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Clinical Trial Results:
A Randomized, Placebo-Controlled, Double-Blind Study of LY2216684 Fixed-Dose 12 milligrams (mg) and 18 mg Once Daily as Adjunctive Treatment for Patients with Major Depressive Disorder Who Are Partial Responders to Selective Serotonin Reuptake Inhibitor Treatment

Summary
EudraCT number	2010-021214-39
Trial protocol	LV
Global end of trial date	21 Oct 2013

Results information
Results version number	v1(current)
This version publication date	06 Mar 2018
First version publication date	06 Mar 2018
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

H9P-MC-LNBM

ISRCTN number

US NCT number

NCT01173601

WHO universal trial number (UTN)

Other trial identifiers

Tral Alias: 11316

Sponsor organisation name

Eli Lilly and Company

Sponsor organisation address

Lilly Corporate Center, Indianapolis, United States,

Public contact

Available Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company, 1 877‐CTLilly,

Scientific contact

Available Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company, 1 877‐285‐4559,

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

21 Oct 2013

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

21 Oct 2013

Was the trial ended prematurely?

Main objective of the trial

The primary purpose of this study is to assess whether at least 1 dose of LY2216684 (12 milligrams [mg] or 18 mg once daily) is superior to placebo once daily in the adjunctive treatment of participants with major depressive disorder (MDD) who were identified as partial responders to an adequate course of treatment with a selective serotonin reuptake inhibitor (SSRI) during an 8-week, double-blind, acute adjunctive treatment phase.

Protection of trial subjects

This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.

Background therapy

Selective Serotonin Reuptake Inhibitor (SSRI): Participants were treated with one of the following SSRIs that have been approved for MDD treatment within the participating country: escitalopram, citalopram, sertraline, fluoxetine, paroxetine, and fluvoxamine; and have been treated with their SSRI at least 6 weeks prior to Visit 2 with at least the last 4 consecutive weeks at a stable optimized dose prior to Visit 2. The SSRI prescribed, including dose, was maintained consistently with labeling guidelines within the participating country.

Evidence for comparator

Actual start date of recruitment

16 Dec 2010

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 594

Country: Number of subjects enrolled

Poland: 220

Country: Number of subjects enrolled

Ukraine: 134

Country: Number of subjects enrolled

Russian Federation: 36

Country: Number of subjects enrolled

South Africa: 77

Country: Number of subjects enrolled

Latvia: 85

Country: Number of subjects enrolled

Japan: 270

Worldwide total number of subjects

1416

EEA total number of subjects

305

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

1363

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

First 3 weeks was double-blind adjunctive placebo lead-in Confirmation Phase during which participants(pts) continued SSRI with adjunctive placebo. If randomization criteria were met, pts were randomized to receive LY2216684 12 mg, 18 mg, or placebo. If criteria were not met, pts continued on placebo and remained in the study to maintain the blind.

Period 1 title

Confirmation (CF) Phase, 3 weeks

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Placebo + SSRI (Pre-Randomized Participants)

Arm description

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo taken by mouth once daily for 11 weeks.

Number of subjects in period 1	Placebo + SSRI (Pre-Randomized Participants)
Started	1416
Entered Discontinuation Phase	21 ^[1]
Completed	1328
Not completed	88
Physician decision	3
Consent withdrawn by subject	25
Adverse event, non-fatal	23
Sponsor Decision	6
Lost to follow-up	7
Lack of efficacy	9
Protocol deviation	15

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants who discontinued the CF Phase had the option to enter the DC phase. Participants who completed the CF Phase entered the AT Phase.

Period 2 title

Adjunctive Treatment (AT) Phase, 8 weeks

Is this the baseline period?

Yes ^[2]

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

12 mg LY2216684 + SSRI (Randomized Participants)

Arm description

LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a SSRI

Arm type

Experimental

Investigational medicinal product name

LY2216684

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Double-blind Study of LY2216684 Fixed-dose 12 mg and 18 mg Once Daily as Adjunctive Treatment for Patients With Major Depressive Disorder Who Are Partial Responders to Selective Serotonin Reuptake Inhibitor Treatment.

18 mg LY2216684 + SSRI (Randomized Participants)

Arm description

LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI

Arm type

Experimental

Investigational medicinal product name

LY2216684

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI

Placebo + SSRI (Randomized Participants)

Arm description

Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo taken by mouth once daily for 11 weeks.

Placebo + SSRI (Non-Randomized Participants)

Arm description

Placebo: Administered orally, once daily for 8 weeks

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo taken by mouth once daily for 11 weeks.

Notes
[2] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
Justification: Period 1 is the confirmatory phase, baseline and analytical data is based on Period 2 (Adjunctive phase).

Number of subjects in period 2 ^[3]	12 mg LY2216684 + SSRI (Randomized Participants)	18 mg LY2216684 + SSRI (Randomized Participants)	Placebo + SSRI (Randomized Participants)	Placebo + SSRI (Non-Randomized Participants)
Started	231	230	240	627
Entered Taper Discontinuation Phase	100 ^[4]	107 ^[5]	0 ^[6]	0 ^[7]
Entered Abrupt Discontinuation Phase	100 ^[8]	108 ^[9]	221	586
Completed	196	197	210	559
Not completed	35	33	30	68
Physician decision	2	-	2	1
Consent withdrawn by subject	9	7	5	24
Adverse event, non-fatal	10	15	7	14
Sponsor Decision	-	-	2	6
Lost to follow-up	3	-	2	9
Lack of efficacy	10	6	8	9
Protocol deviation	1	5	4	5

Notes
[3] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: Participants who completed the AT Phase or discontinued early entered the taper DC phase or abrupt DC phase.
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants who completed the AT Phase or discontinued early entered the taper DC phase or abrupt DC phase.
[5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants who completed the AT Phase or discontinued early entered the taper DC (discontinuation) phase or abrupt DC phase.
[6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants who completed the AT Phase or discontinued early entered the taper DC phase or abrupt DC phase.
[7] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants who completed the AT Phase or discontinued early entered the taper DC phase or abrupt DC phase.
[8] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants who completed the AT Phase or discontinued early entered the taper DC phase or abrupt DC phase.
[9] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants who completed the AT Phase or discontinued early entered the taper DC phase or abrupt DC phase.

