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Clinical Trial Results:
A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of LY2127399 in Patients with Moderate to Severe Rheumatoid Arthritis (RA) who had an Inadequate Response to one or more TNF-α Inhibitors (FLEX V)

Summary
EudraCT number	2010-022207-22
Trial protocol	DE ES GR IT PL
Global end of trial date	06 Jan 2014

Results information
Results version number	v1(current)
This version publication date	09 Apr 2018
First version publication date	09 Apr 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

H9B-MC-BCDV

ISRCTN number

US NCT number

NCT01202773

WHO universal trial number (UTN)

Other trial identifiers

Trial Number: 13732

Sponsor organisation name

Eli Lilly and Company

Sponsor organisation address

Lilly Corporate Center, Indianapolis, IN, United States, 46285

Public contact

Available Mon - Fri 9 AM - 5 PM EST, Eli Lilly and Company, 1 877-CTLilly,

Scientific contact

Available Mon - Fri 9 AM - 5 PM 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

06 Jan 2014

Is this the analysis of the primary completion data?

Yes

Primary completion date

01 Mar 2013

Global end of trial reached?

Yes

Global end of trial date

06 Jan 2014

Was the trial ended prematurely?

Yes

Main objective of the trial

The primary purpose of this study is to help answer if LY2127399 is safe and effective in the treatment of rheumatoid arthritis in participants with an inadequate response to one or more tumor necrosis factor-alpha (TNF-α) inhibitors. This study is comprised of 2 periods: Period 1: 24-week blinded treatment Period 2: 48-week post-treatment follow-up

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

Evidence for comparator

Actual start date of recruitment

18 Jan 2011

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

48 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 268

Country: Number of subjects enrolled

Taiwan: 1

Country: Number of subjects enrolled

Greece: 4

Country: Number of subjects enrolled

Spain: 6

Country: Number of subjects enrolled

Russian Federation: 14

Country: Number of subjects enrolled

Colombia: 29

Country: Number of subjects enrolled

France: 3

Country: Number of subjects enrolled

Mexico: 8

Country: Number of subjects enrolled

Argentina: 13

Country: Number of subjects enrolled

Malaysia: 1

Country: Number of subjects enrolled

Brazil: 21

Country: Number of subjects enrolled

Poland: 42

Country: Number of subjects enrolled

Australia: 3

Country: Number of subjects enrolled

South Africa: 1

Country: Number of subjects enrolled

Germany: 10

Country: Number of subjects enrolled

New Zealand: 5

Country: Number of subjects enrolled

Japan: 18

Country: Number of subjects enrolled

Korea, Republic of: 9

Worldwide total number of subjects

456

EEA total number of subjects

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)

393

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Study had a treatment period (Weeks 0-24) and a post-treatment follow-up period (24-48 weeks in length). All participants were assessed for nonresponse at Week 16 with non-responders (NR) defined as participants with <20% improvement from baseline in both tender and swollen joint counts.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer

Are arms mutually exclusive

Yes

120 mg LY2127399

Arm description

A loading dose of 240 milligrams (mg) (2 injections of 120 mg) of LY2127399 followed by maintenance dosing of 120 mg of LY2127399 administered subcutaneously (SC) every 4 weeks (Q4W) for 24 weeks. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the 24-week treatment period. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo every 2 weeks (Q2W). At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 24-week treatment period.

Arm type

Experimental

Investigational medicinal product name

120 mg Tabalumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

120 milligrams (mg) Tabalumab given subcutaneously (SC) every 4 weeks (Q4W) for 24 weeks. Participants receive a 240-mg loading dose when initiating treatment. During the Treatment Period, for blinding purposes, participants will alternate injections of Tabalumab and injections of placebo every 2 weeks (Q2W). At Week 16, responders will receive 1 injection of 120 mg of Tabalumab SC and 1 injection of placebo SC, followed by 120 mg of Tabalumab Q4W for the rest of the 24-week treatment period.

Investigational medicinal product name

90 mg Tabalumab

Investigational medicinal product code

LY2127399

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

At Week 16, non-responders (NR) will receive 1 injection of 90 mg of Tabalumab and 1 injection of placebo, followed by 90 mg of Tabalumab Q2W for the rest of the 24-week treatment period.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo given SC Q2W for 24 weeks. Participants receive 2 injections of placebo when initiating treatment. At Week 16, responders will receive 2 injections of placebo SC, followed by 1 injection of placebo SC Q2W for the rest of the 24-week treatment period.

90 mg LY2127399

Arm description

A loading dose of 180 mg of LY2127399 (2 injections of 90 mg) followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W for 24 weeks. At Week 16, both responders and NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 24-week treatment period.

Arm type

Experimental

Investigational medicinal product name

Tabalumab

Investigational medicinal product code

LY2127399

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

90 mg Tabalumab given SC Q2W for 24 weeks. Participants receive a 180-mg loading dose when initiating treatment. At Week 16, both responders and NR will receive 1 injection of 90 mg of Tabalumab SC and 1 injection of placebo SC, followed by 90 mg of Tabalumab SC Q2W for the rest of the 24-week treatment period

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

At Week 16, both responders and NR received 1 injection of 90 mg of Tabalumab SC and 1 injection of placebo SC, followed by 90 mg of Tabalumab SC Q2W for the rest of the 24-week treatment period.

Placebo

Arm description

A loading dose of 2 injections of placebo followed by maintenance dosing of 1 injection of placebo administered SC Q2W for 24 weeks. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the 24-week treatment period. At Week 16, NR received a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 24-week treatment period.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo given SC Q2W for 24 weeks. Participants receive 2 injections of placebo when initiating treatment. At Week 16, responders will receive 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the 24-week treatment period.

Number of subjects in period 1	120 mg LY2127399	90 mg LY2127399	Placebo
Started	153	148	155
Received at least 1 dose of study drug	153	147	154
Week 16 NR	23 ^[1]	33 ^[2]	37 ^[3]
Post-Treatment Follow-Up Population	46 ^[4]	36 ^[5]	51 ^[6]
Completed	96	105	100
Not completed	57	43	55
Consent withdrawn by subject	13	6	5
Physician decision	2	-	-
Adverse event, non-fatal	4	5	5
Sponsor Decision	19	20	23
Lost to follow-up	1	2	2
Entry Criteria Not Met	2	-	1
Lack of efficacy	5	4	9
Protocol deviation	11	6	10

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 were assessed for nonresponse at Week 16. Responders received an injection of 120mg LY2127399 and 1 injection of placebo, then followed by 120mg LY2127399 every 4 weeks for the remaining 24 week treatment period. Non-responders received 1 injection of 90 mg LY2127366 and 1 injection of placebo, then followed by 90 mg LY2127399 every 2 weeks for the remaining 24-week treatment period.
[2] - 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 were assessed for nonresponse at Week 16. Responders and non-responders received 1 injection of 90 mg LY2127399 and 1 injection of placebo, then followed by 90 mg LY2127399 every 2 weeks for the remaining 24-week treatment period.
[3] - 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 were assessed for nonresponse at Week 16. Responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the 24-week treatment period. At Week 16, non-responders received a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the remaining 24-week treatment period.
[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 were assessed for nonresponse at Week 16. Responders received an injection of 120mg LY2127399 and 1 injection of placebo, then followed by 120mg LY2127399 every 4 weeks for the remaining 24 week treatment period. Non-responders received 1 injection of 90 mg LY2127366 and 1 injection of placebo, then followed by 90 mg LY2127399 every 2 weeks for the remaining 24-week treatment period.
[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 were assessed for nonresponse at Week 16. Responders and non-responders received 1 injection of 90 mg LY2127399 and 1 injection of placebo, then followed by 90 mg LY2127399 every 2 weeks for the remaining 24-week treatment period.
[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 were assessed for nonresponse at Week 16. Responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the 24-week treatment period. At Week 16, non-responders received a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the remaining 24-week treatment period.

