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A Safety Study in Participants With Major Depressive Disorder

Primary Purpose

Depressive Disorder, Major

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

LY2216684 (edivoxetine)

SSRI

About this trial

This is an interventional treatment trial for Depressive Disorder, Major

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Adults competent and able to give informed consent
Women of child-bearing potential may participate but must test negative for pregnancy at the time of study entry; both women/men agree to use a reliable method of birth control
Participants who are being treated with one of the following selective serotonin reuptake inhibitors (SSRIs): escitalopram, citalopram, sertraline, fluoxetine, paroxetine, and fluvoxamine; for at least 6 weeks prior to investigational product dispensing with at least the last 4 weeks at a stable, optimized dose
Drug and dosage should be within the labeling guidelines for the specific country
Meet criteria for Major Depressive Disorder (MDD), as defined by the Diagnostic and Statistical Manual, Fourth Edition, Text Revision (DSM-IV-TR) criteria
Meet criteria for partial response, as defined by investigator's opinion that participant has experienced a minimal clinically meaningful improvement with SSRI
Have a Grid Hamilton Rating Scale for Depression (GRID-HAMD17) total score greater than or equal to 16 at screening
Have less than or equal to 75 percent improvement on the current SSRI at screening determined by the Massachusetts General Hospital Antidepressant Response Questionnaire (MGH-ATRQ)
Meet all other inclusion criteria per protocol

Exclusion Criteria:

Presence of another primary psychiatric illnesses:
- Have had or currently have any additional ongoing DSM-IV-TR Axis I condition other than major depression within 1 year of screening
- Have had any anxiety disorder that was considered a primary diagnosis within the past year (including panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, generalized anxiety disorder, and social phobia, but excluding specific phobias)
- Have a current or previous diagnosis of a bipolar disorder, schizophrenia, or other psychotic disorder
- Have a history of substance abuse and/or dependence within the past 1 year (drug categories defined by DSM-IV-TR), not including caffeine and nicotine
- Have a DSM-IV-TR Axis II disorder that, in the judgment of the investigator, would interfere with compliance with protocol
Unstable medical conditions that contraindicate the use of LY2216684
- Have any diagnosed medical condition which could be exacerbated by noradrenergic agents including unstable hypertension, unstable heart disease, tachycardia, tachyarrhythmia, narrow-angled glaucoma, urinary hesitation or retention
Use of excluded concomitant or psychotropic medication other than SSRI
Have initiated or discontinued hormone therapy within the previous 3 months of prior to enrollment
History of treatment resistant depression as shown by:
- Have had lack of response of the current depressive episode to 2 or more adequate courses of antidepressant therapy at a clinically appropriate dose for at least 4 weeks, or in the judgment of the investigator, the participant has treatment-resistant depression
- Have a history of electroconvulsive therapy, transcranial magnetic stimulation, or psychosurgery within the last year
Meet any other exclusion criteria per protocol

Sites / Locations

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

LY2216684 (edivoxetine) + SSRI

Arm Description

Outcomes

Primary Outcome Measures

The Number of Participants Experiencing Clinically Significant Effects

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.

Secondary Outcome Measures

Percent of Participants With Suicidal Ideation and Behavior Based on the Columbia-Suicide Severity Rating Scale (C-SSRS)

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.

Change From Baseline to 54 Week Endpoint in the Arizona Sexual Experiences (ASEX) Scale

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.

Change From Baseline to 54 Week Endpoint in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ)

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.

Change From Baseline to 54 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Items

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.

Change From Baseline to 54 Week Endpoint in Hospital Anxiety and Depression Scale (HADS) Depression Subscale Score

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.

Change From Baseline to 54 Week Endpoint in Clinical Global Impression - Severity (CGI-S)

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.

Change From Baseline to 54 Week Endpoint in Fatigue Associated With Depression (FAsD) Average Score and Subscale Scores

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.

Probability of Meeting the Response Criteria for Depressive Symptoms at Week 54 Endpoint

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.

Probability of Meeting the Remission Criteria for Depressive Symptoms at Week 54 Endpoint

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.

Percentage of Participants Who Meet Response Criteria of Depressive Symptoms by Week 8

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.

Change From Baseline to 54 Week Endpoint in Hospital Anxiety and Depression Scale (HADS) Anxiety Subscale Score

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.