Baseline characteristics

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Reporting group title

12 mg LY2216684 + SSRI (Randomized Participants)

Reporting group description

LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a SSRI

Reporting group title

18 mg LY2216684 + SSRI (Randomized Participants)

Reporting group description

LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI

Reporting group title

Placebo + SSRI (Randomized Participants)

Reporting group description

Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI

Reporting group title

Placebo + SSRI (Non-Randomized Participants)

Reporting group description

Placebo: Administered orally, once daily for 8 weeks

Reporting group values	12 mg LY2216684 + SSRI (Randomized Participants)	18 mg LY2216684 + SSRI (Randomized Participants)	Placebo + SSRI (Randomized Participants)	Placebo + SSRI (Non-Randomized Participants)	Total
Number of subjects	231	230	240	627	1328
Age categorical
Units: Subjects
Age Continuous
Units: years
arithmetic mean (standard deviation)	44.95 ( 12.38 )	46.06 ( 12.82 )	44.38 ( 10.6 )	44.73 ( 11.89 )	-
Gender, Male/Female
Units:
Male	86	81	85	176	428
Female	145	149	155	451	900
Region of Enrollment
Units: Subjects
United States	73	76	74	318	541
Poland	46	52	51	63	212
Ukraine	33	29	29	36	127
Russian Federation	6	6	6	15	33
South Africa	10	9	10	44	73
Latvia	16	14	17	34	81
Japan	47	44	53	117	261
Race
Units: Subjects
American Indian or Alaska Native	0	0	0	2	2
Asian	47	45	56	121	269
Native Hawaiian or Other Pacific Islander	0	0	0	0	0
Black or African American	14	14	19	65	112
White	164	170	164	429	927
More than one race	5	1	0	9	15
Unknown or Not Reported	1	0	1	1	3
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	9	7	7	28	51
Not Hispanic or Latino	181	172	188	520	1061
Unknown or Not Reported	41	51	45	79	216

End points

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Reporting group title

Placebo + SSRI (Pre-Randomized Participants)

Reporting group description

Reporting group title

12 mg LY2216684 + SSRI (Randomized Participants)

Reporting group description

LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a SSRI

Reporting group title

18 mg LY2216684 + SSRI (Randomized Participants)

Reporting group description

LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI

Reporting group title

Placebo + SSRI (Randomized Participants)

Reporting group description

Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI

Reporting group title

Placebo + SSRI (Non-Randomized Participants)

Reporting group description

Placebo: Administered orally, once daily for 8 weeks

Subject analysis set title

12 mg LY2216684 + SSRI (Randomized Participants)

Subject analysis set type

Full analysis

Subject analysis set description

LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI)

Subject analysis set title

18 mg LY2216684 + SSRI (Randomized Participants)

Subject analysis set type

Full analysis

Subject analysis set description

LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI

Subject analysis set title

Placebo + SSRI (Randomized Participants)

Subject analysis set type

Full analysis

Subject analysis set description

Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI

Subject analysis set title

Placebo + SSRI (Non-Randomized Participants)

Subject analysis set type

Full analysis

Subject analysis set description

Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI

Subject analysis set title

LY2216684 + SSRI

Subject analysis set type

Full analysis

Subject analysis set description

LY2216684: fixed doses of 12 milligrams (mg) administered orally, once daily for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI) or 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI

Primary: Change from Randomization to Week 8 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score

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End point title

Change from Randomization to Week 8 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score ^[1]

End point description

The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS had a 10-item checklist. 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. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Primary

End point timeframe

Randomization, 8 weeks

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are being reported for all randomized participants per the protocol or Statistical Analysis Plan.

End point values	12 mg LY2216684 + SSRI (Randomized Participants)	18 mg LY2216684 + SSRI (Randomized Participants)	Placebo + SSRI (Randomized Participants)
Number of subjects analysed	230	230	240
Units: units on a scale
least squares mean (standard error)	-8.47 ( 0.52 )	-8.7 ( 0.53 )	-7.77 ( 0.51 )

Statistical Analysis 1

Comparison groups

12 mg LY2216684 + SSRI (Randomized Participants) v Placebo + SSRI (Randomized Participants)

Number of subjects included in analysis

470

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.338 ^[2]

Method

Mixed models analysis

Confidence interval

Notes
[2] - In order to test the primary outcome between each LY2216684 dose and placebo while controlling the overall Type I error at 0.05, the significance level was a priori partitioned equally between the 2 LY2216684 dose-placebo comparisons at 0.025.

Statistical Analysis 2

Comparison groups

18 mg LY2216684 + SSRI (Randomized Participants) v Placebo + SSRI (Randomized Participants)

Number of subjects included in analysis

470

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.201 ^[3]

Method

Mixed models analysis

Confidence interval

Notes
[3] - In order to test the primary outcome between each LY2216684 dose and placebo while controlling the overall Type I error at 0.05, the significance level was a priori partitioned equally between the 2 LY2216684 dose-placebo comparisons at 0.025.

Secondary: Change from Randomization to Week 8 in Sheehan Disability Scale (SDS) Global Functional Impairment Scale

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End point title

Change from Randomization to Week 8 in Sheehan Disability Scale (SDS) Global Functional Impairment Scale ^[4]

End point description

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 Function Impairment Score is the sum of the 3 items, and scores ranged from 0 to 30 with higher values indicating 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. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Secondary

End point timeframe

Randomization, 8 weeks

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are being reported for all randomized participants per the protocol or Statistical Analysis Plan.

