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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 Methotrexate Therapy (FLEX M)

Summary
EudraCT number	2010-022205-17
Trial protocol	HU LT BG PL
Global end of trial date	21 Jan 2014

Results information
Results version number	v1(current)
This version publication date	11 Apr 2018
First version publication date	11 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-BCDM

ISRCTN number

US NCT number

NCT01198002

WHO universal trial number (UTN)

Other trial identifiers

Trial Number: 11352

Sponsor organisation name

Eli Lilly and Company

Sponsor organisation address

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

Public contact

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

Scientific contact

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

21 Jan 2014

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

21 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 while on a background treatment of methotrexate. This study is comprised of 3 periods: Period 1: 52-week blinded treatment Period 2: additional 48-week unblinded treatment Period 3: 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

02 Dec 2010

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 167

Country: Number of subjects enrolled

Taiwan: 31

Country: Number of subjects enrolled

Slovakia: 11

Country: Number of subjects enrolled

Ukraine: 68

Country: Number of subjects enrolled

Lithuania: 20

Country: Number of subjects enrolled

Russian Federation: 72

Country: Number of subjects enrolled

Colombia: 51

Country: Number of subjects enrolled

Sri Lanka: 5

Country: Number of subjects enrolled

India: 14

Country: Number of subjects enrolled

Hungary: 25

Country: Number of subjects enrolled

Mexico: 64

Country: Number of subjects enrolled

Argentina: 50

Country: Number of subjects enrolled

Malaysia: 8

Country: Number of subjects enrolled

Brazil: 41

Country: Number of subjects enrolled

Poland: 100

Country: Number of subjects enrolled

Croatia: 2

Country: Number of subjects enrolled

Romania: 4

Country: Number of subjects enrolled

South Africa: 48

Country: Number of subjects enrolled

Bulgaria: 32

Country: Number of subjects enrolled

Japan: 158

Country: Number of subjects enrolled

New Zealand: 2

Country: Number of subjects enrolled

Korea, Republic of: 68

Worldwide total number of subjects

1041

EEA total number of subjects

194

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)

900

From 65 to 84 years

141

85 years and over

Subject disposition

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Recruitment details

Screening details

Study had a blinded Treatment Period 1 (Weeks 0-52), a non-blinded Treatment Period 2 (Weeks 52-100) and a post-treatment follow-up (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

Treatment Period 1 (Weeks 0-52)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

120 mg LY2127399

Arm description

Treatment Period 1 (Weeks 0-52): 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 blinding purposes, participants alternated injections of LY2127399 and injections of placebo every 2 weeks (Q2W). 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 Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, 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 Treatment Period 2. 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 100-week treatment period.

Arm type

Experimental

Investigational medicinal product name

120 mg LY2127399

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

90 mg LY2127399

Arm description

Treatment Period 1 (Weeks 0-52): 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. At Week 16, responders 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 Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders 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 Treatment Period 2. 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 100-week treatment period.

Arm type

Experimental

Investigational medicinal product name

90 mg LY2127399

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo

Arm description

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2. 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 100-week treatment period.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Number of subjects in period 1	120 mg LY2127399	90 mg LY2127399	Placebo
Started	345	347	349
Received at Least 1 Dose of Study Drug	345	345	348
Week 16 NR	58 ^[1]	62 ^[2]	90
Post-Treatment Follow-Up Population	293	303	307
Completed	70	73	80
Not completed	275	274	269
Adverse event, serious fatal	2	-	1
Consent withdrawn by subject	16	21	12
Physician decision	1	2	2
Adverse event, non-fatal	18	11	11
Sponsor Decision	213	216	224
Lost to follow-up	-	2	-
Entry Criteria Not Met	1	3	3
Lack of efficacy	10	9	6
Protocol deviation	14	10	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: 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.
[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: 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 2 title

Treatment Period 2 (Weeks 52-100)

Is this the baseline period?

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

120 mg LY2127399

Arm description

Arm type

Experimental

Investigational medicinal product name

120 mg LY2127399

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

90 mg LY2127399

Arm description

Arm type

Experimental

Investigational medicinal product name

90 mg LY2127399

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo

Arm description

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Number of subjects in period 2	120 mg LY2127399	90 mg LY2127399	Placebo
Started	70	73	80
Completed	1	0	2
Not completed	69	73	78
Physician decision	1	-	1
Adverse event, non-fatal	2	-	1
Sponsor Decision	62	70	75
Lost to follow-up	-	2	-
Entry Criteria Not Met	1	-	-
Lack of efficacy	3	1	1

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	345	347	349	1041
Age categorical
Units: Subjects
In utero	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0
Newborns (0-27 days)	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0
Children (2-11 years)	0	0	0	0
Adolescents (12-17 years)	0	0	0	0
Adults (18-64 years)	290	311	299	900
From 65-84 years	55	36	50	141
85 years and over	0	0	0	0
Gender, Male/Female
Units:
Male	51	56	57	164
Female	294	291	292	877
Race
Units: Subjects
American Indian or Alaska Native	20	18	15	53
Asian	100	102	101	303
Native Hawaiian or Other Pacific Islander	0	1	0	1
Black or African American	22	19	22	63
White	191	197	200	588
More than once Race	9	7	7	23
Unknown or Not Reported	3	3	4	10
Ethnicity
Units: Subjects
Hispanic or Latino	63	67	61	191
Not Hispanic or Latino	140	131	140	411
Unknown or Not Reported	142	149	148	439

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

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

PK subset

Subject analysis set type

Sub-group analysis

Subject analysis set description

Population PK subset of all participants who received LY2127399.

Primary: Percentage of participants with American College of Rheumatology 20% response (ACR20) at Week 24

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End point title

Percentage of participants with American College of Rheumatology 20% response (ACR20) at Week 24

End point description

ACR Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis (RA). ACR20 Responder: had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥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. All randomized participants with evaluable ACR20 responder data.

End point type

Primary

End point timeframe

Baseline through 24 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	330 ^[1]	332 ^[2]	335 ^[3]
Units: percentage of participants
number (not applicable)	29.7	32.8	25.1

Notes
[1] - All randomized participants with evaluable ACR20 responder data.
[2] - All randomized participants with evaluable ACR20 responder data.
[3] - All randomized participants with evaluable ACR20 responder data.

Statistical Analysis 1

Comparison groups

120 mg LY2127399 v 90 mg LY2127399 v Placebo

Number of subjects included in analysis

997

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

> 0.05

Method

t-test, 2-sided

Confidence interval

Primary: Change from baseline to Week 52 in van der Heijde modified Total Sharp Score (mTSS)

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End point title

Change from baseline to Week 52 in van der Heijde modified Total Sharp Score (mTSS)

End point description

The mTSS quantifies the extent of bone erosions and joint space narrowing for 44 and 42 joints. X-rays of the hands/wrists and feet are scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (ankylosis or complete dislocation). Erosions scores (range = 0 to 220 for 44 joints) and narrowing scores (range = 0 to 168 for 42 joints) were added to obtain the mTSS (range = 0 [normal] to 388 [maximal disease]). Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with treatment and region as fixed factors and baseline as a covariate.

End point type

Primary

End point timeframe

Baseline, 52 Weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	295 ^[4]	304 ^[5]	306 ^[6]
Units: units on a scale
least squares mean (standard error)	1.43 ± 0.27	0.84 ± 0.27	1.57 ± 0.27

Notes
[4] - All randomized participants with evaluable mTSS data.
[5] - All randomized participants with evaluable mTSS data.
[6] - All randomized participants with evaluable mTSS data.

Statistical Analysis 3

Comparison groups

120 mg LY2127399 v 90 mg LY2127399 v Placebo

Number of subjects included in analysis

905

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

> 0.05

Method

t-test, 2-sided

Confidence interval

Primary: 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.

End point type

Primary

End point timeframe

Baseline, 24 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	329 ^[7]	329 ^[8]	328 ^[9]
Units: units on a scale
least squares mean (standard error)	-0.26 ± 0.03	-0.30 ± 0.03	-0.20 ± 0.03

Notes
[7] - All randomized participants with evaluable HAQ-DI data.
[8] - All randomized participants with evaluable HAQ-DI data.
[9] - All randomized participants with evaluable HAQ-DI data.

Stats analysis 2

Comparison groups

120 mg LY2127399 v 90 mg LY2127399 v Placebo

Number of subjects included in analysis

986

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

> 0.05

Method

t-test, 2-sided

Confidence interval

Secondary: Change from baseline 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 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 (mg/L)], and participant's global assessment of disease activity using visual analog scale (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 1.0-9.4, 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.

End point type

Secondary

End point timeframe

Baseline, 24 weeks and 52 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	328 ^[10]	327 ^[11]	328 ^[12]
Units: units on a scale
least squares mean (standard error)
Week 24	-1.02 ± 0.07	-1.00 ± 0.07	-0.78 ± 0.07
Week 52	-1.07 ± 0.07	-1.00 ± 0.07	-0.80 ± 0.07

Notes
[10] - All randomized participants with evaluable DAS28-CRP data
[11] - All randomized participants with evaluable DAS28-CRP data
[12] - All randomized participants with evaluable DAS28-CRP data

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 ≥50% improvement from baseline in both 68 tender joint (TJ) and 66 swollen joint (SJ) counts and ≥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 ≥70% improvement from baseline in both TJ and SJ counts and ≥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 Weeks 24 and 52 endpoints.

End point type

Secondary

End point timeframe

Baseline through 24 weeks and 52 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	330 ^[13]	332 ^[14]	335 ^[15]
Units: percentage of participants
number (not applicable)
ACR50- Week 24	10.6	11.1	10.1
ACR50- Week52	4.2	3.0	4.8
ACR70- Week 24	3.9	3.0	1.8
ACR70- Week 52	1.5	1.2	1.8

Notes
[13] - All randomized participants with evaluable ACR50 or ACR70 responder data.
[14] - All randomized participants with evaluable ACR50 or ACR70 responder data.
[15] - All randomized participants with evaluable ACR50 or ACR70 responder data.

