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A Study in Participants With Major Depressive Disorder Who Are Partial Responders to Selective Serotonin Reuptake Inhibitor

Primary Purpose

Major Depressive Disorder

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

LY2216684

Placebo

SSRI

About this trial

This is an interventional treatment trial for Major Depressive Disorder focused on measuring Depression, MDD

Eligibility Criteria

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

Inclusion Criteria:

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
Are being treated with one of the following selective serotonin reuptake inhibitors (SSRIs): escitalopram, citalopram, sertraline, fluoxetine, paroxetine, or 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 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision® (DSM-IV-TR) criteria
Meet criteria for partial response, as defined by investigator's opinion that the participant has experienced a minimal clinically meaningful improvement with SSRI
Have a GRID 17-Item Hamilton Depression Rating Scale (GRID-HAMD17) total score greater than or equal to 16 at screening
Have less than or equal to 75% improvement on the current SSRI at screening determined by the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH-ATRQ)

Exclusion Criteria:

Have had or currently have any additional ongoing DSM-IV-TR Axis 1 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 [OCD], post-traumatic stress disorder [PTSD], generalized anxiety disorder [GAD], 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 year (drug categories defined by DSM-IV-TR), not including caffeine and nicotine
Have an 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 that could be exacerbated by noradrenergic agents, including unstable hypertension, unstable heart disease, tachycardia, tachyarrhythmia, narrow-angled glaucoma, history of urinary hesitancy or retention
Use of excluded concomitant or psychotropic medication other than SSRI
Have initiated or discontinued hormone therapy within the 3 months prior to enrollment
History of treatment-resistant depression as shown by 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 lifetime history of vagal nerve stimulation (VNS), transcranial magnetic stimulation (TMS), or psychosurgery
Have received electroconvulsive therapy (ECT) in the past year

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.
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 2

Arm Type

Experimental

Placebo Comparator

Arm Label

LY2216684 + SSRI

Placebo + SSRI

Arm Description

LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI) Prior to entering the Adjunctive Treatment (AT) Phase, participants completed a 3-week Confirmation (CF) Phase where they received placebo (administered orally, QD) adjunctive to their SSRI. After the CF Phase, and after randomization criteria were met, participants were randomized to the LY2216684 treatment arm. For the first 2 weeks of the AT Phase, participants received a starting dose of 12 mg QD. Then, based on efficacy and tolerability, the dose could be increased to 18 mg QD over the next 6 weeks. Participants who had their dose increased to 18 mg QD could have had their dose decreased to 12 mg QD. Participants who completed the AT Phase or discontinued early had the option to enter the Discontinuation (DC) Phase. During the 1-week abrupt DC Phase, participants maintained their SSRI treatment.

Placebo: Administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI) Prior to entering the Adjunctive Treatment (AT) Phase, participants completed a 3-week Confirmation (CF) Phase where they received placebo (administered orally, QD) adjunctive to their SSRI. After the CF Phase, and after randomization criteria were met, participants were randomized to the placebo treatment arm. During the AT Phase, participants received placebo (administered orally, QD) adjunctive to their SSRI for 8 weeks. Participants who completed the AT Phase or discontinued early had the option to enter the Discontinuation (DC) Phase. During the 1-week abrupt DC Phase, participants maintained their SSRI treatment.

Outcomes

Primary Outcome Measures

Change From Randomization to Week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score

The Montgomery-Asberg Depression Rating Scale (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.

Secondary Outcome Measures

Change From Randomization to Week 8 in Sheehan Disability Scale (SDS) Global Functional Impairment Score

The Sheehan Disability Scale (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 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 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.

Change From Randomization to Week 8 in Fatigue Associated With Depression (FAsD) Impact Subscale Score

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 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. The FAsD impact subscale score ranges from 1 to 5. 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.

Probability of Participants Achieving a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of Less Than or Equal to 10 at Week 8

A Montgomery-Asberg Depression Rating Scale (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). A categorical repeated measures analysis modeled the probability of remission at each visit, and the estimated probabilities were adjusted for treatment, visit, baseline MADRS total score, and treatment-by-visit.

Percentage of Participants Achieving a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of Less Than or Equal to 10 for at Least 2 Consecutive Measurements, Including the Participant's Last Measurement

A Montgomery-Asberg Depression Rating Scale (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%.

Change From Randomization to Week 8 in Hospital and 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 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.

