Trial Outcomes & Findings for A Study of Flexible or Fixed Dose LY2216684 as Adjunctive Treatment for Participants With Major Depressive Disorder Who Have Had a Partial Response to Selective Serotonin Reuptake Inhibitor (SSRI) Treatment (NCT NCT01187407)
NCT ID: NCT01187407
Last Updated: 2018-04-24
Results Overview
The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS had a 10-item checklist (sadness \[apparent\], sadness \[reported\], inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Items were rated on a scale of 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 calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.
COMPLETED
PHASE3
1480 participants
Randomization, 8 weeks
2018-04-24
Participant Flow
The first 3 weeks of the study was a double-blind Confirmation Phase during which participants continued to receive their SSRI with adjunctive placebo. If randomization criteria were met, participants were randomized to adjunctive LY2216684 or adjunctive placebo. If criteria were not met, participants continued on placebo to maintain the blind.
Participant milestones
| Measure |
Placebo + SSRI (Pre-randomized Participants)
Placebo: administered orally, once daily (QD) for 3 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
|
12 or 18 mg LY2216684 + SSRI (Randomized Participants)
LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, QD for 8 weeks, adjunctive to an SSRI
|
6 mg LY2216684 + SSRI (Randomized Participants)
LY2216684: fixed dose of 6 mg, administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Placebo + SSRI (Randomized Participants)
Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Placebo + SSRI (Non-randomized Participants)
Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
|
|---|---|---|---|---|---|
|
Confirmation (CF) Phase, 3 Weeks
STARTED
|
1480
|
0
|
0
|
0
|
0
|
|
Confirmation (CF) Phase, 3 Weeks
Entered Discontinuation (DC) Phase
|
25
|
0
|
0
|
0
|
0
|
|
Confirmation (CF) Phase, 3 Weeks
COMPLETED
|
1390
|
0
|
0
|
0
|
0
|
|
Confirmation (CF) Phase, 3 Weeks
NOT COMPLETED
|
90
|
0
|
0
|
0
|
0
|
|
Adjunctive Treatment (AT) Phase, 8 Weeks
STARTED
|
0
|
232
|
226
|
231
|
701
|
|
Adjunctive Treatment (AT) Phase, 8 Weeks
Entered Discontinuation (DC) Phase
|
0
|
212
|
215
|
220
|
660
|
|
Adjunctive Treatment (AT) Phase, 8 Weeks
COMPLETED
|
0
|
196
|
191
|
202
|
626
|
|
Adjunctive Treatment (AT) Phase, 8 Weeks
NOT COMPLETED
|
0
|
36
|
35
|
29
|
75
|
Reasons for withdrawal
| Measure |
Placebo + SSRI (Pre-randomized Participants)
Placebo: administered orally, once daily (QD) for 3 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
|
12 or 18 mg LY2216684 + SSRI (Randomized Participants)
LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, QD for 8 weeks, adjunctive to an SSRI
|
6 mg LY2216684 + SSRI (Randomized Participants)
LY2216684: fixed dose of 6 mg, administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Placebo + SSRI (Randomized Participants)
Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Placebo + SSRI (Non-randomized Participants)
Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
|
|---|---|---|---|---|---|
|
Confirmation (CF) Phase, 3 Weeks
Adverse Event
|
29
|
0
|
0
|
0
|
0
|
|
Confirmation (CF) Phase, 3 Weeks
Lack of Efficacy
|
4
|
0
|
0
|
0
|
0
|
|
Confirmation (CF) Phase, 3 Weeks
Lost to Follow-up
|
9
|
0
|
0
|
0
|
0
|
|
Confirmation (CF) Phase, 3 Weeks
Physician Decision
|
2
|
0
|
0
|
0
|
0
|
|
Confirmation (CF) Phase, 3 Weeks
Protocol Violation
|
13
|
0
|
0
|
0
|
0
|
|
Confirmation (CF) Phase, 3 Weeks
Withdrawal by Subject
|
29
|
0
|
0
|
0
|
0
|
|
Confirmation (CF) Phase, 3 Weeks
Sponsor Decision
|
4
|
0
|
0
|
0
|
0
|
|
Adjunctive Treatment (AT) Phase, 8 Weeks
Adverse Event
|
0
|
13
|
6
|
5
|
12
|
|
Adjunctive Treatment (AT) Phase, 8 Weeks
Lack of Efficacy
|
0
|
3
|
8
|
5
|
13
|
|
Adjunctive Treatment (AT) Phase, 8 Weeks
Lost to Follow-up
|
0
|
3
|
5
|
2
|
9
|
|
Adjunctive Treatment (AT) Phase, 8 Weeks
Physician Decision
|
0
|
0
|
0
|
1
|
2
|
|
Adjunctive Treatment (AT) Phase, 8 Weeks
Protocol Violation
|
0
|
6
|
5
|
3
|
10
|
|
Adjunctive Treatment (AT) Phase, 8 Weeks
Withdrawal by Subject
|
0
|
9
|
9
|
11
|
22
|
|
Adjunctive Treatment (AT) Phase, 8 Weeks
Sponsor Decision
|
0
|
2
|
2
|
2
|
7
|
Baseline Characteristics
A Study of Flexible or Fixed Dose LY2216684 as Adjunctive Treatment for Participants With Major Depressive Disorder Who Have Had a Partial Response to Selective Serotonin Reuptake Inhibitor (SSRI) Treatment
Baseline characteristics by cohort
| Measure |
12 or 18 mg LY2216684 + SSRI (Randomized Participants)
n=232 Participants
LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
|
6 mg LY2216684 + SSRI (Randomized Participants)
n=226 Participants
LY2216684: fixed dose of 6 mg, administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Placebo + SSRI (Randomized Participants)
n=231 Participants
Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Placebo + SSRI (Non-randomized Participants)
n=701 Participants
Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Total
n=1390 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
46.63 years
STANDARD_DEVIATION 12.00 • n=5 Participants
|
47.06 years
STANDARD_DEVIATION 12.76 • n=7 Participants
|
47.30 years
STANDARD_DEVIATION 12.10 • n=5 Participants
|
46.35 years
STANDARD_DEVIATION 12.42 • n=4 Participants
|
46.67 years
STANDARD_DEVIATION 12.35 • n=21 Participants
|
|
Sex: Female, Male
Female
|
149 Participants
n=5 Participants
|
153 Participants
n=7 Participants
|
156 Participants
n=5 Participants
|
465 Participants
n=4 Participants
|
923 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
83 Participants
n=5 Participants
|
73 Participants
n=7 Participants
|
75 Participants
n=5 Participants
|
236 Participants
n=4 Participants
|
467 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
11 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
49 Participants
n=4 Participants
|
83 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
183 Participants
n=5 Participants
|
181 Participants
n=7 Participants
|
178 Participants
n=5 Participants
|
562 Participants
n=4 Participants
|
1104 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
38 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
90 Participants
n=4 Participants
|
203 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
21 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
54 Participants
n=4 Participants
|
121 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