No statistical analyses for this end point

Secondary: Change from baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey domain scores and summary scores

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End point title

Change from baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey domain scores 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 were calculated by summing each item for each domain and transforming scores into a 0-100 scale. Higher scores indicated better health status. If < 50% of the questions within a domain were answered, raw scores were 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. Higher score indicated 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, 24 weeks and 52 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	320 ^[16]	322 ^[17]	323 ^[18]
Units: units on a scale
least squares mean (standard error)
Physical functioning - Week 24 (n=320, 322, 323)	2.70 ± 0.48	3.16 ± 0.47	2.06 ± 0.47
Physical functioning - Week 52 (n=320, 322, 323)	2.15 ± 0.50	3.22 ± 0.49	1.82 ± 0.49
Bodily pain - Week 24 (n=319, 322, 323)	4.07 ± 0.46	4.08 ± 0.45	2.52 ± 0.45
Bodily pain - Week 52 (n=319, 322, 323)	3.77 ± 0.47	4.48 ± 0.46	2.32 ± 0.46
RL - physical problems - Week 24 (n=320, 322, 323)	2.77 ± 0.46	3.64 ± 0.46	1.99 ± 0.45
RL - physical problems - Week 52 (n=320, 322, 323)	3.01 ± 0.47	3.79 ± 0.46	1.82 ± 0.46
RL - emotional problems- Week 24 (n=319, 322, 323)	3.20 ± 0.60	4.81 ± 0.59	2.91 ± 0.59
RL - emotional problems- Week 52 (n=319, 322, 323)	2.84 ± 0.61	4.34 ± 0.59	2.56 ± 0.59
GH Perception - Week 24 (n=319, 322, 323)	2.60 ± 0.41	3.72 ± 0.40	2.54 ± 0.40
GH Perception - Week 52 (n=319, 322, 323)	2.89 ± 0.42	3.41 ± 0.41	2.18 ± 0.41
Mental Health - Week 24 (n=319, 322, 323)	3.39 ± 0.53	4.47 ± 0.53	3.28 ± 0.52
Mental Health - Week 52 (n=319, 322, 323)	3.01 ± 0.55	4.37 ± 0.54	3.10 ± 0.54
Social function - Week 24 (n=319, 322, 323)	3.25 ± 0.53	4.18 ± 0.52	2.79 ± 0.52
Social function - Week 52 (n=319, 322, 323)	3.04 ± 0.53	3.99 ± 0.52	2.87 ± 0.52
Vitality - Week 24 (n=319, 322, 323)	3.43 ± 0.50	4.41 ± 0.49	2.99 ± 0.48
Vitality - Week 52 (n=319, 322, 323)	3.10 ± 0.51	3.96 ± 0.50	3.02 ± 0.49
PCS - Week 24 (n=319, 322, 323)	2.80 ± 0.43	3.08 ± 0.43	1.76 ± 0.42
PCS - Week 52 (n=319, 322, 323)	2.79 ± 0.44	3.30 ± 0.43	1.55 ± 0.43
MCS - Week 24 (n=319, 322, 323)	3.34 ± 0.56	4.74 ± 0.55	3.33 ± 0.55
MCS - Week 52 (n=319, 322, 323)	2.98 ± 0.57	4.27 ± 0.56	3.22 ± 0.56

Notes
[16] - All randomized participants with evaluable SF-36 domain and summary scores.
[17] - All randomized participants with evaluable SF-36 domain and summary scores.
[18] - All randomized participants with evaluable SF-36 domain and summary scores.

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 based on 28 joint counts categorizes clinical response based on improvement since baseline in DAS28-CRP. 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 24 weeks and 52 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	328 ^[19]	327 ^[20]	328 ^[21]
Units: percentage of participants
number (not applicable)
Week 24- Good	17.7	16.2	14.3
Week 24 - Moderate	41.5	38.5	30.8
Week 24 - No Response	40.9	45.3	54.9
Week 52 - Good	18.6	14.7	15.9
Week 52 - Moderate	37.5	39.1	29.0
Week 52 - No Response	43.9	46.2	55.2

Notes
[19] - All randomized participants with evaluable EULAR response data
[20] - All randomized participants with evaluable EULAR response data
[21] - All randomized participants with evaluable EULAR response data

No statistical analyses for this end point

Secondary: Change from baseline in Brief Fatigue Inventory (BFI) individual items and impact score

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End point title

Change from baseline in Brief Fatigue Inventory (BFI) individual items and impact score

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, Item 1 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, 24 weeks and 52 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	320 ^[22]	322 ^[23]	323 ^[24]
Units: units on a scale
least squares mean (standard error)
Fatigue-Now - Week 24 (n=320, 322, 323)	-0.86 ± 0.14	-1.12 ± 0.13	-0.61 ± 0.13
Fatigue-Now - Week 52 (n=320, 322, 323)	-0.79 ± 0.14	-1.01 ± 0.13	-0.56 ± 0.13
Fatigue-Usual - Week 24 (n=320, 322, 323)	-0.93 ± 0.13	-1.06 ± 0.13	-0.61 ± 0.13
Fatigue-Usual - Week 52 (n=320, 322, 323)	-0.91 ± 0.14	-0.97 ± 0.13	-0.66 ± 0.13
Fatigue-Worst - Week 24 (n=320, 322, 323)	-0.98 ± 0.14	-1.22 ± 0.14	-0.71 ± 0.14
Fatigue-Worst - Week 52 (n=320, 322, 323)	-1.22 ± 0.15	-1.19 ± 0.14	-0.81 ± 0.14
General Activity - Week 24 (n=320, 322, 323)	-0.93 ± 0.14	-1.09 ± 0.13	-0.61 ± 0.13
General Activity - Week 52 (n=320, 322, 323	-1.03 ± 0.14	-1.07 ± 0.13	-0.61 ± 0.13
Mood - Week 24 (n=320, 322, 323)	-0.67 ± 0.14	-1.01 ± 0.14	-0.47 ± 0.14
Mood - Week 52 (n=320, 322, 323)	-0.86 ± 0.14	-0.82 ± 0.14	-0.53 ± 0.14
Walking Ability - Week 24 (n=320, 322, 323)	-0.92 ± 0.15	-1.02 ± 0.14	-0.44 ± 0.14
Walking Ability - Week 52 (n=320, 322, 323)	-0.88 ± 0.14	-0.98 ± 0.14	-0.45 ± 0.14
Normal Work - Week 24 (n=320, 322, 322)	-0.78 ± 0.14	-1.07 ± 0.14	-0.48 ± 0.14
Normal Work - Week 52 (n=320, 322, 323)	-0.88 ± 0.14	-1.00 ± 0.14	-0.52 ± 0.14
Relations with Other - Week 24 (n=320, 322, 322)	-0.39 ± 0.14	-0.64 ± 0.14	-0.13 ± 0.14
Relations with Other - Week 52 (n=320, 322, 323)	-0.47 ± 0.14	-0.46 ± 0.14	-0.16 ± 0.14
Enjoyment of Life - Week 24 (n=320, 322, 322)	-0.58 ± 0.15	-0.82 ± 0.15	-0.36 ± 0.14
Enjoyment of Life - Week 52 (n=320, 322, 323)	-0.66 ± 0.15	-0.74 ± 0.14	-0.46 ± 0.14
Fatigue Impact Subscale- Week 24(n=320, 322, 323)	-0.71 ± 0.13	-0.93 ± 0.13	-0.42 ± 0.23
Fatigue Impact Subscale- Week 52 (n=320, 322, 323)	-0.80 ± 0.13	-0.83 ± 0.13	-0.46 ± 0.13

Notes
[22] - All randomized participants with evaluable BFI data.
[23] - All randomized participants with evaluable BFI data.
[24] - All randomized participants with evaluable BFI data.

No statistical analyses for this end point

Secondary: Change from baseline in Brief Pain Inventory Short Form (BPI-SF) individual items and interference scores

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End point title

Change from baseline 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 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 were 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, 24 weeks and 52 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	320 ^[25]	322 ^[26]	323 ^[27]
Units: units on a scale
least squares mean (standard error)
Pain- Worst- Week 24	-1.1 ± 0.1	-1.1 ± 0.1	-0.7 ± 0.1
Pain-Worst- Week 52	-1.1 ± 0.1	-1.3 ± 0.1	-0.8 ± 0.1
Pain-Least- Week 24	-0.3 ± 0.1	-0.6 ± 0.1	-0.1 ± 0.1
Pain-Least - Week 52	-0.3 ± 0.1	-0.6 ± 0.1	-0.1 ± 0.1
Pain-Average - Week 24	-0.8 ± 0.1	-0.9 ± 0.1	-0.3 ± 0.1
Pain-Average - Week 52	-0.7 ± 0.1	-1.0 ± 0.1	-0.3 ± 0.1
Pain-Now - Week 24	-1.1 ± 0.1	-1.2 ± 0.1	-0.5 ± 0.1
Pain-Now - Week 52	-1.0 ± 0.1	-1.3 ± 0.1	-0.5 ± 0.1
General Activity - Week 24	-1.0 ± 0.1	-1.0 ± 0.1	-0.6 ± 0.1
General Activity - Week 52	-1.0 ± 0.1	-1.3 ± 0.1	-0.8 ± 0.1
Mood - Week 24	-0.9 ± 0.1	-1.0 ± 0.1	-0.6 ± 0.1
Mood - Week 52	-1.0 ± 0.1	-1.1 ± 0.1	-0.7 ± 0.1
Walking Ability - Week 24	-0.9 ± 0.1	-1.2 ± 0.1	-0.5 ± 0.1
Walking Ability - Week 52	-0.8 ± 0.1	-1.1 ± 0.1	-0.6 ± 0.1
Relations with Other - Week 24	-0.5 ± 0.1	-0.6 ± 0.1	-0.6 ± 0.1
Relations with Other - Week 52	-0.5 ± 0.1	-0.5 ± 0.1	-0.3 ± 0.1
Sleep - Week 24	-1.0 ± 0.1	-1.1 ± 0.1	-0.4 ± 0.1
Sleep - Week 52	-0.9 ± 0.1	-0.6 ± 0.1	-0.5 ± 0.1
Enjoyment of Life - Week 24	-0.8 ± 0.1	-1.2 ± 0.1	-0.5 ± 0.1
Enjoyment of Life - Week 52	-0.9 ± 0.1	-1.1 ± 0.1	-0.5 ± 0.1
Pain Interference Score - Week 24	-0.89 ± 0.12	-1.02 ± 0.12	-0.50 ± 0.12
Pain Interference Score - Week 52	-0.85 ± 0.12	-1.00 ± 0.12	-0.58 ± 0.12

Notes
[25] - All randomized participants with evaluable BPI-SF scores.
[26] - All randomized participants with evaluable BPI-SF scores.
[27] - All randomized participants with evaluable BPI-SF scores.

