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Trial record 27 of 2690 for:    "Depressive Disorder" [DISEASE] AND depressive symptoms

A Study in Prevention of Re-emergence of Depression Symptoms

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ClinicalTrials.gov Identifier: NCT01299272
Recruitment Status : Completed
First Posted : February 18, 2011
Results First Posted : April 17, 2018
Last Update Posted : April 17, 2018
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE February 16, 2011
First Posted Date  ICMJE February 18, 2011
Results First Submitted Date  ICMJE February 17, 2018
Results First Posted Date  ICMJE April 17, 2018
Last Update Posted Date April 17, 2018
Study Start Date  ICMJE May 2011
Actual Primary Completion Date November 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 16, 2018)
Percentage of Participants Who Meet Criteria for Re-emergence of Depressive Symptoms Estimated by Kaplan-Meier Product Limit Method (Double-blind Randomized Withdrawal Period) [ Time Frame: Randomization up to 44 weeks ]
Participants meeting any of the following criteria were determined as having major depressive disorder symptom re-emergence: 1) a Montgomery-Asberg Depression Rating Scale (MADRS) total score greater ≥14 or a Clinical Global Impressions of Severity (CGI-S) increase of 2 or more points from Week 18 at 2 consecutive visits or 2) discontinuation due to lack of efficacy/worsening of depression/suicidality. Time from randomization to the first visit at which the participant met the reemergence criteria was calculated. The percentage of participants who meet criteria was estimated using the Kaplan-Meier product limit method. The MADRS is a rating scale for severity of depressive mood symptoms and has a 10-item checklist with items rated on a scale of 0-6, for a total score range of 0 (low severity) to 60 (high 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 (extremely ill).
Original Primary Outcome Measures  ICMJE
 (submitted: February 16, 2011)
Time to re-emergence of depressive symptoms [ Time Frame: Randomization up to 44 weeks ]
Change History Complete list of historical versions of study NCT01299272 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 16, 2018)
  • Percentage of Participants With Re-emergence of Depressive Symptoms (Double-blind Randomized Withdrawal Period) [ Time Frame: Week 44 ]
    Participants meeting any of the following criteria were determined as having major depressive disorder symptom re-emergence: 1) a Montgomery-Asberg Depression Rating Scale (MADRS) total score greater ≥14 or a Clinical Global Impressions of Severity (CGI-S) increase of 2 or more points from Week 18 at 2 consecutive visits or 2) discontinuation due to lack of efficacy/worsening of depression/suicidality. The percentage of participants with re-emergence of depressive symptoms was calculated by dividing the number of participants who meet any of the criteria by the total number of participants analyzed, multiplied by 100. The MADRS is a rating scale for severity of depressive mood symptoms and has a 10-item checklist with items rated on a scale of 0-6, for a total score range of 0 (low severity) to 60 (high 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 (extremely ill).
  • Change From Randomization in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Item Scores at Week 44 (Double-blind Randomized Withdrawal Period) [ Time Frame: Randomization, Week 44 ]
    Montgomery-Asberg Depression Rating Scale (MADRS) is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist (sadness [apparent], sadness [reported], inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Items are rated on a scale of 0-6, 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 a mixed model repeated measures (MMRM) analysis which includes terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline MADRS total score (individual item score) and baseline MADRS total score (individual item score)-by-visit interaction.
  • Change From Randomization in the Hospital Anxiety and Depression Scale (HADS) Depression and Anxiety Subscale Scores at Week 44 (Double-blind Randomized Withdrawal Period) [ Time Frame: Randomization, Week 44 ]
    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. 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 represent 'normal'. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline subscale score and baseline subscale score-by-visit interaction.
  • Change From Randomization in the Clinical Global Impression of Severity (CGI-S) Scores at Week 44 (Double-blind Randomized Withdrawal Period) [ Time Frame: Randomization, Week 44 ]
    The Clinical Global Impression of Severity (CGI-S) instrument is used to record the severity of mental illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline CGI-S score and baseline CGI-S score-by-visit interaction.
  • Change From Randomization in the Fatigue Associated With Depression (FAsD) Average Score, Experience Subscale Score, and Impact Subscale Score at Week 44 (Double-blind Randomized Withdrawal Period) [ Time Frame: Randomization, Week 44 ]
