A Study in Adult Patients With Major Depressive Disorder

Eli Lilly and Company495 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

495

Conditions

Depressive Disorder, Major

Interventions

LY2216684DRUG

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

PlaceboDRUG

Dose: 3 tablets QD for 10 weeks

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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last 30 days from a clinical trial involving an off-label use of an investigational drug * Have previously completed or withdrawn from this study or any other study investigating LY2216684 * Have had or currently have any additional ongoing DSM-IV-TR Axis 1 condition other than MDD * Have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

Locations (37)

Outcomes

Primary Outcomes

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.

Time frame: Baseline, Week 10

Secondary Outcomes

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.

Time frame: Baseline (Week 10), Week 62

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.

Time frame: Baseline, Week 10

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.

Data from ClinicalTrials.gov

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Birmingham, Alabama, United States

Little Rock, Arkansas, United States

Beverly Hills, California, United States

Cerritos, California, United States

Denver, Colorado, United States

Hamden, Connecticut, United States

North Miami, Florida, United States

Orlando, Florida, United States

West Palm Beach, Florida, United States

Atlanta, Georgia, United States

...and 27 more locations

Time frame: Baseline (Week 10), Week 62

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.

Time frame: Baseline, Week 10

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.

Time frame: Baseline (Week 10), Week 62

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.

Time frame: Baseline, Week 10

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.

Time frame: Baseline (Week 10), Week 62

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.

Time frame: Baseline, Week 10

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

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.

Time frame: Baseline, Week 10

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.

Time frame: Baseline (Week 10), Week 62

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.

Time frame: Baseline, Week 10

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.

Time frame: Baseline (Week 10), Week 62

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.

Time frame: Baseline, Week 10

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.

Time frame: Baseline (Week 10), Week 62

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.

Time frame: Baseline, Week 10

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.

Time frame: Baseline (Week 10), Week 62

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.

Time frame: Baseline, Week 10

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

Time frame: Baseline (Week 10), 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.

Time frame: Baseline, Week 10

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.

Time frame: Baseline (Week 10), Week 62

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.

Time frame: Baseline through Week 10

Percentage of Participants Reporting Resource Utilization at Week 62

Time frame: Baseline (Week 10) through 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.

Time frame: Baseline through Week 10

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

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.

Time frame: Baseline, Week 10

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.

Time frame: Baseline (Week 10), Week 62

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.

Time frame: Baseline, Week 10

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.

Time frame: Baseline (Week 10), Week 62

Pharmacokinetic (PK) Parameter: Plasma Concentration of LY2216684

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

Time frame: Baseline through Week 62