No statistical analyses for this end point

Secondary: Change from baseline in duration of morning stiffness (minutes)

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End point title

Change from baseline 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 the 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.

End point type

Secondary

End point timeframe

Baseline, 24 weeks and 52 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	307 ^[28]	319 ^[29]	314 ^[30]
Units: minutes
least squares mean (standard error)
Week 24 (n=306, 318, 313)	-41.2 ± 5.0	-32.0 ± 4.8	-34.5 ± 4.9
Week 52 (n= 307, 319, 314)	-41.4 ± 5.2	-31.2 ± 5.0	-37.3 ± 5.1

Notes
[28] - All randomized participants with evaluable morning stiffness data.
[29] - All randomized participants with evaluable morning stiffness data.
[30] - All randomized participants with evaluable morning stiffness data.

No statistical analyses for this end point

Secondary: Percentage of participants with change from baseline in mTSS less than or equal to (≤) 0

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End point title

Percentage of participants with change from baseline in mTSS less than or equal to (≤) 0

End point description

The mTSS quantifies the extent of bone erosions and joint space narrowing for 44 and 42 joints. X-rays of the hands/wrists and feet are scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (ankylosis or complete dislocation). Erosions scores (range=0 to 220 for 44 joints) and narrowing scores (range=0 to 168 for 42 joints) were added to obtain the mTSS (range = 0 [normal] to 388 [maximal disease]). Percentage of participants = (number of participants with mTSS ≤0 at Week 24) / (total number of participants analyzed in the group) * 100.

End point type

Secondary

End point timeframe

Baseline through 24 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	295 ^[31]	304 ^[32]	306 ^[33]
Units: percentage of participants
number (not applicable)	61.0	61.8	56.2

Notes
[31] - All randomized participants with evaluable mTSS data.
[32] - All randomized participants with evaluable mTSS data.
[33] - All randomized participants with evaluable mTSS data.

No statistical analyses for this end point

Secondary: Percentage of participants with Major Clinical Response (MCR) during 52 weeks

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End point title

Percentage of participants with Major Clinical Response (MCR) during 52 weeks

End point description

Zero participants were analyzed due to early termination of the study and statistical analysis plan (SAP) amendment.

End point type

Secondary

End point timeframe

Baseline through 52 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	0 ^[34]	0 ^[35]	0 ^[36]
Units: Participants
number (not applicable)

Notes
[34] - Zero participants were analyzed.
[35] - Zero participants were analyzed.
[36] - Zero participants were analyzed.

No statistical analyses for this end point

Secondary: Change from baseline to week 52 in B cell subset counts

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End point title

Change from baseline to week 52 in B cell subset counts

End point description

B cell subset counts are: cluster designation (CD)19+ B cell counts, Immature/transitional [CD19+immunoglobulin D (IgD)-CD27-], Mature naïve (CD19+IgD+CD27-), Non-switched memory (CD19+IgD+CD27+) and Memory (CD19+IgD-CD27+). 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.

End point type

Secondary

End point timeframe

Baseline, 52 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	326 ^[37]	333 ^[38]	339 ^[39]
Units: cells/microliter (cells/µL)
least squares mean (standard error)
CD19+ (n=326, 333, 339)	-57.1 ± 4.9	-60.9 ± 4.9	0.7 ± 4.8
CD19+IgD-CD27- (n=321, 330, 336)	-3.1 ± 0.7	-3.9 ± 0.07	0.2 ± 0.7
CD19+IgD+CD27- (n=321, 330, 336)	-89.4 ± 3.3	-92.4 ± 3.3	-3.5 ± 3.2
CD19+IgD+CD27+ (n=321, 330, 336)	9.5 ± 1.0	8.9 ± 1.0	1.0 ± 1.0
CD19+IgD-CD27+ (n=321, 330, 336)	19.7 ± 1.9	20.6 ± 1.8	3.2 ± 1.8

Notes
[37] - All randomized participants with evaluable B cell subset counts data
[38] - All randomized participants with evaluable B cell subset counts data
[39] - All randomized participants with evaluable B cell subset counts data

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.

End point type

Secondary

End point timeframe

Baseline through 52 weeks

End point values	PK subset
Number of subjects analysed	825 ^[40]
Units: milliliter per hour (mL/h)
arithmetic mean (confidence interval 95%)	3.60 (3.46 to 3.73)

Notes
[40] - All randomized participants who received at least 1 dose LY2127399 with evaluable PK data

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 antibodies (ADA) were participants who had any sample from baseline up to and through Week 24 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.

End point type

Secondary

End point timeframe

Baseline through 52 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	344 ^[41]	344 ^[42]	347 ^[43]
Units: percentage of participants
number (not applicable)	3.8	1.5	4.9

Notes
[41] - All randomized participants who received 1 dose of study drug evaluable ADA baseline & postbaseline
[42] - All randomized participants who received 1 dose of study drug evaluable ADA baseline & postbaseline
[43] - All randomized participants who received 1 dose of study drug evaluable ADA baseline & postbaseline

No statistical analyses for this end point

Secondary: Percentage of participants with No structural progression at Week 52

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End point title

Percentage of participants with No structural progression at Week 52

End point description

No structural progression is defined as the change in mTSS from baseline ≤0. The mTSS quantifies the extent of bone erosions and joint space narrowing for 44 and 42 joints. X-rays of the hands/wrists and feet are scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (ankylosis or complete dislocation). Erosions scores (range=0 to 220 for 44 joints) and narrowing scores (range=0 to 168 for 42 joints) were added to obtain the mTSS (range=0 [normal] to 388 [maximal disease]). Percentage of participants=(number of participants with mTSS ≤0 at Week 52) / (total number of participants analyzed in the group) * 100.

End point type

Secondary

End point timeframe

Baseline through 52 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	295 ^[44]	304 ^[45]	306 ^[46]
Units: percentage of participants
number (not applicable)	55.6	57.6	53.9

Notes
[44] - All randomized participants with evaluable mTSS data.
[45] - All randomized participants with evaluable mTSS data.
[46] - All randomized participants with evaluable mTSS data.

No statistical analyses for this end point

Secondary: Change from baseline to Week 24 in mTSS

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End point title

Change from baseline to Week 24 in mTSS

End point description

The mTSS quantifies the extent of bone erosions and joint space narrowing for 44 and 42 joints. X-rays of the hands/wrists and feet are scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (ankylosis or complete dislocation). Erosions scores (range=0 to 220 for 44 joints) and narrowing scores (range=0 to 168 for 42 joints) were added to obtain the mTSS (range=0 [normal] to 388 [maximal disease]). 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, 24 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	295 ^[47]	304 ^[48]	306 ^[49]
Units: units on a scale
least squares mean (standard error)	0.63 ± 0.14	0.45 ± 0.14	0.82 ± 0.14

Notes
[47] - All randomized participants with evaluable mTSS data.
[48] - All randomized participants with evaluable mTSS data.
[49] - All randomized participants with evaluable mTSS data.

No statistical analyses for this end point

Secondary: Change from baseline in serum immunoglobulin (Ig) levels

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End point title

Change from baseline in serum immunoglobulin (Ig) levels

End point description

Immunoglobulins (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 serum immunoglobulin G (IgG), immunoglobulin A (IgA), 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.

End point type

Secondary

End point timeframe

Baseline, 52 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	342 ^[50]	342 ^[51]	347 ^[52]
Units: grams/liter (g/L)
least squares mean (standard error)
IgA	-0.380 ± 0.028	-0.382 ± 0.028	-0.009 ± 0.028
IgG	-1.375 ± 0.096	-1.235 ± 0.097	-0.176 ± 0.096
IgM	-0.235 ± 0.016	-0.274 ± 0.016	-0.032 ± 0.016

Notes
[50] - All randomized participants with evaluable serum Ig data.
[51] - All randomized participants with evaluable serum Ig data.
[52] - All randomized participants with evaluable serum Ig data.

No statistical analyses for this end point

Secondary: Change from baseline in joint space narrowing score and bone erosions score (components of mTSS)

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End point title

Change from baseline in joint space narrowing score and bone erosions score (components of mTSS)

End point description

The mTSS quantifies the extent of bone erosions and joint space narrowing for 44 and 42 joints. X-rays of the hands/wrists and feet are scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (ankylosis or complete dislocation). Erosions scores (range=0 to 220 for 44 joints) and narrowing scores (range=0 to 168 for 42 joints) were added to obtain the mTSS (range=0 [normal] to 388 [maximal disease]). 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, 24 weeks and 52 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	295 ^[53]	304 ^[54]	306 ^[55]
Units: units on a scale
least squares mean (standard error)
Joint Space Narrowing - Week 24	0.22 ± 0.09	0.19 ± 0.09	0.34 ± 0.09
Joint Space Narrowing - Week 52	0.56 ± 0.16	0.35 ± 0.16	0.61 ± 0.16
Bone Erosions - Week 24	0.40 ± 0.09	0.26 ± 0.08	0.48 ± 0.08
Bone Erosions - Week 52	0.86 ± 0.17	0.49 ± 0.17	0.96 ± 0.17

Notes
[53] - All randomized participants with evaluable mTSS data.
[54] - All randomized participants with evaluable mTSS data.
[55] - All randomized participants with evaluable mTSS data.

