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A Study for Participants With Major Depression

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00420004
Recruitment Status : Completed
First Posted : January 9, 2007
Results First Posted : April 27, 2018
Last Update Posted : April 27, 2018
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Drug: LY2216684
Drug: Placebo
Drug: Escitalopram
Enrollment 469
Recruitment Details  
Pre-assignment Details A total of 701 participants were included in a screening/washout period (from 3 to 30 days in duration) prior to group assignments; 232 participants discontinued during this period, and 469 participants were randomized. There was an 8-week Double-blind Phase followed by a 1-week Discontinuation Phase after abrupt discontinuation of treatment.
Arm/Group Title LY2216684 Placebo Escitalopram
Hide Arm/Group Description LY2216684: flexible dose of 3, 6, 9, or 12 milligrams (mg), tablets, administered orally, once daily for 8 weeks Placebo: tablet and capsule equivalents to LY2216684 and escitalopram, respectively, administered orally, once daily for 8 weeks Escitalopram: flexible dose of 10 or 20 mg, capsules, administered orally, once daily for 8 weeks
Period Title: Overall Study
Started 269 138 62
Received at Least 1 Dose of Study Drug 249 [1] 122 [1] 54 [1]
Completed 140 67 30
Not Completed 129 71 32
Reason Not Completed
Adverse Event             4             1             1
Lack of Efficacy             5             4             1
Lost to Follow-up             31             12             10
Entry Criteria Not Met             0             1             0
Physician Decision             14             4             2
Protocol Violation             5             4             3
Withdrawal by Subject             67             42             14
Sponsor Decision             3             3             1
[1]
Participants who received >=1 dose of study drug and had baseline and post-baseline data available
Arm/Group Title LY2216684 Placebo Escitalopram Total
Hide Arm/Group Description LY2216684: flexible dose of 3, 6, 9, or 12 milligrams (mg), tablets, administered orally, once daily for 8 weeks Placebo: tablet and capsule equivalents to LY2216684 and escitalopram, respectively, administered orally, once daily for 8 weeks Escitalopram: flexible dose of 10 or 20 mg, capsules, administered orally, once daily for 8 weeks Total of all reporting groups
Overall Number of Baseline Participants 269 138 62 469
Hide Baseline Analysis Population Description
All randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 269 participants 138 participants 62 participants 469 participants
36.64  (10.21) 37.54  (10.97) 34.32  (9.66) 36.60  (10.40)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 269 participants 138 participants 62 participants 469 participants
Female 130 65 22 217
Male 139 73 40 252
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 269 participants 138 participants 62 participants 469 participants
Caucasian 30 21 8 59
African 6 5 0 11
Hispanic 23 7 4 34
Native American 1 0 0 1
West Asian (Indian subcontinent) 209 105 50 364
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 269 participants 138 participants 62 participants 469 participants
United States 39 23 8 70
Romania 7 4 1 12
India 208 105 50 363
Mexico 15 6 3 24
1.Primary Outcome
Title Change From Baseline to Week 8 in the 17-item Hamilton Depression Rating Scale (HAMD-17) Total Score
Hide Description The HAMD-17 is a 17-item assessment used to assess the severity of depression and its improvement during the course of therapy. Each item was evaluated and scored using either a 5-point scale of 0 (not present/absent) to 4 (very severe) or a 3-point scale of 0 (not present/absent) to 2 (marked). Higher scores indicate greater symptom severity. The total score was the sum of the scores from HAMD-17 Items 1 through 17 and ranged from 0 (not at all depressed) to 52 (severely depressed). 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.
Time Frame Baseline, Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of double-blind study drug and who had a baseline and at least one post-baseline HAMD-17 value.