End point values	12 mg LY2216684 + SSRI (Randomized Participants)	18 mg LY2216684 + SSRI (Randomized Participants)	Placebo + SSRI (Randomized Participants)
Number of subjects analysed	224	222	236
Units: units on a scale
least squares mean (standard error)	-5.36 ( 0.44 )	-5.27 ( 0.44 )	-4.47 ( 0.43 )

No statistical analyses for this end point

Secondary: Change from Randomization to Week 8 in Fatigue Associated with Depression (FAsD) Impact Subscale Score

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End point title

Change from Randomization to Week 8 in Fatigue Associated with Depression (FAsD) Impact Subscale Score ^[5]

End point description

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. 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. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Secondary

End point timeframe

Randomization, 8 weeks

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are being reported for all randomized participants per the protocol or Statistical Analysis Plan.

End point values	12 mg LY2216684 + SSRI (Randomized Participants)	18 mg LY2216684 + SSRI (Randomized Participants)	Placebo + SSRI (Randomized Participants)
Number of subjects analysed	224	221	236
Units: units on a scale
least squares mean (standard error)	-0.74 ( 0.06 )	-0.66 ( 0.06 )	-0.53 ( 0.06 )

No statistical analyses for this end point

Secondary: Percentage of Participants Achieving a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of Less Than or Equal 10 up to Week 8

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End point title

Percentage of Participants Achieving a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of Less Than or Equal 10 up to Week 8 ^[6]

End point description

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. 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%. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Secondary

End point timeframe

Randomization up to 8 weeks

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are being reported for all randomized participants per the protocol or Statistical Analysis Plan.

End point values	12 mg LY2216684 + SSRI (Randomized Participants)	18 mg LY2216684 + SSRI (Randomized Participants)	Placebo + SSRI (Randomized Participants)
Number of subjects analysed	230	230	240
Units: percentage of participants
number (not applicable)	27.83	26.96	26.67

No statistical analyses for this end point

Secondary: 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

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End point title

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 ^[7]

End point description

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. 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%. Analysis population included all randomized participants with a baseline and at least one post-baseline value.

End point type

Secondary

End point timeframe

Randomization up to 8 weeks

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are being reported for all randomized participants per the protocol or Statistical Analysis Plan.

End point values	12 mg LY2216684 + SSRI (Randomized Participants)	18 mg LY2216684 + SSRI (Randomized Participants)	Placebo + SSRI (Randomized Participants)
Number of subjects analysed	230	230	240
Units: percentage of participants
number (not applicable)	16.96	19.13	19.58

No statistical analyses for this end point

Secondary: Change from Randomization to Week 8 in Hospital and Anxiety and Depression Scale (HADS) Anxiety Subscale Score

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End point title

Change from Randomization to Week 8 in Hospital and Anxiety and Depression Scale (HADS) Anxiety Subscale Score ^[8]

End point description

The HADS is a 14-item questionnaire with 2 subscales: anxiety and depression. Each item was rated on a 4-point scale (0-3), 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 8-10 represent 'borderline' and 0-7 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. Analysis population included all randomized participants with a baseline and at least one post-baseline value.

End point type

Secondary

End point timeframe

Randomization, 8 weeks

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are being reported for all randomized participants per the protocol or Statistical Analysis Plan.

End point values	12 mg LY2216684 + SSRI (Randomized Participants)	18 mg LY2216684 + SSRI (Randomized Participants)	Placebo + SSRI (Randomized Participants)
Number of subjects analysed	230	230	239
Units: units on a scale
least squares mean (standard error)	-1.97 ( 0.22 )	-2.05 ( 0.22 )	-1.85 ( 0.22 )

No statistical analyses for this end point

Secondary: 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

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End point title

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 ^[9]

End point description

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. 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%. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Secondary

End point timeframe

Randomization up to 8 weeks

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are being reported for all randomized participants per the protocol or Statistical Analysis Plan.

End point values	12 mg LY2216684 + SSRI (Randomized Participants)	18 mg LY2216684 + SSRI (Randomized Participants)	Placebo + SSRI (Randomized Participants)
Number of subjects analysed	230	230	240
Units: percentage of participants
number (not applicable)	30.43	34.35	27.08

No statistical analyses for this end point

Secondary: Change from Randomization to Week 8 in Hospital Anxiety and Depression Scale (HADS) depression subscale score

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End point title

Change from Randomization to Week 8 in Hospital Anxiety and Depression Scale (HADS) depression subscale score ^[10]

End point description

The HADS is a 14-item questionnaire with 2 subscales: anxiety and depression. Each item was rated on a 4-point scale (0-3), 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 8-10 represent 'borderline' and 0-7 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. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Secondary

End point timeframe

Randomization, 8 weeks

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are being reported for all randomized participants per the protocol or Statistical Analysis Plan.

End point values	12 mg LY2216684 + SSRI (Randomized Participants)	18 mg LY2216684 + SSRI (Randomized Participants)	Placebo + SSRI (Randomized Participants)
Number of subjects analysed	230	230	239
Units: units on a scale
least squares mean (standard error)	-3.19 ( 0.26 )	-3.38 ( 0.27 )	-2.76 ( 0.26 )

No statistical analyses for this end point

Secondary: Change from randomization to week 8 in Clinical Global Impressions of Severity (CGI-S)

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End point title

Change from randomization to week 8 in Clinical Global Impressions of Severity (CGI-S) ^[11]

End point description

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. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Secondary

End point timeframe

Randomization, 8 weeks

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are being reported for all randomized participants per the protocol or Statistical Analysis Plan.

End point values	12 mg LY2216684 + SSRI (Randomized Participants)	18 mg LY2216684 + SSRI (Randomized Participants)	Placebo + SSRI (Randomized Participants)
Number of subjects analysed	230	230	240
Units: units on a scale
least squares mean (standard error)	-1.01 ( 0.07 )	-1.08 ( 0.07 )	-0.95 ( 0.07 )

No statistical analyses for this end point

Secondary: Change From Randomization to Week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) Individual Items

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End point title

Change From Randomization to Week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) Individual Items ^[12]

End point description

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. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Secondary

End point timeframe

Randomization, 8 weeks

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are being reported for all randomized participants per the protocol or Statistical Analysis Plan.