Probability of Participants Who Have a Greater Than or Equal to 50 Percent Improvement in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 8

A greater than or equal to 50 percent improvement (that is, a decrease from baseline) in the Montgomery-Asberg Depression Rating Scale (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). A categorical repeated measures analysis modeled the probability of response at each visit, and the estimated probabilities were adjusted for treatment, visit, baseline MADRS total score, and treatment-by-visit.

Change From Randomization to Week 8 in The Hospital Anxiety and Depression Scale (HADS) Depression Subscale Score

Change From Randomization to Week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) Individual Items

The Montgomery-Asberg Depression Rating Scale (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 item score, treatment-by-visit and baseline item score-by-visit.

Change From Randomization to Week 8 in Clinical Global Impressions of 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 treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.

Change From Randomization to Week 8 in Fatigue Associated With Depression (FAsD) Average Score and Experience Subscale Score

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 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.

Change From Randomization to Week 8 in Sheehan Disability Scale (SDS) Items

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.

Change From Randomization to Week 8 in the 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 treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.

Change From Randomization to Week 8 in the 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 treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.

Percentage of Participants With Treatment-emergent Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)

The Columbia-Suicide Severity Rating Scale (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 treatment-emergent (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.

Change From Randomization to Week 8 in Arizona Sexual Experiences (ASEX) Scale

The Arizona Sexual Experiences (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]) of 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.

Change From Randomization to Week 8 in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ)

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

Change From Randomization to Week 8 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 treatment, investigator, visit, baseline value, treatment-by-visit, and baseline value-by-visit.

Change From Randomization to Week 8 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 treatment, investigator, visit, baseline value, treatment-by-visit, and baseline value-by-visit.

Full Information

NCT ID

NCT01185340

First Posted

August 18, 2010

Last Updated

March 26, 2018

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT01185340

Brief Title

A Study in Participants With Major Depressive Disorder Who Are Partial Responders to Selective Serotonin Reuptake Inhibitor

Official Title

A Randomized Placebo-Controlled, Double-Blind Study of LY2216684 Flexible-Dose 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

March 2011 (undefined)

Primary Completion Date

April 2013 (Actual)

Study Completion Date

April 2013 (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 assess whether LY2216684 12 milligrams (mg) or 18 mg flexible dose once daily is superior to placebo once daily in the adjunctive treatment of participants with major depressive disorder (MDD) who are partial responders to their selective serotonin reuptake inhibitor (SSRI) treatment.

Detailed Description

Following the Confirmation (CF) Phase, participants were randomized to adjunctive LY2216684 or adjunctive placebo if they had <25% improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score over the past 3 weeks and a current MADRS total score ≥14. Participants who did not meet criteria received adjunctive placebo to preserve the blind.

6. Conditions and Keywords

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

Major Depressive Disorder

Keywords

Depression, MDD

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

1056 (Actual)

8. Arms, Groups, and Interventions

Arm Title

LY2216684 + SSRI

Arm Type

Experimental

Arm Description

Arm Title

Placebo + SSRI

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

LY2216684

Other Intervention Name(s)

Edivoxetine

Intervention Type

Drug

Intervention Name(s)

Placebo

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

Change From Randomization to Week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score

Description

Time Frame

Randomization, 8 weeks

Secondary Outcome Measure Information:

Title

Change From Randomization to Week 8 in Sheehan Disability Scale (SDS) Global Functional Impairment Score

Description

Time Frame

Randomization, 8 weeks

Title

Change From Randomization to Week 8 in Fatigue Associated With Depression (FAsD) Impact Subscale Score

Description

Time Frame

Randomization, 8 weeks

Title

Probability of Participants Achieving a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of Less Than or Equal to 10 at Week 8

Description

Time Frame

8 weeks

Title

Description

Time Frame

Randomization up to 8 weeks

Title

Change From Randomization to Week 8 in Hospital and Anxiety and Depression Scale (HADS) Anxiety Subscale Score

Description

Time Frame

Randomization, 8 weeks

Title

Probability of Participants Who Have a Greater Than or Equal to 50 Percent Improvement in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 8

Description

Time Frame

8 weeks

Title

Change From Randomization to Week 8 in The Hospital Anxiety and Depression Scale (HADS) Depression Subscale Score

Description

Time Frame

Randomization, 8 weeks

Title

Change From Randomization to Week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) Individual Items

Description

The Montgomery-Asberg Depression Rating Scale (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 item score, treatment-by-visit and baseline item score-by-visit.

