Back to results

A Study in Adult Patients With Major Depressive Disorder

Primary Purpose

Depressive Disorder, Major

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

LY2216684

Placebo

About this trial

This is an interventional treatment trial for Depressive Disorder, Major

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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Have previously completed or withdrawn from this study or any other study investigating LY2216684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

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.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

LY2216684

Placebo

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

Mean Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) at 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

Mean Change From Baseline (Week 10) in Montgomery-Asberg Depression Rating Scale (MADRS) at 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.

Mean Change From Baseline in Sheehan Disability Scale (SDS) Global Functional Impairment at 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.

Mean Change From Baseline (Week 10) in Sheehan Disability Scale (SDS) Global Functional Impairment at 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.

Mean Change From Baseline in Clinical Global Impressions of Severity (CGI-Severity) Scale at 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.

Mean Change From Baseline (Week 10) in Clinical Global Impressions of Severity (CGI-Severity) Scale at 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.

Mean Change From Baseline in the 16-Item Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR16) at 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.

Mean Change From Baseline (Week 10) in the 16-Item Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR16) at 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.

Mean Change From Baseline in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) at 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.

Mean Change From Baseline (Week 10) in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) at Week 62

Mean Change From Baseline in the EuroQol Questionnaire-5 Dimension (EQ-5D) United States (US) Index Score at 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.

Mean Change From Baseline (Week 10) in the EuroQol Questionnaire-5 Dimension (EQ-5D) United States (US) Index Score at 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.

Mean Change From Baseline in the Fatigue Associated With Depression (FAsD) Patient Reported Outcome (PRO): Average Score at 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.

Mean Change From Baseline (Week 10) in Fatigue Associated With Depression (FAsD) Patient Reported Outcome (PRO): Average Score at 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.

Mean Change From Baseline in the Fatigue Associated With Depression (FAsD) Patient Reported Outcome (PRO): Fatigue Experience Average Score at 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.

Mean Change From Baseline (Week 10) in Fatigue Associated With Depression (FAsD) Patient Reported Outcome (PRO): Fatigue Experience Average Score at 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.

Mean Change From Baseline in the Fatigue Associated With Depression (FAsD) Patient Reported Outcome (PRO): Fatigue Impact Average Score at 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.

Mean Change From Baseline (Week 10) in Fatigue Associated With Depression (FAsD) Patient Reported Outcome (PRO): Fatigue Impact Average Score at 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.

Mean Change From Baseline in the Brief Fatigue Inventory (BFI) Global Total Score at 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.

Mean Change From Baseline (Week 10) in Brief Fatigue Inventory (BFI) Global Total Score at Week 62

Mean Change From Baseline in the Visual Analogue Scale for Fatigue (VAS-F) Overall Severity and Interference With Daily Activities Scores at 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.

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

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.

Percentage of Participants Reporting Resource Utilization at 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.

Percentage of Participants Reporting Resource Utilization at Week 62

Percentage of Participants With Suicidal Ideation, Behavior, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at 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.

Percentage of Participants With Suicidal Ideation, Behavior, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 62

Mean Change From Baseline in Supine Systolic and Diastolic Blood Pressure at 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.

Mean Change From Baseline (Week 10) in Supine Systolic and Diastolic Blood Pressure at 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.

Mean Change From Baseline in Supine Pulse at 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.

Mean Change From Baseline (Week 10) in Supine Pulse at 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.

Pharmacokinetic (PK) Parameter: Plasma Concentration of LY2216684

Blood samples collected from participants that received LY2216684 were measured to determine the plasma LY2216684 concentrations.

Full Information

NCT ID

NCT00795821

First Posted

November 19, 2008

Last Updated

March 16, 2018

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT00795821

Brief Title

A Study in Adult Patients With Major Depressive Disorder

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 Type

Interventional

2. Study Status

Record Verification Date

March 2018

Overall Recruitment Status

Completed

Study Start Date

December 2008 (undefined)

Primary Completion Date

February 2010 (Actual)

Study Completion Date

March 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

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

Depressive Disorder, Major

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

495 (Actual)

8. Arms, Groups, and Interventions

Arm Title

LY2216684

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

LY2216684

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Dose: 3 tablets QD for 10 weeks

Primary Outcome Measure Information:

Title

Mean Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) at Week 10

Description

Time Frame

Baseline, Week 10

Secondary Outcome Measure Information:

Title

Mean Change From Baseline (Week 10) in Montgomery-Asberg Depression Rating Scale (MADRS) at Week 62

Description

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.