Baseline characteristics

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Reporting group title

120 mg LY2127399

Reporting group description

Reporting group title

90 mg LY2127399

Reporting group description

Reporting group title

Placebo

Reporting group description

Reporting group values	120 mg LY2127399	90 mg LY2127399	Placebo	Total
Number of subjects	153	148	155	456
Age categorical
Units: Subjects
Gender, Male/Female
Units:
Female	124	126	131	381
Male	29	22	24	75
Region of Enrollment
Units: Subjects
United States	89	90	89	268
Taiwan	0	0	1	1
Greece	2	1	1	4
Spain	2	2	2	6
Russian Federation	6	4	4	14
Colombia	10	7	12	29
France	1	1	1	3
Mexico	3	3	2	8
Argentina	5	4	4	13
Malaysia	0	0	1	1
Brazil	7	7	7	21
Poland	14	14	14	42
Australia	0	1	2	3
South Africa	0	0	1	1
Germany	3	4	3	10
New Zealand	2	2	1	5
Japan	6	6	6	18
Korea, Republic of	3	2	4	9
Race
Units: Subjects
American Indian or Alaska Native	8	9	6	23
Asian	10	9	13	32
Native Hawaiian or Other Pacific Islander	0	0	0	0
Black or African American	14	16	18	48
White	119	108	112	339
More than One Race	0	4	2	6
Unknown or Not Reported	2	2	4	8
Ethnicity
Units: Subjects
Hispanic or Latino	39	36	33	108
Not Hispanic or Latino	93	95	101	289
Unknown or Not Reported	21	17	21	59
Age Continuous
Units: years
arithmetic mean (standard deviation)	54.2 ± 11.6	51.3 ± 11.7	54 ± 11.1	-

End points

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Reporting group title

120 mg LY2127399

Reporting group description

Reporting group title

90 mg LY2127399

Reporting group description

Reporting group title

Placebo

Reporting group description

Subject analysis set title

Population Pharmacokinetics (PK): Constant Clearance

Subject analysis set type

Sub-group analysis

Subject analysis set description

Population estimate of constant clearance as determined by population PK analysis. A 2-compartment model was used in PK modeling. Constant clearance is the PK parameter which describes the linear elimination of LY2127399 from serum. All randomized participants who received at least 1 dose of LY2127399 with evaluable LY2127399 PK data.

Primary: Percentage of participants with American College of Rheumatology 20% (ACR20) response

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End point title

Percentage of participants with American College of Rheumatology 20% (ACR20) response ^[1]

End point description

ACR Responder Index: composite of clinical, laboratory, and functional measures of rheumatoid arthritis (RA). ACR20 Responder: a ≥20% improvement from baseline in both 68 tender joint counts (TJC) and 66 swollen joint counts (SJC) and a ≥20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and C-reactive protein (CRP). Percentage of participants achieving ACR20 response = (number of ACR20 responders / number of participants treated) * 100. All NR at Week 16, as well as all participants who discontinued study treatment at any time for any reason, were defined as NR starting at that time-point and going forward, including Week 24 endpoint.

End point type

Primary

End point timeframe

Baseline through Week 24

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The study was terminated early due to insufficient efficacy; statistical analysis was not conducted.

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	153	148	155
Units: percentage of participants
number (not applicable)	17.6	24.3	20

No statistical analyses for this end point

Secondary: Percentage of Participants with American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response

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End point title

Percentage of Participants with American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response

End point description

ACR Responder Index: composite of clinical, laboratory, and functional measures of RA. ACR50 Responder: had a ≥50% improvement from baseline in both 68 TJC and 66 SJC and a ≥50% improvement in at least 3 of 5 criteria: participant's (Pt's) and physician's global assessment of disease activity, HAQ-DI (measured Pts' perceived degree of difficulty performing daily activities), joint pain, and CRP. Percentage of Pt achieving ACR50 response = [number (No.) of ACR50 responders / No. of Pts treated]*100. ACR70 Responder: had a ≥70% improvement from baseline in both TJC and SJC and a ≥70% improvement in at least 3 of same 5 criteria for ACR50. Percentage of Pts achieving ACR70 response = (No. of ACR70 responders / No. of Pts treated)*100. All NR at Week 16, as well as all Pts who discontinued study treatment at any time for any reason, were defined as NR starting at that time-point and going forward, including Week 24 endpoint.

End point type

Secondary

End point timeframe

Baseline through Week 24

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	153	148	155
Units: percentage of participants
number (not applicable)
ACR50	7.2	5.4	3.9
ACR70	2.6	2	0.6

No statistical analyses for this end point

Secondary: Change From Baseline to Week 24 in Tender Joint Count (68 Joint Count)

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End point title

Change From Baseline to Week 24 in Tender Joint Count (68 Joint Count)

End point description

Tender joint count is the number of tender and painful joints determined for each participant by examination of 68 joints. Joints were assessed by pressure and joint manipulation on physical examination. Participants were asked for pain sensations on these manipulations and watched for spontaneous pain reactions. Any positive response on pressure, movement, or both was translated into a single tender-versus-nontender dichotomy. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate. Analysis Population Description (APD): All randomized participants with evaluable tender joint count data. Modified Baseline Observation Carried Forward (mBOCF) was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	153	147	154
Units: joint counts
least squares mean (standard error)	-6.37 ± 1.4	-6.08 ± 1.42	-6.56 ± 1.38

No statistical analyses for this end point

Secondary: American College of Rheumatology Percent Improvement (ACR-N)

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End point title

American College of Rheumatology Percent Improvement (ACR-N)

End point description

ACR-N is a continuous measure of clinical, laboratory, and functional outcomes in RA that characterizes percentage (%) of improvement in disease activity from baseline based on ACR core set. This index was calculated as minimum of either a) % change in TJC, b) % change in SJC, or c) the median % change of remaining 5 ACR core criteria: If ≥3 components of the 5 ACR core criteria were missing, then c) was set to missing; if any of 3 components a), b), or c) were missing, then ACR-N was set to missing. Percentage of improvement was truncated to range of -100 to 100 to minimize impact of outliers (greater values indicate greater % improvement) and negative scores indicate a decline. Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with treatment and region as fixed factors and baseline Disease Activity Score based on 28 joint counts -CRP (DAS28-CRP) as a covariate.