Arm/Group Title LY2216684 Placebo Escitalopram
Hide Arm/Group Description:
LY2216684: flexible dose of 3, 6, 9, or 12 milligrams (mg), tablets, administered orally, once daily for 8 weeks
Placebo: tablet and capsule equivalents to LY2216684 and escitalopram, respectively, administered orally, once daily for 8 weeks
Escitalopram: flexible dose of 10 or 20 mg, capsules, administered orally, once daily for 8 weeks
Overall Number of Participants Analyzed 248 122 54
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-13.2  (0.53) -12.6  (0.74) -14.7  (1.14)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LY2216684, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.494
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline to Week 8 in Maier-Philipp Subscale of the 17-item Hamilton Depression Rating Scale (HAMD-17)
Hide Description The HAMD-17 is a 17-item assessment used to assess the severity of depression and its improvement during the course of therapy. Each item was evaluated and scored using either a 5-point scale of 0 (not present/absent) to 4 (very severe) or a 3-point scale of 0 (not present/absent) to 2 (marked). Higher scores indicate greater symptom severity. The Maier-Phillip subscale of the HAMD-17 represents the 6 "core" symptoms of depression (items: 1=depressed mood, 2=feelings of guilt, 7=work and activities, 8=retardation, 9=agitation, 10=anxiety/psychic). The subscale scores range from 0 (normal) to 24 (severe). 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.
Time Frame Baseline, Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of double-blind study drug and who had a baseline and at least one post-baseline Maier-Philipp subscale value.
Arm/Group Title LY2216684 Placebo Escitalopram
Hide Arm/Group Description:
LY2216684: flexible dose of 3, 6, 9, or 12 milligrams (mg), tablets, administered orally, once daily for 8 weeks
Placebo: tablet and capsule equivalents to LY2216684 and escitalopram, respectively, administered orally, once daily for 8 weeks
Escitalopram: flexible dose of 10 or 20 mg, capsules, administered orally, once daily for 8 weeks
Overall Number of Participants Analyzed 248 122 54
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-6.7  (0.26) -6.2  (0.36) -7.6  (0.55)
3.Secondary Outcome
Title Response and Remission Rates
Hide Description A participant meets response criteria if there is at least a 50% reduction in the 17-item Hamilton Depression Rating Scale (HAMD-17) total score from baseline to the last observation carried forward (LOCF) endpoint visit. A participant meets remission criteria if the HAMD-17 total score is less than or equal to 7 at the LOCF endpoint visit. The percent of participants meeting criteria is summarized. HAMD-17 is a 17-item assessment used to assess the severity of depression and its improvement during the course of therapy. Each item was evaluated and scored using either a 5-point scale of 0 (not present/absent) to 4 (very severe) or a 3-point scale of 0 (not present/absent) to 2 (marked). Higher scores indicate greater symptom severity. The total score was the sum of the scores from HAMD-17 Items 1 through 17 and ranged from 0 (not at all depressed) to 52 (severely depressed).
Time Frame Baseline, up to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of double-blind study drug and who had a baseline and at least one post-baseline HAMD-17 total score value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 Placebo Escitalopram
Hide Arm/Group Description:
LY2216684: flexible dose of 3, 6, 9, or 12 milligrams (mg), tablets, administered orally, once daily for 8 weeks
Placebo: tablet and capsule equivalents to LY2216684 and escitalopram, respectively, administered orally, once daily for 8 weeks
Escitalopram: flexible dose of 10 or 20 mg, capsules, administered orally, once daily for 8 weeks
Overall Number of Participants Analyzed 248 122 54
Measure Type: Number
Unit of Measure: percentage of participants
Response 54.0 48.4 53.7
Remission 38.7 31.1 42.6
4.Secondary Outcome
Title Clinical Global Impression of Improvement Score at Week 8
Hide Description The Clinical Global Impression of Improvement (CGI-I) scale measures the clinician's perception of participant improvement at the time of assessment compared with the start of treatment. Scores range from 1 (very much improved) to 7 (very much worse). Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, and treatment-by-visit.
Time Frame Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of double-blind study drug and who had a baseline and at least one post-baseline CGI-I value.