Time Frame

Baseline (Week 10), Week 62

Title

Mean Change From Baseline in Sheehan Disability Scale (SDS) Global Functional Impairment at Week 10

Description

Time Frame

Baseline, Week 10

Title

Mean Change From Baseline (Week 10) in Sheehan Disability Scale (SDS) Global Functional Impairment at Week 62

Description

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.

Time Frame

Baseline (Week 10), Week 62

Title

Mean Change From Baseline in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 10

Description

Time Frame

Baseline, Week 10

Title

Mean Change From Baseline (Week 10) in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 62

Description

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.

Time Frame

Baseline (Week 10), Week 62

Title

Mean Change From Baseline in the 16-Item Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR16) at Week 10

Description

Time Frame

Baseline, Week 10

Title

Mean Change From Baseline (Week 10) in the 16-Item Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR16) at Week 62

Description

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.

Time Frame

Baseline (Week 10), Week 62

Title

Mean Change From Baseline in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) at Week 10

Description

Time Frame

Baseline, Week 10

Title

Mean Change From Baseline (Week 10) in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) at Week 62

Description

Time Frame

Baseline (Week 10), Week 62

Title

Mean Change From Baseline in the EuroQol Questionnaire-5 Dimension (EQ-5D) United States (US) Index Score at Week 10

Description

Time Frame

Baseline, Week 10

Title

Mean Change From Baseline (Week 10) in the EuroQol Questionnaire-5 Dimension (EQ-5D) United States (US) Index Score at Week 62

Description

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.

Time Frame

Baseline (Week 10), Week 62

Title

Mean Change From Baseline in the Fatigue Associated With Depression (FAsD) Patient Reported Outcome (PRO): Average Score at Week 10

Description

Time Frame

Baseline, Week 10

Title

Mean Change From Baseline (Week 10) in Fatigue Associated With Depression (FAsD) Patient Reported Outcome (PRO): Average Score at Week 62

Description

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.

Time Frame

Baseline (Week 10), Week 62

Title

Mean Change From Baseline in the Fatigue Associated With Depression (FAsD) Patient Reported Outcome (PRO): Fatigue Experience Average Score at Week 10

Description

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.

Time Frame

Baseline, Week 10

Title

Mean Change From Baseline (Week 10) in Fatigue Associated With Depression (FAsD) Patient Reported Outcome (PRO): Fatigue Experience Average Score at Week 62

Description

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.

Time Frame

Baseline (Week 10), Week 62

Title

Mean Change From Baseline in the Fatigue Associated With Depression (FAsD) Patient Reported Outcome (PRO): Fatigue Impact Average Score at Week 10

Description

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.

Time Frame

Baseline, Week 10

Title

Mean Change From Baseline (Week 10) in Fatigue Associated With Depression (FAsD) Patient Reported Outcome (PRO): Fatigue Impact Average Score at Week 62

Description

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.

Time Frame

Baseline (Week 10), Week 62

Title

Mean Change From Baseline in the Brief Fatigue Inventory (BFI) Global Total Score at Week 10

Description

Time Frame

Baseline, Week 10

Title

Mean Change From Baseline (Week 10) in Brief Fatigue Inventory (BFI) Global Total Score at Week 62

Description

Time Frame

Baseline (Week 10), Week 62

Title

Mean Change From Baseline in the Visual Analogue Scale for Fatigue (VAS-F) Overall Severity and Interference With Daily Activities Scores at Week 10

Description

Time Frame

Baseline, Week 10

Title

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

Description

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.

Time Frame

Baseline (Week 10), Week 62

Title

Percentage of Participants Reporting Resource Utilization at Week 10

Description

Time Frame

Baseline through Week 10

Title

Percentage of Participants Reporting Resource Utilization at Week 62

Description

Time Frame

Baseline (Week 10) through Week 62

Title

Percentage of Participants With Suicidal Ideation, Behavior, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 10

Description

Time Frame

Baseline through Week 10

Title

Percentage of Participants With Suicidal Ideation, Behavior, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 62

Description

Time Frame

Baseline (Week 10) through Week 62

Title

Mean Change From Baseline in Supine Systolic and Diastolic Blood Pressure at Week 10

Description

Time Frame

Baseline, Week 10

Title

Mean Change From Baseline (Week 10) in Supine Systolic and Diastolic Blood Pressure at Week 62

Description

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.