End point type

Secondary

End point timeframe

Baseline through Week 24

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	153	146	153 ^[2]
Units: percentage of improvement
least squares mean (standard error)	-9.03 ± 4	-8.03 ± 4.11	-12.72 ± 4

Notes
[2] - All randomized participants with evaluable ACR-N data. Week 16 NR data were not included.

No statistical analyses for this end point

Secondary: Change from Baseline to Week 24 in Participant's Assessment of Pain [Visual Analog Scale (VAS)]

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End point title

Change from Baseline to Week 24 in Participant's Assessment of Pain [Visual Analog Scale (VAS)]

End point description

Participant's assessment of their current arthritis pain using VAS ranged from 0 millimeters (mm) (no pain) to 100 mm (worst possible pain). A decrease in pain score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate. Analysis Population Description: All randomized participants with evaluable participant's assessment of pain data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	153	146	153
Units: mm
least squares mean (standard error)	-9.89 ± 2.1	-9.15 ± 2.15	-5.76 ± 2.1

No statistical analyses for this end point

Secondary: Change from Baseline to Week 24 in Swollen Joint Count (66 Joint Count)

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End point title

Change from Baseline to Week 24 in Swollen Joint Count (66 Joint Count)

End point description

Swollen joint count is the number of swollen joints determined for each participant by examination of 66 joints. Joints were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate. Analysis Population Description: All randomized participants with evaluable swollen joint count data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	153	147	154
Units: joint counts
least squares mean (standard error)	-6.02 ± 0.98	-5.64 ± 1	-5.41 ± 0.98

No statistical analyses for this end point

Secondary: Change from Baseline to Week 24 in Participant’s Global Assessment of Disease Activity (VAS)

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End point title

Change from Baseline to Week 24 in Participant’s Global Assessment of Disease Activity (VAS)

End point description

Participant's assessment of their current arthritis disease activity using VAS ranged from 0 mm (no arthritis activity) to 100 mm (extremely active arthritis). A decrease in disease activity score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate. Analysis Population Description: All randomized participants with evaluable participant's global assessment of disease activity data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	153	146	153
Units: mm
least squares mean (standard error)	-11.29 ± 2.14	-8.72 ± 2.19	-7.12 ± 2.13

No statistical analyses for this end point

Secondary: Change from Baseline to Week 24 in Physician’s Global Assessment of Disease Activity (VAS)

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End point title

Change from Baseline to Week 24 in Physician’s Global Assessment of Disease Activity (VAS)

End point description

Physician's assessment of the participant's current arthritis disease activity using VAS ranged from 0 mm (no arthritis activity) to 100 mm (extremely active arthritis). A decrease in disease activity score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate. Analysis Population Description: All randomized participants with evaluable physician's global assessment of disease activity data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	147	140	150
Units: mm
least squares mean (standard error)	-15.9 ± 2.16	-16.38 ± 2.23	-13.17 ± 2.13

No statistical analyses for this end point

Secondary: Change From Baseline to Week 24 in Disease Activity Score Based on 28 Joint Count and C-Reactive Protein Level (DAS28-CRP)

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End point title

Change From Baseline to Week 24 in Disease Activity Score Based on 28 Joint Count and C-Reactive Protein Level (DAS28-CRP)

End point description

Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP (milligrams per liter), and participant's global assessment of disease activity using VAS (participant global VAS). DAS28-CRP=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.36*natural log(CRP+1)+0.014*participant global VAS+0.96. Scores ranged from 1.0 to 9.4, where lower scores indicated less disease activity and remission is DAS28-CRP <2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate. Analysis Population Description: All randomized participants with evaluable DAS28-CRP data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	152	146	152
Units: units on a scale
least squares mean (standard error)	-0.76 ± 0.12	-0.79 ± 0.13	-0.72 ± 0.12

No statistical analyses for this end point

Secondary: Change From Baseline to Week 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI)

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End point title

Change From Baseline to Week 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI)

End point description

The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty [0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (severe disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate. Analysis Population Description: All randomized participants with evaluable HAQ-DI data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	153	146	153
Units: units on a scale
least squares mean (standard error)	-0.13 ± 0.05	-0.09 ± 0.05	-0.08 ± 0.05

No statistical analyses for this end point

Secondary: Percentage of Participants With DAS28-CRP Based European League Against Rheumatism (EULAR) Response

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End point title

Percentage of Participants With DAS28-CRP Based European League Against Rheumatism (EULAR) Response

End point description

EULAR Responder index categorizes clinical response based on improvement since baseline in DAS28-CRP. DAS28-CRP=0.56*sqrt(TJC28)+0.28*sqrt(SJC28)+0.36*natural log(CRP+1)+0.014*participant global VAS+0.96. DAS28-CRP scores range from 1.0-9.4, where lower scores indicated less disease activity. High disease activity: DAS28-CRP >5.1, low disease activity: DAS28-CRP <3.2, and remission: DAS28-CRP <2.6. Participants are categorized as EULAR responders or NR based on improvement of DAS28-CRP scores from baseline. EULAR DAS28-CRP responder index defines a good (absolute: <3.2 or >1.2 improvement from baseline), moderate (absolute: 3.2-5.1 or 0.6-1.2 improvement from baseline), or no response (absolute: >5.1 or <0.6 improvement from baseline). Percentage of participants with DAS28-CRP based EULAR response = ( number of participants with specific response) / (number of participants analyzed in the group) * 100.

End point type

Secondary

End point timeframe

Baseline through Week 24

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	152 ^[3]	146 ^[4]	152 ^[5]
Units: percentage of participants
number (not applicable)
Good	11.8	9.6	8.6
Moderate	36.2	36.3	36.2
No response	52	54.1	55.3

Notes
[3] - All randomized participants with evaluable EULAR response data.
[4] - All randomized participants with evaluable EULAR response data.
[5] - All randomized participants with evaluable EULAR response data.

No statistical analyses for this end point

Secondary: Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores

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End point title

Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores

End point description

SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, 2 component scores (CS), physical CS (PCS) and mental CS (MCS). Domain scores calculated by summing each item for each domain and transforming scores into 0-100 scale; higher scores indicated better health status. If < 50% of the questions within a domain were answered, the raw score was not calculated. PCS score consisted of physical functioning, bodily pain, role-physical, and general health scales. MCS score consisted of social functioning, vitality, mental health, and role-emotional scales. Both PCS and MCS range from 0-100 with higher score indicating better mental or physical health. LS means were calculated using ANCOVA with treatment, region as fixed factors and baseline as a covariate.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	146 ^[6]	138 ^[7]	149 ^[8]
Units: units on a scale
least squares mean (standard error)
Physical Functioning	1.81 ± 0.78	1.78 ± 0.82	1 ± 0.77
Bodily Pain	2.36 ± 0.75	2.95 ± 0.78	1.97 ± 0.74
Role Limitations Due to Physical Problems	1.92 ± 0.72	2.08 ± 0.75	0.35 ± 0.72
Role Limitations Due to Emotional Problems	1.07 ± 0.97	2.55 ± 1.01	1.19 ± 0.96
General Health Perception	1.9 ± 0.64	0.91 ± 0.67	1.88 ± 0.64
Mental Health	0.83 ± 0.85	1.57 ± 0.88	0.98 ± 0.84
Social Function	2.51 ± 0.87	1.68 ± 0.91	1.32 ± 0.86
Vitality	2.71 ± 0.77	2.4 ± 0.8	2.05 ± 0.76
PCS	2.3 ± 0.71	1.83 ± 0.74	1.21 ± 0.71
MCS	1.22 ± 0.87	1.86 ± 0.9	1.38 ± 0.86

Notes
[6] - All randomized participants with evaluable SF-36 domain and summary scores.
[7] - All randomized participants with evaluable SF-36 domain and summary scores.
[8] - All randomized participants with evaluable SF-36 domain and summary scores.