End point values	12 mg LY2216684 + SSRI (Randomized Participants)	18 mg LY2216684 + SSRI (Randomized Participants)	Placebo + SSRI (Randomized Participants)
Number of subjects analysed	230	230	240
Units: units on a scale
least squares mean (standard error)
Apparent sadness	-1.18 ( 0.08 )	-1.04 ( 0.08 )	-1.01 ( 0.08 )
Reported sadness	-1.21 ( 0.08 )	-1.2 ( 0.08 )	-1 ( 0.08 )
Inner tension	-0.71 ( 0.07 )	-0.74 ( 0.07 )	-0.65 ( 0.07 )
Reduced sleep	-0.97 ( 0.09 )	-0.94 ( 0.09 )	-0.83 ( 0.08 )
Reduced appetite	-0.82 ( 0.08 )	-0.74 ( 0.08 )	-0.75 ( 0.08 )
Concentration difficulties	-0.88 ( 0.08 )	-1.01 ( 0.08 )	-0.94 ( 0.08 )
Lassitude	-1.04 ( 0.08 )	-1.12 ( 0.08 )	-0.89 ( 0.08 )
Inability to feel	-1.05 ( 0.08 )	-1.07 ( 0.08 )	-0.9 ( 0.08 )
Pessimistic thoughts	-0.77 ( 0.07 )	-0.74 ( 0.07 )	-0.74 ( 0.07 )
Suicidal thoughts	-0.09 ( 0.03 )	-0.13 ( 0.03 )	-0.15 ( 0.03 )

No statistical analyses for this end point

Secondary: Change From Randomization to Week 8 in Sheehan Disability Scale (SDS) Items

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End point title

Change From Randomization to Week 8 in Sheehan Disability Scale (SDS) Items ^[13]

End point description

The Sheehan Disability Scale (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. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Secondary

End point timeframe

Randomization, 8 weeks

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are being reported for all randomized participants per the protocol or Statistical Analysis Plan.

End point values	12 mg LY2216684 + SSRI (Randomized Participants)	18 mg LY2216684 + SSRI (Randomized Participants)	Placebo + SSRI (Randomized Participants)
Number of subjects analysed	224	222	236
Units: units on a scale
least squares mean (standard error)
Work impairment score (n=149, 145, 167)	-1.77 ( 0.19 )	-1.74 ( 0.2 )	-1.44 ( 0.19 )
Social life impairment score (n=224, 222, 236)	-1.85 ( 0.16 )	-1.81 ( 0.16 )	-1.64 ( 0.16 )
Family life impairment score (224, 222, 236)	-1.72 ( 0.16 )	-1.71 ( 0.16 )	-1.43 ( 0.15 )

No statistical analyses for this end point

Secondary: Change From Randomization to Week 8 in Fatigue Associated with Depression (FAsD) Average Score and Experience Subscale Score

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End point title

Change From Randomization to Week 8 in Fatigue Associated with Depression (FAsD) Average Score and Experience Subscale Score ^[14]

End point description

The FAsD is a participant-rated scale with a total of 13 items. 6 of the 13 items ask how often participants experience different aspects of fatigue with responses from 1 (never) to 5 (always). 7 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. LS means were calculated using MMRM adjusting for treatment, investigator, visit, baseline score, treatment-by-visit and baseline score-by-visit. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Secondary

End point timeframe

Randomization, 8 weeks

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are being reported for all randomized participants per the protocol or Statistical Analysis Plan.

End point values	12 mg LY2216684 + SSRI (Randomized Participants)	18 mg LY2216684 + SSRI (Randomized Participants)	Placebo + SSRI (Randomized Participants)
Number of subjects analysed	224	221	236
Units: units on a scale
least squares mean (standard error)
Average score	-0.69 ( 0.05 )	-0.67 ( 0.05 )	-0.57 ( 0.05 )
Experience score	-0.66 ( 0.06 )	-0.67 ( 0.06 )	-0.6 ( 0.05 )

No statistical analyses for this end point

Secondary: Change From Randomization to Week 8 in the EuroQol Questionnaire-5 Dimension (EQ-5D)

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End point title

Change From Randomization to Week 8 in the EuroQol Questionnaire-5 Dimension (EQ-5D) ^[15]

End point description

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 the 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. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Secondary

End point timeframe

Randomization, 8 weeks

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are being reported for all randomized participants per the protocol or Statistical Analysis Plan.

End point values	12 mg LY2216684 + SSRI (Randomized Participants)	18 mg LY2216684 + SSRI (Randomized Participants)	Placebo + SSRI (Randomized Participants)
Number of subjects analysed	224	222	236
Units: units on a scale
least squares mean (standard error)	12.201 ( 1.218 )	12.762 ( 1.225 )	9.756 ( 1.188 )

No statistical analyses for this end point

Secondary: Change From Randomization to Week 8 in the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF)

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End point title

Change From Randomization to Week 8 in the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) ^[16]

End point description

The Q-LES-Q-SF is a self-administered 16-item questionnaire that measures 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. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Secondary

End point timeframe

Randomization, 8 weeks

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are being reported for all randomized participants per the protocol or Statistical Analysis Plan.

End point values	12 mg LY2216684 + SSRI (Randomized Participants)	18 mg LY2216684 + SSRI (Randomized Participants)	Placebo + SSRI (Randomized Participants)
Number of subjects analysed	224	222	236
Units: percentage of maximum possible score
least squares mean (standard error)	10.51 ( 0.98 )	9.93 ( 0.98 )	8.47 ( 0.95 )

No statistical analyses for this end point

Secondary: Percentage of Treatment Emergent (TE) Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)

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End point title

Percentage of Treatment Emergent (TE) Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) ^[17]

End point description

The C-SSRS captured occurrence, severity, and frequency of suicide-related thoughts and behaviors.Suicidal ideation (SI) was defined as a 'yes' answer to any 1 of 5 SI questions, which included a wish to be dead and 4 different categories of active SI. 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.SI and behavior are defined as 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 at risk, multiplied by 100%. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Secondary

End point timeframe

Randomization through 8 weeks

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are being reported for all randomized participants per the protocol or Statistical Analysis Plan.