Change From Baseline to 54 Week Endpoint in Sheehan Disability Scale (SDS) Total Score and Subscores

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.

Change From Baseline to 54 Week Endpoint in EuroQol Questionnaire - 5 Dimension (EQ-5D)

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.

Change From Baseline to 54 Week Endpoint in Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF)

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.

Percentage of Participants Who Reported Resource Utilization (RU) at Baseline and at the Week 54 Endpoint

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.

Percentage of Participants With Discontinuation-Emergent Adverse Events (DEAEs)

Discontinuation-emergent adverse events (DEAEs) were events that first occurred or worsened within 1-week after abrupt discontinuation of LY2216684 (edivoxetine) treatment.

Percentage of Participants Who Meet Remission Criteria of Depressive Symptoms by Week 8

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.

Plasma Concentration of LY2216684

The Number of Participants Experiencing Clinically Significant Effects as a Function of CYP2D6 Predicted Phenotype at Week 54 Endpoint

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.

Change From Baseline to 54 Week Endpoint in Blood Pressure

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.

Change From Baseline to Week 54 Endpoint in Pulse Rate

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.

Full Information

NCT ID

NCT01155661

First Posted

June 30, 2010

Last Updated

March 16, 2018

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT01155661

Brief Title

A Safety Study in Participants With Major Depressive Disorder

Official Title

Long-Term, Open-Label, Safety Study of LY2216684 12 to 18 mg Once Daily as Adjunctive Treatment for Patients With Major Depressive Disorder Who Are Partial Responders to Selective Serotonin Reuptake Inhibitor Treatment

Study Type

Interventional

2. Study Status

Record Verification Date

March 2018

Overall Recruitment Status

Completed

Study Start Date

October 2010 (undefined)

Primary Completion Date

December 2012 (Actual)

Study Completion Date

December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The primary objective of this study is to evaluate the long-term safety and tolerability of LY2216684 administered once daily (QD) in the adjunctive treatment with a selective serotonin reuptake inhibitor (SSRI) for up to approximately 1 year in participants with major depressive disorder (MDD) who are partial responders to their SSRI treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Depressive Disorder, Major

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

608 (Actual)

8. Arms, Groups, and Interventions

Arm Title

LY2216684 (edivoxetine) + SSRI

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

LY2216684 (edivoxetine)

Other Intervention Name(s)

LY2216684, edivoxetine

Intervention Description

12 to 18 milligrams (mg), administered orally, once daily for 54 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)

Intervention Type

Drug

Intervention Name(s)

SSRI

Other Intervention Name(s)

Selective Serotonin Reuptake Inhibitor

Intervention Description

Participants should have been on their SSRI for at least 6 weeks prior and were to continue on their stable dose throughout the study.

Primary Outcome Measure Information:

Title

The Number of Participants Experiencing Clinically Significant Effects

Description

Time Frame

Baseline through 54 weeks

Secondary Outcome Measure Information:

Title

Percent of Participants With Suicidal Ideation and Behavior Based on the Columbia-Suicide Severity Rating Scale (C-SSRS)

Description

Time Frame

Baseline through Week 54

Title

Change From Baseline to 54 Week Endpoint in the Arizona Sexual Experiences (ASEX) Scale

Description

Time Frame

Baseline, Week 54

Title

Change From Baseline to 54 Week Endpoint in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ)

Description

Time Frame

Baseline, Week 54

Title

Change From Baseline to 54 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Items

Description

Time Frame

Baseline, Week 54

Title

Change From Baseline to 54 Week Endpoint in Hospital Anxiety and Depression Scale (HADS) Depression Subscale Score

Description

Time Frame

Baseline, Week 54

Title

Change From Baseline to 54 Week Endpoint in Clinical Global Impression - Severity (CGI-S)

Description

Time Frame

Baseline, Week 54

Title

Change From Baseline to 54 Week Endpoint in Fatigue Associated With Depression (FAsD) Average Score and Subscale Scores

Description

Time Frame

Baseline, Week 54

Title

Probability of Meeting the Response Criteria for Depressive Symptoms at Week 54 Endpoint

Description

Time Frame

Baseline, Week 54

Title

Probability of Meeting the Remission Criteria for Depressive Symptoms at Week 54 Endpoint

Description

Time Frame

Baseline, Week 54

Title

Percentage of Participants Who Meet Response Criteria of Depressive Symptoms by Week 8