No statistical analyses for this end point

Secondary: Change from Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores

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End point title

Change from Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores

End point description

The BFI is a brief participant-reported questionnaire for the rapid assessment of fatigue severity and the impact of fatigue on daily functioning in the past 24 hours. The BFI contains 10 items; however, the first item is not included in the scoring of the scale as it asks about usual fatigue over the past week with the participant answering 'yes' or 'no'. The remaining 9 items assess fatigue severity (3 items) and impact of fatigue on daily functioning (6 items) using an 11-point numeric scale, with 0 = no fatigue and 10 = fatigue as bad as you can imagine. The fatigue impact subscale score is the average of the non-missing responses to 6 items: general activity, mood, walking ability, normal work, relations with other people, and enjoyment of life. If more than 3 items within the fatigue impact subscale were not answered by a participant, the subscale is set to missing. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	146 ^[9]	138 ^[10]	149 ^[11]
Units: units on a scale
least squares mean (standard error)
Fatigue - Now	-0.68 ± 0.12	-0.55 ± 0.12	-0.6 ± 0.12
Fatigue - Usual	-0.65 ± 0.11	-0.58 ± 0.11	-0.56 ± 0.11
Fatigue – Worst	-0.75 ± 0.12	-0.65 ± 0.12	-0.72 ± 0.12
General Activity	-0.55 ± 0.12	-0.5 ± 0.12	-0.52 ± 0.12
Mood	-0.54 ± 0.12	-0.35 ± 0.12	-0.35 ± 0.12
Walking Ability	-0.53 ± 0.12	-0.38 ± 0.13	-0.36 ± 0.12
Normal Work	-0.6 ± 0.12	-0.46 ± 0.12	-0.42 ± 0.12
Relations with Other People	-0.41 ± 0.12	-0.43 ± 0.12	-0.29 ± 0.12
Enjoyment of Life	-0.53 ± 0.13	-0.55 ± 0.13	-0.41 ± 0.13
Fatigue Impact Subscale	-0.52 ± 0.11	-0.43 ± 0.11	-0.39 ± 0.11

Notes
[9] - All randomized participants with evaluable BFI data.
[10] - All randomized participants with evaluable BFI data.
[11] - All randomized participants with evaluable BFI data.

No statistical analyses for this end point

Secondary: Change from Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores

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End point title

Change from Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores

End point description

The BPI-SF is a self-reported scale that measures the severity of pain based on the worst pain, least pain, average pain experienced during the past 24 hours and pain based on the pain right now, with scores ranging from 0 (no pain) to 10 (pain as severe as you can imagine). Pain interference score is the average of the responses in the past 24 hours to 7 items: general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life [each item scored from 0 (does not interfere) to 10 (completely interferes)]. If more than 3 items of the Pain Interference Score are not answered by a participant, the score is set to missing. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate. Analysis Population Description: All randomized participants with evaluable BPI-SF scores. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	146	138	149
Units: units on a scale
least squares mean (standard error)
Pain - Worst (n=146, 138, 149)	-0.9 ± 0.2	-0.8 ± 0.2	-0.4 ± 0.2
Pain - Least (n=146, 138, 149)	-0.5 ± 0.2	-0.5 ± 0.2	-0.1 ± 0.2
Pain - Average (n=146, 138, 149)	-0.7 ± 0.2	-0.7 ± 0.2	-0.3 ± 0.2
Pain - Now (n=146, 137, 149)	-0.8 ± 0.2	-0.5 ± 0.2	-0.3 ± 0.2
General Activity (n=146, 137, 149)	-0.7 ± 0.2	-0.4 ± 0.2	-0.3 ± 0.2
Mood (n=146, 137, 149)	-0.6 ± 0.2	-0.2 ± 0.2	0 ± 0.2
Walking Ability (n=146, 137, 149)	-0.8 ± 0.2	-0.4 ± 0.2	-0.4 ± 0.2
Normal Work (n=146, 137, 149)	-0.7 ± 0.2	-0.4 ± 0.2	-0.2 ± 0.2
Relations with Other People (n=146, 137, 149)	-0.3 ± 0.2	-0.2 ± 0.2	-0.1 ± 0.2
Sleep (n=146, 137, 149)	-0.7 ± 0.2	-0.3 ± 0.2	-0.4 ± 0.2
Enjoyment of Life (n=146, 137, 149)	-0.7 ± 0.2	-0.4 ± 0.2	-0.4 ± 0.2
Pain Interference Score (n=146, 137, 149)	-0.6 ± 0.2	-0.3 ± 0.2	-0.3 ± 0.2

No statistical analyses for this end point

Secondary: Change From Baseline to Week 24 in Duration of Morning Stiffness (Minutes)

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End point title

Change From Baseline to Week 24 in Duration of Morning Stiffness (Minutes)

End point description

The Investigator asks participants about the duration of their morning stiffness (in minutes) in and around the joints and records the duration. The Investigator should ask participants about duration of morning stiffness on the day prior to the study visit to capture actual symptoms. If morning stiffness duration is longer than 12 hours (720 minutes), it was truncated to 720 minutes for statistical presentations and analyses.LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate. Analysis Population Description: All randomized participants with evaluable morning stiffness data; mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	141	138	139
Units: minutes
least squares mean (standard error)	-20.6 ± 11.5	-1 ± 11.7	-18 ± 11.9

No statistical analyses for this end point

Secondary: Time to ACR20 response

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End point title

Time to ACR20 response

End point description

End point type

Secondary

End point timeframe

Baseline through Week 24

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	0 ^[12]	0 ^[13]	0 ^[14]
Units: participants
number (not applicable)

Notes
[12] - Zero participants were analyzed because of the limited efficacy of Tabalumab in the treatment of RA.
[13] - Zero participants were analyzed because of the limited efficacy of Tabalumab in the treatment of RA.
[14] - Zero participants were analyzed because of the limited efficacy of Tabalumab in the treatment of RA.