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 TJ count, b) % change in SJ count, 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. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline DAS28-CRP as a covariate.

End point type

Secondary

End point timeframe

Baseline through 24 weeks and 52 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	329 ^[56]	326 ^[57]	327 ^[58]
Units: percentage of improvement
least squares mean (standard error)
Week 24	2.0 ± 2.5	2.1 ± 2.5	-6.9 ± 2.5
Week 52	2.9 ± 2.5	0.3 ± 2.5	-7.3 ± 2.5

Notes
[56] - All randomized participants with evaluable ACR-N data.
[57] - All randomized participants with evaluable ACR-N data.
[58] - All randomized participants with evaluable ACR-N data.

No statistical analyses for this end point

Secondary: Change from baseline in Tender Joint Count (68 joint count)

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End point title

Change from baseline 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.

End point type

Secondary

End point timeframe

Baseline, 24 weeks and 52 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	329 ^[59]	329 ^[60]	334 ^[61]
Units: joint counts
least squares mean (standard error)
Week 24	-7.41 ± 0.72	-7.88 ± 0.72	-6.40 ± 0.72
Week 52	-7.88 ± 0.73	-8.09 ± 0.73	-5.72 ± 0.73

Notes
[59] - All randomized participants with evaluable tender joint count data.
[60] - All randomized participants with evaluable tender joint count data.
[61] - All randomized participants with evaluable tender joint count data.

No statistical analyses for this end point

Secondary: Change from baseline in Swollen Joint Count (66 joint count)

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End point title

Change from baseline 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.

End point type

Secondary

End point timeframe

Baseline, 24 weeks and 52 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	329 ^[62]	329 ^[63]	334 ^[64]
Units: joint counts
least squares mean (standard error)
Week 24	-5.38 ± 0.49	-5.64 ± 0.49	-4.61 ± 0.49
Week 52	-6.10 ± 0.49	-5.53 ± 0.49	-4.67 ± 0.49

Notes
[62] - All randomized participants with evaluable swollen joint count data.
[63] - All randomized participants with evaluable swollen joint count data.
[64] - All randomized participants with evaluable swollen joint count data.

No statistical analyses for this end point

Secondary: Change from baseline in Participant's Assessment of Pain [Visual Analog Scale (VAS)]

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End point title

Change from baseline 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.

End point type

Secondary

End point timeframe

Baseline, 24 weeks and 52 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	329 ^[65]	327 ^[66]	328 ^[67]
Units: mm
least squares mean (standard error)
Week 24	-13.2 ± 1.2	-14.6 ± 1.2	-9.0 ± 1.2
Week 52	-13.6 ± 1.2	-14.6 ± 1.2	-8.7 ± 1.2

Notes
[65] - All randomized participants with evaluable participant's assessment of pain data.
[66] - All randomized participants with evaluable participant's assessment of pain data.
[67] - All randomized participants with evaluable participant's assessment of pain data.

No statistical analyses for this end point

Secondary: Change from baseline in Participant's Global Assessment of Disease Activity (VAS)

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End point title

Change from baseline 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.

End point type

Secondary

End point timeframe

Baseline, 24 weeks and 52 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	329 ^[68]	327 ^[69]	328 ^[70]
Units: mm
least squares mean (standard error)
Week 24	-13.6 ± 1.2	-14.6 ± 1.2	-9.0 ± 1.2
Week 52	-13.2 ± 1.2	-14.6 ± 1.2	-8.7 ± 1.2

Notes
[68] - All randomized participants with evaluable participant's assessment of pain data.
[69] - All randomized participants with evaluable participant's assessment of pain data.
[70] - All randomized participants with evaluable participant's assessment of pain data.

No statistical analyses for this end point

Secondary: Change from baseline in Physician's Global Assessment of Disease Activity (VAS)

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End point title

Change from baseline 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.

End point type

Secondary

End point timeframe

Baseline, 24 weeks and 52 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	321 ^[71]	315 ^[72]	314 ^[73]
Units: mm
least squares mean (standard error)
Week 24	-20.7 ± 1.3	-22.0 ± 1.3	-17.2 ± 1.3
Week 52	-20.4 ± 1.3	-20.6 ± 1.3	-17.8 ± 1.3

Notes
[71] - All randomized participants with evaluable physician's global assessment of disease activity data.
[72] - All randomized participants with evaluable physician's global assessment of disease activity data.
[73] - All randomized participants with evaluable physician's global assessment of disease activity data.

No statistical analyses for this end point

Secondary: Change from baseline to Week 52 in HAQ-DI

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End point title

Change from baseline to Week 52 in HAQ-DI

End point description

End point type

Secondary

End point timeframe

Baseline, 52 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	329 ^[74]	327 ^[75]	328 ^[76]
Units: units on a scale
least squares mean (standard error)	-0.24 ± 0.03	-0.30 ± 0.03	-0.18 ± 0.03

Notes
[74] - All randomized participants with evaluable HAQ-DI data.
[75] - All randomized participants with evaluable HAQ-DI data.
[76] - All randomized participants with evaluable HAQ-DI data.

No statistical analyses for this end point

Secondary: Change from baseline to week 52 in absolute B cell counts

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End point title

Change from baseline to week 52 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. 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.

End point type

Secondary

End point timeframe

Baseline, 52 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	343 ^[77]	344 ^[78]	348 ^[79]
Units: cells/microliter (cells/µL)
least squares mean (standard error)	-56.5 ± 4.5	-58.6 ± 4.5	-6.8 ± 4.5

Notes
[77] - All randomized participants with evaluable B cell subset counts data.
[78] - All randomized participants with evaluable B cell subset counts data
[79] - All randomized participants with evaluable B cell subset counts data

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

ACR Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis (RA). ACR20 Responder: had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, HAQ-DI (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and CRP. The Kaplan-Meier was used to estimate time to ACR20 response over the Treatment Period (52 weeks). Time to ACR20 response = (Date of the first post-baseline visit during the Treatment Period meeting ACR20 response criteria - Date of first injection of study treatment + 1) / 7. Week 16 NR are counted as responders if they responded prior to Week 16. Otherwise, they are censored at the date of the Week 16 injection. All participants ongoing at Week 52 and had not yet responded are censored at the date of the Week 52 visit.

End point type

Secondary

End point timeframe

Baseline through 52 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	327 ^[80]	327 ^[81]	329 ^[82]
Units: weeks
median (confidence interval 95%)	16.1 (12.1 to 16.4)	16.1 (12.3 to 20.0)	20.1 (16.4 to 24.7)

Notes
[80] - All randomized participants with evaluable ACR20 responder data.
[81] - All randomized participants with evaluable ACR20 responder data.
[82] - All randomized participants with evaluable ACR20 responder data.

No statistical analyses for this end point

Secondary: Percentage of participants with ACR20 at Week 52

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End point title

Percentage of participants with ACR20 at Week 52

End point description

ACR Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis (RA). ACR20 Responder: had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, HAQ-DI (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and 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 52 endpoint.

End point type

Secondary

End point timeframe

Baseline through 52 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	330 ^[83]	332 ^[84]	335 ^[85]
Units: percentage of participants
number (not applicable)	7.9	9.6	10.7

Notes
[83] - All randomized participants with evaluable ACR20 responder data.
[84] - All randomized participants with evaluable ACR20 responder data.
[85] - All randomized participants with evaluable ACR20 responder data.

No statistical analyses for this end point

Secondary: Change from baseline in CRP

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End point title

Change from baseline 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.

End point type

Secondary

End point timeframe

Baseline, 24 weeks and 52 weeks

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	329 ^[86]	328 ^[87]	334 ^[88]
Units: milligrams/liter (mg/L)
least squares mean (standard error)
Week 24	-3.30 ± 0.83	-2.03 ± 0.84	-0.54 ± 0.83
Week 52	-1.72 ± 0.96	-2.04 ± 0.97	-0.40 ± 0.96

Notes
[86] - All randomized participants with evaluable CRP data.
[87] - All randomized participants with evaluable CRP data.
[88] - All randomized participants with evaluable CRP data.

No statistical analyses for this end point

Other pre-specified: Number of participants who died during post-Treatment follow-Up period

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End point title

Number of participants who died during post-Treatment follow-Up period

End point description

End point type

Other pre-specified

End point timeframe

Discontinuation from study treatment up to 48 weeks during follow-up period

End point values	120 mg LY2127399	90 mg LY2127399	Placebo
Number of subjects analysed	293 ^[89]	303 ^[90]	307 ^[91]
Units: participants
number (not applicable)	0	1	2

Notes
[89] - All randomized participants who received study drug and entered follow up period.
[90] - All randomized participants who received study drug and entered follow up period.
[91] - All randomized participants who received study drug and entered follow up period.