16 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
63 Participants
n=4 Participants
|
122 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
192 Participants
n=5 Participants
|
173 Participants
n=7 Participants
|
186 Participants
n=5 Participants
|
572 Participants
n=4 Participants
|
1123 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
15 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
103 Participants
n=5 Participants
|
98 Participants
n=7 Participants
|
104 Participants
n=5 Participants
|
377 Participants
n=4 Participants
|
682 Participants
n=21 Participants
|
|
Region of Enrollment
Czechia
|
44 Participants
n=5 Participants
|
44 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
119 Participants
n=4 Participants
|
253 Participants
n=21 Participants
|
|
Region of Enrollment
Slovakia
|
33 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
39 Participants
n=4 Participants
|
141 Participants
n=21 Participants
|
|
Region of Enrollment
Finland
|
18 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
61 Participants
n=4 Participants
|
108 Participants
n=21 Participants
|
|
Region of Enrollment
Croatia
|
9 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
26 Participants
n=4 Participants
|
52 Participants
n=21 Participants
|
|
Region of Enrollment
Japan
|
20 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
53 Participants
n=4 Participants
|
115 Participants
n=21 Participants
|
|
Region of Enrollment
Hungary
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
|
Region of Enrollment
Romania
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
23 Participants
n=4 Participants
|
31 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Randomization, 8 weeksPopulation: All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.
The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS had a 10-item checklist (sadness \[apparent\], sadness \[reported\], inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Items were rated on a scale of 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 calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.
Outcome measures
| Measure |
12 or 18 mg Flexible Dose LY2216684 + SSRI
n=231 Participants
LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
|
6 mg Fixed Dose LY2216684 + SSRI
n=220 Participants
LY2216684: fixed dose of 6 mg, administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Placebo + SSRI
n=228 Participants
Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
|
|---|---|---|---|
|
Change From Randomization to Week 8 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
|
-9.36 units on a scale
Standard Error 0.55
|
-9.59 units on a scale
Standard Error 0.55
|
-9.36 units on a scale
Standard Error 0.54
|
SECONDARY outcome
Timeframe: Randomization, 8 weeksPopulation: All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.
The SDS was completed by the participant and used to assess the effect of the participant's symptoms on their work (Item 1), social (Item 2), and family life (Item 3). Each item is measured on a 0 (not at all) to 10 (extremely) point scale with higher values indicating greater disruption. The Global Functional Impairment Score is the sum of the 3 items, and scores ranged from 0 to 30 with higher values indicating greater disruption in the participant's work life (work/school impairment score), social life (social life/leisure activities impairment score), and family life (family life/home responsibilities impairment score). Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.
Outcome measures
| Measure |
12 or 18 mg Flexible Dose LY2216684 + SSRI
n=225 Participants
LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
|
6 mg Fixed Dose LY2216684 + SSRI
n=210 Participants
LY2216684: fixed dose of 6 mg, administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Placebo + SSRI
n=221 Participants
Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
|
|---|---|---|---|
|
Change From Randomization to Week 8 in the Sheehan Disability Scale (SDS) Global Functional Impairment Score
|
-5.30 units on a scale
Standard Error 0.43
|
-6.29 units on a scale
Standard Error 0.44
|
-4.30 units on a scale
Standard Error 0.43
|
SECONDARY outcome
Timeframe: Randomization, 8 weeksPopulation: All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.
The FAsD is a participant-rated scale with a total of 13 items. Six of the 13 items ask how often participants experience different aspects of fatigue with responses from 1 (never) to 5 (always). Seven of the 13 items ask how often fatigue impacts various aspects of the participant's lives with responses from 1 (not at all) to 5 (very much). The impact subscale score was derived by taking the mean of Items 7 through 13 (applicable items only). Item 12 applied only to participants with a spouse or significant other and Item 13 applied to participants who had a job or who went to school. The FAsD impact subscale score ranges from 1 to 5. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline subscale score, treatment-by-visit, and baseline subscale score-by-visit.
Outcome measures
| Measure |
12 or 18 mg Flexible Dose LY2216684 + SSRI
n=225 Participants
LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
|
6 mg Fixed Dose LY2216684 + SSRI
n=210 Participants
LY2216684: fixed dose of 6 mg, administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Placebo + SSRI
n=221 Participants
Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
|
|---|---|---|---|
|
Change From Randomization to Week 8 in the Fatigue Associated With Depression (FAsD) Impact Subscale Score
|
-0.71 units on a scale
Standard Error 0.06
|
-0.67 units on a scale
Standard Error 0.06
|
-0.56 units on a scale
Standard Error 0.06
|
SECONDARY outcome
Timeframe: Randomization up to 8 weeksPopulation: All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value. Last observation carried forward (LOCF) methodology was used.
A MADRS total score of less than or equal to 10 was defined as remission criteria. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS had a 10-item checklist (sadness \[apparent\], sadness \[reported\], inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Items were rated on a scale of 0 to 6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Percentage of participants was calculated by dividing the number of participants who meet criteria for remission by the total number of participants analyzed, multiplied by 100%.