No statistical analyses for this end point

Secondary: Change From Baseline to Week 24 in Absolute B Cell Counts

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End point title

Change From Baseline to Week 24 in Absolute B Cell Counts

End point description

Cell-surface marker cluster designation (CD) 3 negative, CD20 positive (CD3-CD20+) defines total mature B cells. B-lymphocyte antigen CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all mature B cells. Baseline B cell count is the average of the values on or prior to the date of first injection of study treatment, including unscheduled visits. A positive or negative change indicated an increase or decrease, respectively in B cell count. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate. Analysis Population Description: All randomized participants with evaluable CD3-CD20+ B cell counts. mLOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	151	147	155
Units: cells/microliter (cells/µL)
least squares mean (standard error)	-55.3 ± 9.9	-65.8 ± 10.1	3.2 ± 9.8

No statistical analyses for this end point

Secondary: Population Pharmacokinetics (PK): Constant Clearance

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End point title

Population Pharmacokinetics (PK): Constant Clearance

End point description

Population estimate of constant clearance as determined by population PK analysis. A 2-compartment model was used in PK modeling. Constant clearance is the PK parameter which describes the linear elimination of LY2127399 from serum. Analysis Population Description: All randomized participants who received at least 1 dose of LY2127399 with evaluable LY2127399 PK data.

End point type

Secondary

End point timeframe

Baseline through Week 24

End point values	Population Pharmacokinetics (PK): Constant Clearance
Number of subjects analysed	309
Units: milliliters/hour (mL/h)
arithmetic mean (standard error)	4.16 ± 3.58

No statistical analyses for this end point

Secondary: Change From Baseline to Week 24 in Serum Immunoglobulin (Ig) Levels

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End point title

Change From Baseline to Week 24 in Serum Immunoglobulin (Ig) Levels

End point description

Immunoglobulin (Ig), or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Change from baseline in serum immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) levels are reported. A negative change indicated a decrease in Ig levels. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate. Analysis Population Description: All randomized participants with evaluable serum Ig data. mLOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	151	146	153
Units: grams/liter (g/L)
least squares mean (standard error)
IgA	-0.33 ± 0.049	-0.324 ± 0.05	0.003 ± 0.049
IgG	-0.955 ± 0.161	-0.978 ± 0.163	0.058 ± 0.158
IgM	-0.273 ± 0.043	-0.239 ± 0.044	-0.019 ± 0.042

No statistical analyses for this end point

Secondary: Percentage of Participants Developing Anti-LY2127399 Antibodies

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End point title

Percentage of Participants Developing Anti-LY2127399 Antibodies

End point description

Participants with treatment-emergent anti-drug antibody (ADA) were participants who had any sample from baseline up to and through Week 52 that was a 4-fold increase (2-dilution increase) in immunogenicity titer over baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20). Percentage of participants with ADA = (number of participants with treatment-emergent ADA) / (number of participants assessed) * 100. Analysis Population Description: All randomized participants who received at least 1 dose of study drug with an evaluable baseline ADA result and a post-baseline ADA result. Participants missing an evaluable baseline result with all negative post-baseline results were included. Data after Week 16 for Week 16 NR were not included.

End point type

Secondary

End point timeframe

Baseline through Week 24

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	153	147	154
Units: percentage of participants
number (not applicable)	3.9	4.8	3.9

No statistical analyses for this end point

Secondary: Change from Baseline to Week 24 in CRP

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End point title

Change from Baseline to Week 24 in CRP

End point description

CRP is an indicator of inflammation. A negative change indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate. Analysis Population Description: All randomized participants with evaluable CRP data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	152	147	154
Units: milligrams/liter (mg/L)
least squares mean (standard error)	2.91 ± 1.83	0.95 ± 1.87	2.93 ± 1.81