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-BCDM

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

16.0

Reporting group title

LY 120 mg Q4W, Randomized Treatment Period 1

Reporting group description

Reporting group title

LY 90 mg Q2W, Randomized Treatment Period 1

Reporting group description

Reporting group title

Placebo, Randomized Treatment Period 1

Reporting group description

Reporting group title

LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Rescue Period

Reporting group description

Reporting group title

LY 90 mg Q2W, Rescue Period

Reporting group description

Reporting group title

Placebo to LY 90 mg Q2W (Week 16), Rescue Period

Reporting group description

Reporting group title

LY 120 mg Q4W, Treatment Period 2

Reporting group description

Reporting group title

LY 90 mg Q2W, Treatment Period 2

Reporting group description

Reporting group title

Placebo to LY 120 mg Q4W (Week 52), Treatment Period 2

Reporting group description

Reporting group title

Placebo to LY 90 mg Q2W (Week 52), Treatment Period 2

Reporting group description

Reporting group title

LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Treatment Period 2

Reporting group description

Reporting group title

Placebo to LY 90 mg Q2W (Week 16), Treatment Period 2

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 to LY 120 mg Q4W (Week 52), Follow-up Period

Reporting group description

Reporting group title

Placebo to LY 90 mg Q2W (Week 52), 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

Reporting group title

Placebo, Follow-up Period

Reporting group description

LY 120 mg Q4W, Randomized Treatment Period 1

LY 90 mg Q2W, Randomized Treatment Period 1

Placebo, Randomized Treatment Period 1

LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Rescue Period

LY 90 mg Q2W, Rescue Period

Placebo to LY 90 mg Q2W (Week 16), Rescue Period

LY 120 mg Q4W, Treatment Period 2

LY 90 mg Q2W, Treatment Period 2

Placebo to LY 120 mg Q4W (Week 52), Treatment Period 2

Placebo to LY 90 mg Q2W (Week 52), Treatment Period 2

LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Treatment Period 2

Placebo to LY 90 mg Q2W (Week 16), Treatment Period 2

LY 120 mg Q4W, Follow-up Period

LY 90 mg Q2W, Follow-up Period

Placebo to LY 120 mg Q4W (Week 52), Follow-up Period

Placebo to LY 90 mg Q2W (Week 52), 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

Placebo, Follow-up Period

Total subjects affected by serious adverse events

subjects affected / exposed

19 / 345 (5.51%)

17 / 345 (4.93%)

17 / 348 (4.89%)

3 / 58 (5.17%)

3 / 62 (4.84%)

2 / 90 (2.22%)

1 / 57 (1.75%)

1 / 73 (1.37%)

2 / 27 (7.41%)

1 / 31 (3.23%)

0 / 13 (0.00%)

0 / 22 (0.00%)

8 / 241 (3.32%)

11 / 303 (3.63%)

1 / 27 (3.70%)

4 / 52 (7.69%)

4 / 85 (4.71%)

12 / 168 (7.14%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

b-cell lymphoma stage i

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

1 / 345 (0.29%)

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

basal cell carcinoma

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

1 / 52 (1.92%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

bladder transitional cell carcinoma stage iii

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

1 / 31 (3.23%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

breast cancer

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

1 / 168 (0.60%)

occurrences causally related to treatment / all

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

cervix carcinoma

alternative dictionary used: MedDRA 16.0

subjects affected / exposed ^[1]

0 / 294 (0.00%)

1 / 289 (0.35%)

0 / 291 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

intraductal proliferative breast lesion

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

1 / 241 (0.41%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

metastatic gastric cancer

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

1 / 241 (0.41%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ovarian cancer

alternative dictionary used: MedDRA 16.0

subjects affected / exposed ^[2]

0 / 294 (0.00%)

1 / 289 (0.35%)

0 / 291 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

rectal adenocarcinoma

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

1 / 52 (1.92%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

squamous cell carcinoma

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

1 / 168 (0.60%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

uterine leiomyoma

alternative dictionary used: MedDRA 16.0

subjects affected / exposed ^[3]

1 / 294 (0.34%)

0 / 289 (0.00%)

0 / 291 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

deep vein thrombosis

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

1 / 345 (0.29%)

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hypotension

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

1 / 85 (1.18%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

peripheral ischaemia

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

1 / 345 (0.29%)

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

death

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

1 / 85 (1.18%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

device dislocation

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

1 / 90 (1.11%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

non-cardiac chest pain

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 348 (0.29%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pyrexia

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

1 / 241 (0.41%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Immune system disorders

drug hypersensitivity

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 345 (0.29%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Reproductive system and breast disorders

menorrhagia

alternative dictionary used: MedDRA 16.0

subjects affected / exposed ^[4]

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 211 (0.00%)

1 / 255 (0.39%)

0 / 22 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 66 (0.00%)

0 / 146 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

vaginal haemorrhage

alternative dictionary used: MedDRA 16.0

subjects affected / exposed ^[5]

1 / 294 (0.34%)

0 / 289 (0.00%)

0 / 291 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

acute pulmonary oedema

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

1 / 168 (0.60%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

chronic respiratory failure

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 348 (0.29%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

interstitial lung disease

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 345 (0.29%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

2 / 303 (0.66%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

lung disorder

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

1 / 168 (0.60%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

nasal septum deviation

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 345 (0.29%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

obliterative bronchiolitis

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

1 / 27 (3.70%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pulmonary embolism

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

1 / 345 (0.29%)

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

depression

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 348 (0.29%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

mental status changes

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

1 / 85 (1.18%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

stress

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

1 / 58 (1.72%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

suicide attempt

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

1 / 58 (1.72%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

femoral neck fracture

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

1 / 241 (0.41%)

1 / 303 (0.33%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

femur fracture

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

1 / 345 (0.29%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

2 / 27 (7.41%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

foot fracture

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

1 / 303 (0.33%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

head injury

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 345 (0.29%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

joint dislocation

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 345 (0.29%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

joint injury

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

1 / 62 (1.61%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

multiple injuries

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 345 (0.29%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pubis fracture

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 348 (0.29%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

radius fracture

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 348 (0.29%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

spinal compression fracture

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 345 (0.29%)

1 / 348 (0.29%)

1 / 58 (1.72%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

synovial rupture

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

1 / 303 (0.33%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

tendon rupture

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

2 / 345 (0.58%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

1 / 303 (0.33%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

acute myocardial infarction

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

1 / 303 (0.33%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

1 / 168 (0.60%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

arrhythmia

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

1 / 303 (0.33%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

atrial fibrillation

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

1 / 168 (0.60%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

cardiac failure chronic

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 348 (0.29%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cardiogenic shock

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 348 (0.29%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

congestive cardiomyopathy

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

1 / 168 (0.60%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

coronary artery insufficiency

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 348 (0.29%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

myocardial infarction

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

1 / 345 (0.29%)

0 / 345 (0.00%)

2 / 348 (0.57%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

1 / 303 (0.33%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

1 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

sick sinus syndrome

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

1 / 62 (1.61%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

cerebral atrophy

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

1 / 85 (1.18%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cerebral small vessel ischaemic disease

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

1 / 85 (1.18%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cerebrovascular accident

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

1 / 85 (1.18%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

convulsion

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

1 / 85 (1.18%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

encephalopathy

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

1 / 85 (1.18%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

headache

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 345 (0.29%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hemiparesis

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

1 / 85 (1.18%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

lumbar radiculopathy

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

1 / 345 (0.29%)

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

presyncope

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

1 / 303 (0.33%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

radiculitis lumbosacral

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 345 (0.29%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

syncope

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 345 (0.29%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

transient ischaemic attack

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

1 / 345 (0.29%)

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

anaemia

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

1 / 345 (0.29%)

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

1 / 85 (1.18%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

iron deficiency anaemia

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

1 / 73 (1.37%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pancytopenia

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

1 / 241 (0.41%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Eye disorders

ulcerative keratitis

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

1 / 345 (0.29%)

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

gastric haemorrhage

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

1 / 345 (0.29%)

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

gastric ulcer

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 348 (0.29%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hiatus hernia

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

1 / 303 (0.33%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

mechanical ileus

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

1 / 241 (0.41%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

nausea

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 345 (0.29%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pancreatitis acute

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

1 / 345 (0.29%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pancreatitis chronic

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 345 (0.29%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

vomiting

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 345 (0.29%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

cholecystitis

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 348 (0.29%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cholelithiasis

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 348 (0.29%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

calculus ureteric

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

1 / 58 (1.72%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

nephrolithiasis

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 345 (0.29%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

renal failure acute

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

1 / 345 (0.29%)

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

1 / 85 (1.18%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

arthralgia

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

1 / 168 (0.60%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

foot deformity

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 345 (0.29%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

intervertebral disc protrusion

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

1 / 345 (0.29%)

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

monarthritis

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 348 (0.29%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

osteoarthritis

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

1 / 345 (0.29%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

1 / 303 (0.33%)

0 / 27 (0.00%)

0 / 52 (0.00%)

1 / 85 (1.18%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

rheumatoid arthritis

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

1 / 345 (0.29%)

4 / 348 (1.15%)

1 / 58 (1.72%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

1 / 241 (0.41%)

1 / 303 (0.33%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

3 / 168 (1.79%)

occurrences causally related to treatment / all

0 / 1

1 / 4

0 / 1

0 / 0

0 / 1

1 / 1

0 / 0

0 / 3

deaths causally related to treatment / all

0 / 0

spinal column stenosis

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

1 / 241 (0.41%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

spondylolisthesis

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 348 (0.29%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

bronchitis

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

1 / 345 (0.29%)

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cellulitis

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

1 / 57 (1.75%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

1 / 52 (1.92%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

device related infection

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

1 / 52 (1.92%)

0 / 85 (0.00%)

1 / 168 (0.60%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

diverticulitis

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

1 / 345 (0.29%)

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

enteritis infectious

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

1 / 345 (0.29%)

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

gastroenteritis

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

1 / 62 (1.61%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

1 / 168 (0.60%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

herpes zoster

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

2 / 345 (0.58%)

1 / 345 (0.29%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

2 / 2

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

infective tenosynovitis

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

1 / 168 (0.60%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

influenza

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

1 / 241 (0.41%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

peritonitis

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

1 / 345 (0.29%)

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pneumonia

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

1 / 90 (1.11%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

1 / 303 (0.33%)

0 / 27 (0.00%)

0 / 52 (0.00%)

1 / 85 (1.18%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

post procedural infection

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

1 / 85 (1.18%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pseudomembranous colitis

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 348 (0.29%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pyelonephritis acute

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

1 / 241 (0.41%)

0 / 303 (0.00%)

0 / 27 (0.00%)

1 / 27 (3.70%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pyelonephritis chronic

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

0 / 345 (0.00%)

1 / 345 (0.29%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

sepsis

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

1 / 345 (0.29%)

0 / 345 (0.00%)

1 / 348 (0.29%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

1 / 1

0 / 0

urinary tract infection

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

1 / 345 (0.29%)

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

diabetes mellitus inadequate control

alternative dictionary used: MedDRA 16.0

subjects affected / exposed

1 / 345 (0.29%)

0 / 345 (0.00%)

0 / 348 (0.00%)

0 / 58 (0.00%)

0 / 62 (0.00%)

0 / 90 (0.00%)

0 / 57 (0.00%)

0 / 73 (0.00%)

0 / 27 (0.00%)

0 / 31 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 241 (0.00%)

0 / 303 (0.00%)

0 / 27 (0.00%)

0 / 52 (0.00%)

0 / 85 (0.00%)

0 / 168 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. 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 to this adverse event. 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.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. 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.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. 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.
[5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. 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.