End point values	12 mg LY2216684 + SSRI (Randomized Participants)	18 mg LY2216684 + SSRI (Randomized Participants)	Placebo + SSRI (Randomized Participants)
Number of subjects analysed	230	230	240
Units: percentage of participants
number (not applicable)
TE of suicidal ideation (n=230, 230, 240)	3.91	3.91	3.33
TE of suicidal behavior (n=209, 214, 226)	0	0.47	0.44

No statistical analyses for this end point

Secondary: Change From Randomization to Week 8 in Arizona Sexual Experiences (ASEX) Scale

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End point title

Change From Randomization to Week 8 in Arizona Sexual Experiences (ASEX) Scale ^[18]

End point description

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]) to 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. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Secondary

End point timeframe

Randomization, 8 weeks

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are being reported for all randomized participants per the protocol or Statistical Analysis Plan.

End point values	12 mg LY2216684 + SSRI (Randomized Participants)	18 mg LY2216684 + SSRI (Randomized Participants)	Placebo + SSRI (Randomized Participants)
Number of subjects analysed	222	220	233
Units: units on a scale
least squares mean (standard error)	-1.32 ( 0.26 )	-1.27 ( 0.26 )	-0.79 ( 0.25 )

No statistical analyses for this end point

Secondary: Change From Randomization to Week 8 in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ)

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End point title

Change From Randomization to Week 8 in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) ^[19]

End point description

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. 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. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Secondary

End point timeframe

Randomization, 8 weeks

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are being reported for all randomized participants per the protocol or Statistical Analysis Plan.

End point values	12 mg LY2216684 + SSRI (Randomized Participants)	18 mg LY2216684 + SSRI (Randomized Participants)	Placebo + SSRI (Randomized Participants)
Number of subjects analysed	224	222	236
Units: units on a scale
least squares mean (standard error)	-4.7 ( 0.37 )	-4.41 ( 0.38 )	-3.79 ( 0.36 )

No statistical analyses for this end point

Secondary: Change From Randomization to Week 8 in Blood Pressure (BP)

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End point title

Change From Randomization to Week 8 in Blood Pressure (BP) ^[20]

End point description

Blood pressure (BP) measurements were collected when the participant was in a sitting position. Three measurements of sitting BP 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. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Secondary

End point timeframe

Randomization, 8 weeks

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are being reported for all randomized participants per the protocol or Statistical Analysis Plan.

End point values	12 mg LY2216684 + SSRI (Randomized Participants)	18 mg LY2216684 + SSRI (Randomized Participants)	Placebo + SSRI (Randomized Participants)
Number of subjects analysed	230	230	240
Units: millimeters of mercury (mmHg)
least squares mean (standard error)
Sitting systolic BP	2.11 ( 0.57 )	3.18 ( 0.57 )	0.02 ( 0.55 )
Sitting diastolic BP	3.57 ( 0.43 )	4 ( 0.43 )	0.66 ( 0.42 )

No statistical analyses for this end point

Secondary: The Percentage of Participants Experiencing Treatment-Emergent Adverse Events as a Function of CYP2D6 Phenotype

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End point title

The Percentage of Participants Experiencing Treatment-Emergent Adverse Events as a Function of CYP2D6 Phenotype ^[21]

End point description

Treatment-emergent adverse events (TEAEs) were events that first occurred or worsened during the treatment phase. CYP2D6 functional phenotype was classified as poor metabolizer (PM) or non-poor metabolizer (non-PM). The percentage of participants who reported the TEAE is presented for each phenotype classification. Only TEAEs for which there was a statistically significant treatment-by-SSRI therapy interaction were included: tinnitus and influenza. A summary of serious and other non-serious adverse events regardless of causality is located in the Report of Adverse Events module. Analysis population included all randomized patients who do not discontinue from the study for the reason 'Lost to follow-up' at the first post-baseline visit.

End point type

Secondary

End point timeframe

Through 8 weeks

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are being reported for all randomized participants per the protocol or Statistical Analysis Plan.

End point values	12 mg LY2216684 + SSRI (Randomized Participants)	18 mg LY2216684 + SSRI (Randomized Participants)	Placebo + SSRI (Randomized Participants)
Number of subjects analysed	144	140	157
Units: percentage of participants
number (not applicable)
Tinnitus non-PM (n=144, 140, 157)	0	0	1.27
Tinnitus PM (n=77, 83, 76)	0	3.61	0
Influenza non-PM (n=144, 140, 157)	1.39	0	0.64
Influenza PM (n=77, 83, 76)	0	2.41	0

No statistical analyses for this end point

Secondary: Pharmacokinetics: Plasma Concentrations of LY2216684

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End point title

Pharmacokinetics: Plasma Concentrations of LY2216684

End point description

A validated bioanalytical assay was used to determine plasma LY2216684 concentrations. 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 pharmacokinetics assessment. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Secondary

End point timeframe

1 week, 4 weeks, and 8 weeks

End point values	LY2216684 + SSRI
Number of subjects analysed	442
Units: nanograms per milliliter (ng/mL)
arithmetic mean (standard deviation)
12 mg dose (n=427)	37.8 ( 20.7 )
18 mg dose (n=202)	55.3 ( 30.4 )

No statistical analyses for this end point

Secondary: Change From Randomization to Week 8 in Pulse Rate

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End point title

Change From Randomization to Week 8 in Pulse Rate ^[22]

End point description

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. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Secondary

End point timeframe

Randomization, 8 weeks

Notes
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistics are being reported for all randomized participants per the protocol or Statistical Analysis Plan.

End point values	12 mg LY2216684 + SSRI (Randomized Participants)	18 mg LY2216684 + SSRI (Randomized Participants)	Placebo + SSRI (Randomized Participants)
Number of subjects analysed	230	230	240
Units: beats per minute (bpm)
least squares mean (standard error)	8.66 ( 0.64 )	9.12 ( 0.64 )	-1.41 ( 0.62 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Entire Study

Adverse event reporting additional description

H9P-MC-LNBM

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

16.1

Reporting group title

Placebo + SSRI (Pre-randomized) CF Phase

Reporting group description

Placebo: Administered orally, once daily for 3 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI) Includes all enrolled participants who did not discontinue for the reason 'Lost to Follow-up' at the first post-baseline visit during the Confirmation (CF) Phase.