Outcome measures
| Measure |
12 or 18 mg Flexible Dose LY2216684 + SSRI
n=231 Participants
LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
|
6 mg Fixed Dose LY2216684 + SSRI
n=221 Participants
LY2216684: fixed dose of 6 mg, administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Placebo + SSRI
n=228 Participants
Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
|
|---|---|---|---|
|
Percentage of Participants Achieving a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of Less Than or Equal to 10 up to Week 8
|
26.84 percentage of participants
|
29.41 percentage of participants
|
26.32 percentage of participants
|
SECONDARY outcome
Timeframe: Randomization up to 8 weeksPopulation: All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.
A MADRS total score of less than or equal to 10 for at least 2 consecutive measurements, including the participant's last measurement was defined as remission criteria at last 2 consecutive visits. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS had a 10-item checklist (sadness \[apparent\], sadness \[reported\], inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Items were rated on a scale of 0 to 6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Percentage of participants was calculated by dividing the number of participants who meet criteria for remission at last 2 consecutive visits by the total number of participants analyzed, multiplied by 100%.
Outcome measures
| Measure |
12 or 18 mg Flexible Dose LY2216684 + SSRI
n=231 Participants
LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
|
6 mg Fixed Dose LY2216684 + SSRI
n=221 Participants
LY2216684: fixed dose of 6 mg, administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Placebo + SSRI
n=228 Participants
Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
|
|---|---|---|---|
|
Percentage of Participants Achieving a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of Less Than or Equal 10 for at Least 2 Consecutive Measurements, Including the Participant's Last Measurement
|
17.75 percentage of participants
|
19.00 percentage of participants
|
14.47 percentage of participants
|
SECONDARY outcome
Timeframe: Randomization, 8 weeksPopulation: All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.
The HADS is a 14-item questionnaire with 2 subscales: anxiety and depression. Each item was rated on a 4-point scale (0 to 3), giving maximum scores of 21 for anxiety and depression subscale. Scores of 11 or more on either subscale were considered to be a significant 'case' of psychological morbidity, while scores of 8 to 10 represent 'borderline' and scores of 0 to 7 represent 'normal'. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline subscale score, treatment-by-visit, and baseline subscale score-by-visit.
Outcome measures
| Measure |
12 or 18 mg Flexible Dose LY2216684 + SSRI
n=231 Participants
LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
|
6 mg Fixed Dose LY2216684 + SSRI
n=220 Participants
LY2216684: fixed dose of 6 mg, administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Placebo + SSRI
n=228 Participants
Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
|
|---|---|---|---|
|
Change From Randomization to Week 8 in the Hospital and Anxiety and Depression Scale (HADS) Anxiety Subscale Score
|
-2.24 units on a scale
Standard Error 0.24
|
-2.64 units on a scale
Standard Error 0.24
|
-2.05 units on a scale
Standard Error 0.24
|
SECONDARY outcome
Timeframe: Randomization up to 8 weeksPopulation: All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value. Last observation carried forward (LOCF) methodology was used.
A greater than or equal to 50 percent improvement (that is, a decrease from baseline) in the MADRS total score was defined as response criteria. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS had a 10-item checklist (sadness \[apparent\], sadness \[reported\], inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Items were rated on a scale of 0 to 6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Percentage of participants was calculated by dividing the number of participants meeting response criteria at last visit by the total number of participants analyzed, multiplied by 100%.
Outcome measures
| Measure |
12 or 18 mg Flexible Dose LY2216684 + SSRI
n=231 Participants
LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
|
6 mg Fixed Dose LY2216684 + SSRI
n=221 Participants
LY2216684: fixed dose of 6 mg, administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Placebo + SSRI
n=228 Participants
Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
|
|---|---|---|---|
|
Percentage of Participants Who Have a Greater Than or Equal to 50 Percent Improvement in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Randomization up to Week 8
|
30.74 percentage of participants
|
34.84 percentage of participants
|
32.46 percentage of participants
|
SECONDARY outcome
Timeframe: Randomization, 8 weeksPopulation: All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.
The HADS is a 14-item questionnaire with 2 subscales: anxiety and depression. Each item was rated on a 4-point scale (0 to 3), giving maximum scores of 21 for anxiety and depression subscale. Scores of 11 or more on either subscale were considered to be a significant 'case' of psychological morbidity, while scores of 8 to 10 represent 'borderline' and scores of 0 to 7 represent 'normal'. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline subscale score, treatment-by-visit, and baseline subscale score-by-visit.
Outcome measures
| Measure |
12 or 18 mg Flexible Dose LY2216684 + SSRI
n=231 Participants
LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
|
6 mg Fixed Dose LY2216684 + SSRI
n=220 Participants
LY2216684: fixed dose of 6 mg, administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Placebo + SSRI
n=228 Participants
Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
|
|---|---|---|---|
|
Change From Randomization to Week 8 in the Hospital Anxiety and Depression Scale (HADS) Depression Subscale Score
|
-3.40 units on a scale
Standard Error 0.26
|
-3.62 units on a scale
Standard Error 0.27
|
-2.55 units on a scale
Standard Error 0.26
|
SECONDARY outcome
Timeframe: Randomization, 8 weeksPopulation: All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.
The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS had a 10-item checklist (sadness \[apparent\], sadness \[reported\], inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Items were rated on a scale of 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 calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline item score, treatment-by-visit and baseline item score-by-visit.