Time Frame

Randomization, 8 weeks

Title

Change From Randomization to Week 8 in Clinical Global Impressions of Severity (CGI-S)

Description

Time Frame

Randomization, 8 weeks

Title

Change From Randomization to Week 8 in Fatigue Associated With Depression (FAsD) Average Score and Experience Subscale Score

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 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

Title

Change From Randomization to Week 8 in Sheehan Disability Scale (SDS) Items

Description

Time Frame

Randomization, 8 weeks

Title

Change From Randomization to Week 8 in the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF)

Description

Time Frame

Randomization, 8 weeks

Title

Change From Randomization to Week 8 in the EuroQol Questionnaire-5 Dimension (EQ-5D)

Description

Time Frame

Randomization, 8 weeks

Title

Percentage of Participants With Treatment-emergent Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)

Description

Time Frame

Randomization up to 8 weeks

Title

Change From Randomization to Week 8 in Arizona Sexual Experiences (ASEX) Scale

Description

Time Frame

Randomization, 8 weeks

Title

Change From Randomization to Week 8 in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ)

Description

Time Frame

Randomization, 8 weeks

Title

Change From Randomization to Week 8 in Blood Pressure

Description

Time Frame

Randomization, 8 weeks

Title

Change From Randomization to Week 8 in Pulse Rate

Description

Time Frame

Randomization, 8 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Are being treated with one of the following selective serotonin reuptake inhibitors (SSRIs): escitalopram, citalopram, sertraline, fluoxetine, paroxetine, or 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 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision® (DSM-IV-TR) criteria Meet criteria for partial response, as defined by investigator's opinion that the participant has experienced a minimal clinically meaningful improvement with SSRI Have a GRID 17-Item Hamilton Depression Rating Scale (GRID-HAMD17) total score greater than or equal to 16 at screening Have less than or equal to 75% improvement on the current SSRI at screening determined by the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH-ATRQ) Exclusion Criteria: Have had or currently have any additional ongoing DSM-IV-TR Axis 1 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 [OCD], post-traumatic stress disorder [PTSD], generalized anxiety disorder [GAD], 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 year (drug categories defined by DSM-IV-TR), not including caffeine and nicotine Have an 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 that could be exacerbated by noradrenergic agents, including unstable hypertension, unstable heart disease, tachycardia, tachyarrhythmia, narrow-angled glaucoma, history of urinary hesitancy or retention Use of excluded concomitant or psychotropic medication other than SSRI Have initiated or discontinued hormone therapy within the 3 months prior to enrollment History of treatment-resistant depression as shown by 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 lifetime history of vagal nerve stimulation (VNS), transcranial magnetic stimulation (TMS), or psychosurgery Have received electroconvulsive therapy (ECT) in the past year