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

Title

Change From Baseline to 54 Week Endpoint in Hospital Anxiety and Depression Scale (HADS) Anxiety Subscale Score

Description

Time Frame

Baseline, Week 54

Title

Change From Baseline to 54 Week Endpoint in Sheehan Disability Scale (SDS) Total Score and Subscores

Description

Time Frame

Baseline, Week 54

Title

Change From Baseline to 54 Week Endpoint in EuroQol Questionnaire - 5 Dimension (EQ-5D)

Description

Time Frame

Baseline, Week 54

Title

Change From Baseline to 54 Week Endpoint in Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF)

Description

Time Frame

Baseline, Week 54

Title

Percentage of Participants Who Reported Resource Utilization (RU) at Baseline and at the Week 54 Endpoint

Description

Time Frame

Baseline, Week 54

Title

Percentage of Participants With Discontinuation-Emergent Adverse Events (DEAEs)

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

Title

Percentage of Participants Who Meet Remission Criteria of Depressive Symptoms by Week 8

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

Title

Plasma Concentration of LY2216684

Time Frame

Weeks 2, 6, and 8

Title

The Number of Participants Experiencing Clinically Significant Effects as a Function of CYP2D6 Predicted Phenotype at Week 54 Endpoint

Description

Time Frame

Baseline, Week 54

Title

Change From Baseline to 54 Week Endpoint in Blood Pressure

Description

Time Frame

Baseline, Week 54

Title

Change From Baseline to Week 54 Endpoint in Pulse Rate

Description

Time Frame

Baseline, Week 54

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Adults competent and able to give informed consent Women of child-bearing potential may participate but must test negative for pregnancy at the time of study entry; both women/men agree to use a reliable method of birth control Participants who are being treated with one of the following selective serotonin reuptake inhibitors (SSRIs): escitalopram, citalopram, sertraline, fluoxetine, paroxetine, and fluvoxamine; for at least 6 weeks prior to investigational product dispensing with at least the last 4 weeks at a stable, optimized dose Drug and dosage should be within the labeling guidelines for the specific country Meet criteria for Major Depressive Disorder (MDD), as defined by the Diagnostic and Statistical Manual, Fourth Edition, Text Revision (DSM-IV-TR) criteria Meet criteria for partial response, as defined by investigator's opinion that participant has experienced a minimal clinically meaningful improvement with SSRI Have a Grid Hamilton Rating Scale for Depression (GRID-HAMD17) total score greater than or equal to 16 at screening Have less than or equal to 75 percent improvement on the current SSRI at screening determined by the Massachusetts General Hospital Antidepressant Response Questionnaire (MGH-ATRQ) Meet all other inclusion criteria per protocol Exclusion Criteria: Presence of another primary psychiatric illnesses: Have had or currently have any additional ongoing DSM-IV-TR Axis I condition other than major depression within 1 year of screening Have had any anxiety disorder that was considered a primary diagnosis within the past year (including panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, generalized anxiety disorder, and social phobia, but excluding specific phobias) Have a current or previous diagnosis of a bipolar disorder, schizophrenia, or other psychotic disorder Have a history of substance abuse and/or dependence within the past 1 year (drug categories defined by DSM-IV-TR), not including caffeine and nicotine Have a DSM-IV-TR Axis II disorder that, in the judgment of the investigator, would interfere with compliance with protocol Unstable medical conditions that contraindicate the use of LY2216684 Have any diagnosed medical condition which could be exacerbated by noradrenergic agents including unstable hypertension, unstable heart disease, tachycardia, tachyarrhythmia, narrow-angled glaucoma, urinary hesitation or retention Use of excluded concomitant or psychotropic medication other than SSRI Have initiated or discontinued hormone therapy within the previous 3 months of prior to enrollment History of treatment resistant depression as shown by: Have had lack of response of the current depressive episode to 2 or more adequate courses of antidepressant therapy at a clinically appropriate dose for at least 4 weeks, or in the judgment of the investigator, the participant has treatment-resistant depression Have a history of electroconvulsive therapy, transcranial magnetic stimulation, or psychosurgery within the last year Meet any other exclusion criteria per protocol