Outcome measures
| Measure |
12 or 18 mg Flexible Dose LY2216684 + SSRI
n=231 Participants
LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
|
6 mg Fixed Dose LY2216684 + SSRI
n=220 Participants
LY2216684: fixed dose of 6 mg, administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Placebo + SSRI
n=228 Participants
Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
|
|---|---|---|---|
|
Change From Randomization to Week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) Individual Items
Apparent sadness
|
-1.34 units on a scale
Standard Error 0.08
|
-1.25 units on a scale
Standard Error 0.08
|
-1.26 units on a scale
Standard Error 0.08
|
|
Change From Randomization to Week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) Individual Items
Reported sadness
|
-1.41 units on a scale
Standard Error 0.09
|
-1.31 units on a scale
Standard Error 0.09
|
-1.26 units on a scale
Standard Error 0.09
|
|
Change From Randomization to Week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) Individual Items
Inner tension
|
-0.96 units on a scale
Standard Error 0.08
|
-0.91 units on a scale
Standard Error 0.08
|
-0.87 units on a scale
Standard Error 0.08
|
|
Change From Randomization to Week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) Individual Items
Reduced sleep
|
-0.82 units on a scale
Standard Error 0.09
|
-0.96 units on a scale
Standard Error 0.09
|
-0.92 units on a scale
Standard Error 0.09
|
|
Change From Randomization to Week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) Individual Items
Reduced appetite
|
-0.57 units on a scale
Standard Error 0.08
|
-0.67 units on a scale
Standard Error 0.08
|
-0.71 units on a scale
Standard Error 0.08
|
|
Change From Randomization to Week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) Individual Items
Concentration difficulties
|
-1.13 units on a scale
Standard Error 0.08
|
-1.14 units on a scale
Standard Error 0.08
|
-0.98 units on a scale
Standard Error 0.08
|
|
Change From Randomization to Week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) Individual Items
Lassitude
|
-1.15 units on a scale
Standard Error 0.09
|
-1.07 units on a scale
Standard Error 0.09
|
-1.16 units on a scale
Standard Error 0.09
|
|
Change From Randomization to Week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) Individual Items
Inability to feel
|
-1.11 units on a scale
Standard Error 0.09
|
-1.30 units on a scale
Standard Error 0.09
|
-1.14 units on a scale
Standard Error 0.09
|
|
Change From Randomization to Week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) Individual Items
Pessimistic thoughts
|
-0.84 units on a scale
Standard Error 0.07
|
-0.82 units on a scale
Standard Error 0.07
|
-0.91 units on a scale
Standard Error 0.07
|
|
Change From Randomization to Week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) Individual Items
Suicidal thoughts
|
-0.17 units on a scale
Standard Error 0.03
|
-0.19 units on a scale
Standard Error 0.03
|
-0.17 units on a scale
Standard Error 0.03
|
SECONDARY outcome
Timeframe: Randomization, 8 weeksPopulation: All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.
CGI-S measures severity of depression at the time of assessment compared with the start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit
Outcome measures
| Measure |
12 or 18 mg Flexible Dose LY2216684 + SSRI
n=231 Participants
LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
|
6 mg Fixed Dose LY2216684 + SSRI
n=220 Participants
LY2216684: fixed dose of 6 mg, administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Placebo + SSRI
n=228 Participants
Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
|
|---|---|---|---|
|
Change From Randomization to Week 8 in Clinical Global Impressions of Severity (CGI-S)
|
-1.20 units on a scale
Standard Error 0.08
|
-1.21 units on a scale
Standard Error 0.08
|
-1.14 units on a scale
Standard Error 0.07
|
SECONDARY outcome
Timeframe: Randomization, 8 weeksPopulation: All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.
The FAsD is a participant-rated scale with a total of 13 items. Six of the 13 items ask how often participants experience different aspects of fatigue with responses from 1 (never) to 5 (always). Seven of the 13 items ask how often fatigue impacts various aspects of the participant's lives with responses from 1 (not at all) to 5 (very much). The experience subscale score was derived by taking the mean of Items 1 through 6, and the average score was the mean of Items 1 through 13 (derived by taking the mean of all applicable items for each participant). Item 12 applied only to participants with a spouse or significant other and Item 13 applied to participants who had a job or who went to school. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.
Outcome measures
| Measure |
12 or 18 mg Flexible Dose LY2216684 + SSRI
n=225 Participants
LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
|
6 mg Fixed Dose LY2216684 + SSRI
n=210 Participants
LY2216684: fixed dose of 6 mg, administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Placebo + SSRI
n=221 Participants
Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
|
|---|---|---|---|
|
Change From Randomization to Week 8 in The Fatigue Associated With Depression (FAsD) Average Score and Experience Subscale Score
FAsD average score
|
-0.67 units on a scale
Standard Error 0.05
|
-0.68 units on a scale
Standard Error 0.06
|
-0.53 units on a scale
Standard Error 0.05
|
|
Change From Randomization to Week 8 in The Fatigue Associated With Depression (FAsD) Average Score and Experience Subscale Score
FAsD experience score
|
-0.63 units on a scale
Standard Error 0.06
|
-0.67 units on a scale
Standard Error 0.06
|
-0.50 units on a scale
Standard Error 0.06
|
SECONDARY outcome
Timeframe: Randomization, 8 weeksPopulation: All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.
The SDS was completed by the participant and used to assess the effect of the participant's symptoms on their work (work/school impairment score), social life (social life/leisure activities impairment score), and family life (family life/home responsibilities impairment score). Each item is measured on a 0 (not at all) to 10 (extremely) point scale with higher values indicating greater disruption. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline item score, treatment-by-visit, and baseline item score-by-visit.
Outcome measures
| Measure |
12 or 18 mg Flexible Dose LY2216684 + SSRI
n=225 Participants
LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
|
6 mg Fixed Dose LY2216684 + SSRI
n=210 Participants
LY2216684: fixed dose of 6 mg, administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Placebo + SSRI
n=221 Participants
Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
|
|---|---|---|---|
|
Change From Randomization to Week 8 in Sheehan Disability Scale (SDS) Items
Work impairment score
|
-1.81 units on a scale
Standard Error 0.19
|
-1.93 units on a scale
Standard Error 0.20
|
-1.32 units on a scale
Standard Error 0.19
|
|
Change From Randomization to Week 8 in Sheehan Disability Scale (SDS) Items
Social life impairment score
|
-1.79 units on a scale
Standard Error 0.16
|
-2.11 units on a scale
Standard Error 0.16
|
-1.52 units on a scale
Standard Error 0.16
|
|
Change From Randomization to Week 8 in Sheehan Disability Scale (SDS) Items
Family life impairment score
|
-1.75 units on a scale
Standard Error 0.15
|
-2.16 units on a scale
Standard Error 0.15
|
-1.47 units on a scale
Standard Error 0.15
|
SECONDARY outcome
Timeframe: Randomization, 8 weeksPopulation: All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.