Arm/Group Title LY2216684 Placebo Escitalopram
Hide Arm/Group Description:
LY2216684: flexible dose of 3, 6, 9, or 12 milligrams (mg), tablets, administered orally, once daily for 8 weeks
Placebo: tablet and capsule equivalents to LY2216684 and escitalopram, respectively, administered orally, once daily for 8 weeks
Escitalopram: flexible dose of 10 or 20 mg, capsules, administered orally, once daily for 8 weeks
Overall Number of Participants Analyzed 247 122 53
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
2.2  (0.09) 2.3  (0.12) 2.0  (0.19)
5.Secondary Outcome
Title Change From Baseline in Hamilton Anxiety Rating Scale (HAMA) Total Score up to Week 8 Endpoint
Hide Description The HAMA is a 14-item assessment used to assess the severity of anxiety. The investigator talked to the participant about the symptoms he or she experienced during the previous week. Each item was scored using a 5-point scale (0=not present to 4=very severe). The total score of HAMA ranged from 0 (normal) to 56 (severe). Least Squares (LS) means were adjusted for treatment, investigator, and baseline score.
Time Frame Baseline, up to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of double-blind study drug and who had a baseline and at least one post-baseline HAMA value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 Placebo Escitalopram
Hide Arm/Group Description:
LY2216684: flexible dose of 3, 6, 9, or 12 milligrams (mg), tablets, administered orally, once daily for 8 weeks
Placebo: tablet and capsule equivalents to LY2216684 and escitalopram, respectively, administered orally, once daily for 8 weeks
Escitalopram: flexible dose of 10 or 20 mg, capsules, administered orally, once daily for 8 weeks
Overall Number of Participants Analyzed 212 106 44
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-9.7  (0.62) -9.6  (0.82) -11.6  (1.19)
6.Secondary Outcome
Title Change From Baseline on the 36-item Short-Form (SF-36) Health Status Survey Mental and Physical Components up to Week 8 Endpoint
Hide Description The SF-36 Health Status Survey is a generic, health-related scale assessing a participant’s quality of life on 8 domains: general health (GH), physical functioning (PF), role-physical, role-emotional, social functioning, bodily pain, vitality, and mental health. Each domain is scored by summing the individual items (GH [range: 5-25]; PF [range: 10-30]; role-physical [range: 4-8]; role-emotional [range: 3-6]; social functioning [range: 2-10]; bodily pain [range: 2-11]; vitality [range: 4-24]; mental health [range: 5-30]) and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning. Two summary scores (mental component and physical component scores) were constructed based on the 8 SF-36 domains. Mental component summary and physical component summary scores range from 0 to 100 (higher scores indicate better health status).
Time Frame Baseline, up to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of double-blind study drug and who had a baseline and at least one post-baseline SF-36 Health Status Survey value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 Placebo Escitalopram
Hide Arm/Group Description:
LY2216684: flexible dose of 3, 6, 9, or 12 milligrams (mg), tablets, administered orally, once daily for 8 weeks
Placebo: tablet and capsule equivalents to LY2216684 and escitalopram, respectively, administered orally, once daily for 8 weeks
Escitalopram: flexible dose of 10 or 20 mg, capsules, administered orally, once daily for 8 weeks
Overall Number of Participants Analyzed 192 99 41
Mean (Standard Deviation)
Unit of Measure: units on a scale
Mental Component Summary 13.4  (13.1) 12.6  (13.9) 12.4  (12.4)
Physical Component Summary 4.17  (9.00) 2.37  (8.26) 2.74  (7.65)
7.Secondary Outcome
Title Change From Baseline in Quick Inventory of Depressive Symptomatology Total Score up to Week 8 Endpoint
Time Frame Baseline, up to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of double-blind study drug and who had a baseline and at least one post-baseline Quick Inventory of Depressive Symptomatology value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 Placebo Escitalopram
Hide Arm/Group Description:
LY2216684: flexible dose of 3, 6, 9, or 12 milligrams (mg), tablets, administered orally, once daily for 8 weeks
Placebo: tablet and capsule equivalents to LY2216684 and escitalopram, respectively, administered orally, once daily for 8 weeks
Escitalopram: flexible dose of 10 or 20 mg, capsules, administered orally, once daily for 8 weeks
Overall Number of Participants Analyzed 198 103 42
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-10.2  (0.54) -8.3  (0.71) -11.6  (1.04)
8.Secondary Outcome
Title Change From Baseline in Beck Scale for Suicide Ideation up to Week 8 Endpoint
Hide Description Beck Scale for Suicide Ideation (BSI) is a 21-item participant-completed questionnaire designed to assess severity of suicidal ideation in adults and adolescents. The BSI total score is calculated as the sum of the responses (rated from 0 to 2 in terms of severity) to the first 19 items of the BSI scale. The BSI total score ranges from 0 to 38, with a higher score indicating a higher degree of suicide ideation.
