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A Study in Adult Patients With Major Depressive Disorder

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00795821
Recruitment Status : Completed
First Posted : November 21, 2008
Results First Posted : March 20, 2018
Last Update Posted : March 20, 2018
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Brief Summary:
The purpose of this study is to assess whether LY2216684 is superior to placebo in the treatment of adult patients with major depressive disorder.

Condition or disease Intervention/treatment Phase
Depressive Disorder, Major Drug: LY2216684 Drug: Placebo Phase 2 Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 495 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind Comparison of LY2216684 and Placebo and Long Term Treatment With LY2216684 in Adult Patients With Major Depressive Disorder
Study Start Date : December 2008
Actual Primary Completion Date : February 2010
Actual Study Completion Date : March 2011

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: LY2216684

10-week Acute Treatment Phase: Day after Week 0=start of 6 milligram (mg) once daily (QD) dosing; Week 1=all participants titrated to 9 mg QD; After Week 1=dose increased, maintained, or decreased to a minimum of 6 mg QD and maximum of 18 mg QD, depending on participant's tolerance of study drug.

1-year Long-term Extension Phase: Day after Week 10=start of same LY2216684 dose participant was taking at the end of acute treatment phase; After Week 11=dose increased, maintained, or decreased to minimum of 6 mg QD and maximum of 18 mg QD based on investigator's judgment of safety and tolerability (up to Week 62).

Drug: LY2216684
Flexible Dosing: 6 mg, 9 mg, 12 mg and 18 mg (3 tablets) administered QD for up to 62 weeks
Placebo Comparator: Placebo

10-week Acute Treatment Phase: 3 tablets QD for 10 weeks

1-year Long-term Extension Phase: Day after Week 10=6 mg LY2216684 dose; After 1 week=dose escalated to 9 mg QD; After Week 11=dose increased, maintained, or decreased to minimum of 6 mg QD and maximum of 18 mg QD based on investigator's judgment of safety and tolerability (up to Week 62).

Drug: Placebo
Dose: 3 tablets QD for 10 weeks



Primary Outcome Measures :
  1. Mean Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) at Week 10 [ Time Frame: Baseline, Week 10 ]
    The MADRS measured severity of depressive mood symptoms. The 10-item checklist rating scale was 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 adjusted for treatment, investigator, visit, treatment-by-visit, baseline score, and baseline-by-visit.


Secondary Outcome Measures :
  1. Mean Change From Baseline (Week 10) in Montgomery-Asberg Depression Rating Scale (MADRS) at Week 62 [ Time Frame: Baseline (Week 10), Week 62 ]
    The MADRS measured severity of depressive mood symptoms. The 10-item checklist rating scale was 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 adjusted for investigator, visit, baseline score, and baseline-by-visit.

  2. Mean Change From Baseline in Sheehan Disability Scale (SDS) Global Functional Impairment at Week 10 [ Time Frame: Baseline, Week 10 ]
    The SDS was completed by the participant and used to assess the effect of the participant's symptoms on their work/social/family life. Total of these 3 items=Global Functional Impairment score; scores ranged from 0 to 30, with higher values indicating greater disruption in the participant's work/social/family life. Least Squares (LS) Means were adjusted for treatment, investigator, visit, treatment-by-visit, baseline score, and baseline-by-visit.

  3. Mean Change From Baseline (Week 10) in Sheehan Disability Scale (SDS) Global Functional Impairment at Week 62 [ Time Frame: Baseline (Week 10), Week 62 ]
    The SDS was completed by the participant and used to assess the effect of the participant's symptoms on their work/social/family life. Total of these 3 items=Global Functional Impairment score; scores ranged from 0 to 30, with higher values indicating greater disruption in the participant's work/social/family life. Least Squares (LS) Means were adjusted for investigator, visit, baseline score, and baseline-by-visit.

  4. Mean Change From Baseline in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 10 [ Time Frame: Baseline, Week 10 ]
    CGI-S measured severity of depression at the time of assessment. Scores ranged from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). Least Squares (LS) Means were adjusted for treatment, investigator, visit, treatment-by-visit, baseline score, and baseline-by-visit.