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

Non-serious adverse events	LY 120 mg Q4W, Randomized Treatment Period 1	LY 90 mg Q2W, Randomized Treatment Period 1	Placebo, Randomized Treatment Period 1	LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Rescue Period	LY 90 mg Q2W, Rescue Period	Placebo to LY 90 mg Q2W (Week 16), Rescue Period	LY 120 mg Q4W, Treatment Period 2	LY 90 mg Q2W, Treatment Period 2	Placebo to LY 120 mg Q4W (Week 52), Treatment Period 2	Placebo to LY 90 mg Q2W (Week 52), Treatment Period 2	LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Treatment Period 2	Placebo to LY 90 mg Q2W (Week 16), Treatment Period 2	LY 120 mg Q4W, Follow-up Period	LY 90 mg Q2W, Follow-up Period	Placebo to LY 120 mg Q4W (Week 52), Follow-up Period	Placebo to LY 90 mg Q2W (Week 52), 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	Placebo, Follow-up Period
Total subjects affected by non serious adverse events
subjects affected / exposed	137 / 345 (39.71%)	117 / 345 (33.91%)	129 / 348 (37.07%)	22 / 58 (37.93%)	25 / 62 (40.32%)	20 / 90 (22.22%)	22 / 57 (38.60%)	20 / 73 (27.40%)	7 / 27 (25.93%)	4 / 31 (12.90%)	7 / 13 (53.85%)	9 / 22 (40.91%)	43 / 241 (17.84%)	39 / 303 (12.87%)	6 / 27 (22.22%)	9 / 27 (33.33%)	10 / 52 (19.23%)	10 / 85 (11.76%)	26 / 168 (15.48%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
neuroma
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 345 (0.00%)	0 / 345 (0.00%)	0 / 348 (0.00%)	0 / 58 (0.00%)	0 / 62 (0.00%)	1 / 90 (1.11%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 22 (4.55%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0
ovarian germ cell teratoma benign
alternative dictionary used: MedDRA 16.0
subjects affected / exposed ^[6]	0 / 345 (0.00%)	0 / 345 (0.00%)	0 / 348 (0.00%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 211 (0.00%)	0 / 255 (0.00%)	0 / 22 (0.00%)	1 / 24 (4.17%)	0 / 40 (0.00%)	0 / 66 (0.00%)	0 / 146 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
uterine leiomyoma
alternative dictionary used: MedDRA 16.0
subjects affected / exposed ^[7]	1 / 294 (0.34%)	1 / 289 (0.35%)	0 / 291 (0.00%)	1 / 44 (2.27%)	0 / 57 (0.00%)	0 / 69 (0.00%)	1 / 51 (1.96%)	1 / 62 (1.61%)	0 / 22 (0.00%)	0 / 27 (0.00%)	0 / 9 (0.00%)	0 / 19 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	1	1	0	1	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0
Vascular disorders
haematoma
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 345 (0.00%)	0 / 345 (0.00%)	0 / 348 (0.00%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	2 / 57 (3.51%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0
hypertension
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	12 / 345 (3.48%)	3 / 345 (0.87%)	7 / 348 (2.01%)	2 / 58 (3.45%)	0 / 62 (0.00%)	0 / 90 (0.00%)	2 / 57 (3.51%)	2 / 73 (2.74%)	1 / 27 (3.70%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	1 / 241 (0.41%)	2 / 303 (0.66%)	0 / 27 (0.00%)	1 / 27 (3.70%)	0 / 52 (0.00%)	0 / 85 (0.00%)	1 / 168 (0.60%)
occurrences all number	13	3	7	2	0	0	2	2	1	0	0	0	1	2	0	1	0	0	1
hypotension
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 345 (0.29%)	2 / 345 (0.58%)	0 / 348 (0.00%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	1 / 27 (3.70%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	1 / 27 (3.70%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	1	2	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0
General disorders and administration site conditions
injection site erythema
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	4 / 345 (1.16%)	4 / 345 (1.16%)	1 / 348 (0.29%)	0 / 58 (0.00%)	2 / 62 (3.23%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	1 / 303 (0.33%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	5	5	1	0	2	0	0	0	0	0	0	0	0	1	0	0	0	0	0
malaise
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 345 (0.29%)	0 / 345 (0.00%)	2 / 348 (0.57%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	1 / 27 (3.70%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	1	0	2	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
oedema peripheral
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	3 / 345 (0.87%)	1 / 345 (0.29%)	3 / 348 (0.86%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 22 (4.55%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	1 / 85 (1.18%)	1 / 168 (0.60%)
occurrences all number	3	1	3	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	1
pyrexia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	3 / 345 (0.87%)	3 / 345 (0.87%)	1 / 348 (0.29%)	1 / 58 (1.72%)	0 / 62 (0.00%)	1 / 90 (1.11%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	2 / 303 (0.66%)	0 / 27 (0.00%)	1 / 27 (3.70%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	3	3	1	1	0	2	0	0	0	0	0	0	0	3	0	1	0	0	0
Reproductive system and breast disorders
benign prostatic hyperplasia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed ^[8]	0 / 51 (0.00%)	1 / 56 (1.79%)	0 / 57 (0.00%)	0 / 14 (0.00%)	1 / 5 (20.00%)	0 / 21 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 30 (0.00%)	1 / 48 (2.08%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 12 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0
metrorrhagia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed ^[9]	0 / 345 (0.00%)	0 / 345 (0.00%)	0 / 348 (0.00%)	1 / 44 (2.27%)	0 / 57 (0.00%)	0 / 69 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
uterine prolapse
alternative dictionary used: MedDRA 16.0
subjects affected / exposed ^[10]	1 / 294 (0.34%)	0 / 289 (0.00%)	0 / 291 (0.00%)	1 / 44 (2.27%)	0 / 57 (0.00%)	0 / 69 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
asthma
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 345 (0.00%)	0 / 345 (0.00%)	0 / 348 (0.00%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	1 / 27 (3.70%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
cough
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	7 / 345 (2.03%)	3 / 345 (0.87%)	5 / 348 (1.44%)	1 / 58 (1.72%)	0 / 62 (0.00%)	2 / 90 (2.22%)	1 / 57 (1.75%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	3 / 241 (1.24%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	1 / 85 (1.18%)	0 / 168 (0.00%)
occurrences all number	8	3	5	1	0	2	1	0	0	0	0	0	3	0	0	0	0	1	0
Psychiatric disorders
anxiety
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	3 / 345 (0.87%)	1 / 345 (0.29%)	1 / 348 (0.29%)	0 / 58 (0.00%)	0 / 62 (0.00%)	1 / 90 (1.11%)	0 / 57 (0.00%)	2 / 73 (2.74%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 22 (4.55%)	1 / 241 (0.41%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	1 / 168 (0.60%)
occurrences all number	3	1	1	0	0	1	0	2	0	0	0	1	1	0	0	0	0	0	1
depression
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	2 / 345 (0.58%)	1 / 345 (0.29%)	1 / 348 (0.29%)	0 / 58 (0.00%)	2 / 62 (3.23%)	1 / 90 (1.11%)	0 / 57 (0.00%)	3 / 73 (4.11%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 22 (4.55%)	0 / 241 (0.00%)	1 / 303 (0.33%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	2	1	1	0	2	1	0	3	0	0	0	1	0	1	0	0	0	0	0
insomnia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	7 / 345 (2.03%)	3 / 345 (0.87%)	3 / 348 (0.86%)	0 / 58 (0.00%)	0 / 62 (0.00%)	1 / 90 (1.11%)	2 / 57 (3.51%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	7	3	3	0	0	1	2	0	0	0	0	0	0	0	0	0	0	0	0
Investigations
alanine aminotransferase increased
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	4 / 345 (1.16%)	2 / 345 (0.58%)	6 / 348 (1.72%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 22 (4.55%)	1 / 241 (0.41%)	1 / 303 (0.33%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	4	2	6	0	0	0	0	0	0	0	0	2	1	1	0	0	0	0	0
blood alkaline phosphatase increased
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 345 (0.00%)	0 / 345 (0.00%)	1 / 348 (0.29%)	1 / 58 (1.72%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 22 (4.55%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	1 / 52 (1.92%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0
blood glucose increased
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	2 / 345 (0.58%)	0 / 345 (0.00%)	0 / 348 (0.00%)	1 / 58 (1.72%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 22 (0.00%)	1 / 241 (0.41%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	2	0	0	1	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0
blood potassium decreased
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 345 (0.00%)	0 / 345 (0.00%)	0 / 348 (0.00%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	1 / 303 (0.33%)	0 / 27 (0.00%)	1 / 27 (3.70%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	1	0	0	0
gamma-glutamyltransferase increased
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 345 (0.00%)	2 / 345 (0.58%)	1 / 348 (0.29%)	2 / 58 (3.45%)	1 / 62 (1.61%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	1 / 22 (4.55%)	0 / 241 (0.00%)	1 / 303 (0.33%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	0	2	1	2	1	0	0	0	0	1	0	1	0	1	0	0	0	0	0
haemoglobin decreased
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	2 / 345 (0.58%)	0 / 345 (0.00%)	1 / 348 (0.29%)	1 / 58 (1.72%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 22 (0.00%)	1 / 241 (0.41%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	2	0	1	1	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0
liver function test abnormal
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 345 (0.29%)	0 / 345 (0.00%)	0 / 348 (0.00%)	1 / 58 (1.72%)	1 / 62 (1.61%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 22 (0.00%)	0 / 241 (0.00%)	1 / 303 (0.33%)	0 / 27 (0.00%)	0 / 27 (0.00%)	1 / 52 (1.92%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	1	0	0	1	1	0	0	0	0	0	1	0	0	1	0	0	1	0	0
white blood cell count decreased
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 345 (0.00%)	1 / 345 (0.29%)	1 / 348 (0.29%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	1 / 73 (1.37%)	1 / 27 (3.70%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	0	1	1	0	0	0	0	1	1	0	1	0	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
contusion
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	3 / 345 (0.87%)	1 / 345 (0.29%)	4 / 348 (1.15%)	0 / 58 (0.00%)	1 / 62 (1.61%)	0 / 90 (0.00%)	0 / 57 (0.00%)	2 / 73 (2.74%)	0 / 27 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	1 / 168 (0.60%)
occurrences all number	3	1	4	0	1	0	0	2	0	1	0	0	0	0	0	0	0	0	1
ligament sprain
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	2 / 345 (0.58%)	1 / 345 (0.29%)	2 / 348 (0.57%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	2 / 57 (3.51%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	1 / 241 (0.41%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	2	1	2	0	0	0	2	0	0	0	0	0	1	0	0	0	0	0	0
muscle strain
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 345 (0.00%)	0 / 345 (0.00%)	0 / 348 (0.00%)	0 / 58 (0.00%)	0 / 62 (0.00%)	1 / 90 (1.11%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 22 (4.55%)	0 / 241 (0.00%)	0 / 303 (0.00%)	1 / 27 (3.70%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	1	0	0	1	0	0	0	0
radius fracture
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 345 (0.00%)	0 / 345 (0.00%)	0 / 348 (0.00%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	1 / 27 (3.70%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
tendon injury
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 345 (0.00%)	0 / 345 (0.00%)	0 / 348 (0.00%)	1 / 58 (1.72%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Cardiac disorders
tachycardia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	2 / 345 (0.58%)	0 / 345 (0.00%)	0 / 348 (0.00%)	0 / 58 (0.00%)	0 / 62 (0.00%)	1 / 90 (1.11%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	1 / 27 (3.70%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	2	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0
Nervous system disorders
carpal tunnel syndrome
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	2 / 345 (0.58%)	0 / 345 (0.00%)	2 / 348 (0.57%)	0 / 58 (0.00%)	0 / 62 (0.00%)	1 / 90 (1.11%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 22 (4.55%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	2	0	3	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0
dizziness
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	4 / 345 (1.16%)	6 / 345 (1.74%)	5 / 348 (1.44%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	2 / 57 (3.51%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	1 / 85 (1.18%)	0 / 168 (0.00%)
occurrences all number	4	6	5	0	0	0	2	1	0	0	0	0	0	0	0	0	0	1	0
headache
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	7 / 345 (2.03%)	6 / 345 (1.74%)	3 / 348 (0.86%)	1 / 58 (1.72%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	2 / 241 (0.83%)	1 / 303 (0.33%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	2 / 85 (2.35%)	1 / 168 (0.60%)
occurrences all number	10	6	3	1	0	0	0	1	0	0	0	0	2	1	0	0	0	2	1
hypoaesthesia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 345 (0.00%)	0 / 345 (0.00%)	2 / 348 (0.57%)	1 / 58 (1.72%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	0	0	2	1	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0
migraine
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 345 (0.29%)	2 / 345 (0.58%)	0 / 348 (0.00%)	0 / 58 (0.00%)	1 / 62 (1.61%)	0 / 90 (0.00%)	0 / 57 (0.00%)	2 / 73 (2.74%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	1	2	0	0	1	0	0	2	0	0	0	0	0	0	0	0	0	0	0
paraesthesia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 345 (0.29%)	0 / 345 (0.00%)	1 / 348 (0.29%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	1 / 57 (1.75%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	1 / 27 (3.70%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	1	0	1	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0
Blood and lymphatic system disorders
anaemia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	8 / 345 (2.32%)	6 / 345 (1.74%)	11 / 348 (3.16%)	1 / 58 (1.72%)	0 / 62 (0.00%)	5 / 90 (5.56%)	0 / 57 (0.00%)	0 / 73 (0.00%)	1 / 27 (3.70%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	1 / 241 (0.41%)	1 / 303 (0.33%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	8	6	11	1	0	5	0	0	1	0	0	0	1	1	0	0	0	0	0
leukocytosis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 345 (0.29%)	0 / 345 (0.00%)	0 / 348 (0.00%)	1 / 58 (1.72%)	1 / 62 (1.61%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	1 / 27 (3.70%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	1	0	0	1	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0
lymphopenia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	5 / 345 (1.45%)	1 / 345 (0.29%)	2 / 348 (0.57%)	1 / 58 (1.72%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	2 / 241 (0.83%)	1 / 303 (0.33%)	1 / 27 (3.70%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	6	2	2	1	0	0	0	0	0	0	0	0	2	1	1	0	0	0	0
Eye disorders
cataract
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	2 / 345 (0.58%)	2 / 345 (0.58%)	1 / 348 (0.29%)	0 / 58 (0.00%)	2 / 62 (3.23%)	0 / 90 (0.00%)	1 / 57 (1.75%)	3 / 73 (4.11%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	1 / 241 (0.41%)	1 / 303 (0.33%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	1 / 168 (0.60%)
occurrences all number	2	2	1	0	3	0	1	3	0	0	0	0	1	1	0	0	0	0	1
Gastrointestinal disorders
abdominal pain upper
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	2 / 345 (0.58%)	2 / 345 (0.58%)	1 / 348 (0.29%)	1 / 58 (1.72%)	0 / 62 (0.00%)	1 / 90 (1.11%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	1 / 303 (0.33%)	0 / 27 (0.00%)	0 / 27 (0.00%)	2 / 52 (3.85%)	0 / 85 (0.00%)	1 / 168 (0.60%)
occurrences all number	2	2	1	1	0	1	0	0	0	0	0	0	0	1	0	0	2	0	1
constipation
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	4 / 345 (1.16%)	3 / 345 (0.87%)	6 / 348 (1.72%)	0 / 58 (0.00%)	1 / 62 (1.61%)	0 / 90 (0.00%)	3 / 57 (5.26%)	0 / 73 (0.00%)	0 / 27 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 22 (0.00%)	3 / 241 (1.24%)	2 / 303 (0.66%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	4	3	6	0	1	0	3	0	0	1	0	0	3	2	0	0	0	0	0
diarrhoea
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	7 / 345 (2.03%)	9 / 345 (2.61%)	5 / 348 (1.44%)	1 / 58 (1.72%)	1 / 62 (1.61%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	3 / 241 (1.24%)	1 / 303 (0.33%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	1 / 168 (0.60%)
occurrences all number	7	9	6	1	1	0	0	0	0	0	0	0	3	1	0	0	0	0	1
dyspepsia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	3 / 345 (0.87%)	1 / 345 (0.29%)	2 / 348 (0.57%)	2 / 58 (3.45%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	1 / 85 (1.18%)	0 / 168 (0.00%)
occurrences all number	3	1	2	2	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
gastrooesophageal reflux disease
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	2 / 345 (0.58%)	1 / 345 (0.29%)	5 / 348 (1.44%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	1 / 57 (1.75%)	0 / 73 (0.00%)	1 / 27 (3.70%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	2 / 241 (0.83%)	1 / 303 (0.33%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	1 / 168 (0.60%)
occurrences all number	2	1	5	0	0	0	1	0	1	0	0	0	2	1	0	0	0	0	1
nausea
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	7 / 345 (2.03%)	7 / 345 (2.03%)	3 / 348 (0.86%)	2 / 58 (3.45%)	1 / 62 (1.61%)	1 / 90 (1.11%)	1 / 57 (1.75%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 22 (4.55%)	1 / 241 (0.41%)	1 / 303 (0.33%)	0 / 27 (0.00%)	0 / 27 (0.00%)	1 / 52 (1.92%)	0 / 85 (0.00%)	3 / 168 (1.79%)
occurrences all number	7	11	3	2	1	1	1	0	0	0	0	1	1	1	0	0	1	0	3
stomatitis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	3 / 345 (0.87%)	0 / 345 (0.00%)	1 / 348 (0.29%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	1 / 27 (3.70%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 22 (0.00%)	1 / 241 (0.41%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	1 / 168 (0.60%)
occurrences all number	4	0	1	0	0	0	0	0	1	1	0	0	1	0	0	0	0	0	1
Hepatobiliary disorders
hepatic function abnormal
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	3 / 345 (0.87%)	1 / 345 (0.29%)	2 / 348 (0.57%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	1 / 27 (3.70%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	3	1	2	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Skin and subcutaneous tissue disorders
alopecia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 345 (0.29%)	3 / 345 (0.87%)	1 / 348 (0.29%)	0 / 58 (0.00%)	1 / 62 (1.61%)	0 / 90 (0.00%)	1 / 57 (1.75%)	2 / 73 (2.74%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	1	3	1	0	1	0	1	2	0	0	0	0	0	0	0	0	0	0	0
rash
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	6 / 345 (1.74%)	3 / 345 (0.87%)	5 / 348 (1.44%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	2 / 57 (3.51%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	1 / 241 (0.41%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	6	3	6	0	0	0	2	0	0	0	0	0	1	0	0	0	0	0	0
Renal and urinary disorders
pollakiuria
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 345 (0.00%)	0 / 345 (0.00%)	0 / 348 (0.00%)	1 / 58 (1.72%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	1 / 241 (0.41%)	1 / 303 (0.33%)	0 / 27 (0.00%)	1 / 27 (3.70%)	0 / 52 (0.00%)	0 / 85 (0.00%)	1 / 168 (0.60%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	1	1	0	1	0	0	1
stress urinary incontinence
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 345 (0.00%)	0 / 345 (0.00%)	0 / 348 (0.00%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	1 / 27 (3.70%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Musculoskeletal and connective tissue disorders