The Q-LES-Q-SF is a self-administered 16 item questionnaire measuring degree of enjoyment and satisfaction experienced in various areas of daily life during the past week on a 5-point Likert scale (1=very poor and 5=very good). The total raw score is the sum of Items 1 to 14 and ranges from 14 to 70. The raw scores are converted to and expressed as the percentage of the maximum possible score. Higher scores indicate higher levels of enjoyment/satisfaction. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.
Outcome measures
| Measure |
12 or 18 mg Flexible Dose LY2216684 + SSRI
n=224 Participants
LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
|
6 mg Fixed Dose LY2216684 + SSRI
n=210 Participants
LY2216684: fixed dose of 6 mg, administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Placebo + SSRI
n=221 Participants
Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
|
|---|---|---|---|
|
Change From Randomization to Week 8 in the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF)
|
10.54 percentage of maximum possible score
Standard Error 1.00
|
10.05 percentage of maximum possible score
Standard Error 1.02
|
8.74 percentage of maximum possible score
Standard Error 0.99
|
SECONDARY outcome
Timeframe: Randomization, 8 weeksPopulation: All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.
The EQ-5D Visual Analog Scale is a generic, multidimensional, health-related, quality-of-life instrument. Overall health state score is self-reported using a visual analogue scale, marked on a scale of 0 to 100 with 0 representing worst imaginable health state and 100 representing best imaginable health state. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.
Outcome measures
| Measure |
12 or 18 mg Flexible Dose LY2216684 + SSRI
n=225 Participants
LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
|
6 mg Fixed Dose LY2216684 + SSRI
n=210 Participants
LY2216684: fixed dose of 6 mg, administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Placebo + SSRI
n=221 Participants
Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
|
|---|---|---|---|
|
Change From Randomization to Week 8 in the EuroQol Questionnaire-5 Dimension (EQ-5D)
|
11.457 units on a scale
Standard Error 1.218
|
11.895 units on a scale
Standard Error 1.239
|
9.530 units on a scale
Standard Error 1.207
|
SECONDARY outcome
Timeframe: Randomization through 8 weeksPopulation: All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.
The C-SSRS captured occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation was defined as a "yes" answer to any 1 of 5 suicidal ideation questions, which included a wish to be dead and 4 different categories of active suicidal ideation. Suicidal behavior was defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation and behavior are defined as treatment-emergent (TE) if not present at baseline. Percentage of participants was calculated by dividing the number of participants with suicide-related TE events by the total number of participants analyzed, multiplied by 100%. A summary of serious and other non-serious adverse events, regardless of causality, is located in the Reported Adverse Event module.
Outcome measures
| Measure |
12 or 18 mg Flexible Dose LY2216684 + SSRI
n=232 Participants
LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
|
6 mg Fixed Dose LY2216684 + SSRI
n=221 Participants
LY2216684: fixed dose of 6 mg, administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Placebo + SSRI
n=228 Participants
Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
|
|---|---|---|---|
|
Percentage of Participants With Treatment-emergent (TE) Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
TE suicidal ideation
|
5.17 percentage of participants
|
3.62 percentage of participants
|
4.39 percentage of participants
|
|
Percentage of Participants With Treatment-emergent (TE) Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
TE suicidal behavior
|
0.00 percentage of participants
|
0.00 percentage of participants
|
0.00 percentage of participants
|
SECONDARY outcome
Timeframe: Randomization, 8 weeksPopulation: All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.
The ASEX scale was used to assess sexual functioning in both males and females. The ASEX total score for the male and female version was calculated as the sum of the responses (rated from 1 \[extremely\] to 6 \[no/never\]) of the 5 items of the ASEX scale. Total scores ranged from 5 to 30, with higher scores indicating greater sexual dysfunction. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.
Outcome measures
| Measure |
12 or 18 mg Flexible Dose LY2216684 + SSRI
n=224 Participants
LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
|
6 mg Fixed Dose LY2216684 + SSRI
n=209 Participants
LY2216684: fixed dose of 6 mg, administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Placebo + SSRI
n=220 Participants
Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
|
|---|---|---|---|
|
Change From Randomization to Week 8 in the Arizona Sexual Experiences (ASEX) Scale
|
-1.62 units on a scale
Standard Error 0.29
|
-1.29 units on a scale
Standard Error 0.29
|
-0.97 units on a scale
Standard Error 0.29
|
SECONDARY outcome
Timeframe: Randomization, 8 weeksPopulation: All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.
The CPFQ is a 7-item participant-rated questionnaire pertaining to a participant's cognitive and physical well-being. It assesses motivation, wakefulness, energy, focus, recall, word-finding difficulty, and mental acuity. Each item was scored on a 6-point scale ranging from 1 (greater than normal) to 6 (totally absent). Total scores ranged from 7 to 42. Higher scores indicate greater disease severity. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.
Outcome measures
| Measure |
12 or 18 mg Flexible Dose LY2216684 + SSRI
n=225 Participants
LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
|
6 mg Fixed Dose LY2216684 + SSRI
n=210 Participants
LY2216684: fixed dose of 6 mg, administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Placebo + SSRI
n=221 Participants
Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
|
|---|---|---|---|
|
Change From Randomization to Week 8 in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ)
|
-4.74 units on a scale
Standard Error 0.38
|
-4.67 units on a scale
Standard Error 0.39
|
-3.64 units on a scale
Standard Error 0.38
|
SECONDARY outcome
Timeframe: Randomization, 8 weeksPopulation: All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.
Blood pressure measurements were collected when the participant was in a sitting position. Three measurements of sitting blood pressure collected at approximately 1-minute intervals at every visit were averaged and used as the value for the visit. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline value, treatment-by-visit, and baseline value-by-visit.
Outcome measures
| Measure |
12 or 18 mg Flexible Dose LY2216684 + SSRI
n=232 Participants
LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
|
6 mg Fixed Dose LY2216684 + SSRI
n=220 Participants
LY2216684: fixed dose of 6 mg, administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Placebo + SSRI
n=228 Participants
Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
|
|---|---|---|---|
|
Change From Randomization to Week 8 in Blood Pressure
Systolic blood pressure
|
1.64 millimeters of mercury (mmHg)
Standard Error 0.62
|
2.93 millimeters of mercury (mmHg)
Standard Error 0.63
|
0.78 millimeters of mercury (mmHg)
Standard Error 0.62
|
|
Change From Randomization to Week 8 in Blood Pressure
Diastolic blood pressure
|
3.46 millimeters of mercury (mmHg)
Standard Error 0.49
|
4.47 millimeters of mercury (mmHg)
Standard Error 0.50
|
1.01 millimeters of mercury (mmHg)
Standard Error 0.49
|
SECONDARY outcome
Timeframe: Randomization, 8 weeksPopulation: All randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.
Pulse measurements were collected when the participant was in a sitting position. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline value, treatment-by-visit, and baseline value-by-visit.
Outcome measures
| Measure |
12 or 18 mg Flexible Dose LY2216684 + SSRI
n=232 Participants
LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
|
6 mg Fixed Dose LY2216684 + SSRI
n=220 Participants
LY2216684: fixed dose of 6 mg, administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Placebo + SSRI
n=228 Participants
Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
|
|---|---|---|---|
|
Change From Randomization to Week 8 in Pulse Rate
|
9.26 beats per minute (bpm)
Standard Error 0.65
|
7.32 beats per minute (bpm)
Standard Error 0.66
|
-1.03 beats per minute (bpm)
Standard Error 0.65
|
SECONDARY outcome
Timeframe: Pre-randomization, 1 week, 4 weeks, and 8 weeksPopulation: Participants exposed to LY2216684 with evaluable plasma concentration values. Samples with concentrations below the lower quantification limit (BQL) of the assay were treated as missing values for the analysis and samples with incomplete dosing information were not included in the pharmacokinetic assessment.
A validated bioanalytical assay was used to determine plasma LY2216684 concentrations.
Outcome measures
| Measure |
12 or 18 mg Flexible Dose LY2216684 + SSRI
n=400 Participants
LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
|
6 mg Fixed Dose LY2216684 + SSRI
LY2216684: fixed dose of 6 mg, administered orally, QD for 8 weeks, adjunctive to an SSRI
|
Placebo + SSRI
Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI
|
|---|---|---|---|
|
Pharmacokinetics: Plasma Concentrations of LY2216684
6-mg dose
|
17.0 nanograms per milliliter (ng/mL)
Standard Deviation 10.2
|
—
|
—
|
|
Pharmacokinetics: Plasma Concentrations of LY2216684
12-mg dose
|
32.2 nanograms per milliliter (ng/mL)
Standard Deviation 21.1
|
—
|
—
|
|
Pharmacokinetics: Plasma Concentrations of LY2216684
18-mg dose
|
52.4 nanograms per milliliter (ng/mL)
Standard Deviation 34.6
|
—
|
—
|
Adverse Events
Placebo + SSRI (Pre-randomized) - CF Phase
12 or 18 mg LY2216684 + SSRI (Randomized) - AT Phase
6 mg LY2216684 + SSRI (Randomized) - AT Phase
Placebo + SSRI (Randomized) - AT Phase
Placebo + SSRI (Non-randomized) - AT Phase
Placebo + SSRI (Pre-randomized) - DC Phase
12 or 18 mg LY2216684 + SSRI (Randomized) - DC Phase
6 mg LY2216684 + SSRI (Randomized) - DC Phase
Placebo + SSRI (Randomized) - DC Phase
Placebo + SSRI (Non-randomized) - DC Phase
Serious adverse events
| Measure |
Placebo + SSRI (Pre-randomized) - CF Phase
n=1476 participants at risk
Placebo: administered orally, once daily for 3 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Includes all enrolled who did not discontinue for the reason 'Lost to Follow-up' at the first post-baseline visit during the Confirmation (CF) Phase.
|
12 or 18 mg LY2216684 + SSRI (Randomized) - AT Phase
n=232 participants at risk
LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Includes randomized participants who did not discontinue for the reason 'Lost to Follow-up' at the first post-randomization visit during the Adjunctive Treatment (AT) Phase.
|
6 mg LY2216684 + SSRI (Randomized) - AT Phase
n=223 participants at risk
LY2216684: fixed dose of 6 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Includes randomized participants who did not discontinue for the reason 'Lost to Follow-up' at the first post-randomization visit during the Adjunctive Treatment (AT) Phase.
|
Placebo + SSRI (Randomized) - AT Phase
n=231 participants at risk
Placebo: administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Includes randomized participants who did not discontinue for the reason 'Lost to Follow-up' at the first post-randomization visit during the Adjunctive Treatment (AT) Phase.
|
Placebo + SSRI (Non-randomized) - AT Phase
n=699 participants at risk
Placebo: administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Includes all non-randomized participants who did not discontinue for the reason 'Lost to Follow-up' at the first post-randomization visit during the Adjunctive Treatment (AT) Phase.
|
Placebo + SSRI (Pre-randomized) - DC Phase
n=25 participants at risk
No study drug was administered. Participants were to maintain their selective serotonin reuptake inhibitor (SSRI) treatment at a stable dose for 1 week.
Includes all enrolled participants who abruptly discontinued placebo after early withdrawal during the Confirmation (CF) Phase and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation (DC) Phase visit.
|
12 or 18 mg LY2216684 + SSRI (Randomized) - DC Phase
n=212 participants at risk
No study drug was administered. Participants were to maintain their selective serotonin reuptake inhibitor (SSRI) treatment at a stable dose for 1 week.