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

H9B-MC-BCDV

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

16.0

Reporting group title

LY 120 mg Q4W, Randomized Treatment Period

Reporting group description

Reporting group title

LY 90 mg Q2W, Randomized Treatment Period

Reporting group description

Reporting group title

Placebo, Randomized Treatment Period

Reporting group description

Reporting group title

LY 120 mg Q4W, Rescue Period

Reporting group description

Reporting group title

LY 90 mg Q2W, Rescue Period

Reporting group description

Reporting group title

Placebo, Rescue Period

Reporting group description

Reporting group title

LY 120 mg Q4W, Follow-up Period

Reporting group description

Reporting group title

LY 90 mg Q2W, Follow-up Period

Reporting group description

Reporting group title

Placebo, Follow-up Period

Reporting group description

Reporting group title

LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Follow-up Period

Reporting group description

Reporting group title

Placebo to LY 90 mg Q2W (Week 16), Follow-up Period

Reporting group description

Serious adverse events	LY 120 mg Q4W, Randomized Treatment Period	LY 90 mg Q2W, Randomized Treatment Period	Placebo, Randomized Treatment Period	LY 120 mg Q4W, Rescue Period	LY 90 mg Q2W, Rescue Period	Placebo, Rescue Period	LY 120 mg Q4W, Follow-up Period	LY 90 mg Q2W, Follow-up Period	Placebo, Follow-up Period	LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Follow-up Period	Placebo to LY 90 mg Q2W (Week 16), Follow-up Period
Total subjects affected by serious adverse events
subjects affected / exposed	7 / 153 (4.58%)	6 / 147 (4.08%)	6 / 154 (3.90%)	1 / 23 (4.35%)	2 / 33 (6.06%)	1 / 37 (2.70%)	1 / 43 (2.33%)	1 / 36 (2.78%)	3 / 44 (6.82%)	0 / 3 (0.00%)	0 / 7 (0.00%)
number of deaths (all causes)	0	0	0	0	1	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
adenocarcinoma gastric
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	1 / 33 (3.03%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
deep vein thrombosis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	1 / 147 (0.68%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
hypotension
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	1 / 147 (0.68%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
non-cardiac chest pain
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	1 / 147 (0.68%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	1 / 36 (2.78%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
chronic obstructive pulmonary disease
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	1 / 154 (0.65%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
pneumothorax
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	1 / 23 (4.35%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
pulmonary embolism
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	1 / 147 (0.68%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
alcohol abuse
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	1 / 154 (0.65%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
somatoform disorder
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 153 (0.65%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
femoral neck fracture
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	1 / 44 (2.27%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
femur fracture
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	1 / 44 (2.27%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
jaw fracture
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 153 (0.65%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
procedural pain
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	1 / 36 (2.78%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
coronary artery stenosis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	1 / 154 (0.65%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
myocardial infarction
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	1 / 36 (2.78%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
anaemia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	1 / 147 (0.68%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
iron deficiency anaemia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	1 / 43 (2.33%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
meniere's disease
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	1 / 147 (0.68%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
retinal detachment
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	1 / 147 (0.68%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
abdominal pain
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	1 / 154 (0.65%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
arthritis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	1 / 33 (3.03%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
intervertebral disc protrusion
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	1 / 147 (0.68%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
lumbar spinal stenosis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	1 / 36 (2.78%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
osteoarthritis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	1 / 154 (0.65%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	1 / 44 (2.27%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
rheumatoid arthritis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	2 / 153 (1.31%)	0 / 147 (0.00%)	1 / 154 (0.65%)	0 / 23 (0.00%)	1 / 33 (3.03%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
rotator cuff syndrome
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 153 (0.65%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
synovitis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	1 / 147 (0.68%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
abscess
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	1 / 44 (2.27%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
device related infection
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	1 / 37 (2.70%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
pneumonia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	2 / 153 (1.31%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
pyomyositis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	1 / 44 (2.27%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	LY 120 mg Q4W, Randomized Treatment Period	LY 90 mg Q2W, Randomized Treatment Period	Placebo, Randomized Treatment Period	LY 120 mg Q4W, Rescue Period	LY 90 mg Q2W, Rescue Period	Placebo, Rescue Period	LY 120 mg Q4W, Follow-up Period	LY 90 mg Q2W, Follow-up Period	Placebo, Follow-up Period	LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Follow-up Period	Placebo to LY 90 mg Q2W (Week 16), Follow-up Period
Total subjects affected by non serious adverse events
subjects affected / exposed	71 / 153 (46.41%)	51 / 147 (34.69%)	61 / 154 (39.61%)	10 / 23 (43.48%)	11 / 33 (33.33%)	16 / 37 (43.24%)	6 / 43 (13.95%)	11 / 36 (30.56%)	14 / 44 (31.82%)	0 / 3 (0.00%)	1 / 7 (14.29%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
dysplastic naevus
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	1 / 36 (2.78%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0
melanocytic naevus
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	1 / 23 (4.35%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
neoplasm prostate
alternative dictionary used: MedDRA 16.0
subjects affected / exposed ^[1]	1 / 29 (3.45%)	0 / 22 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Vascular disorders
hypertension
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	2 / 153 (1.31%)	1 / 147 (0.68%)	4 / 154 (2.60%)	0 / 23 (0.00%)	1 / 33 (3.03%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	1	4	0	1	0	0	0	0	0	0
hypertensive crisis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	1 / 44 (2.27%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
General disorders and administration site conditions
asthenia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 153 (0.65%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	1 / 36 (2.78%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0	0	0
chest pain
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 153 (0.65%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	1 / 36 (2.78%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0	0	0
chills
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 153 (0.65%)	0 / 147 (0.00%)	1 / 154 (0.65%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	1 / 43 (2.33%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	1	0	0	0	1	0	0	0	0
injection site erythema
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 153 (0.65%)	3 / 147 (2.04%)	1 / 154 (0.65%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	3	1	0	0	0	0	0	0	0	0
injection site pain
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	2 / 153 (1.31%)	5 / 147 (3.40%)	4 / 154 (2.60%)	0 / 23 (0.00%)	0 / 33 (0.00%)	1 / 37 (2.70%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	6	18	21	0	0	2	0	0	0	0	0
injection site reaction
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	4 / 153 (2.61%)	7 / 147 (4.76%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	3 / 37 (8.11%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	6	19	0	0	0	10	0	0	0	0	0
oedema peripheral
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	4 / 147 (2.72%)	2 / 154 (1.30%)	1 / 23 (4.35%)	0 / 33 (0.00%)	1 / 37 (2.70%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	4	3	1	0	1	0	0	0	0	0
pyrexia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 153 (0.65%)	1 / 147 (0.68%)	2 / 154 (1.30%)	0 / 23 (0.00%)	1 / 33 (3.03%)	0 / 37 (0.00%)	0 / 43 (0.00%)	1 / 36 (2.78%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	1	3	0	1	0	0	1	0	0	0
Immune system disorders
seasonal allergy
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	1 / 147 (0.68%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	1 / 36 (2.78%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	0	0	1	0	0	0
Reproductive system and breast disorders
cervical dysplasia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed ^[2]	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	1 / 19 (5.26%)	0 / 28 (0.00%)	0 / 33 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
allergic cough
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	1 / 33 (3.03%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
chronic obstructive pulmonary disease
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 153 (0.65%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	1 / 43 (2.33%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	1	0	0	0	0
cough
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	3 / 153 (1.96%)	1 / 147 (0.68%)	3 / 154 (1.95%)	0 / 23 (0.00%)	1 / 33 (3.03%)	0 / 37 (0.00%)	0 / 43 (0.00%)	1 / 36 (2.78%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	3	1	3	0	1	0	0	1	0	0	0
Psychiatric disorders
depressed mood
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	1 / 44 (2.27%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
depression
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	2 / 153 (1.31%)	0 / 147 (0.00%)	4 / 154 (2.60%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	4	0	0	0	0	0	0	0	0
Investigations
haemoglobin decreased
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 153 (0.65%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	1 / 44 (2.27%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	1	0	0
lipase increased
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	1 / 37 (2.70%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
neutrophil count increased
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 153 (0.65%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	1 / 43 (2.33%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	1	0	0	0	0
weight decreased
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	1 / 37 (2.70%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
white blood cell count decreased
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	1 / 43 (2.33%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
white blood cell count increased
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 153 (0.65%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	1 / 43 (2.33%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	1	0	0	0	0
Injury, poisoning and procedural complications
hand fracture
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 153 (0.65%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	1 / 33 (3.03%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0	0	0	0
