A Study in Adult Patients With Major Depressive Disorder

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

Population: The analysis population included all randomized participants with a baseline and at least 1 post-baseline value.

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

Population: The analysis population included all randomized participants with a baseline and at least 1 post-baseline value.

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

Population: The analysis population included all randomized participants with a baseline and at least 1 post-baseline value.

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

Population: The analysis population included all randomized participants with a baseline and at least 1 post-baseline value.

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

Population: The analysis population included all randomized participants with a baseline and at least 1 post-baseline value.

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

Population: The analysis population included all participants with a baseline and at least 1 post-baseline value in the Per Protocol population, defined as the subset of randomized participants who had baseline and post-baseline data collected using the correct version of the QIDS-SR16 worksheet.

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

Population: The analysis population included all randomized participants with a baseline and at least 1 post-baseline value.

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

Population: The analysis population included all randomized participants with a baseline and at least 1 post-baseline value.

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

Population: The analysis population included all randomized participants with a baseline and at least 1 post-baseline value.

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

Population: The analysis population included all randomized participants with a baseline and at least 1 post-baseline value.

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

Population: The analysis population included all randomized participants with a baseline and at least 1 post-baseline value.

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

Population: The analysis population included all randomized participants with a baseline and at least 1 post-baseline value.

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

Population: The analysis population included all randomized participants with a baseline and at least 1 post-baseline value.

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.

Time frame: Baseline (Week 10), Week 62

Population: The analysis population included all participants in the Long-term Extension Phase with a baseline and at least 1 post-baseline value.

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

Population: The analysis population included all participants in the Long-term Extension Phase with a baseline and at least 1 post-baseline value.

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

Population: The analysis population included all participants in the Long-term Extension Phase with a baseline and at least 1 post-baseline value.

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

Population: The analysis population included all participants in the Long-term Extension Phase with a baseline and at least 1 post-baseline value.

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

Population: The analysis population included all participants in the Long-term Extension Phase with a baseline and at least 1 post-baseline value.

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

Population: The analysis population included all participants in the Long-term Extension Phase with a baseline and at least 1 post-baseline value.

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

Population: The analysis population included all participants in the Long-term Extension Phase with a baseline and at least 1 post-baseline value.

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

Population: The analysis population included all participants in the Long-term Extension Phase with a baseline and at least 1 post-baseline value.

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

Population: The analysis population included all participants in the Long-term Extension Phase with a baseline and at least 1 post-baseline value.

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

Population: The analysis population included all participants in the Long-term Extension Phase with a baseline and at least 1 post-baseline value.

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

Population: The analysis population included all participants in the Long-term Extension Phase with a baseline and at least 1 post-baseline value.

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.

Time frame: Baseline (Week 10), Week 62

Population: The analysis population included all participants in the Long-term Extension Phase with a baseline and at least 1 post-baseline value.

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

Population: The analysis population included all participants in the Long-term Extension Phase with a baseline and at least 1 post-baseline value.

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

Population: The analysis population included all randomized participants.

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 (Week 10) through Week 62

Population: The analysis population included all participants in the Long-term Extension Phase with a baseline and at least 1 post-baseline value.

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

Population: The analysis population included all randomized participants with a baseline and at least 1 post-baseline C-SSRS value.

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 (Week 10) through Week 62

Population: The analysis population included all participants in the Long-term Extension Phase with a baseline and at least 1 post-baseline value.

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

Time frame: Baseline through Week 62

Population: N=number of participants analyzed (N=365); n=number of plasma LY2216684 concentration observations. The sum of the individual 'n' values for each dose group does not equal 365 since the same participant could have received various doses during his/her participation in the study.