  5. Mean Change From Baseline (Week 10) in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 62 [ Time Frame: Baseline (Week 10), Week 62 ]
    CGI-S measured severity of depression at the time of assessment. Scores ranged from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). Least Squares (LS) Means were adjusted for investigator, baseline score, and baseline-by-visit.

  6. Mean Change From Baseline in the 16-Item Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR16) at Week 10 [ Time Frame: Baseline, Week 10 ]
    The QIDS-SR16 was a 16-item participant-rated measure of depressive symptomatology. The total score ranged from 0 to 27, with higher scores indicative of greater severity. Least Squares (LS) Means were adjusted for treatment, investigator, visit, treatment-by-visit, baseline score, and baseline-by-visit.

  7. Mean Change From Baseline (Week 10) in the 16-Item Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR16) at Week 62 [ Time Frame: Baseline (Week 10), Week 62 ]
    The QIDS-SR16 was a 16-item participant-rated measure of depressive symptomatology. The total score ranged from 0 to 27, with higher scores indicative of greater severity. Least Squares (LS) Means were adjusted for investigator, visit, baseline score, and baseline-by-visit.

  8. Mean Change From Baseline in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) at Week 10 [ Time Frame: Baseline, Week 10 ]
    The CPFQ was a 7-item participant-rated questionnaire pertaining to a participant's cognitive and physical well-being. It assessed 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 score ranged from 7 to 42. Least Squares (LS) Means were adjusted for treatment, investigator, and baseline score.

  9. Mean Change From Baseline (Week 10) in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) at Week 62 [ Time Frame: Baseline (Week 10), Week 62 ]
    The CPFQ was a 7-item participant-rated questionnaire pertaining to a participant's cognitive and physical well-being. It assessed 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 score ranged from 7 to 42. Least Squares (LS) Means were adjusted for investigator, visit, baseline score, and baseline-by-visit.

  10. Mean Change From Baseline in the EuroQol Questionnaire-5 Dimension (EQ-5D) United States (US) Index Score at Week 10 [ Time Frame: Baseline, Week 10 ]
    EQ-5D was a generic, multidimensional, health-related, quality of life (Qol) instrument allowing participants to rate their health state in 5 domains: mobility, self-care, usual activities, pain/discomfort, and mood. A single score between 1 and 3 was generated for each domain. For each participant, the outcome rating on the 5 domains was mapped to a single index through an algorithm. The index ranged between 0 and 1, with the higher score indicating a better health state perceived by the participant. Least Squares (LS) Means were adjusted for treatment, investigator, and baseline score.

  11. Mean Change From Baseline (Week 10) in the EuroQol Questionnaire-5 Dimension (EQ-5D) United States (US) Index Score at Week 62 [ Time Frame: Baseline (Week 10), Week 62 ]
    EQ-5D was a generic, multidimensional, health-related, quality of life (Qol) instrument allowing participants to rate their health state in 5 domains: mobility, self-care, usual activities, pain/discomfort, mood. Single score between 1 and 3 was generated for each domain. For each participant, outcome rating on the 5 domains was mapped to a single index through an algorithm. The index ranged between 0 and 1, with higher score indicating a better health state perceived by the participant. Least Squares (LS) Means were adjusted for investigator, visit, baseline score, and baseline-by-visit.

  12. Mean Change From Baseline in the Fatigue Associated With Depression (FAsD) Patient Reported Outcome (PRO): Average Score at Week 10 [ Time Frame: Baseline, Week 10 ]
    The FAsD was a participant-rated scale with 7 items that asked how often they experience different aspects of fatigue: responses from 1 (Never) to 5 (Always); 9 items that asked how often fatigue impacts various aspects of their lives: responses from 1 (Not at all) to 5 (Very much). Average Score=mean of Items 1-5, 7-12, 14, and 16. Scores ranged from 1 to 5. Least Squares (LS) Means were adjusted for treatment, investigator, visit, treatment-by-visit, baseline score, and baseline-by-visit.