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

Garden Grove

State/Province

California

ZIP/Postal Code

92845

Country

United States

Facility Name

City

Oakland

State/Province

California

ZIP/Postal Code

94612

Country

United States

Facility Name

City

Temecula

State/Province

California

ZIP/Postal Code

92591

Country

United States

Facility Name

City

Waterbury

State/Province

Connecticut

ZIP/Postal Code

06708

Country

United States

Facility Name

City

Boca Raton

State/Province

Florida

ZIP/Postal Code

33432

Country

United States

Facility Name

City

Fort Myers

State/Province

Florida

ZIP/Postal Code

33912

Country

United States

Facility Name

City

North Bay Village

State/Province

Florida

ZIP/Postal Code

33141

Country

United States

Facility Name

City

Oakland Park

State/Province

Florida

ZIP/Postal Code

33334

Country

United States

Facility Name

City

Orlando

State/Province

Florida

ZIP/Postal Code

32839

Country

United States

Facility Name

City

West Palm Beach

State/Province

Florida

ZIP/Postal Code

33407

Country

United States

Facility Name

City

Shreveport

State/Province

Louisiana

ZIP/Postal Code

71101

Country

United States

Facility Name

City

Lincoln

State/Province

Nebraska

ZIP/Postal Code

68526

Country

United States

Facility Name

City

Marlton

State/Province

New Jersey

ZIP/Postal Code

08053

Country

United States

Facility Name

City

Brooklyn

State/Province

New York

ZIP/Postal Code

11241

Country

United States

Facility Name

City

New York

State/Province

New York

ZIP/Postal Code

10003

Country

United States

Facility Name

City

Staten Island

State/Province

New York

ZIP/Postal Code

10312

Country

United States

Facility Name

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45215

Country

United States

Facility Name

City

Media

State/Province

Pennsylvania

ZIP/Postal Code

19063

Country

United States

Facility Name

City

Herndon

State/Province

Virginia

ZIP/Postal Code

20170

Country

United States

Facility Name

City

Richmond

State/Province

Virginia

ZIP/Postal Code

23230

Country

United States

Facility Name

City

Everton Park

State/Province

Queensland

ZIP/Postal Code

4053

Country

Australia

Facility Name

City

Spring Hill

State/Province

Queensland

ZIP/Postal Code

4000

Country

Australia

Facility Name

City

Frankston

State/Province

Victoria

ZIP/Postal Code

3199

Country

Australia

Facility Name

City

Heidelberg

State/Province

Victoria

ZIP/Postal Code

3084

Country

Australia

Facility Name

City

Malvern

State/Province

Victoria

ZIP/Postal Code

3144

Country

Australia

Facility Name

City

Melbourne

State/Province

Victoria

ZIP/Postal Code

3004

Country

Australia

Facility Name

City

Vienna

ZIP/Postal Code

A1090

Country

Austria

Facility Name

City

Diest

ZIP/Postal Code

3290

Country

Belgium

Facility Name

City

Liège

ZIP/Postal Code

4000

Country

Belgium

Facility Name

City

Mont-Godinne

ZIP/Postal Code

5530

Country

Belgium

Facility Name

City

Bad Saarow

ZIP/Postal Code

15526

Country

Germany

Facility Name

City

Berlin

ZIP/Postal Code

12209

Country

Germany

Facility Name

City

Bochum

ZIP/Postal Code

44892

Country

Germany

Facility Name

City

Cham

ZIP/Postal Code

93413

Country

Germany

Facility Name

City

Dresden

ZIP/Postal Code

01097

Country

Germany

Facility Name

City

Hattingen

ZIP/Postal Code

45525

Country

Germany

Facility Name

City

Leipzig

ZIP/Postal Code

04107

Country

Germany

Facility Name

City

Munich

ZIP/Postal Code

80331

Country

Germany

Facility Name

City

Nürnberg

ZIP/Postal Code

90402

Country

Germany

Facility Name

City

Prien

ZIP/Postal Code

83209

Country

Germany

Facility Name

City

Schwerin

ZIP/Postal Code

19053

Country

Germany

Facility Name

City

Goteborg

ZIP/Postal Code

41685

Country

Sweden

Facility Name

City

Lund

ZIP/Postal Code

222 22

Country

Sweden

Facility Name

City

Malmo

ZIP/Postal Code

21153

Country

Sweden

Facility Name

City

Solna

ZIP/Postal Code

171 45

Country

Sweden

Facility Name

City

Stockholm

ZIP/Postal Code

11486

Country

Sweden

Facility Name

City

Bexhill-On-Sea

State/Province

East Sussex

ZIP/Postal Code

TN40 1JJ

Country

United Kingdom

Facility Name

City

Glasgow

State/Province

Scotland

ZIP/Postal Code

G20 0XA

Country

United Kingdom

Facility Name

City

Chesterfield

ZIP/Postal Code

S40 4TF

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

27685842

Citation

Stauffer VL, Liu P, Goldberger C, Marangell LB, Nelson C, Gorwood P, Fava M. Is the Noradrenergic Symptom Cluster a Valid Construct in Adjunctive Treatment of Major Depressive Disorder? J Clin Psychiatry. 2017 Mar;78(3):317-323. doi: 10.4088/JCP.15m09972.

Results Reference

derived

PubMed Identifier

27035159

Citation

Ball SG, Ferguson MB, Martinez JM, Pangallo BA, Nery ES, Dellva MA, Sparks J, Zhang Q, Liu P, Bangs M, Goldberger C. Efficacy outcomes from 3 clinical trials of edivoxetine as adjunctive treatment for patients with major depressive disorder who are partial responders to selective serotonin reuptake inhibitor treatment. J Clin Psychiatry. 2016 May;77(5):635-42. doi: 10.4088/JCP.14m09619.

Results Reference

derived

Learn more about this trial

A Study in Participants With Major Depressive Disorder Who Are Partial Responders to Selective Serotonin Reuptake Inhibitor

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