Reporting group title

12 mg LY2216684 + SSRI (Randomized) AT Phase

Reporting group description

LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a SSRI, during the adjunctive treatment phase. 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.

Reporting group title

18 mg LY2216684 + SSRI (Randomized) AT Phase

Reporting group description

LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI, during the adjunctive treatment phase. 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.

Reporting group title

Placebo + SSRI (Randomized) AT Phase

Reporting group description

Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI, during the adjunctive treatment phase 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.

Reporting group title

Placebo + SSRI (Non-randomized) AT Phase

Reporting group description

Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI, during the adjunctive treatment phase. 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.

Reporting group title

Placebo + SSRI (Pre-randomized) Discontinuation Phase

Reporting group description

Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI, during the adjunctive treatment phase. 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.

Reporting group title

18 mg LY2216684 + SSRI (Taper Discontinuation Phase)

Reporting group description

LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI, during the adjunctive treatment phase Includes all randomized participants who tapered discontinuation of 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.

Reporting group title

12 mg LY2216684 + SSRI (Abrupt Discontinuation Phase)

Reporting group description

LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a SSRI 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.

Reporting group title

12 mg LY2216684 + SSRI (Taper Discontinuation Phase)

Reporting group description

LY2216684: 12 milligrams (mg), administered orally, once daily for 8 weeks, adjunctive to a SSRI Includes all randomized participants who tapered discontinuation of 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.

Reporting group title

18 mg LY2216684 + SSRI (Abrupt Discontinuation Phase)

Reporting group description

LY2216684: 12 mg, administered orally, once daily for 1 week, followed by 18 mg, administered orally, once daily for 7 weeks, adjunctive to a SSRI, during the adjunctive treatment phase 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.

Reporting group title

Placebo + SSRI (Randomized) Discontinuation Phase

Reporting group description

Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI, during the adjunctive treatment phase. Includes all randomized participants who 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.

Reporting group title

Placebo + SSRI (Non-randomized) Discontinuation Phase

Reporting group description

Placebo: Administered orally, once daily for 8 weeks, adjunctive to a SSRI, during the adjunctive treatment phase. Includes all non-randomized participants who 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 (Pre-randomized) CF Phase

12 mg LY2216684 + SSRI (Randomized) AT Phase

18 mg LY2216684 + SSRI (Randomized) AT Phase

Placebo + SSRI (Randomized) AT Phase

Placebo + SSRI (Non-randomized) AT Phase

Placebo + SSRI (Pre-randomized) Discontinuation Phase

18 mg LY2216684 + SSRI (Taper Discontinuation Phase)

12 mg LY2216684 + SSRI (Abrupt Discontinuation Phase)

12 mg LY2216684 + SSRI (Taper Discontinuation Phase)

18 mg LY2216684 + SSRI (Abrupt Discontinuation Phase)

Placebo + SSRI (Randomized) Discontinuation Phase

Placebo + SSRI (Non-randomized) Discontinuation Phase

Total subjects affected by serious adverse events

subjects affected / exposed

2 / 1413 (0.14%)

3 / 231 (1.30%)

2 / 230 (0.87%)

1 / 240 (0.42%)

5 / 627 (0.80%)

1 / 20 (5.00%)

1 / 107 (0.93%)

1 / 108 (0.93%)

1 / 100 (1.00%)

0 / 108 (0.00%)

0 / 221 (0.00%)

1 / 585 (0.17%)

number of deaths (all causes)

number of deaths resulting from adverse events

Investigations

blood pressure increased

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 1413 (0.00%)

0 / 231 (0.00%)

0 / 230 (0.00%)

0 / 240 (0.00%)

1 / 627 (0.16%)

0 / 20 (0.00%)

0 / 107 (0.00%)

0 / 108 (0.00%)

0 / 100 (0.00%)

0 / 108 (0.00%)

0 / 221 (0.00%)

0 / 585 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

electrocardiogram qt prolonged

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 1413 (0.00%)

0 / 231 (0.00%)

0 / 230 (0.00%)

0 / 240 (0.00%)

1 / 627 (0.16%)

0 / 20 (0.00%)

0 / 107 (0.00%)

0 / 108 (0.00%)

0 / 100 (0.00%)

0 / 108 (0.00%)

0 / 221 (0.00%)

0 / 585 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

colon cancer metastatic

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 1413 (0.00%)

0 / 231 (0.00%)

0 / 230 (0.00%)

0 / 240 (0.00%)

1 / 627 (0.16%)

0 / 20 (0.00%)

0 / 107 (0.00%)

0 / 108 (0.00%)

0 / 100 (0.00%)

0 / 108 (0.00%)

0 / 221 (0.00%)

1 / 585 (0.17%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

oesophageal carcinoma

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

1 / 1413 (0.07%)

0 / 231 (0.00%)

0 / 230 (0.00%)

0 / 240 (0.00%)

0 / 627 (0.00%)

1 / 20 (5.00%)

0 / 107 (0.00%)

0 / 108 (0.00%)

0 / 100 (0.00%)

0 / 108 (0.00%)

0 / 221 (0.00%)

0 / 585 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

arteriosclerosis

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 1413 (0.00%)

0 / 231 (0.00%)

1 / 230 (0.43%)

0 / 240 (0.00%)

0 / 627 (0.00%)

0 / 20 (0.00%)

1 / 107 (0.93%)

0 / 108 (0.00%)

0 / 100 (0.00%)

0 / 108 (0.00%)

0 / 221 (0.00%)

0 / 585 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

gastritis

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 1413 (0.00%)

1 / 231 (0.43%)

0 / 230 (0.00%)

0 / 240 (0.00%)

0 / 627 (0.00%)

0 / 20 (0.00%)

0 / 107 (0.00%)

0 / 108 (0.00%)

0 / 100 (0.00%)

0 / 108 (0.00%)