    The FAsD is a 13-item participant-rated scale. Items 1-6 ask how often participants experience different aspects of fatigue with responses from 1 (never) to 5 (always). Items 7-13 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 is derived by taking the mean of Items 1-6. The impact subscale score is derived by taking the mean of applicable Items 7-13. The average score is the mean of applicable Items 1-13. Item 12 applies only to participants with a spouse or significant other and Item 13 applies to participants who had a job or who went to school. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline score and baseline score-by-visit interaction.
  • Change From Randomization in the Sheehan Disability Scale (SDS) Items at Week 44 (Double-blind Randomized Withdrawal Period) [ Time Frame: Randomization, Week 44 ]
    The Sheehan Disability Scale (SDS) is 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 a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline score and baseline score-by-visit interaction
  • Change From Randomization in the EuroQol Questionnaire-5 Dimension (EQ-5D) Index Scores, Visual Analog Scale up to Week 44 (Double-blind Randomized Withdrawal Period) [ Time Frame: Randomization, up to Week 44 ]
    The EQ-5D, a health-related, quality-of-life instrument, contains 2 parts: a health status profile and a visual analog scale (VAS). The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a 3-level scale (no problem, some problems, and major problems). These dimensions are converted into weighted health-state index scores according to United States (US) and United Kingdom (UK) population-based algorithms. The US and UK based index scores range from -0.11 to 1.0 (where a score of 1.0 indicates perfect health) and from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension), respectively. The VAS consists of participants rating their current health state from 0 (worst imaginable health state) to 100 (best imaginable health). Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) model with main effects of treatment, country, and baseline score.
  • Number of Participants With Treatment-emergent Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) (Double-blind Randomized Withdrawal Period) [ Time Frame: Randomization through Week 44 ]
    The Columbia-Suicide Severity Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation is defined as a "yes" answer to any 1 of 5 suicidal ideation questions, which includes a wish to be dead and 4 different categories of active suicidal ideation. Suicidal behavior is 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 during the period up through randomization. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module.
  • Change From Randomization in the Arizona Sexual Experiences (ASEX) Questionnaire at Week 44 (Double-blind Randomized Withdrawal Period) [ Time Frame: Randomization, Week 44 ]
    Arizona Sexual Experiences (ASEX) Questionnaire is a 5-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. Each item is rated from 1 (extremely) to 6 (no/never). Possible total scores ranged from 5 to 30, with the higher scores indicating more sexual dysfunction. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline ASEX total score and baseline ASEX total score-by-visit interaction.
  • Change From Randomization in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) Total Score at Week 44 (Double-blind Randomized Withdrawal Period) [ Time Frame: Randomization, Week 44 ]
    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 is scored on a 6-point scale ranging from 1 (greater than normal) to 6 (totally absent). Total score is reported and ranges from 7 to 42, with higher scores indicating greater impairment. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline CPFQ total score and baseline CPFQ total score-by-visit interaction.
  • Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Item Scores up to Week 8 (Acute Open-label Period) [ Time Frame: Baseline, up to Week 8 ]
    Montgomery-Asberg Depression Rating Scale (MADRS) is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist (sadness [apparent], sadness [reported], inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
  • Change From Week 8 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Item Scores up to Week 20 (Stabilization Open-label Period) [ Time Frame: Week 8, up to Week 20 ]
    Montgomery-Asberg Depression Rating Scale (MADRS) is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist (sadness [apparent], sadness [reported], inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
  • Change From Baseline in the Hospital Anxiety and Depression Scale (HADS) Depression and Anxiety Subscale Scores up to Week 8 (Acute Open-label Period) [ Time Frame: Baseline, up to Week 8 ]
    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. 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'.
  • Change From Week 8 in the Hospital Anxiety and Depression Scale (HADS) Depression and Anxiety Subscale Scores up to Week 20 (Stabilization Open-label Period) [ Time Frame: Week 8, up to Week 20 ]