Time Frame Baseline, up to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of double-blind study drug and who had a baseline and at least one post-baseline BSI value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 Placebo Escitalopram
Hide Arm/Group Description:
LY2216684: flexible dose of 3, 6, 9, or 12 milligrams (mg), tablets, administered orally, once daily for 8 weeks
Placebo: tablet and capsule equivalents to LY2216684 and escitalopram, respectively, administered orally, once daily for 8 weeks
Escitalopram: flexible dose of 10 or 20 mg, capsules, administered orally, once daily for 8 weeks
Overall Number of Participants Analyzed 245 122 51
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.90  (3.39) -0.54  (2.14) -0.78  (2.16)
9.Secondary Outcome
Title Change From Baseline in Modified Overt Aggression (OAS-M) Scale up to Week 8 Endpoint
Hide Description OAS-M is a clinician-administered semistructured interview designed to assess various manifestations of aggressive behavior. Final scores are rated on 3 scales: Aggression (Agg), Irritability (Irrt), Suicidality (Suic). Agg scale has 4 subscales: Verbal Assault (Aslt), Aslt Against Objects, Aslt Against Others, Aslt Against Self; each item is scored 0-5, multiplied by the frequency of the behavior, then summed together. Agg total score is the weighted sum of the subscale scores (weights: 1=Verbal Aslt, 2=Aslt Against Objects, 3=Aslt Against Others, 4=Aslt Against Self). The Irrt scale has 2 subscales: Global Irrt, Subjective Irrt. Suic scale has 3 subscales: Suicidal Tendencies, Intent of Attempt, Lethality of Attempt. The 2 Irrt and 3 Suic subscales are rated on 6 or 7 point scales from 0=none/not at all to 6/7=very extreme. The total score ranges from 0-10 for the Irrt scale and 0-16 on the Suic scale. Least Squares means were adjusted for treatment, investigator, and baseline s
Time Frame Baseline, up to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of double-blind study drug and who had a baseline and at least one post-baseline OAS-M value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 Placebo Escitalopram
Hide Arm/Group Description:
LY2216684: flexible dose of 3, 6, 9, or 12 milligrams (mg), tablets, administered orally, once daily for 8 weeks
Placebo: tablet and capsule equivalents to LY2216684 and escitalopram, respectively, administered orally, once daily for 8 weeks
Escitalopram: flexible dose of 10 or 20 mg, capsules, administered orally, once daily for 8 weeks
Overall Number of Participants Analyzed 227 113 47
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Aggression total score -4.1  (0.52) -4.2  (0.71) -3.9  (1.06)
Irritability total score -1.0  (0.10) -0.9  (0.14) -1.0  (0.20)
Suicidality total score -0.2  (0.04) -0.2  (0.05) -0.2  (0.08)
10.Secondary Outcome
Title Change From Baseline in Arizona Sexual Experiences Scale up to Week 8 Endpoint
Hide Description The Arizona Sexual Experiences Scale (ASEX) is used to assess sexual functioning in both males and females. The ASEX total score for the male and female version is calculated as the sum of the responses (rated from 1 [extremely] to 6 [no/never]) to the 5 items of the ASEX scale. Total scores ranged from 5 to 30 with higher scores indicating greater sexual dysfunction.
Time Frame Baseline, up to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of double-blind study drug and who had a baseline and at least one post-baseline ASEX value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 Placebo Escitalopram
Hide Arm/Group Description:
LY2216684: flexible dose of 3, 6, 9, or 12 milligrams (mg), tablets, administered orally, once daily for 8 weeks
Placebo: tablet and capsule equivalents to LY2216684 and escitalopram, respectively, administered orally, once daily for 8 weeks
Escitalopram: flexible dose of 10 or 20 mg, capsules, administered orally, once daily for 8 weeks
Overall Number of Participants Analyzed 219 109 43
Mean (Standard Deviation)
Unit of Measure: units on a scale
-2.68  (6.65) -1.69  (6.35) -1.65  (7.43)
11.Secondary Outcome
Title Change From Baseline in Insomnia Severity Index up to Week 8 Endpoint
Hide Description The Insomnia Severity Index (ISI) is a brief self-report instrument measuring the participant's perception of his or her insomnia. The ISI score is calculated as the sum of the responses to the 7 items of the ISI scale. Each item is rated on a 0 to 4 scale and the total score ranges from 0 to 28 with a higher score suggesting more severe insomnia.