0 / 221 (0.00%)

0 / 585 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

oesophageal achalasia

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

1 / 1413 (0.07%)

1 / 231 (0.43%)

0 / 230 (0.00%)

0 / 240 (0.00%)

0 / 627 (0.00%)

0 / 20 (0.00%)

0 / 107 (0.00%)

1 / 108 (0.93%)

0 / 100 (0.00%)

0 / 108 (0.00%)

0 / 221 (0.00%)

0 / 585 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

cholecystitis

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 1413 (0.00%)

0 / 231 (0.00%)

0 / 230 (0.00%)

0 / 240 (0.00%)

0 / 627 (0.00%)

0 / 20 (0.00%)

0 / 107 (0.00%)

0 / 108 (0.00%)

1 / 100 (1.00%)

0 / 108 (0.00%)

0 / 221 (0.00%)

0 / 585 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cholelithiasis

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 1413 (0.00%)

0 / 231 (0.00%)

0 / 230 (0.00%)

0 / 240 (0.00%)

1 / 627 (0.16%)

0 / 20 (0.00%)

0 / 107 (0.00%)

0 / 108 (0.00%)

0 / 100 (0.00%)

0 / 108 (0.00%)

0 / 221 (0.00%)

0 / 585 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

depression

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 1413 (0.00%)

0 / 231 (0.00%)

1 / 230 (0.43%)

0 / 240 (0.00%)

0 / 627 (0.00%)

0 / 20 (0.00%)

0 / 107 (0.00%)

0 / 108 (0.00%)

0 / 100 (0.00%)

0 / 108 (0.00%)

0 / 221 (0.00%)

0 / 585 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

suicidal ideation

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 1413 (0.00%)

1 / 231 (0.43%)

0 / 230 (0.00%)

0 / 240 (0.00%)

0 / 627 (0.00%)

0 / 20 (0.00%)

0 / 107 (0.00%)

0 / 108 (0.00%)

0 / 100 (0.00%)

0 / 108 (0.00%)

0 / 221 (0.00%)

0 / 585 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

suicide attempt

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 1413 (0.00%)

0 / 231 (0.00%)

0 / 230 (0.00%)

1 / 240 (0.42%)

0 / 627 (0.00%)

0 / 20 (0.00%)

0 / 107 (0.00%)

0 / 108 (0.00%)

0 / 100 (0.00%)

0 / 108 (0.00%)

0 / 221 (0.00%)

0 / 585 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

sialoadenitis

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 1413 (0.00%)

0 / 231 (0.00%)

0 / 230 (0.00%)

0 / 240 (0.00%)

1 / 627 (0.16%)

0 / 20 (0.00%)

0 / 107 (0.00%)

0 / 108 (0.00%)

0 / 100 (0.00%)

0 / 108 (0.00%)

0 / 221 (0.00%)

0 / 585 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Placebo + SSRI (Pre-randomized) CF Phase

12 mg LY2216684 + SSRI (Randomized) AT Phase

18 mg LY2216684 + SSRI (Randomized) AT Phase

Placebo + SSRI (Randomized) AT Phase

Placebo + SSRI (Non-randomized) AT Phase

Placebo + SSRI (Pre-randomized) Discontinuation Phase

18 mg LY2216684 + SSRI (Taper Discontinuation Phase)

12 mg LY2216684 + SSRI (Abrupt Discontinuation Phase)

12 mg LY2216684 + SSRI (Taper Discontinuation Phase)

18 mg LY2216684 + SSRI (Abrupt Discontinuation Phase)

Placebo + SSRI (Randomized) Discontinuation Phase

Placebo + SSRI (Non-randomized) Discontinuation Phase

Total subjects affected by non serious adverse events

subjects affected / exposed

240 / 1413 (16.99%)

71 / 231 (30.74%)

73 / 230 (31.74%)

36 / 240 (15.00%)

100 / 627 (15.95%)

3 / 20 (15.00%)

19 / 107 (17.76%)

17 / 108 (15.74%)

15 / 100 (15.00%)

18 / 108 (16.67%)

39 / 221 (17.65%)

106 / 585 (18.12%)

Cardiac disorders

tachycardia

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

4 / 1413 (0.28%)

16 / 231 (6.93%)

23 / 230 (10.00%)

0 / 240 (0.00%)

3 / 627 (0.48%)

0 / 20 (0.00%)

1 / 107 (0.93%)

0 / 108 (0.00%)

0 / 100 (0.00%)

0 / 108 (0.00%)

0 / 221 (0.00%)

0 / 585 (0.00%)

occurrences all number

Nervous system disorders

dizziness

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

45 / 1413 (3.18%)

8 / 231 (3.46%)

12 / 230 (5.22%)

5 / 240 (2.08%)

13 / 627 (2.07%)

0 / 20 (0.00%)

8 / 107 (7.48%)

3 / 108 (2.78%)

5 / 100 (5.00%)

3 / 108 (2.78%)

7 / 221 (3.17%)

34 / 585 (5.81%)

occurrences all number

headache

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

116 / 1413 (8.21%)

22 / 231 (9.52%)

18 / 230 (7.83%)

14 / 240 (5.83%)

39 / 627 (6.22%)

3 / 20 (15.00%)

10 / 107 (9.35%)

13 / 108 (12.04%)

7 / 100 (7.00%)

10 / 108 (9.26%)

26 / 221 (11.76%)

69 / 585 (11.79%)

occurrences all number

136

108

Reproductive system and breast disorders

erectile dysfunction

alternative dictionary used: MedDRA 16.1

subjects affected / exposed ^[1]

3 / 447 (0.67%)

2 / 86 (2.33%)

1 / 81 (1.23%)

0 / 85 (0.00%)

2 / 176 (1.14%)

1 / 6 (16.67%)

0 / 37 (0.00%)

0 / 41 (0.00%)

0 / 38 (0.00%)

0 / 81 (0.00%)

0 / 168 (0.00%)

occurrences all number

Gastrointestinal disorders

nausea

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

55 / 1413 (3.89%)