Time Frame

Baseline (Week 10), Week 62

Title

Mean Change From Baseline in Supine Pulse at Week 10

Description

Time Frame

Baseline, Week 10

Title

Mean Change From Baseline (Week 10) in Supine Pulse at Week 62

Description

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.

Time Frame

Baseline (Week 10), Week 62

Title

Pharmacokinetic (PK) Parameter: Plasma Concentration of LY2216684

Description

Blood samples collected from participants that received LY2216684 were measured to determine the plasma LY2216684 concentrations.

Time Frame

Baseline through Week 62

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

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

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name

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

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35226

Country

United States

Facility Name

City

Little Rock

State/Province

Arkansas

ZIP/Postal Code

72223

Country

United States

Facility Name

City

Beverly Hills

State/Province

California

ZIP/Postal Code

90210

Country

United States

Facility Name

City

Cerritos

State/Province

California

ZIP/Postal Code

90703

Country

United States

Facility Name

City

Denver

State/Province

Colorado

ZIP/Postal Code

80239

Country

United States

Facility Name

City

Hamden

State/Province

Connecticut

ZIP/Postal Code

06518

Country

United States

Facility Name

City

North Miami

State/Province

Florida

ZIP/Postal Code

33161

Country

United States

Facility Name

City

Orlando

State/Province

Florida

ZIP/Postal Code

32806

Country

United States

Facility Name

City

West Palm Beach

State/Province

Florida

ZIP/Postal Code

33407

Country

United States

Facility Name

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30328

Country

United States

Facility Name

City

Smyrna

State/Province

Georgia

ZIP/Postal Code

30080

Country

United States

Facility Name

City

Overland Park

State/Province

Kansas

ZIP/Postal Code

66212

Country

United States

Facility Name

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21208

Country

United States

Facility Name

City

Willingboro

State/Province

New Jersey

ZIP/Postal Code

08046

Country

United States

Facility Name

City

Albuquerque

State/Province

New Mexico

ZIP/Postal Code

87109

Country

United States

Facility Name

City

Portland

State/Province

Oregon

ZIP/Postal Code

97210

Country

United States

Facility Name

City

Memphis

State/Province

Tennessee

ZIP/Postal Code

38119

Country

United States

Facility Name

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

Facility Name

City

Bellevue

State/Province

Washington

ZIP/Postal Code

98007

Country

United States

Facility Name

City

Buenos Aires

ZIP/Postal Code

C1425AHQ

Country

Argentina

Facility Name

City

La Plata

ZIP/Postal Code

1900

Country

Argentina

Facility Name

City

Helsinki

ZIP/Postal Code

00530

Country

Finland

Facility Name

City

Oulu

ZIP/Postal Code

90100

Country

Finland

Facility Name

City

Tampere

ZIP/Postal Code

33100

Country

Finland

Facility Name

City

Turku

ZIP/Postal Code

20100

Country

Finland

Facility Name

City

Belchatow

ZIP/Postal Code

97-400

Country

Poland

Facility Name

City

Bialystok

ZIP/Postal Code

18-879

Country

Poland

Facility Name

City

Gdansk

ZIP/Postal Code

80 282

Country

Poland

Facility Name

City

Gorlice

ZIP/Postal Code

38-300

Country

Poland

Facility Name

City

Leszno

ZIP/Postal Code

64-100

Country

Poland

Facility Name

City

Lublin

ZIP/Postal Code

20-015

Country

Poland

Facility Name

City

Torun

ZIP/Postal Code

87-100

Country

Poland

Facility Name

City

Tuszyn

ZIP/Postal Code

95-080

Country

Poland

Facility Name

City

Kazan

ZIP/Postal Code

420012

Country

Russian Federation

Facility Name

City

Rostov-On-Don

ZIP/Postal Code

344010

Country

Russian Federation

Facility Name

City

Saint Petersburg

ZIP/Postal Code

191025

Country

Russian Federation

Facility Name

City

Tomsk

ZIP/Postal Code

634014

Country

Russian Federation

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

Learn more about this trial

A Study in Adult Patients With Major Depressive Disorder

We'll reach out to this number within 24 hrs