Time Frame Baseline, up to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of double-blind study drug and who had a baseline and at least one post-baseline ISI value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 Placebo Escitalopram
Hide Arm/Group Description:
LY2216684: flexible dose of 3, 6, 9, or 12 milligrams (mg), tablets, administered orally, once daily for 8 weeks
Placebo: tablet and capsule equivalents to LY2216684 and escitalopram, respectively, administered orally, once daily for 8 weeks
Escitalopram: flexible dose of 10 or 20 mg, capsules, administered orally, once daily for 8 weeks
Overall Number of Participants Analyzed 227 113 45
Mean (Standard Deviation)
Unit of Measure: units on a scale
-7.53  (7.57) -7.44  (7.73) -8.02  (7.72)
12.Secondary Outcome
Title Change From Baseline to Week 8 in Fatigue Severity Scale
Hide Description Fatigue Severity Scale (FSS) is a 9-item measure of fatigue severity. Each item is scored by the participant on a scale of 1 (“Disagree”) to 7 (“Agree”), with a higher score indicating a stronger agreement with the item statement regarding the participant’s fatigue symptoms. The FSS total score ranges from 1 to 7, and is obtained by averaging the responses to the 9 items. 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.
Time Frame Baseline, Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of double-blind study drug and who had a baseline and at least one post-baseline FSS value.
Arm/Group Title LY2216684 Placebo Escitalopram
Hide Arm/Group Description:
LY2216684: flexible dose of 3, 6, 9, or 12 milligrams (mg), tablets, administered orally, once daily for 8 weeks
Placebo: tablet and capsule equivalents to LY2216684 and escitalopram, respectively, administered orally, once daily for 8 weeks
Escitalopram: flexible dose of 10 or 20 mg, capsules, administered orally, once daily for 8 weeks
Overall Number of Participants Analyzed 225 109 47
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.0  (0.14) -1.8  (0.19) -2.2  (0.29)
13.Secondary Outcome
Title Pharmacokinetics: Predicted Maximal Concentration of LY2216684 at Steady State (Cmax,ss) at Week 8 Endpoint
Hide Description Predicted maximal LY2216684 plasma concentrations at steady state (Cmax,ss) are reported, using the dose at the last visit in the study for participants included in the primary efficacy analysis.
Time Frame Up to 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized to LY2216684 included in the primary efficacy analysis with a pharmacokinetic (PK) sample at the participants' final study visit.
Arm/Group Title LY2216684
Hide Arm/Group Description:
LY2216684: flexible dose of 3, 6, 9, or 12 milligrams (mg), tablets, administered orally, once daily for 8 weeks.
Overall Number of Participants Analyzed 193
Mean (Standard Deviation)
Unit of Measure: nanograms per milliliter (ng/mL)
3 mg dose Number Analyzed 31 participants
10.5  (2.0)
6 mg dose Number Analyzed 52 participants
22.6  (5.4)
9 mg dose Number Analyzed 44 participants
32  (6.4)
12 mg dose Number Analyzed 66 participants
40.6  (9.9)
14.Secondary Outcome
Title Number of Participants With at Least 1 Serious Adverse Event (Safety and Tolerability)
Hide Description The number of participants with at least one serious adverse event, regardless of causality is reported cumulatively through Week 8. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module.
Time Frame Baseline through Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title LY2216684 Placebo Escitalopram
Hide Arm/Group Description:
LY2216684: flexible dose of 3, 6, 9, or 12 milligrams (mg), tablets, administered orally, once daily for 8 weeks
Placebo: tablet and capsule equivalents to LY2216684 and escitalopram, respectively, administered orally, once daily for 8 weeks
Escitalopram: flexible dose of 10 or 20 mg, capsules, administered orally, once daily for 8 weeks
Overall Number of Participants Analyzed 269 138 62
Measure Type: Count of Participants
Unit of Measure: Participants
2 1 2
15.Secondary Outcome
Title Change From Baseline to Week 8 in the 21-item Hamilton Depression Rating Scale (HAM-21) Total Score
Hide Description The HAMD-21 is a 21-item assessment used to measure depression severity. Items were rated on a scale from 0 (symptoms not present) to a maximum of 2 to 4 (symptom extremely severe) for a total score ranging from 0 (not at all depressed) to 60 (severely depressed). 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.
Time Frame Baseline, Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of double-blind study drug and who had a baseline and at least one post-baseline HAMD-21 value.
Arm/Group Title LY2216684 Placebo Escitalopram
Hide Arm/Group Description:
LY2216684: flexible dose of 3, 6, 9, or 12 milligrams (mg), tablets, administered orally, once daily for 8 weeks
Placebo: tablet and capsule equivalents to LY2216684 and escitalopram, respectively, administered orally, once daily for 8 weeks
Escitalopram: flexible dose of 10 or 20 mg, capsules, administered orally, once daily for 8 weeks
Overall Number of Participants Analyzed 239 120 52
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-13.6  (0.57) -13.0  (0.79) -15.0  (1.24)
16.Secondary Outcome
Title Cognitive Assessment Battery: Change From Baseline in Word List Learning and Delayed Recall Test (WLDRT) up to Week 8 Endpoint
Hide Description The WLDRT is a test of visual learning and recall. Participants are shown a series of words (commonly used nouns) and asked to say each of the words aloud, then are asked to recall the words and the total number of correct words recalled is recorded (possible score ranged from 0 to 15 words). The process is repeated 3 times. The Word List Learning Test score is calculated as the average number of words recalled during the first 3 trials. After a 30-minute delay, participants are again asked to recall the words, and the total number of correct words remembered after the delay is recorded as the Delayed Recall Test score. The baseline value was the last non-missing value before the first randomized double-blind study drug administration. Least Squares (LS) means were adjusted for treatment, investigator, and baseline score.
Time Frame Baseline, up to week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of double-blind study drug and who have a baseline and at least one post-baseline WLDRT value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 Placebo Escitalopram
Hide Arm/Group Description:
LY2216684: flexible dose of 3, 6, 9, or 12 milligrams (mg), tablets, administered orally, once daily for 8 weeks
Placebo: tablet and capsule equivalents to LY2216684 and escitalopram, respectively, administered orally, once daily for 8 weeks
Escitalopram: flexible dose of 10 or 20 mg, capsules, administered orally, once daily for 8 weeks
Overall Number of Participants Analyzed 207 107 43
Least Squares Mean (Standard Error)
Unit of Measure: number of correct words
Word List Learning Test Number Analyzed 207 participants 107 participants 43 participants
0.5  (0.15) 0.3  (0.19) 0.3  (0.28)
Delayed Recall Test Number Analyzed 206 participants 107 participants 43 participants
0.4  (0.19) 0.2  (0.25) 0.0  (0.37)
17.Secondary Outcome
Title Cognitive Assessment Battery: Change From Baseline in Symbol Digit Substitution Test (SDST) up to Week 8 Endpoint
Hide Description The SDST is an attention-demanding psychomotor component based on the Digit Symbol Substitution Test from the Wechsler Adult Intelligence Scale. The participant is given a symbol/digit code in which each of the digits 1 through 9 is paired with a different symbol. Below the code, a series of symbols selected from those in the code are presented in an irregular order. The participant is instructed to write the number that is appropriate for each symbol in the space below each symbol and to complete as many correct digits as possible within a 90-second test period. For this test, the number of attempts and number of correct digits is collected. The percentage of correct digits is presented based on the number of correct digits divided by the number of attempts, multiplied by 100 (score ranged from 0 to 100% correct). Least squares (LS) means were adjusted for treatment, investigator, and baseline score.
Time Frame Baseline, up to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of double-blind study drug and who had a baseline and at least one post-baseline SDST value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 Placebo Escitalopram
Hide Arm/Group Description:
LY2216684: flexible dose of 3, 6, 9, or 12 milligrams (mg), tablets, administered orally, once daily for 8 weeks
Placebo: tablet and capsule equivalents to LY2216684 and escitalopram, respectively, administered orally, once daily for 8 weeks
Escitalopram: flexible dose of 10 or 20 mg, capsules, administered orally, once daily for 8 weeks
Overall Number of Participants Analyzed 182 94 39
Least Squares Mean (Standard Error)
Unit of Measure: percentage of correct digits
3.2  (1.12) 2.5  (1.42) 2.2  (2.10)
18.Secondary Outcome
Title Cognitive Assessment Battery: Change From Baseline in Two Digit Cancellation Test up to Week 8 Endpoint
Hide Description The Two Digit Cancellation Test (2DCT) is a clinical adaptation of the visual search tasks that have been used to investigate cognitive processes involved in attention and visual information processing. For this test, the participant is presented with a piece of paper containing rows of digits. At the top of the page are two target digits. The participant is instructed to examine each row of digits working from top to bottom and left to right crossing off each number that matches either of the two numbers at the top of the page. The number of targets hit, number of errors, and number of times the participant had to be reminded of the task are recorded for the 45-second test. The 2DCT composite cognitive score is calculated as the number of targets hit – number of errors – number of reminders. 2DCT score ranges 0-40 with higher score indicating better cognition. Least squares (LS) means were adjusted for treatment, investigator, and baseline score.
Time Frame Baseline, up to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of double-blind study drug and who had a baseline and at least one post-baseline 2DCT value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 Placebo Escitalopram
Hide Arm/Group Description:
LY2216684: flexible dose of 3, 6, 9, or 12 milligrams (mg), tablets, administered orally, once daily for 8 weeks
Placebo: tablet and capsule equivalents to LY2216684 and escitalopram, respectively, administered orally, once daily for 8 weeks
Escitalopram: flexible dose of 10 or 20 mg, capsules, administered orally, once daily for 8 weeks
Overall Number of Participants Analyzed 194 99 49
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.8  (0.62) 1.2  (0.83) 1.0  (1.26)
19.Secondary Outcome
Title Cognitive Assessment Battery: Change From Baseline in Trail Making A up to Week 8 Endpoint
Hide Description Trail Making A is a neurocognitive test associated with general brain function. While being timed, the participant is instructed to connect 25 randomly placed circled numbers on a page in numerical sequence without lifting their pencil. If a participant makes a mistake, the mistake is pointed out and the participant must start again from the last correct circle. The total time to complete the task (up to 300 seconds, with a lower value indicating better brain function) is recorded. Least squares (LS) means were adjusted for treatment, investigator, and baseline score.
Time Frame Baseline, up to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of double-blind study drug and who had a baseline and at least one post-baseline Trail Making A value. Last observation carried forward (LOCF) methodology was used.
Arm/Group Title LY2216684 Placebo Escitalopram
Hide Arm/Group Description:
LY2216684: flexible dose of 3, 6, 9, or 12 milligrams (mg), tablets, administered orally, once daily for 8 weeks
Placebo: tablet and capsule equivalents to LY2216684 and escitalopram, respectively, administered orally, once daily for 8 weeks
Escitalopram: flexible dose of 10 or 20 mg, capsules, administered orally, once daily for 8 weeks
Overall Number of Participants Analyzed 203 104 43
Least Squares Mean (Standard Error)
Unit of Measure: seconds
-9.9  (2.97) -11.1  (3.85) -5.6  (5.68)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title LY2216684 Double Blind Phase Placebo Double Blind Phase Escitalopram Double Blind Phase LY2216684 Discontinuation Phase Placebo Discontinuation Phase Escitalopram Discontinuation Phase
Hide Arm/Group Description LY2216684: 3, 6, 9, or 12 milligrams (mg) tablets, administered orally with flexible dosing, once daily for 8 weeks Placebo: tablet and capsule equivalents to LY2216684 and escitalopram, respectively, administered orally once daily for 8 weeks Escitalopram: 10 or 20 mg capsules, administered orally with flexible dosing, once daily for 8 weeks Included all randomized participants who discontinued LY2216684 treatment Included all randomized participants who discontinued placebo Included all randomized participants who discontinued escitalopram treatment
All-Cause Mortality
LY2216684 Double Blind Phase Placebo Double Blind Phase Escitalopram Double Blind Phase LY2216684 Discontinuation Phase Placebo Discontinuation Phase Escitalopram Discontinuation Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
LY2216684 Double Blind Phase Placebo Double Blind Phase Escitalopram Double Blind Phase LY2216684 Discontinuation Phase Placebo Discontinuation Phase Escitalopram Discontinuation Phase
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/269 (0.74%)      1/138 (0.72%)      2/62 (3.23%)      0/269 (0.00%)      1/138 (0.72%)      0/62 (0.00%)    
Blood and lymphatic system disorders             
Anaemia  1  1/269 (0.37%)  1 0/138 (0.00%)  0 0/62 (0.00%)  0 0/269 (0.00%)  0 0/138 (0.00%)  0 0/62 (0.00%)  0
Infections and infestations             
Gastroenteritis  1  0/269 (0.00%)  0 1/138 (0.72%)  1 1/62 (1.61%)  1 0/269 (0.00%)  0 0/138 (0.00%)  0 0/62 (0.00%)  0
Malaria  1  0/269 (0.00%)  0 0/138 (0.00%)  0 1/62 (1.61%)  1 0/269 (0.00%)  0 0/138 (0.00%)  0 0/62 (0.00%)  0
Injury, poisoning and procedural complications             
Near drowning  1  0/269 (0.00%)  0 0/138 (0.00%)  0 0/62 (0.00%)  0 0/269 (0.00%)  0 1/138 (0.72%)  1 0/62 (0.00%)  0
Psychiatric disorders             
Depression  1  1/269 (0.37%)  1 0/138 (0.00%)  0 0/62 (0.00%)  0 0/269 (0.00%)  0 0/138 (0.00%)  0 0/62 (0.00%)  0
Suicide attempt  1  0/269 (0.00%)  0 0/138 (0.00%)  0 1/62 (1.61%)  1 0/269 (0.00%)  0 0/138 (0.00%)  0 0/62 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
LY2216684 Double Blind Phase Placebo Double Blind Phase Escitalopram Double Blind Phase LY2216684 Discontinuation Phase Placebo Discontinuation Phase Escitalopram Discontinuation Phase
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   70/269 (26.02%)      26/138 (18.84%)      19/62 (30.65%)      3/269 (1.12%)      2/138 (1.45%)      2/62 (3.23%)    
Gastrointestinal disorders             
Constipation  1  18/269 (6.69%)  19 7/138 (5.07%)  7 1/62 (1.61%)  1 0/269 (0.00%)  0 0/138 (0.00%)  0 0/62 (0.00%)  0
Dry mouth  1  17/269 (6.32%)  17 6/138 (4.35%)  6 4/62 (6.45%)  4 0/269 (0.00%)  0 1/138 (0.72%)  1 0/62 (0.00%)  0
Nausea  1  24/269 (8.92%)  27 5/138 (3.62%)  5 7/62 (11.29%)  7 0/269 (0.00%)  0 0/138 (0.00%)  0 1/62 (1.61%)  1
Nervous system disorders             
Headache  1  26/269 (9.67%)  34 9/138 (6.52%)  9 7/62 (11.29%)  7 2/269 (0.74%)  2 1/138 (0.72%)  1 1/62 (1.61%)  1
Psychiatric disorders             
Insomnia  1  14/269 (5.20%)  15 4/138 (2.90%)  4 2/62 (3.23%)  2 2/269 (0.74%)  2 0/138 (0.00%)  0 0/62 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00420004     History of Changes
Other Study ID Numbers: 11174
H9P-MC-LNBD ( Other Identifier: Eli Lilly and Company )
First Submitted: January 5, 2007
First Posted: January 9, 2007
Results First Submitted: February 17, 2018
Results First Posted: April 27, 2018
Last Update Posted: April 27, 2018