    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. 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 represent 'normal'.
  • Change From Baseline in the Clinical Global Impression of Severity (CGI-S) Scores up to Week 8 (Acute Open-label Period) [ Time Frame: Baseline, up to Week 8 ]
    The Clinical Global Impression of Severity (CGI-S) instrument is used to record the severity of mental illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants).
  • Change From Week 8 in the Clinical Global Impression of Severity (CGI-S) Scores up to Week 20 (Stabilization Open-label Period) [ Time Frame: Week 8, up to Week 20 ]
    The Clinical Global Impression of Severity (CGI-S) instrument is used to record the severity of mental illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants).
  • Change From Baseline in the Fatigue Associated With Depression (FAsD) Average Score, Experience Subscale Score, and Impact Subscale Score up to Week 8 (Acute Open-label Period) [ Time Frame: Baseline, up to Week 8 ]
    The Fatigue Associated With Depression (FAsD) is a 13-item participant-rated scale. Items 1-6 ask how often participants experience different aspects of fatigue with responses from 1 (never) to 5 (always). Items 7-13 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 is derived by taking the mean of Items 1-6. The impact subscale score is derived by taking the mean of applicable Items 7-13. The average score is the mean of applicable Items 1-13. Item 12 applies only to participants with a spouse or significant other and Item 13 applies to participants who had a job or who went to school.
  • Change From Week 8 in the Fatigue Associated With Depression (FAsD) Average Score, Experience Subscale Score, and Impact Subscale Score up to Week 20 (Stabilization Open-label Period) [ Time Frame: Week 8, up to Week 20 ]
    The Fatigue Associated with Depression (FAsD) is a 13-item participant-rated scale. Items 1-6 ask how often participants experience different aspects of fatigue with responses from 1 (never) to 5 (always). Items 7-13 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 is derived by taking the mean of Items 1-6. The impact subscale score is derived by taking the mean of applicable Items 7-13. The average score is the mean of applicable Items 1-13. Item 12 applies only to participants with a spouse or significant other and Item 13 applies to participants who had a job or who went to school.
  • Change From Baseline in the Sheehan Disability Scale (SDS) Items up to Week 8 (Acute Open-label Period) [ Time Frame: Baseline, up to Week 8 ]
    The Sheehan Disability Scale (SDS) is 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.
  • Change From Week 8 in the Sheehan Disability Scale (SDS) Items up to Week 20 (Stabilization Open-label Period) [ Time Frame: Week 8, up to Week 20 ]
    The Sheehan Disability Scale (SDS) is 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.
  • Change From Baseline in the EuroQol Questionnaire-5 Dimension (EQ-5D) Index Scores, Visual Analog Scale up to Week 20 (Open-label Period) [ Time Frame: Baseline, up to Week 20 ]
    The EQ-5D, a health-related, quality-of-life instrument, contains 2 parts: a health status profile and a visual analog scale (VAS). The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a 3-level scale (no problem, some problems, and major problems). These dimensions are converted into weighted health-state index scores according to United States (US) and United Kingdom (UK) population-based algorithms. The US and UK based index scores range from -0.11 to 1.0 (where a score of 1.0 indicates perfect health) and from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension), respectively. The VAS consists of participants rating their current health state from 0 (worst imaginable health state) to 100 (best imaginable health).
  • Number of Participants With Treatment-emergent Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) (Open-label Period) [ Time Frame: Baseline through Week 20 ]
    The Columbia-Suicide Severity Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation is 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 is 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. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module.
  • Change From Baseline in the Arizona Sexual Experiences (ASEX) Questionnaire up to Week 20 (Open-label Period) [ Time Frame: Baseline, up to Week 20 ]
    Arizona Sexual Experiences (ASEX) Questionnaire is a 5-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. Each item is rated from 1 (extremely) to 6 (no/never). Possible total scores ranged from 5 to 30, with the higher scores indicating more sexual dysfunction.
  • Change From Baseline in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) Total Score at Week 20 (Open-label Period) [ Time Frame: Baseline, up to Week 20 ]
    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 is scored on a 6-point scale ranging from 1 (greater than normal) to 6 (totally absent). Total score is reported and ranges from 7 to 42, with higher scores indicating greater impairment.