Includes all randomized participants who abruptly discontinued LY2216684 either at the end of the study or after early withdrawal from the study and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation (DC) Phase visit.
|
6 mg LY2216684 + SSRI (Randomized) - DC Phase
n=213 participants at risk
No study drug was administered. Participants were to maintain their selective serotonin reuptake inhibitor (SSRI) treatment at a stable dose for 1 week.
Includes all randomized participants who abruptly discontinued LY2216684 either at the end of the study or after early withdrawal from the study and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation (DC) Phase visit.
|
Placebo + SSRI (Randomized) - DC Phase
n=220 participants at risk
No study drug was administered. Participants were to maintain their selective serotonin reuptake inhibitor (SSRI) treatment at a stable dose for 1 week.
Includes all randomized participants who abruptly discontinued placebo either at the end of the study or after early withdrawal from the study and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation (DC) Phase visit.
|
Placebo + SSRI (Non-randomized) - DC Phase
n=659 participants at risk
No study drug was administered. Participants were to maintain their selective serotonin reuptake inhibitor (SSRI) treatment at a stable dose for 1 week.
Includes all non-randomized participants who abruptly discontinued placebo either at the end of the study or after early withdrawal from the study and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation (DC) Phase visit.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
0.14%
2/1476 • Number of events 2
|
0.00%
0/232
|
0.00%
0/223
|
0.00%
0/231
|
0.00%
0/699
|
4.0%
1/25 • Number of events 1
|
0.00%
0/212
|
0.00%
0/213
|
0.00%
0/220
|
0.00%
0/659
|
|
General disorders
Inflammation
|
0.00%
0/1476
|
0.43%
1/232 • Number of events 1
|
0.00%
0/223
|
0.00%
0/231
|
0.00%
0/699
|
0.00%
0/25
|
0.00%
0/212
|
0.00%
0/213
|
0.00%
0/220
|
0.00%
0/659
|
|
Infections and infestations
Appendicitis
|
0.00%
0/1476
|
0.43%
1/232 • Number of events 1
|
0.00%
0/223
|
0.00%
0/231
|
0.00%
0/699
|
0.00%
0/25
|
0.00%
0/212
|
0.00%
0/213
|
0.00%
0/220
|
0.00%
0/659
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/1476
|
0.00%
0/232
|
0.00%
0/223
|
0.00%
0/231
|
0.14%
1/699 • Number of events 1
|
0.00%
0/25
|
0.00%
0/212
|
0.00%
0/213
|
0.00%
0/220
|
0.00%
0/659
|
|
Infections and infestations
Mastitis
|
0.00%
0/1476
|
0.00%
0/232
|
0.00%
0/223
|
0.00%
0/231
|
0.14%
1/699 • Number of events 1
|
0.00%
0/25
|
0.00%
0/212
|
0.00%
0/213
|
0.00%
0/220
|
0.15%
1/659 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
0.00%
0/1476
|
0.00%
0/232
|
0.00%
0/223
|
0.00%
0/231
|
0.14%
1/699 • Number of events 1
|
0.00%
0/25
|
0.00%
0/212
|
0.00%
0/213
|
0.00%
0/220
|
0.15%
1/659 • Number of events 1
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
0.00%
0/1476
|
0.00%
0/232
|
0.00%
0/223
|
0.00%
0/231
|
0.14%
1/699 • Number of events 1
|
0.00%
0/25
|
0.00%
0/212
|
0.00%
0/213
|
0.00%
0/220
|
0.00%
0/659
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.07%
1/1476 • Number of events 1
|
0.00%
0/232
|
0.00%
0/223
|
0.43%
1/231 • Number of events 1
|
0.00%
0/699
|
0.00%
0/25
|
0.00%
0/212
|
0.00%
0/213
|
0.45%
1/220 • Number of events 1
|
0.00%
0/659
|
|
Nervous system disorders
Syncope
|
0.00%
0/1476
|
0.00%
0/232
|
0.00%
0/223
|
0.00%
0/231
|
0.00%
0/699
|
0.00%
0/25
|
0.00%
0/212
|
0.47%
1/213 • Number of events 1
|
0.00%
0/220
|
0.00%
0/659
|
|
Psychiatric disorders
Mania
|
0.07%
1/1476 • Number of events 1
|
0.00%
0/232
|
0.00%
0/223
|
0.00%
0/231
|
0.00%
0/699
|
4.0%
1/25 • Number of events 1
|
0.00%
0/212
|
0.00%
0/213
|
0.00%
0/220
|
0.00%
0/659
|
|
Psychiatric disorders
Suicidal ideation
|
0.14%
2/1476 • Number of events 2
|
0.00%
0/232
|
0.00%
0/223
|
0.00%
0/231
|
0.00%
0/699
|
4.0%
1/25 • Number of events 1
|
0.00%
0/212
|
0.00%
0/213
|
0.00%
0/220
|
0.00%
0/659
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/1476
|
0.00%
0/232
|
0.00%
0/223
|
0.00%
0/231
|
0.14%
1/699 • Number of events 1
|
0.00%
0/25
|
0.00%
0/212
|
0.00%
0/213
|
0.00%
0/220
|
0.00%
0/659
|
|
Reproductive system and breast disorders
Cervical dysplasia
|
0.10%
1/979 • Number of events 1
|
0.00%
0/149
|
0.66%
1/152 • Number of events 1
|
0.00%
0/156
|
0.00%
0/464
|
0.00%
0/16
|
0.00%
0/133
|
0.68%
1/148 • Number of events 1
|
0.00%
0/145
|
0.00%
0/441
|
|
Reproductive system and breast disorders
Fibrocystic breast disease
|
0.00%
0/1476
|
0.00%
0/232
|
0.00%
0/223
|
0.00%
0/231
|
0.14%
1/699 • Number of events 1
|
0.00%
0/25
|
0.00%
0/212
|
0.00%
0/213
|
0.00%
0/220
|
0.15%
1/659 • Number of events 1
|
|
Reproductive system and breast disorders
Metrorrhagia
|
0.00%
0/979
|
0.00%
0/149
|
0.00%
0/152
|
0.64%
1/156 • Number of events 1
|
0.00%
0/464
|
0.00%
0/16
|
0.00%
0/133
|
0.00%
0/148
|
0.00%
0/145
|
0.00%
0/441
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/1476
|
0.00%
0/232
|
0.00%
0/223
|
0.00%
0/231
|
0.14%
1/699 • Number of events 1
|
0.00%
0/25
|
0.00%
0/212
|
0.00%
0/213
|
0.00%
0/220
|
0.00%
0/659
|
Other adverse events
| Measure |
Placebo + SSRI (Pre-randomized) - CF Phase
n=1476 participants at risk
Placebo: administered orally, once daily for 3 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Includes all enrolled who did not discontinue for the reason 'Lost to Follow-up' at the first post-baseline visit during the Confirmation (CF) Phase.
