDS) subscale score.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
LY2216684 (edivoxetine): 12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI)
Overall Number of Participants Analyzed 491
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
SDS Global Functional Impairment(Imp) Score Number Analyzed 490 participants
-10.71  (0.37)
Work/School Imp Score Number Analyzed 318 participants
-3.36  (0.15)
Social Life/Leisure Activity Imp Score Number Analyzed 491 participants
-3.74  (0.13)
Family Life/Home Responsibility Imp Score Number Analyzed 490 participants
-3.61  (0.13)
14.Secondary Outcome
Title Change From Baseline to 54 Week Endpoint in 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 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 investigator, visit, baseline score, and baseline-by-visit.
Time Frame Baseline, Week 54
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants with a baseline and at least one post-baseline EuroQol Questionnaire - 5 Dimension (EQ-5D) visual analog scale value.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
LY2216684 (edivoxetine): 12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI)
Overall Number of Participants Analyzed 488
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
23.607  (1.019)
15.Secondary Outcome
Title Change From Baseline to 54 Week Endpoint in Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF)
Hide Description The Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (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 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 investigator, visit, baseline score, and baseline-by-visit.
Time Frame Baseline, Week 54
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants with a baseline and at least one post-baseline Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) percent of maximum possible score value.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
LY2216684 (edivoxetine): 12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI)
Overall Number of Participants Analyzed 491
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
21.56  (0.90)
16.Secondary Outcome
Title Percentage of Participants Who Reported Resource Utilization (RU) at Baseline and at the Week 54 Endpoint
Hide Description The Resource Utilization (RU) form assesses the frequency and type of medical services (a primary care visit and/or a psychiatrist visit) that participants used within the previous year (for the baseline visit) or within approximately the previous 3 months (for post-baseline visits or the Week 54 endpoint). The percentage of participants who reported greater than zero number of primary care doctor visits and greater than zero number of psychiatrist visits is presented.
Time Frame Baseline, Week 54
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants with a baseline and at least one post-baseline Resource Utilization value.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
LY2216684 (edivoxetine): 12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI)
Overall Number of Participants Analyzed 607
Measure Type: Number
Unit of Measure: percentage of participants
Primary Care Doctor Visits, Baseline Number Analyzed 607 participants
62.27
Primary Care Doctor Visits, Week 54 Number Analyzed 338 participants
30.18
Psychiatrist Visits, Baseline Number Analyzed 607 participants
44.15
Psychiatrist Visits, Week 54 Number Analyzed 337 participants
4.75
17.Secondary Outcome
Title Percentage of Participants With Discontinuation-Emergent Adverse Events (DEAEs)
Hide Description Discontinuation-emergent adverse events (DEAEs) were events that first occurred or worsened within 1-week after abrupt discontinuation of LY2216684 (edivoxetine) treatment.
Time Frame Up to1 week after discontinuation of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who abruptly discontinued LY2216684 (edivoxetine) treatment either at the end of the study or after early withdrawal from the study and who did not discontinue from the study for the reason 'Lost to follow-up' at the first post-baseline visit.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
LY2216684 (edivoxetine): 12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI)
Overall Number of Participants Analyzed 472
Measure Type: Number
Unit of Measure: percentage of participants
20.97
18.Secondary Outcome
Title Percentage of Participants Who Meet Remission Criteria of Depressive Symptoms by Week 8
Hide Description Remission criteria was defined as a Montgomery-Asberg Depression Rating Scale (MADRS) total score of <= 10. 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). The Kaplan-Meier product limit method of time to first remission was calculated. In the calculation, participants who did not meet remission criteria were considered as right-censored observations. The estimated percentage of participants who meet remission criteria by Week 8 from the Kaplan-Meier method is presented.
Time Frame Baseline, Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants with a baseline and at least one post-baseline Montgomery-Asberg Depression Rating Scale (MADRS) total score value.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
LY2216684 (edivoxetine): 12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI)
Overall Number of Participants Analyzed 589
Measure Type: Number
Unit of Measure: percentage of participants
47.7
19.Secondary Outcome
Title Plasma Concentration of LY2216684
Hide Description [Not Specified]
Time Frame Weeks 2, 6, and 8
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants with at least one plasma sample.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
LY2216684: 12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI)
Overall Number of Participants Analyzed 512
Mean (Standard Deviation)
Unit of Measure: nanograms per milliliter (ng/mL)
12 mg dose Number Analyzed 496 participants
29.6  (21.4)
18 mg dose Number Analyzed 262 participants
53.6  (35.7)
20.Secondary Outcome
Title The Number of Participants Experiencing Clinically Significant Effects as a Function of CYP2D6 Predicted Phenotype at Week 54 Endpoint
Hide Description A clinically significant effect was defined as a treatment-emergent adverse event; a reported adverse event that first occurred or worsened during the treatment phase. CYP2D6 predicted phenotype was classified as poor metabolizer (PM) or non-poor metabolizer (non-PM). The number of participants who reported at least one treatment-emergent adverse event is presented for each phenotype classification.
Time Frame Baseline, Week 54
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who did not discontinue from the study for the reason 'Lost to follow-up' at the first post-baseline visit.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
LY2216684 (edivoxetine): 12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI)
Overall Number of Participants Analyzed 600
Measure Type: Number
Unit of Measure: participants
Poor Metabolizer Number Analyzed 22 participants
17
Non-poor Metabolizer Number Analyzed 539 participants
408
21.Secondary Outcome
Title Change From Baseline to 54 Week Endpoint in Blood Pressure
Hide Description 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 investigator, visit, baseline value, and baseline-by-visit.