  • Change From Randomization in Blood Pressure at Week 44 (Double-blind Randomized Withdrawal Period) [ Time Frame: Randomization, Week 44 ]
    Blood pressure measurements were taken 3 times at each visit in a sitting position. The average of the 3 values was used for analysis. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline and baseline-by-visit interaction.
  • Change From Baseline in Blood Pressure up to Week 20 (Open-label Period) [ Time Frame: Baseline, up to Week 20 ]
    Blood pressure measurements were taken 3 times at each visit in a sitting position. The average of the 3 values was used for analysis.
  • Change From Randomization in Pulse Rate at Week 44 (Double-blind Randomized Withdrawal Period) [ Time Frame: Randomization, Week 44 ]
    Pulse rate measurements were collected when the participant was in a sitting position. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline and baseline-by-visit interaction.
  • Change From Baseline in Pulse Rate up to Week 20 (Open-label Period) [ Time Frame: Baseline, up to Week 20 ]
    Pulse measurements were collected when the participant was in a sitting position.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 16, 2011)
  • Percentage of participants with re-emergence of depressive symptoms [ Time Frame: Randomization up to 44 weeks ]
  • Change in the Montgomery-Asberg Depression Rating Scale (MADRS) total score and individual item scores (double-blind randomized withdrawal period) [ Time Frame: Randomization up to 44 weeks ]
  • Change in the Hospital Anxiety and Depression Scale (HADS) depression and anxiety subscale scores (double-blind randomized withdrawal period) [ Time Frame: Randomization up to 44 weeks ]
  • Change in the Clinical Global Impression of Severity (CGI-S) scores (double-blind randomized withdrawal period) [ Time Frame: Randomization up to 44 weeks ]
  • Change in the Fatigue Associated with Depression (FAsD) average score, experience subscale score, and impact subscale score (double-blind randomized withdrawal period) [ Time Frame: Randomization up to 44 weeks ]
  • Change in the Sheehan Disability Scale (SDS) items (double-blind randomized withdrawal period) [ Time Frame: Randomization up to 44 weeks ]
  • Change in the EuroQol Questionnaire-5 Dimension (EQ-5D) index scores, visual analog scale (double-blind randomized withdrawal period) [ Time Frame: Randomization up to 44 weeks ]
  • Number of Participants With Treatment-emergent Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) (Double-blind Randomized Withdrawal Period) [ Time Frame: Randomization up 44 weeks ]
  • Change in the Arizona Sexual Experiences (ASEX) Questionnaire (double-blind randomized withdrawal period) [ Time Frame: Randomization up to 44 weeks ]
  • Change in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) scores (double-blind randomized withdrawal period) [ Time Frame: Randomization up to 44 weeks ]
  • Change in the Montgomery-Asberg Depression Rating Scale (MADRS) total score and individual item scores (open-label period) [ Time Frame: Baseline to randomization (up to 18 - 20 weeks) ]
  • Change in the Hospital Anxiety and Depression Scale (HADS) depression and anxiety subscale scores (open-label period) [ Time Frame: Baseline to randomization (up to 18 - 20 weeks) ]
  • Change in the Clinical Global Impression of Severity (CGI-S) scores (open-label period) [ Time Frame: Baseline to randomization (up to 18 - 20 weeks) ]
  • Change in the Fatigue Associated with Depression (FAsD) average score, experience subscale score, and impact subscale score (open-label period) [ Time Frame: Baseline to randomization (up to 18 - 20 weeks) ]
  • Change in the Sheehan Disability Scale (SDS) items (open-label period) [ Time Frame: Baseline to randomization (up to 18 - 20 weeks) ]
  • Change in the EuroQol Questionnaire-5 Dimension (EQ-5D) index scores, visual analog scale (open-label period) [ Time Frame: Baseline to randomization (up to 18 - 20 weeks) ]
  • Number of Participants With Treatment-emergent Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) (Open-label Period) [ Time Frame: Baseline to randomization (up to 18 - 20 weeks) ]
  • Change in the Arizona Sexual Experiences (ASEX) Questionnaire (open-label period) [ Time Frame: Baseline to randomization (up to 18 - 20 weeks) ]
  • Change in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) scores (open-label period) [ Time Frame: Baseline to randomization (up to 18 - 20 weeks) ]
  • Change in blood pressure (double-blind randomized withdrawal period) [ Time Frame: Randomization up to 44 weeks ]
  • Change in blood pressure (open-label period) [ Time Frame: Baseline to randomization (up to 18 - 20 weeks) ]
  • Change in pulse rate (double-blind randomized withdrawal period) [ Time Frame: Randomization up to 44 weeks ]
  • Change in pulse rate (open-label period) [ Time Frame: Baseline to randomization (up to 18 - 20 weeks) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study in Prevention of Re-emergence of Depression Symptoms
Official Title  ICMJE LY2216684 Compared to Placebo as Adjunctive Therapy to SSRI in the Prevention of Symptom Re-emergence in Major Depressive Disorder
Brief Summary