|
12 or 18 mg LY2216684 + SSRI (Randomized) - AT Phase
n=232 participants at risk
LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Includes randomized participants who did not discontinue for the reason 'Lost to Follow-up' at the first post-randomization visit during the Adjunctive Treatment (AT) Phase.
|
6 mg LY2216684 + SSRI (Randomized) - AT Phase
n=223 participants at risk
LY2216684: fixed dose of 6 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Includes randomized participants who did not discontinue for the reason 'Lost to Follow-up' at the first post-randomization visit during the Adjunctive Treatment (AT) Phase.
|
Placebo + SSRI (Randomized) - AT Phase
n=231 participants at risk
Placebo: administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Includes randomized participants who did not discontinue for the reason 'Lost to Follow-up' at the first post-randomization visit during the Adjunctive Treatment (AT) Phase.
|
Placebo + SSRI (Non-randomized) - AT Phase
n=699 participants at risk
Placebo: administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)
Includes all non-randomized participants who did not discontinue for the reason 'Lost to Follow-up' at the first post-randomization visit during the Adjunctive Treatment (AT) Phase.
|
Placebo + SSRI (Pre-randomized) - DC Phase
n=25 participants at risk
No study drug was administered. Participants were to maintain their selective serotonin reuptake inhibitor (SSRI) treatment at a stable dose for 1 week.
Includes all enrolled participants who abruptly discontinued placebo after early withdrawal during the Confirmation (CF) Phase and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation (DC) Phase visit.
|
12 or 18 mg LY2216684 + SSRI (Randomized) - DC Phase
n=212 participants at risk
No study drug was administered. Participants were to maintain their selective serotonin reuptake inhibitor (SSRI) treatment at a stable dose for 1 week.
Includes all randomized participants who abruptly discontinued LY2216684 either at the end of the study or after early withdrawal from the study and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation (DC) Phase visit.
|
6 mg LY2216684 + SSRI (Randomized) - DC Phase
n=213 participants at risk
No study drug was administered. Participants were to maintain their selective serotonin reuptake inhibitor (SSRI) treatment at a stable dose for 1 week.
Includes all randomized participants who abruptly discontinued LY2216684 either at the end of the study or after early withdrawal from the study and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation (DC) Phase visit.
|
Placebo + SSRI (Randomized) - DC Phase
n=220 participants at risk
No study drug was administered. Participants were to maintain their selective serotonin reuptake inhibitor (SSRI) treatment at a stable dose for 1 week.
Includes all randomized participants who abruptly discontinued placebo either at the end of the study or after early withdrawal from the study and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation (DC) Phase visit.
|
Placebo + SSRI (Non-randomized) - DC Phase
n=659 participants at risk
No study drug was administered. Participants were to maintain their selective serotonin reuptake inhibitor (SSRI) treatment at a stable dose for 1 week.
Includes all non-randomized participants who abruptly discontinued placebo either at the end of the study or after early withdrawal from the study and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation (DC) Phase visit.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Cardiac disorders
Tachycardia
|
0.41%
6/1476 • Number of events 6
|
5.2%
12/232 • Number of events 12
|
2.2%
5/223 • Number of events 5
|
0.00%
0/231
|
0.29%
2/699 • Number of events 2
|
0.00%
0/25
|
0.00%
0/212
|
0.00%
0/213
|
0.00%
0/220
|
0.00%
0/659
|
|
Gastrointestinal disorders
Nausea
|
5.2%
77/1476 • Number of events 80
|
5.2%
12/232 • Number of events 17
|
5.4%
12/223 • Number of events 13
|
3.9%
9/231 • Number of events 10
|
3.6%
25/699 • Number of events 41
|
0.00%
0/25
|
0.94%
2/212 • Number of events 2
|
1.9%
4/213 • Number of events 4
|
0.91%
2/220 • Number of events 2
|
2.0%
13/659 • Number of events 13
|
|
Infections and infestations
Nasopharyngitis
|
2.4%
35/1476 • Number of events 35
|
5.2%
12/232 • Number of events 12
|
3.1%
7/223 • Number of events 7
|
3.0%
7/231 • Number of events 7
|
3.9%
27/699 • Number of events 27
|
0.00%
0/25
|
0.47%
1/212 • Number of events 1
|
0.47%
1/213 • Number of events 1
|
0.91%
2/220 • Number of events 2
|
0.76%
5/659 • Number of events 5
|
|
Nervous system disorders
Headache
|
7.6%
112/1476 • Number of events 127
|
6.0%
14/232 • Number of events 15
|
6.7%
15/223 • Number of events 18
|
9.5%
22/231 • Number of events 33
|
8.7%
61/699 • Number of events 81
|
0.00%
0/25
|
6.1%
13/212 • Number of events 14
|
8.9%
19/213 • Number of events 19
|
6.4%
14/220 • Number of events 14
|
7.1%
47/659 • Number of events 54
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
2.3%
34/1476 • Number of events 35
|
7.8%
18/232 • Number of events 19
|
3.1%
7/223 • Number of events 8
|
1.7%
4/231 • Number of events 4
|
1.6%
11/699 • Number of events 11
|
0.00%
0/25
|
1.9%
4/212 • Number of events 4
|
0.00%
0/213
|
0.00%
0/220
|
1.1%
7/659 • Number of events 7
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60