ligament sprain
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 153 (0.65%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	1 / 37 (2.70%)	2 / 43 (4.65%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	1	2	0	0	0	0
post-traumatic neck syndrome
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	1 / 23 (4.35%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
procedural pain
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	1 / 147 (0.68%)	0 / 154 (0.00%)	0 / 23 (0.00%)	1 / 33 (3.03%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	1 / 44 (2.27%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0	1	0	0
spinal compression fracture
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	1 / 154 (0.65%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	1 / 43 (2.33%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0	0	0	0
Nervous system disorders
dizziness
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	3 / 153 (1.96%)	1 / 147 (0.68%)	2 / 154 (1.30%)	0 / 23 (0.00%)	0 / 33 (0.00%)	1 / 37 (2.70%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	3	1	2	0	0	1	0	0	0	0	0
headache
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	7 / 153 (4.58%)	2 / 147 (1.36%)	5 / 154 (3.25%)	0 / 23 (0.00%)	0 / 33 (0.00%)	1 / 37 (2.70%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	8	2	5	0	0	1	0	0	0	0	0
Blood and lymphatic system disorders
anaemia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	2 / 154 (1.30%)	1 / 23 (4.35%)	0 / 33 (0.00%)	0 / 37 (0.00%)	1 / 43 (2.33%)	0 / 36 (0.00%)	1 / 44 (2.27%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	2	1	0	0	1	0	1	0	0
leukopenia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	1 / 36 (2.78%)	1 / 44 (2.27%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	1	0	0
lymphopenia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	1 / 44 (2.27%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Ear and labyrinth disorders
ear pain
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 153 (0.65%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	1 / 36 (2.78%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0	0	0
vertigo
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	1 / 154 (0.65%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	1 / 44 (2.27%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	1	0	0
Gastrointestinal disorders
abdominal pain
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	1 / 37 (2.70%)	0 / 43 (0.00%)	1 / 36 (2.78%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	0
constipation
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 153 (0.65%)	1 / 147 (0.68%)	1 / 154 (0.65%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	1 / 36 (2.78%)	1 / 44 (2.27%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	1	1	0	0	0	0	1	1	0	0
diarrhoea
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	2 / 153 (1.31%)	2 / 147 (1.36%)	3 / 154 (1.95%)	1 / 23 (4.35%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	2	3	1	0	0	0	0	0	0	0
nausea
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	6 / 153 (3.92%)	1 / 147 (0.68%)	2 / 154 (1.30%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	1 / 36 (2.78%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	6	1	2	0	0	0	0	1	0	0	0
oedema mouth
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	1 / 37 (2.70%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
vomiting
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	3 / 153 (1.96%)	1 / 147 (0.68%)	1 / 154 (0.65%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	1 / 36 (2.78%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	3	1	1	0	0	0	0	1	0	0	0
Hepatobiliary disorders
liver disorder
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	1 / 44 (2.27%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Skin and subcutaneous tissue disorders
blister
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	1 / 147 (0.68%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	1 / 37 (2.70%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	1	0	0	0	0	0
dry skin
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	1 / 23 (4.35%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
hyperhidrosis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	4 / 153 (2.61%)	1 / 147 (0.68%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	1 / 37 (2.70%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	4	1	0	0	0	1	0	0	0	0	0
pain of skin
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	1 / 37 (2.70%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
rash macular
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	1 / 44 (2.27%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
urticaria
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	1 / 33 (3.03%)	1 / 37 (2.70%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0	0	0	0
Endocrine disorders
hypothyroidism
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	1 / 147 (0.68%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	1 / 44 (2.27%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	1	0	0
Musculoskeletal and connective tissue disorders
arthralgia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	3 / 153 (1.96%)	3 / 147 (2.04%)	2 / 154 (1.30%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	1 / 43 (2.33%)	0 / 36 (0.00%)	1 / 44 (2.27%)	0 / 3 (0.00%)	1 / 7 (14.29%)
occurrences all number	3	3	2	0	0	0	1	0	3	0	1
back pain
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	2 / 153 (1.31%)	2 / 147 (1.36%)	2 / 154 (1.30%)	0 / 23 (0.00%)	0 / 33 (0.00%)	2 / 37 (5.41%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	2	2	0	0	2	0	0	0	0	0
myalgia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 153 (0.65%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	1 / 36 (2.78%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0	0	0
osteoarthritis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 153 (0.65%)	1 / 147 (0.68%)	1 / 154 (0.65%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	1 / 43 (2.33%)	1 / 36 (2.78%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	1	1	0	0	0	1	1	0	0	0
osteoporosis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 153 (0.65%)	0 / 147 (0.00%)	1 / 154 (0.65%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	2 / 36 (5.56%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	1	0	0	0	0	2	0	0	0
pain in extremity
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 153 (0.65%)	0 / 147 (0.00%)	4 / 154 (2.60%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	1 / 44 (2.27%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	5	0	0	0	0	0	2	0	0
rheumatoid arthritis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	8 / 153 (5.23%)	7 / 147 (4.76%)	11 / 154 (7.14%)	1 / 23 (4.35%)	0 / 33 (0.00%)	2 / 37 (5.41%)	0 / 43 (0.00%)	2 / 36 (5.56%)	2 / 44 (4.55%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	9	7	13	1	0	2	0	2	2	0	0
spinal osteoarthritis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	1 / 154 (0.65%)	1 / 23 (4.35%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0	0	0
synovial cyst
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 153 (0.65%)	1 / 147 (0.68%)	2 / 154 (1.30%)	1 / 23 (4.35%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	1	2	1	0	0	0	0	0	0	0
tendonitis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	2 / 153 (1.31%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	1 / 36 (2.78%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0	0	0	0	0	1	0	0	0
Infections and infestations
adenoiditis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	1 / 44 (2.27%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
alveolar osteitis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	1 / 33 (3.03%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
bacterial infection
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	1 / 23 (4.35%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
bronchitis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	2 / 153 (1.31%)	3 / 147 (2.04%)	3 / 154 (1.95%)	1 / 23 (4.35%)	1 / 33 (3.03%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	3	3	1	1	0	0	0	0	0	0
cellulitis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 153 (0.65%)	0 / 147 (0.00%)	1 / 154 (0.65%)	0 / 23 (0.00%)	0 / 33 (0.00%)	1 / 37 (2.70%)	0 / 43 (0.00%)	1 / 36 (2.78%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	1	0	0	1	0	1	0	0	0
gastroenteritis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	1 / 147 (0.68%)	1 / 154 (0.65%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	1 / 44 (2.27%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	1	0	0	0	0	0	1	0	0
gastroenteritis viral
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	1 / 147 (0.68%)	1 / 154 (0.65%)	0 / 23 (0.00%)	1 / 33 (3.03%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	1	0	1	0	0	0	0	0	0
herpes simplex
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	1 / 33 (3.03%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
herpes zoster
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	2 / 153 (1.31%)	0 / 147 (0.00%)	1 / 154 (0.65%)	0 / 23 (0.00%)	1 / 33 (3.03%)	1 / 37 (2.70%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	1	0	1	1	0	0	0	0	0
influenza
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 153 (0.65%)	3 / 147 (2.04%)	2 / 154 (1.30%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	3	2	0	0	0	0	0	0	0	0
nasopharyngitis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	4 / 153 (2.61%)	2 / 147 (1.36%)	0 / 154 (0.00%)	0 / 23 (0.00%)	1 / 33 (3.03%)	0 / 37 (0.00%)	1 / 43 (2.33%)	1 / 36 (2.78%)	1 / 44 (2.27%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	4	2	0	0	1	0	1	1	1	0	0
pharyngitis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	1 / 154 (0.65%)	0 / 23 (0.00%)	1 / 33 (3.03%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	1 / 44 (2.27%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	1	0	1	0	0	0	1	0	0
respiratory tract infection viral
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	1 / 37 (2.70%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
sinusitis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	5 / 153 (3.27%)	2 / 147 (1.36%)	7 / 154 (4.55%)	1 / 23 (4.35%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	3 / 44 (6.82%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	6	2	7	1	0	0	0	0	3	0	0
staphylococcal infection
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	1 / 44 (2.27%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
subcutaneous abscess
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	1 / 44 (2.27%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
tooth abscess
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	1 / 154 (0.65%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	1 / 36 (2.78%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	1	0	0	0	0	1	0	0	0
tooth infection
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	1 / 147 (0.68%)	1 / 154 (0.65%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	1 / 36 (2.78%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	1	0	0	0	0	1	0	0	0
upper respiratory tract infection
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	9 / 153 (5.88%)	7 / 147 (4.76%)	9 / 154 (5.84%)	1 / 23 (4.35%)	1 / 33 (3.03%)	0 / 37 (0.00%)	0 / 43 (0.00%)	2 / 36 (5.56%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	10	7	11	1	1	0	0	2	0	0	0
urinary tract infection
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	5 / 153 (3.27%)	6 / 147 (4.08%)	2 / 154 (1.30%)	0 / 23 (0.00%)	1 / 33 (3.03%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	5	6	2	0	1	0	0	0	0	0	0
Metabolism and nutrition disorders
decreased appetite
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 153 (0.65%)	0 / 147 (0.00%)	2 / 154 (1.30%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	1 / 36 (2.78%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	2	0	0	0	0	1	0	0	0
gout
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	1 / 37 (2.70%)	0 / 43 (0.00%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
hyperglycaemia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	1 / 147 (0.68%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	0 / 43 (0.00%)	0 / 36 (0.00%)	1 / 44 (2.27%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	1	0	0
vitamin d deficiency
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 153 (0.00%)	0 / 147 (0.00%)	0 / 154 (0.00%)	0 / 23 (0.00%)	0 / 33 (0.00%)	0 / 37 (0.00%)	1 / 43 (2.33%)	0 / 36 (0.00%)	0 / 44 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0