The primary objective of this study was to assess the maintenance of efficacy of LY2216684 compared with placebo as adjunctive therapy to selective serotonin reuptake inhibitors (SSRIs) as measured by the time-to-symptom reemergence among participants with major depressive disorder (MDD) who met randomization criteria with adjunctive LY2216684 during the stabilization period.

This trial consists of two distinct periods: an open-label treatment period, which consists of two parts, 8 weeks acute open-label with movement to 12 weeks open-label stabilization if participants are in remission at end of 8 weeks (open-label for 20 weeks total) followed by a randomized, double-blind, placebo-controlled period for 24 weeks.

Detailed Description In order to enter the Stabilization Open-label Period, participants must have met remission criteria, defined as a Montgomery-Asberg Depression Rating Scale (MADRS) total score ≤10 at Week 8. In order to enter the Double-blind Randomization Withdrawal Period, participants must have met randomization criteria, defined as a MADRS total score ≤10 at Weeks 18, 19, and 20.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Major Depressive Disorder
Intervention  ICMJE
  • Drug: LY2216684
    Other Name: Edivoxetine
  • Drug: Placebo
  • Drug: SSRI
    Participants should have been on their SSRI for at least 8 weeks prior and were to continue on their stable dose throughout the study.
    Other Name: Selective Serotonin Reuptake Inhibitor
Study Arms  ICMJE
  • Experimental: LY2216684 + SSRI

    Acute Open-label (OL) Period: Participants received a starting dose of 12 milligrams (mg) LY2216684, administered orally, once daily for at least 2 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). Then, based on efficacy and tolerability, the dose could be increased to 18 mg (and decreased back to 12 mg) over the next 6 weeks.

    Stabilization OL Period: Participants meeting remission criteria continued on the same dose of LY2216684 for an additional 12 weeks. Participants who discontinued early during either OL Period were discontinued abruptly from LY2216684.

    Double-blind (DB) Randomized Withdrawal Period: At 20 weeks, participants meeting criteria for randomization continued their current dose of LY2216684 for another 24 weeks. Participants who completed this period or discontinued early were randomized to abrupt (placebo for 2 weeks) or tapered (12 mg LY2216684 for 4 days, 6 mg LY2216684 for 4 days, then placebo for 6 days) discontinuation of LY2216684.