  13. Mean Change From Baseline (Week 10) in Fatigue Associated With Depression (FAsD) Patient Reported Outcome (PRO): Average Score at Week 62 [ Time Frame: Baseline (Week 10), Week 62 ]
    The FAsD was a participant-rated scale with 7 items that asked how often they experience different aspects of fatigue: responses from 1 (Never) to 5 (Always); 9 items that asked how often fatigue impacts various aspects of their lives: responses from 1 (Not at all) to 5 (Very much). Average Score=mean of Items 1-5, 7-12, 14, and 16. Scores ranged from 1 to 5. Least Squares (LS) Means were adjusted for investigator, visit, baseline score, and baseline-by-visit.

  14. Mean Change From Baseline in the Fatigue Associated With Depression (FAsD) Patient Reported Outcome (PRO): Fatigue Experience Average Score at Week 10 [ Time Frame: Baseline, Week 10 ]
    The FAsD was a participant-rated scale with 7 items that asked how often they experience different aspects of fatigue: responses from 1 (Never) to 5 (Always); 9 items that asked how often fatigue impacts various aspects of their lives: responses from 1 (Not at all) to 5 (Very much). Fatigue Experience Average Score=mean of Items 1 to 5, and 7. Scores ranged from 1 to 5. Least Squares (LS) Means were adjusted for treatment, investigator, visit, treatment-by-visit, baseline score, and baseline-by-visit.

  15. Mean Change From Baseline (Week 10) in Fatigue Associated With Depression (FAsD) Patient Reported Outcome (PRO): Fatigue Experience Average Score at Week 62 [ Time Frame: Baseline (Week 10), Week 62 ]
    The FAsD was a participant-rated scale with 7 items that asked how often they experience different aspects of fatigue: responses from 1 (Never) to 5 (Always); 9 items that asked how often fatigue impacts various aspects of their lives: responses from 1 (Not at all) to 5 (Very much). Fatigue Experience Average Score=mean of Items 1-5, and 7. Scores ranged from 1 to 5. Least Squares (LS) Means were adjusted for investigator, visit, baseline score, and baseline-by-visit.

  16. Mean Change From Baseline in the Fatigue Associated With Depression (FAsD) Patient Reported Outcome (PRO): Fatigue Impact Average Score at Week 10 [ Time Frame: Baseline, Week 10 ]
    The FAsD was a participant-rated scale with 7 items that asked how often they experience different aspects of fatigue: responses from 1 (Never) to 5 (Always); 9 items that asked how often fatigue impacts various aspects of their lives: responses from 1 (Not at all) to 5 (Very much). Fatigue Impact Average Score=mean of Items 8-12, 14, and 16. Scores ranged from 1 to 5. Least Squares (LS) Means were adjusted for treatment, investigator, visit, treatment-by-visit, baseline score, and baseline-by-visit.

  17. Mean Change From Baseline (Week 10) in Fatigue Associated With Depression (FAsD) Patient Reported Outcome (PRO): Fatigue Impact Average Score at Week 62 [ Time Frame: Baseline (Week 10), Week 62 ]
    The FAsD was a participant-rated scale with 7 items that asked how often they experience different aspects of fatigue: responses from 1 (Never) to 5 (Always); 9 items that asked how often fatigue impacts various aspects of their lives: responses from 1 (Not at all) to 5 (Very much). Fatigue Impact Average Score=mean of Items 8-12, 14, and 16. Scores ranged from 1 to 5. Least Squares (LS) Means were adjusted for investigator, visit, baseline score, and baseline-by-visit.

  18. Mean Change From Baseline in the Brief Fatigue Inventory (BFI) Global Total Score at Week 10 [ Time Frame: Baseline, Week 10 ]
    The BFI was a participant-rated scale consisting of 9 items: 3 items assessed severity of fatigue at its "worst," "usual," and "now" during normal waking hours: 0=no fatigue to 10=fatigue as bad as you can imagine; 6 items assessed the degree to which fatigue has interfered with different aspects of the participant's life during the past 24 hours: 0=does not interfere to 10=completely interferes. The BFI Global Total Score was the mean of the 9 item scores and ranged from 0 to 10. Least Squares (LS) Means were adjusted for treatment, investigator, and baseline score.

  19. Mean Change From Baseline (Week 10) in Brief Fatigue Inventory (BFI) Global Total Score at Week 62 [ Time Frame: Baseline (Week 10), Week 62 ]
    The BFI was a participant-rated scale consisting of 9 items: 3 items assessed severity of fatigue at its "worst," "usual," and "now" during normal waking hours: 0=no fatigue to 10=fatigue as bad as you can imagine; 6 items assessed the degree to which fatigue has interfered with different aspects of the participant's life during the past 24 hours: 0=does not interfere to 10=completely interferes. The BFI Global Total Score was the mean of the 9 item scores and ranged from 0 to 10. Least Squares (LS) Means were adjusted for investigator, visit, baseline score, and baseline-by-visit.

  20. Mean Change From Baseline in the Visual Analogue Scale for Fatigue (VAS-F) Overall Severity and Interference With Daily Activities Scores at Week 10 [ Time Frame: Baseline, Week 10 ]
    The VAS-F was a self-rated assessment with 2 items. For the Overall Severity of Fatigue item, the participant placed a vertical mark on a 100-millimeter (mm) line between 2 anchors (0=not at all to 100=as severe as I can imagine). For the Interference With Daily Activities Due to Fatigue item, the participant placed a vertical mark on a 100 mm line between 2 anchors (0=not at all to 100=complete disability [unable to do any activities]). Least Squares (LS) Means were adjusted for treatment, investigator, visit, treatment-by-visit, baseline score, and baseline-by-visit.

  21. Mean Change From Baseline (Week 10) in the Visual Analogue Scale for Fatigue (VAS-F) Overall Severity and Interference With Daily Activities Scores at Week 62 [ Time Frame: Baseline (Week 10), Week 62 ]
    The VAS-F was a self-rated assessment with 2 items. For the Overall Severity of Fatigue item, the participant placed a vertical mark on a 100-millimeter (mm) line between 2 anchors (0=not at all to 100=as severe as I can imagine). For the Interference With Daily Activities Due to Fatigue item, the participant placed a vertical mark on a 100 mm line between 2 anchors (0=not at all to 100=complete disability [unable to do any activities]). Least Squares (LS) Means were adjusted for investigator, visit, baseline score, and baseline-by-visit.

  22. Percentage of Participants Reporting Resource Utilization at Week 10 [ Time Frame: Baseline through Week 10 ]
    The Resource Utilization form assessed the frequency and type of medical services that participants have used within the last year, or since the last visit. Resources reported by at least 5% of participants in either treatment group were provided.

  23. Percentage of Participants Reporting Resource Utilization at Week 62 [ Time Frame: Baseline (Week 10) through Week 62 ]
    The Resource Utilization form assessed the frequency and type of medical services that participants have used within the last year, or since the last visit. Resources reported by at least 5% of participants in either treatment group were provided.

  24. Percentage of Participants With Suicidal Ideation, Behavior, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 10 [ Time Frame: Baseline through Week 10 ]
    C-SSRS scale captured occurrence, severity, and frequency of suicide-related thoughts and behaviors. Number of participants with suicidal ideation, behavior, and acts were provided. Suicidal ideation=a "yes" answer to any 1 of 5 suicidal ideation questions (including wish to be dead) and 4 different categories of active suicidal ideation. Suicidal behavior=a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal act=a "yes" answer to actual attempt or completed suicide.

  25. Percentage of Participants With Suicidal Ideation, Behavior, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 62 [ Time Frame: Baseline (Week 10) through Week 62 ]
    C-SSRS scale captured occurrence, severity, and frequency of suicide-related thoughts and behaviors. Number of participants with suicidal ideation, behavior, and acts were provided. Suicidal ideation=a "yes" answer to any 1 of 5 suicidal ideation questions (including wish to be dead) and 4 different categories of active suicidal ideation. Suicidal behavior=a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal act=a "yes" answer to actual attempt or completed suicide.

  26. Mean Change From Baseline in Supine Systolic and Diastolic Blood Pressure at Week 10 [ Time Frame: Baseline, Week 10 ]
    Blood pressure was collected while the participant was in the supine position. Least Squares (LS) Means were adjusted for treatment, investigator, visit, treatment-by-visit, baseline score, and baseline-by-visit.

  27. Mean Change From Baseline (Week 10) in Supine Systolic and Diastolic Blood Pressure at Week 62 [ Time Frame: Baseline (Week 10), Week 62 ]
    Blood pressure was collected while the participant was in the supine position. Least Squares (LS) Means were adjusted for investigator, visit, baseline score, and baseline-by-visit.

  28. Mean Change From Baseline in Supine Pulse at Week 10 [ Time Frame: Baseline, Week 10 ]
    Pulse was collected while the participant was in the supine position. Least Squares (LS) Means were adjusted for treatment, investigator, visit, treatment-by-visit, baseline score, and baseline-by-visit.

  29. Mean Change From Baseline (Week 10) in Supine Pulse at Week 62 [ Time Frame: Baseline (Week 10), Week 62 ]
    Pulse was collected while the participant was in the supine position. Least Squares (LS) Means were adjusted for investigator, visit, baseline score, and baseline-by-visit.

  30. Pharmacokinetic (PK) Parameter: Plasma Concentration of LY2216684 [ Time Frame: Baseline through Week 62 ]
    Blood samples collected from participants that received LY2216684 were measured to determine the plasma LY2216684 concentrations.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults age 18-65 years
  • 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 without psychotic features
  • Women of child-bearing potential must test negative for pregnancy and agree to use a reliable method of birth control
  • Grid 17-item Hamilton Rating Scale for Depression (GRID-HAMD17) total score ≥18 at Visit 1 and Visit 2
  • Clinical global impressions of severity (CGI-S) score ≥4 at Visit 1 and Visit 2

Exclusion Criteria:

  • Are currently involved in or discontinued within the last 30 days from a clinical trial involving an off-label use of an investigational drug
  • Have previously completed or withdrawn from this study or any other study investigating LY2216684
  • Have had or currently have any additional ongoing DSM-IV-TR Axis 1 condition other than MDD
  • Have had any anxiety disorder preceding the onset of depression that was considered the primary diagnosis within 1 year of Visit 1
  • Have an Axis II disorder that would interfere with protocol compliance
  • Have a current or previous diagnosis of Bipolar I or II, psychotic depression, schizophrenia, or other psychotic disorder
  • Have a history of substance abuse within the past 1 year
  • Women who are pregnant or breast-feeding
  • Have had a lack of response of the current depressive episode to 2 or more adequate courses of antidepressant therapy, or in the judgment of the investigator, considered to have treatment-resistant depression
  • Participants who are judged to be at serious suicidal risk
  • Have a serious or unstable medical illness
  • Have any diagnosed medical condition which could be exacerbated by noradrenergic agents including unstable hypertension, unstable heart disease, tachycardia or tachyarrhythmia, narrow angle glaucoma, or urinary hesitation or retention
  • Have received treatment with a monoamine oxidase inhibitor (MAOI) within 14 days prior to Visit 1
  • Have a history of severe allergies to more than 1 class of medication or multiple adverse drug reactions
  • Have a history of electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS) or psychosurgery within the last year
  • Have a history of any seizure disorder (other than febrile seizures)
  • Require psychotropic medication other than sedative/hypnotic medication for sleep
  • Have a thyroid stimulating hormone (TSH) level outside the established reference range.
  • Are taking or have received treatment with any excluded medication within 7 days prior to Visit 2
  • Initiation or change in intensity of psychotherapy or other non-drug therapies within 6 weeks prior to enrollment
  • A positive urine drug screen for any substance of abuse at Visit 1
  • Have initiated or discontinued hormone therapy within the previous 3 months prior to enrollment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00795821


  Show 37 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00795821     History of Changes
Other Study ID Numbers: 11313
H9P-MC-LNBI ( Other Identifier: Eli Lilly and Company )
First Posted: November 21, 2008    Key Record Dates
Results First Posted: March 20, 2018
Last Update Posted: March 20, 2018
Last Verified: March 2018

Additional relevant MeSH terms:
Disease
Depressive Disorder
Depression
Depressive Disorder, Major
Pathologic Processes
Mood Disorders
Mental Disorders
Behavioral Symptoms
Phenylethyl Alcohol
Anti-Infective Agents, Local
Anti-Infective Agents
Disinfectants