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, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
[2] - 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, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.

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Were there any global substantial amendments to the protocol? Yes

17 May 2011

Amendment A Added Columbia-Suicide Severity Rating Scale (C-SSRS) for prospective assessment of the occurrence of treatment-emergent suicidality, including addition of: o Statistical methodology for analyses of responses o Exclusion criterion of recent suicidal ideation or behavior o Language for discontinuation of study drug should a patient develop a significant uncontrolled medical condition, such as a neuropsychiatric disorder that in the opinion of the Investigator after appropriate medical assessment, would pose an unacceptable risk to the patient if the patient were to continue receiving study drug. In compliance with changes to in United States of America, 21 Code of Federal Regulation (CFR) Parts 312 and 320: o Added information on reasonably anticipated adverse events also being available in the compound Investigator’s Brochure. o Added a summary of reasonably anticipated serious adverse events for the RA population under study. o Added language that the Sponsor may review unblinded safety data in the event that it would be required for evaluation of selected SAEs to aide in determination of regulatory reporting. Also clarified that DMC may not be the only committee to review unblinded safety data to accommodate the statement immediately preceding this one. Added text clarifying that at least four criteria must be fulfilled for classification of RA to Appendix 4. Appendix 4 is the American Rheumatism Association 1987 Revised Criteria for the Classification of RA referenced in inclusion criterion #2 as the criteria for the diagnosis of adult-onset RA. Modified existing exclusion criteria: o #4 to address biologic DMARD washout periods as DMARDs may interfere with interpretation of efficacy results. o #11 to include the C-SSRS. o #15 to clarify what constitutes HCV positive status. Clarified the standardized sequence of assessments that contribute to blinding being maintained in the

17 May 2011

Amendment A Continued: Concomitant Medications were updated to clarify language associated with NSAIDs and analgesics and to add text regarding proton pump inhibitors and H2 receptor blockers. Clarified the definition of the treatment-adverse events. Statistical Methodology changes: o Correcting the significance level for interaction effects from 0.010 to 0.10. o Modification of the text for non-responder imputation for clinical response (ACR20/50/70).

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.

This study has been terminated not based on safety concerns, but due to insufficient efficacy. Early termination led to lower than expected enrollment and was responsible for the large number of discontinuation reason as Sponsor Decision.

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Clinical trials

Clinical Trial Results: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of LY2127399 in Patients with Moderate to Severe Rheumatoid Arthritis (RA) who had an Inadequate Response to one or more TNF-α Inhibitors (FLEX V)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of participants with American College of Rheumatology 20% (ACR20) response

Primary: Percentage of participants with American College of Rheumatology 20% (ACR20) response

Secondary: Percentage of Participants with American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response

Secondary: Percentage of Participants with American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response

Secondary: Change From Baseline to Week 24 in Tender Joint Count (68 Joint Count)

Secondary: Change From Baseline to Week 24 in Tender Joint Count (68 Joint Count)

Secondary: American College of Rheumatology Percent Improvement (ACR-N)

Secondary: American College of Rheumatology Percent Improvement (ACR-N)

Secondary: Change from Baseline to Week 24 in Participant's Assessment of Pain [Visual Analog Scale (VAS)]

Secondary: Change from Baseline to Week 24 in Participant's Assessment of Pain [Visual Analog Scale (VAS)]

Secondary: Change from Baseline to Week 24 in Swollen Joint Count (66 Joint Count)

Secondary: Change from Baseline to Week 24 in Swollen Joint Count (66 Joint Count)

Secondary: Change from Baseline to Week 24 in Participant’s Global Assessment of Disease Activity (VAS)

Secondary: Change from Baseline to Week 24 in Participant’s Global Assessment of Disease Activity (VAS)

Secondary: Change from Baseline to Week 24 in Physician’s Global Assessment of Disease Activity (VAS)

Secondary: Change from Baseline to Week 24 in Physician’s Global Assessment of Disease Activity (VAS)

Secondary: Change From Baseline to Week 24 in Disease Activity Score Based on 28 Joint Count and C-Reactive Protein Level (DAS28-CRP)

Secondary: Change From Baseline to Week 24 in Disease Activity Score Based on 28 Joint Count and C-Reactive Protein Level (DAS28-CRP)

Secondary: Change From Baseline to Week 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI)

Secondary: Change From Baseline to Week 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI)

Secondary: Percentage of Participants With DAS28-CRP Based European League Against Rheumatism (EULAR) Response

Secondary: Percentage of Participants With DAS28-CRP Based European League Against Rheumatism (EULAR) Response

Secondary: Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores

Secondary: Change From Baseline to Week 24 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain and Summary Scores

Secondary: Change from Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores

Secondary: Change from Baseline to Week 24 in Brief Fatigue Inventory (BFI) Individual Items and Impact Scores

Secondary: Change from Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores

Secondary: Change from Baseline to Week 24 in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores

Secondary: Change From Baseline to Week 24 in Duration of Morning Stiffness (Minutes)

Secondary: Change From Baseline to Week 24 in Duration of Morning Stiffness (Minutes)

Secondary: Time to ACR20 response

Secondary: Time to ACR20 response

Secondary: Change From Baseline to Week 24 in Absolute B Cell Counts

Secondary: Change From Baseline to Week 24 in Absolute B Cell Counts

Secondary: Population Pharmacokinetics (PK): Constant Clearance

Secondary: Population Pharmacokinetics (PK): Constant Clearance

Secondary: Change From Baseline to Week 24 in Serum Immunoglobulin (Ig) Levels

Secondary: Change From Baseline to Week 24 in Serum Immunoglobulin (Ig) Levels

Secondary: Percentage of Participants Developing Anti-LY2127399 Antibodies

Secondary: Percentage of Participants Developing Anti-LY2127399 Antibodies

Secondary: Change from Baseline to Week 24 in CRP

Secondary: Change from Baseline to Week 24 in CRP

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of LY2127399 in Patients with Moderate to Severe Rheumatoid Arthritis (RA) who had an Inadequate Response to one or more TNF-α Inhibitors (FLEX V)