Time Frame Baseline, Week 54
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants with a baseline and at least one post-baseline blood pressure value.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
LY2216684 (edivoxetine): 12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI)
Overall Number of Participants Analyzed 590
Least Squares Mean (Standard Error)
Unit of Measure: millimeters of mercury (mm Hg)
Sitting Systolic Blood Pressure 2.28  (0.50)
Sitting Diastolic Blood Pressure 2.17  (0.40)
22.Secondary Outcome
Title Change From Baseline to Week 54 Endpoint 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 investigator, visit, baseline value, and baseline-by-visit.
Time Frame Baseline, Week 54
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants with a baseline and at least one post-baseline pulse rate value.
Arm/Group Title LY2216684 + SSRI
Hide Arm/Group Description:
LY2216684 (edivoxetine): 12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI)
Overall Number of Participants Analyzed 590
Least Squares Mean (Standard Error)
Unit of Measure: beats per minute (bpm)
7.01  (0.49)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title LY2216684 + SSRI Open-Label Phase Discontinuation Phase
Hide Arm/Group Description LY2216684 (edivoxetine): 12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to selective serotonin reuptake inhibitor (SSRI); included all enrolled participants who did not discontinue from the study for the reason 'Lost to follow-up' at the first post-baseline visit. Included all enrolled participants who abruptly discontinued LY2216684 (edivoxetine) treatment either at the end of the study or after early withdrawal from the study and who did not discontinue from the study for the reason 'Lost to follow-up' at the discontinuation phase visit. All participants maintained their SSRI treatment at the stable dose during the discontinuation phase.
All-Cause Mortality
LY2216684 + SSRI Open-Label Phase Discontinuation Phase
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
LY2216684 + SSRI Open-Label Phase Discontinuation Phase
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/600 (2.17%)      0/472 (0.00%)    
Cardiac disorders     
Myocardial infarction  1 [1]  1/600 (0.17%)  1 0/472 (0.00%)  0
Gastrointestinal disorders     
Colitis  1  1/600 (0.17%)  1 0/472 (0.00%)  0
Large intestinal obstruction  1  1/600 (0.17%)  1 0/472 (0.00%)  0
Oesophageal rupture  1  1/600 (0.17%)  1 0/472 (0.00%)  0
General disorders     
Non-cardiac chest pain  1  1/600 (0.17%)  1 0/472 (0.00%)  0
Infections and infestations     
Appendicitis  1  1/600 (0.17%)  1 0/472 (0.00%)  0
Pharyngitis  1  1/600 (0.17%)  1 0/472 (0.00%)  0
Injury, poisoning and procedural complications     
Joint injury  1  1/600 (0.17%)  1 0/472 (0.00%)  0
Poisoning  1  1/600 (0.17%)  1 0/472 (0.00%)  0
Psychiatric disorders     
Mania  1  1/600 (0.17%)  1 0/472 (0.00%)  0
Suicide attempt  1  1/600 (0.17%)  1 0/472 (0.00%)  0
Reproductive system and breast disorders     
Bartholinitis  1  1/452 (0.22%)  1 0/362 (0.00%)  0
Vascular disorders     
Hypertension  1  1/600 (0.17%)  1 0/472 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
[1]
resulted in death
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
LY2216684 + SSRI Open-Label Phase Discontinuation Phase
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   448/600 (74.67%)      99/472 (20.97%)    
Cardiac disorders     
Palpitations  1  25/600 (4.17%)  26 4/472 (0.85%)  4
Gastrointestinal disorders     
Constipation  1  72/600 (12.00%)  77 0/472 (0.00%)  0
Dry mouth  1  56/600 (9.33%)  58 2/472 (0.42%)  2
Nausea  1  88/600 (14.67%)  99 12/472 (2.54%)  12
Vomiting  1  40/600 (6.67%)  46 1/472 (0.21%)  1
General disorders     
Chills  1  21/600 (3.50%)  23 0/472 (0.00%)  0
Infections and infestations     
Influenza  1  21/600 (3.50%)  25 3/472 (0.64%)  3
Nasopharyngitis  1  19/600 (3.17%)  22 2/472 (0.42%)  2
Upper respiratory tract infection  1  34/600 (5.67%)  39 0/472 (0.00%)  0
Nervous system disorders     
Dizziness  1  45/600 (7.50%)  50 15/472 (3.18%)  18
Headache  1  68/600 (11.33%)  107 51/472 (10.81%)  59
Somnolence  1  21/600 (3.50%)  26 7/472 (1.48%)  7
Psychiatric disorders     
Anxiety  1  20/600 (3.33%)  23 7/472 (1.48%)  7
Insomnia  1  36/600 (6.00%)  38 3/472 (0.64%)  3
Reproductive system and breast disorders     
Erectile dysfunction  1  7/148 (4.73%)  7 0/110 (0.00%)  0
Testicular pain  1  5/148 (3.38%)  5 0/110 (0.00%)  0
Skin and subcutaneous tissue disorders     
Hyperhidrosis  1  85/600 (14.17%)  93 3/472 (0.64%)  3
Vascular disorders     
Hypertension  1  23/600 (3.83%)  25 0/472 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
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
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01155661     History of Changes
Other Study ID Numbers: 11318
H9P-MC-LNBO ( Other Identifier: Eli Lilly and Company )
First Submitted: June 30, 2010
First Posted: July 2, 2010
Results First Submitted: February 17, 2018
Results First Posted: April 17, 2018
Last Update Posted: April 17, 2018