    Interventions:
    • Drug: LY2216684
    • Drug: SSRI
  • Placebo Comparator: Placebo + SSRI

    Acute Open-label (OL) Period: Participants received a starting dose of 12 milligrams (mg) LY2216684, administered orally, once daily for at least 2 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). Then, based on efficacy and tolerability, the dose could be increased to 18 mg (and decreased back to 12 mg) over the next 6 weeks.

    Stabilization OL Period: Participants meeting remission criteria continued on the same dose of LY2216684 for an additional 12 weeks. Participants who discontinued early during either OL Period were discontinued abruptly from LY2216684.

    Double-blind (DB) Randomized Withdrawal Period: At 20 weeks, participants meeting criteria for randomization were tapered from their LY2216684 dose to placebo following the regimen of 12 mg for 7 days, 6 mg for 7 days, and placebo for the remaining 22 weeks. Participants who completed this period or discontinued early continued to receive placebo for an additional 2 weeks

    Interventions:
    • Drug: LY2216684
    • Drug: Placebo
    • Drug: SSRI
Publications * Oakes TM, Dellva MA, Waterman K, Greenbaum M, Poppe C, Goldberger C, Ahl J, Perahia DG. Edivoxetine compared to placebo as adjunctive therapy to selective serotonin reuptake inhibitors in the prevention of symptom re-emergence in major depressive disorder. Curr Med Res Opin. 2015 Jun;31(6):1179-89. doi: 10.1185/03007995.2015.1037732. Epub 2015 May 6.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 16, 2018)
1249
Original Estimated Enrollment  ICMJE
 (submitted: February 16, 2011)
2045
Actual Study Completion Date  ICMJE November 2013
Actual Primary Completion Date November 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Outpatients with clinical diagnosis of Major Depressive Disorder (MDD)
  • Using a reliable method of birth control
  • Are taking a selective serotonin reuptake inhibitor (SSRI) approved for MDD treatment within the participant's country and the SSRI prescribed, including dose, should be consistent with labeling guidelines within the participating country
  • Have a partial response to SSRI treatment
  • Meet inclusion scores on pre-defined psychiatric scales to assess diagnosis of depression, disease severity, and response to SSRI treatment
  • Reliable and able to keep all scheduled appointments
  • Have had at least 1 previous episode of MDD prior to the current episode within the past 5 years

Exclusion Criteria:

  • Have had or currently have any additional ongoing Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) Axis 1 condition other than major depression within 1 year of screening
  • Have a current or any 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
  • Have any diagnosed medical condition which could be exacerbated by noradrenergic agents, including unstable hypertension, unstable heart disease, tachycardia, tachyarrhythmia, narrow-angle glaucoma, or history of urinary hesitation or retention
  • Have initiated or discontinued hormone therapy (including birth control or thyroid hormone) within the previous 3 months prior to enrollment
  • Have a lifetime history of vagal nerve stimulation (VNS), transcranial magnetic stimulation (TMS), or psychosurgery
  • Have received electroconvulsive therapy (ECT) in the past year
  • Have a serious or unstable medical condition
  • Have a history of seizure disorders
  • Have initiated psychotherapy, change in intensity of psychotherapy or other nondrug therapies (such as acupuncture or hypnosis) within 6 weeks prior to enrollment or any time during the study
  • Participants who, in the opinion of the investigator, are judged to be at serious risk for harm to self or others
  • Are pregnant or breastfeeding
  • Meet criteria for treatment-resistant depression
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Belgium,   Croatia,   France,   Germany,   Greece,   Italy,   Korea, Republic of,   Mexico,   Puerto Rico,   Romania,   Russian Federation,   Slovakia,   Spain,   Turkey,   United States
Removed Location Countries Brazil
 
Administrative Information
NCT Number  ICMJE NCT01299272
Other Study ID Numbers  ICMJE 11317
H9P-MC-LNBN ( Other Identifier: Eli Lilly and Company )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eli Lilly and Company
Study Sponsor  ICMJE Eli Lilly and Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: 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) Eli Lilly and Company
PRS Account Eli Lilly and Company
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP