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A Study for Participants With Major Depression

Primary Purpose

Major Depressive Disorder

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
LY2216684
Placebo
Escitalopram
Sponsored by
Eli Lilly and Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Major Depressive Disorder

Eligibility Criteria

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

Inclusion Criteria:

  • Meet criteria for major depressive disorder (MDD) without psychotic features.
  • Have education level and a degree of understanding such that the participant can communicate with the site study personnel.
  • Judged to be reliable and agree to keep all appointments for clinic visits, tests, and procedures, including venipuncture, and examinations required by the protocol.

Exclusion Criteria:

  • Have had any additional, ongoing psychiatric condition other than major depression or dysthymia that was considered the primary diagnosis within 6 months of the first study visit.
  • Have a lifetime history of Bipolar I or II Disorder, psychotic disorder, or a factitious disorder.
  • Are judged to be at high risk for imminently harming themselves or others.
  • Have a serious medical illness, including any cardiovascular, hepatic, respiratory, hematologic, endocrinologic, neurologic disease, or clinically significant laboratory or electrocardiogram (ECG) abnormality. Clinically significant lab abnormalities are those which, in the judgment of the investigator, indicate a serious medical problem or require intervention.
  • Have any diagnosed medical condition which could be exacerbated by treatment with LY2216684, including hypertension, increased heart rate, arrhythmias, heart disease, narrow angle glaucoma, or urinary hesitancy.

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Active Comparator

Arm Label

LY2216684

Placebo

Escitalopram

Arm Description

LY2216684: flexible dose of 3, 6, 9, or 12 milligrams (mg), tablets, administered orally, once daily for 8 weeks. For the first week of treatment, participants received a starting dose of 3 mg/day. Then, based on tolerability, for the next 7 weeks, the dose could remain at 3 mg/day; it could be increased 3 mg at a time (scheduled visit) to a maximum dose of 12 mg/day; or it could be decreased 3 mg at any time (scheduled or unscheduled visits) to a minimum dose of 3 mg/day. All participants were required to take an equal number of tablets (2) and capsules (2) per day. Therefore, participants on 3 mg/day and 6 mg/day of LY2216684 also received 1 LY2216684-matching placebo tablet + 2 escitalopram-matching placebo capsules. Participants on 9 mg/day and 12 mg/day of LY2216684 also received 2 escitalopram-matching placebo capsules.

Placebo: tablet and capsule equivalents to LY2216684 and escitalopram, respectively, administered orally, once daily for 8 weeks.

Escitalopram: flexible dose of 10 or 20 milligram (mg), capsules, administered orally, once daily for 8 weeks. For the first week of treatment, participants received a starting dose of 10 mg/day. Then, based on tolerability, for the next 7 weeks, the dose could remain at 10 mg/day; it could be increased up to a maximum dose of 20 mg/day; or it could be decreased back to 10 mg/day. All participants were required to take an equal number of tablets (2) and capsules (2) per day. Therefore, participants on 10 mg/day of escitalopram also received 1 escitalopram-matching placebo capsule + 2 LY2216684-matching placebo tablets. Participants on 20 mg/day of escitalopram also received 2 LY2216684-matching placebo tablets.

Outcomes

Primary Outcome Measures

Change From Baseline to Week 8 in the 17-item Hamilton Depression Rating Scale (HAMD-17) Total Score
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.

Secondary Outcome Measures

Change From Baseline to Week 8 in Maier-Philipp Subscale of the 17-item Hamilton Depression Rating Scale (HAMD-17)
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.
Response and Remission Rates
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).
Clinical Global Impression of Improvement Score at Week 8
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.
Change From Baseline in Hamilton Anxiety Rating Scale (HAMA) Total Score up to Week 8 Endpoint
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.
Change From Baseline on the 36-item Short-Form (SF-36) Health Status Survey Mental and Physical Components up to Week 8 Endpoint
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).
Change From Baseline in Quick Inventory of Depressive Symptomatology Total Score up to Week 8 Endpoint
The Quick Inventory of Depressive Symptomatology is a 16-item participant-rated measure of depressive symptomatology. There were 4 possible answers per question that are specific to the question; each question (Q) was scored 0 (no problems) to 3 (increased symptoms). The total score was the sum of the highest number from Q1-4, number from Q5, highest number from Q6-9, total for Q10-14, and the highest number from Q15-16. The total score ranges from 0 to 27 with higher scores indicative of greater severity of depression. Least Squares (LS) means were adjusted for treatment, investigator, and baseline score.
Change From Baseline in Beck Scale for Suicide Ideation up to Week 8 Endpoint
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.
Change From Baseline in Modified Overt Aggression (OAS-M) Scale up to Week 8 Endpoint
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
Change From Baseline in Arizona Sexual Experiences Scale up to Week 8 Endpoint
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.
Change From Baseline in Insomnia Severity Index up to Week 8 Endpoint
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.
Change From Baseline to Week 8 in Fatigue Severity Scale
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.
Pharmacokinetics: Predicted Maximal Concentration of LY2216684 at Steady State (Cmax,ss) at Week 8 Endpoint
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.
Number of Participants With at Least 1 Serious Adverse Event (Safety and Tolerability)
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.
Change From Baseline to Week 8 in the 21-item Hamilton Depression Rating Scale (HAM-21) Total Score
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.
Cognitive Assessment Battery: Change From Baseline in Word List Learning and Delayed Recall Test (WLDRT) up to Week 8 Endpoint
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.
Cognitive Assessment Battery: Change From Baseline in Symbol Digit Substitution Test (SDST) up to Week 8 Endpoint
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.
Cognitive Assessment Battery: Change From Baseline in Two Digit Cancellation Test up to Week 8 Endpoint
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.
Cognitive Assessment Battery: Change From Baseline in Trail Making A up to Week 8 Endpoint
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.

Full Information

First Posted
January 5, 2007
Last Updated
March 26, 2018
Sponsor
Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT00420004
Brief Title
A Study for Participants With Major Depression
Official Title
A Study of the Effects of LY2216684, a Selective Norepinephrine Reuptake Inhibitor (NERI), in the Treatment of Major Depression
Study Type
Interventional

2. Study Status

Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
December 2006 (undefined)
Primary Completion Date
March 2008 (Actual)
Study Completion Date
March 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a study to assess the safety and effectiveness of LY2216684 compared to placebo in treating adults with major depressive disorder.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
469 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LY2216684
Arm Type
Experimental
Arm Description
LY2216684: flexible dose of 3, 6, 9, or 12 milligrams (mg), tablets, administered orally, once daily for 8 weeks. For the first week of treatment, participants received a starting dose of 3 mg/day. Then, based on tolerability, for the next 7 weeks, the dose could remain at 3 mg/day; it could be increased 3 mg at a time (scheduled visit) to a maximum dose of 12 mg/day; or it could be decreased 3 mg at any time (scheduled or unscheduled visits) to a minimum dose of 3 mg/day. All participants were required to take an equal number of tablets (2) and capsules (2) per day. Therefore, participants on 3 mg/day and 6 mg/day of LY2216684 also received 1 LY2216684-matching placebo tablet + 2 escitalopram-matching placebo capsules. Participants on 9 mg/day and 12 mg/day of LY2216684 also received 2 escitalopram-matching placebo capsules.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo: tablet and capsule equivalents to LY2216684 and escitalopram, respectively, administered orally, once daily for 8 weeks.
Arm Title
Escitalopram
Arm Type
Active Comparator
Arm Description
Escitalopram: flexible dose of 10 or 20 milligram (mg), capsules, administered orally, once daily for 8 weeks. For the first week of treatment, participants received a starting dose of 10 mg/day. Then, based on tolerability, for the next 7 weeks, the dose could remain at 10 mg/day; it could be increased up to a maximum dose of 20 mg/day; or it could be decreased back to 10 mg/day. All participants were required to take an equal number of tablets (2) and capsules (2) per day. Therefore, participants on 10 mg/day of escitalopram also received 1 escitalopram-matching placebo capsule + 2 LY2216684-matching placebo tablets. Participants on 20 mg/day of escitalopram also received 2 LY2216684-matching placebo tablets.
Intervention Type
Drug
Intervention Name(s)
LY2216684
Other Intervention Name(s)
Edivoxetine
Intervention Description
3-mg and 6-mg tablets
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Type
Drug
Intervention Name(s)
Escitalopram
Other Intervention Name(s)
Lexapro®, Cipralex®
Intervention Description
10-mg capsules
Primary Outcome Measure Information:
Title
Change From Baseline to Week 8 in the 17-item Hamilton Depression Rating Scale (HAMD-17) Total Score
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
Secondary Outcome Measure Information:
Title
Change From Baseline to Week 8 in Maier-Philipp Subscale of the 17-item Hamilton Depression Rating Scale (HAMD-17)
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
Title
Response and Remission Rates
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
Title
Clinical Global Impression of Improvement Score at Week 8
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
Title
Change From Baseline in Hamilton Anxiety Rating Scale (HAMA) Total Score up to Week 8 Endpoint
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
Title
Change From Baseline on the 36-item Short-Form (SF-36) Health Status Survey Mental and Physical Components up to Week 8 Endpoint
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
Title
Change From Baseline in Quick Inventory of Depressive Symptomatology Total Score up to Week 8 Endpoint
Description
The Quick Inventory of Depressive Symptomatology is a 16-item participant-rated measure of depressive symptomatology. There were 4 possible answers per question that are specific to the question; each question (Q) was scored 0 (no problems) to 3 (increased symptoms). The total score was the sum of the highest number from Q1-4, number from Q5, highest number from Q6-9, total for Q10-14, and the highest number from Q15-16. The total score ranges from 0 to 27 with higher scores indicative of greater severity of depression. Least Squares (LS) means were adjusted for treatment, investigator, and baseline score.
Time Frame
Baseline, up to Week 8
Title
Change From Baseline in Beck Scale for Suicide Ideation up to Week 8 Endpoint
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
Title
Change From Baseline in Modified Overt Aggression (OAS-M) Scale up to Week 8 Endpoint
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
Title
Change From Baseline in Arizona Sexual Experiences Scale up to Week 8 Endpoint
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
Title
Change From Baseline in Insomnia Severity Index up to Week 8 Endpoint
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
Title
Change From Baseline to Week 8 in Fatigue Severity Scale
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
Title
Pharmacokinetics: Predicted Maximal Concentration of LY2216684 at Steady State (Cmax,ss) at Week 8 Endpoint
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
Title
Number of Participants With at Least 1 Serious Adverse Event (Safety and Tolerability)
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
Title
Change From Baseline to Week 8 in the 21-item Hamilton Depression Rating Scale (HAM-21) Total Score
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
Title
Cognitive Assessment Battery: Change From Baseline in Word List Learning and Delayed Recall Test (WLDRT) up to Week 8 Endpoint
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
Title
Cognitive Assessment Battery: Change From Baseline in Symbol Digit Substitution Test (SDST) up to Week 8 Endpoint
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
Title
Cognitive Assessment Battery: Change From Baseline in Two Digit Cancellation Test up to Week 8 Endpoint
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
Title
Cognitive Assessment Battery: Change From Baseline in Trail Making A up to Week 8 Endpoint
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Meet criteria for major depressive disorder (MDD) without psychotic features. Have education level and a degree of understanding such that the participant can communicate with the site study personnel. Judged to be reliable and agree to keep all appointments for clinic visits, tests, and procedures, including venipuncture, and examinations required by the protocol. Exclusion Criteria: Have had any additional, ongoing psychiatric condition other than major depression or dysthymia that was considered the primary diagnosis within 6 months of the first study visit. Have a lifetime history of Bipolar I or II Disorder, psychotic disorder, or a factitious disorder. Are judged to be at high risk for imminently harming themselves or others. Have a serious medical illness, including any cardiovascular, hepatic, respiratory, hematologic, endocrinologic, neurologic disease, or clinically significant laboratory or electrocardiogram (ECG) abnormality. Clinically significant lab abnormalities are those which, in the judgment of the investigator, indicate a serious medical problem or require intervention. Have any diagnosed medical condition which could be exacerbated by treatment with LY2216684, including hypertension, increased heart rate, arrhythmias, heart disease, narrow angle glaucoma, or urinary hesitancy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Prairie Village
State/Province
Kansas
ZIP/Postal Code
66206
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Allentown
State/Province
Pennsylvania
ZIP/Postal Code
18104
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Media
State/Province
Pennsylvania
ZIP/Postal Code
19063
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Bucharest
ZIP/Postal Code
73120
Country
Romania
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Cluj-Napoca
Country
Romania
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Lasi
ZIP/Postal Code
6600
Country
Romania

12. IPD Sharing Statement

Learn more about this trial

A Study for Participants With Major Depression

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