11 / 231 (4.76%)

17 / 230 (7.39%)

1 / 240 (0.42%)

13 / 627 (2.07%)

0 / 20 (0.00%)

6 / 107 (5.61%)

2 / 108 (1.85%)

1 / 100 (1.00%)

5 / 108 (4.63%)

4 / 221 (1.81%)

19 / 585 (3.25%)

occurrences all number

Skin and subcutaneous tissue disorders

hyperhidrosis

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

17 / 1413 (1.20%)

19 / 231 (8.23%)

16 / 230 (6.96%)

2 / 240 (0.83%)

6 / 627 (0.96%)

0 / 20 (0.00%)

4 / 107 (3.74%)

0 / 108 (0.00%)

1 / 100 (1.00%)

1 / 108 (0.93%)

1 / 221 (0.45%)

3 / 585 (0.51%)

occurrences all number

Infections and infestations

nasopharyngitis

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

43 / 1413 (3.04%)

18 / 231 (7.79%)

10 / 230 (4.35%)

15 / 240 (6.25%)

34 / 627 (5.42%)

0 / 20 (0.00%)

2 / 107 (1.87%)

3 / 108 (2.78%)

2 / 100 (2.00%)

3 / 108 (2.78%)

11 / 221 (4.98%)

10 / 585 (1.71%)

occurrences all number

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This event is gender specific and that's why the total number of subjects exposed in this reporting group is less than the total number of subjects exposed.

More information

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Were there any global substantial amendments to the protocol? Yes

01 May 2012

Moved Fatigue Associated with Depression (FAsD) subscale from the secondary gatekeeper objective to additional secondary objective; changed statistical methodology; added information on potential interim analysis; Updated the details of how the sample size and power calculations are provided to ERBs.

02 Aug 2012

Added language for "re-screening"; Made modifications to interim analysis based on regulatory input and updated statistical methods.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Randomized, Placebo-Controlled, Double-Blind Study of LY2216684 Fixed-Dose 12 milligrams (mg) and 18 mg Once Daily as Adjunctive Treatment for Patients with Major Depressive Disorder Who Are Partial Responders to Selective Serotonin Reuptake Inhibitor Treatment

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from Randomization to Week 8 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score

Primary: Change from Randomization to Week 8 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score

Secondary: Change from Randomization to Week 8 in Sheehan Disability Scale (SDS) Global Functional Impairment Scale

Secondary: Change from Randomization to Week 8 in Sheehan Disability Scale (SDS) Global Functional Impairment Scale

Secondary: Change from Randomization to Week 8 in Fatigue Associated with Depression (FAsD) Impact Subscale Score

Secondary: Change from Randomization to Week 8 in Fatigue Associated with Depression (FAsD) Impact Subscale Score

Secondary: Percentage of Participants Achieving a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of Less Than or Equal 10 up to Week 8

Secondary: Percentage of Participants Achieving a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of Less Than or Equal 10 up to Week 8

Secondary: 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

Secondary: 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

Secondary: Change from Randomization to Week 8 in Hospital and Anxiety and Depression Scale (HADS) Anxiety Subscale Score

Secondary: Change from Randomization to Week 8 in Hospital and Anxiety and Depression Scale (HADS) Anxiety Subscale Score

Secondary: 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

Secondary: 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

Secondary: Change from Randomization to Week 8 in Hospital Anxiety and Depression Scale (HADS) depression subscale score

Secondary: Change from Randomization to Week 8 in Hospital Anxiety and Depression Scale (HADS) depression subscale score

Secondary: Change from randomization to week 8 in Clinical Global Impressions of Severity (CGI-S)

Secondary: Change from randomization to week 8 in Clinical Global Impressions of Severity (CGI-S)

Secondary: Change From Randomization to Week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) Individual Items

Secondary: Change From Randomization to Week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) Individual Items

Secondary: Change From Randomization to Week 8 in Sheehan Disability Scale (SDS) Items

Secondary: Change From Randomization to Week 8 in Sheehan Disability Scale (SDS) Items

Secondary: Change From Randomization to Week 8 in Fatigue Associated with Depression (FAsD) Average Score and Experience Subscale Score

Secondary: Change From Randomization to Week 8 in Fatigue Associated with Depression (FAsD) Average Score and Experience Subscale Score

Secondary: Change From Randomization to Week 8 in the EuroQol Questionnaire-5 Dimension (EQ-5D)

Secondary: Change From Randomization to Week 8 in the EuroQol Questionnaire-5 Dimension (EQ-5D)

Secondary: Change From Randomization to Week 8 in the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF)

Secondary: Change From Randomization to Week 8 in the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF)

Secondary: Percentage of Treatment Emergent (TE) Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)

Secondary: Percentage of Treatment Emergent (TE) Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)

Secondary: Change From Randomization to Week 8 in Arizona Sexual Experiences (ASEX) Scale

Secondary: Change From Randomization to Week 8 in Arizona Sexual Experiences (ASEX) Scale

Secondary: Change From Randomization to Week 8 in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ)

Secondary: Change From Randomization to Week 8 in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ)

Secondary: Change From Randomization to Week 8 in Blood Pressure (BP)

Secondary: Change From Randomization to Week 8 in Blood Pressure (BP)

Secondary: The Percentage of Participants Experiencing Treatment-Emergent Adverse Events as a Function of CYP2D6 Phenotype

Secondary: The Percentage of Participants Experiencing Treatment-Emergent Adverse Events as a Function of CYP2D6 Phenotype

Secondary: Pharmacokinetics: Plasma Concentrations of LY2216684

Secondary: Pharmacokinetics: Plasma Concentrations of LY2216684

Secondary: Change From Randomization to Week 8 in Pulse Rate

Secondary: Change From Randomization to Week 8 in Pulse Rate

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Randomized, Placebo-Controlled, Double-Blind Study of LY2216684 Fixed-Dose 12 milligrams (mg) and 18 mg Once Daily as Adjunctive Treatment for Patients with Major Depressive Disorder Who Are Partial Responders to Selective Serotonin Reuptake Inhibitor Treatment