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35216

Country

United States

Facility Name

City

Little Rock

State/Province

Arkansas

ZIP/Postal Code

72223

Country

United States

Facility Name

City

Cerritos

State/Province

California

ZIP/Postal Code

90703

Country

United States

Facility Name

City

Irvine

State/Province

California

ZIP/Postal Code

92618

Country

United States

Facility Name

City

Los Alamitos

State/Province

California

ZIP/Postal Code

90720

Country

United States

Facility Name

City

Redlands

State/Province

California

ZIP/Postal Code

92374

Country

United States

Facility Name

City

Riverside

State/Province

California

ZIP/Postal Code

92506

Country

United States

Facility Name

City

San Diego

State/Province

California

ZIP/Postal Code

92121

Country

United States

Facility Name

City

Upland

State/Province

California

ZIP/Postal Code

91786

Country

United States

Facility Name

City

Fort Walton Beach

State/Province

Florida

ZIP/Postal Code

32547

Country

United States

Facility Name

City

Gainesville

State/Province

Florida

ZIP/Postal Code

32607

Country

United States

Facility Name

City

Orlando

State/Province

Florida

ZIP/Postal Code

32806

Country

United States

Facility Name

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46260

Country

United States

Facility Name

City

Prairie Village

State/Province

Kansas

ZIP/Postal Code

66206

Country

United States

Facility Name

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02135

Country

United States

Facility Name

City

Princeton

State/Province

New Jersey

ZIP/Postal Code

08540

Country

United States

Facility Name

City

Albuquerque

State/Province

New Mexico

ZIP/Postal Code

87109

Country

United States

Facility Name

City

Bronx

State/Province

New York

ZIP/Postal Code

10467

Country

United States

Facility Name

City

Mount Kisco

State/Province

New York

ZIP/Postal Code

10549

Country

United States

Facility Name

City

New York

State/Province

New York

ZIP/Postal Code

10021

Country

United States

Facility Name

City

Rochester

State/Province

New York

ZIP/Postal Code

14618

Country

United States

Facility Name

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19139

Country

United States

Facility Name

City

Dallas

State/Province

Texas

ZIP/Postal Code

75231

Country

United States

Facility Name

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

Facility Name

City

Aparecida De Goiania

ZIP/Postal Code

74922-810

Country

Brazil

Facility Name

City

Belo Horizonte

ZIP/Postal Code

30210420

Country

Brazil

Facility Name

City

Botucatu

ZIP/Postal Code

18618 970

Country

Brazil

Facility Name

City

Pelotas

ZIP/Postal Code

96030-000

Country

Brazil

Facility Name

City

Ribeirão Preto

ZIP/Postal Code

14051-140

Country

Brazil

Facility Name

City

Rio De Janeiro

ZIP/Postal Code

22270060

Country

Brazil

Facility Name

City

Salvador

ZIP/Postal Code

40301500

Country

Brazil

Facility Name

City

São Paulo

ZIP/Postal Code

05403-010

Country

Brazil

Facility Name

City

Antofagasta

ZIP/Postal Code

1270244

Country

Chile

Facility Name

City

Santiago

ZIP/Postal Code

7500710

Country

Chile

Facility Name

City

Kaunas

ZIP/Postal Code

LT-3005

Country

Lithuania

Facility Name

City

Klaipeda

ZIP/Postal Code

91251

Country

Lithuania

Facility Name

City

Leon

ZIP/Postal Code

37000

Country

Mexico

Facility Name

City

Mazatlan

ZIP/Postal Code

82000

Country

Mexico

Facility Name

City

Mexico City

ZIP/Postal Code

01030

Country

Mexico

Facility Name

City

Monterrey

ZIP/Postal Code

64040

Country

Mexico

Facility Name

City

San Luis Potosi

ZIP/Postal Code

78250

Country

Mexico

Facility Name

City

Villahermosa

ZIP/Postal Code

86035

Country

Mexico

Facility Name

City

Zapopan

ZIP/Postal Code

45200

Country

Mexico

Facility Name

City

Heerde

ZIP/Postal Code

8181 CX

Country

Netherlands

Facility Name

City

Wildervank

ZIP/Postal Code

9648 BE

Country

Netherlands

Facility Name

City

Alcala De Henares

ZIP/Postal Code

28806

Country

Spain

Facility Name

City

Madrid

ZIP/Postal Code

28029

Country

Spain

Facility Name

City

Zamora

ZIP/Postal Code

49021

Country

Spain

12. IPD Sharing Statement

Learn more about this trial

A Safety Study in Participants With Major Depressive Disorder

We'll reach out to this number within 24 hrs