arthralgia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	6 / 345 (1.74%)	9 / 345 (2.61%)	7 / 348 (2.01%)	2 / 58 (3.45%)	0 / 62 (0.00%)	1 / 90 (1.11%)	1 / 57 (1.75%)	2 / 73 (2.74%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 22 (4.55%)	2 / 241 (0.83%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	1 / 85 (1.18%)	0 / 168 (0.00%)
occurrences all number	9	10	7	8	0	1	1	2	0	0	0	1	2	0	0	0	0	1	0
back pain
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	10 / 345 (2.90%)	6 / 345 (1.74%)	5 / 348 (1.44%)	1 / 58 (1.72%)	0 / 62 (0.00%)	0 / 90 (0.00%)	2 / 57 (3.51%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	1 / 241 (0.41%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	2 / 52 (3.85%)	1 / 85 (1.18%)	0 / 168 (0.00%)
occurrences all number	10	6	5	1	0	0	2	0	0	0	0	0	1	0	0	0	2	1	0
bunion
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 345 (0.00%)	0 / 345 (0.00%)	1 / 348 (0.29%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 22 (4.55%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	1 / 85 (1.18%)	0 / 168 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	2	0
foot deformity
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 345 (0.29%)	1 / 345 (0.29%)	1 / 348 (0.29%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	1 / 57 (1.75%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 22 (4.55%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	1	1	1	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0
osteoarthritis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	3 / 345 (0.87%)	0 / 345 (0.00%)	1 / 348 (0.29%)	2 / 58 (3.45%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	3	0	1	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
pain in extremity
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	4 / 345 (1.16%)	1 / 345 (0.29%)	3 / 348 (0.86%)	2 / 58 (3.45%)	1 / 62 (1.61%)	0 / 90 (0.00%)	0 / 57 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	1 / 303 (0.33%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	5	1	3	3	1	0	0	1	0	0	0	0	0	1	0	0	0	0	0
rheumatoid arthritis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	12 / 345 (3.48%)	19 / 345 (5.51%)	15 / 348 (4.31%)	3 / 58 (5.17%)	5 / 62 (8.06%)	0 / 90 (0.00%)	5 / 57 (8.77%)	3 / 73 (4.11%)	0 / 27 (0.00%)	0 / 31 (0.00%)	2 / 13 (15.38%)	0 / 22 (0.00%)	5 / 241 (2.07%)	4 / 303 (1.32%)	0 / 27 (0.00%)	2 / 27 (7.41%)	1 / 52 (1.92%)	0 / 85 (0.00%)	3 / 168 (1.79%)
occurrences all number	14	20	18	3	5	0	5	3	0	0	2	0	5	4	0	2	1	0	3
tenosynovitis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 345 (0.00%)	1 / 345 (0.29%)	0 / 348 (0.00%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 22 (4.55%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Infections and infestations
bronchitis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	8 / 345 (2.32%)	8 / 345 (2.32%)	11 / 348 (3.16%)	1 / 58 (1.72%)	3 / 62 (4.84%)	1 / 90 (1.11%)	1 / 57 (1.75%)	1 / 73 (1.37%)	1 / 27 (3.70%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	1 / 241 (0.41%)	1 / 303 (0.33%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	1 / 168 (0.60%)
occurrences all number	8	8	11	1	3	1	1	1	1	0	0	0	1	1	0	0	0	0	1
candidiasis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 345 (0.00%)	0 / 345 (0.00%)	0 / 348 (0.00%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	1 / 27 (3.70%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
cellulitis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 345 (0.29%)	1 / 345 (0.29%)	0 / 348 (0.00%)	0 / 58 (0.00%)	0 / 62 (0.00%)	1 / 90 (1.11%)	0 / 57 (0.00%)	0 / 73 (0.00%)	1 / 27 (3.70%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 22 (4.55%)	0 / 241 (0.00%)	1 / 303 (0.33%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	2	1	0	0	0	1	0	0	1	0	0	1	0	1	0	0	0	0	0
cystitis bacterial
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 345 (0.00%)	0 / 345 (0.00%)	0 / 348 (0.00%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	1 / 27 (3.70%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
herpes zoster
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 345 (0.29%)	2 / 345 (0.58%)	2 / 348 (0.57%)	0 / 58 (0.00%)	0 / 62 (0.00%)	1 / 90 (1.11%)	2 / 57 (3.51%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 22 (4.55%)	2 / 241 (0.83%)	1 / 303 (0.33%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	1	2	2	0	0	1	2	0	0	0	0	1	2	1	0	0	0	0	0
influenza
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 345 (0.29%)	2 / 345 (0.58%)	8 / 348 (2.30%)	0 / 58 (0.00%)	1 / 62 (1.61%)	1 / 90 (1.11%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	1 / 241 (0.41%)	2 / 303 (0.66%)	1 / 27 (3.70%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	2 / 168 (1.19%)
occurrences all number	1	2	8	0	1	1	0	0	0	0	0	0	1	2	1	0	0	0	2
nasopharyngitis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	20 / 345 (5.80%)	15 / 345 (4.35%)	25 / 348 (7.18%)	2 / 58 (3.45%)	3 / 62 (4.84%)	2 / 90 (2.22%)	1 / 57 (1.75%)	3 / 73 (4.11%)	1 / 27 (3.70%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	7 / 241 (2.90%)	7 / 303 (2.31%)	0 / 27 (0.00%)	3 / 27 (11.11%)	1 / 52 (1.92%)	0 / 85 (0.00%)	5 / 168 (2.98%)
occurrences all number	25	22	34	2	4	2	1	3	1	0	0	0	8	9	0	3	1	0	5
onychomycosis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 345 (0.00%)	0 / 345 (0.00%)	0 / 348 (0.00%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 22 (0.00%)	1 / 241 (0.41%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0
pharyngitis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	7 / 345 (2.03%)	4 / 345 (1.16%)	5 / 348 (1.44%)	0 / 58 (0.00%)	0 / 62 (0.00%)	1 / 90 (1.11%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	1 / 303 (0.33%)	0 / 27 (0.00%)	0 / 27 (0.00%)	1 / 52 (1.92%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	7	4	5	0	0	1	0	0	0	0	0	0	0	1	0	0	1	0	0
pulpitis dental
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 345 (0.00%)	0 / 345 (0.00%)	0 / 348 (0.00%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	1 / 27 (3.70%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
upper respiratory tract infection
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	18 / 345 (5.22%)	20 / 345 (5.80%)	18 / 348 (5.17%)	0 / 58 (0.00%)	1 / 62 (1.61%)	2 / 90 (2.22%)	1 / 57 (1.75%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 22 (4.55%)	4 / 241 (1.66%)	4 / 303 (1.32%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	2 / 85 (2.35%)	5 / 168 (2.98%)
occurrences all number	21	21	20	0	1	2	1	0	0	0	0	1	4	5	0	0	0	2	5
upper respiratory tract infection bacterial
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 345 (0.00%)	0 / 345 (0.00%)	1 / 348 (0.29%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	1 / 27 (3.70%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
urinary tract infection
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	10 / 345 (2.90%)	6 / 345 (1.74%)	5 / 348 (1.44%)	1 / 58 (1.72%)	1 / 62 (1.61%)	1 / 90 (1.11%)	1 / 57 (1.75%)	0 / 73 (0.00%)	0 / 27 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 22 (0.00%)	2 / 241 (0.83%)	3 / 303 (0.99%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	1 / 85 (1.18%)	2 / 168 (1.19%)
occurrences all number	12	8	6	1	1	1	1	0	0	1	0	0	2	3	0	0	0	1	2
viral infection
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 345 (0.00%)	0 / 345 (0.00%)	2 / 348 (0.57%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	1 / 27 (3.70%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
vulvovaginitis
alternative dictionary used: MedDRA 16.0
subjects affected / exposed ^[11]	0 / 345 (0.00%)	0 / 345 (0.00%)	0 / 348 (0.00%)	1 / 44 (2.27%)	0 / 57 (0.00%)	0 / 69 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Metabolism and nutrition disorders
diabetes mellitus
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 345 (0.29%)	1 / 345 (0.29%)	1 / 348 (0.29%)	1 / 58 (1.72%)	1 / 62 (1.61%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	1 / 27 (3.70%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	1 / 52 (1.92%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	1	1	1	1	1	0	0	0	1	0	0	0	0	0	0	0	1	0	0
hypercholesterolaemia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 345 (0.29%)	0 / 345 (0.00%)	1 / 348 (0.29%)	0 / 58 (0.00%)	1 / 62 (1.61%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	1 / 27 (3.70%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	1 / 168 (0.60%)
occurrences all number	1	0	1	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	1
hyperglycaemia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	1 / 345 (0.29%)	1 / 345 (0.29%)	0 / 348 (0.00%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	1 / 27 (3.70%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
hyperlipidaemia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 345 (0.00%)	0 / 345 (0.00%)	0 / 348 (0.00%)	1 / 58 (1.72%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 22 (0.00%)	0 / 241 (0.00%)	1 / 303 (0.33%)	0 / 27 (0.00%)	0 / 27 (0.00%)	1 / 52 (1.92%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	1	0	0	1	0	0	1	0	0
hypoalbuminaemia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 345 (0.00%)	0 / 345 (0.00%)	0 / 348 (0.00%)	2 / 58 (3.45%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
hyponatraemia
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	0 / 345 (0.00%)	0 / 345 (0.00%)	0 / 348 (0.00%)	0 / 58 (0.00%)	0 / 62 (0.00%)	0 / 90 (0.00%)	0 / 57 (0.00%)	0 / 73 (0.00%)	1 / 27 (3.70%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
type 2 diabetes mellitus
alternative dictionary used: MedDRA 16.0
subjects affected / exposed	4 / 345 (1.16%)	0 / 345 (0.00%)	0 / 348 (0.00%)	0 / 58 (0.00%)	1 / 62 (1.61%)	1 / 90 (1.11%)	0 / 57 (0.00%)	1 / 73 (1.37%)	0 / 27 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	2 / 22 (9.09%)	0 / 241 (0.00%)	0 / 303 (0.00%)	0 / 27 (0.00%)	0 / 27 (0.00%)	0 / 52 (0.00%)	0 / 85 (0.00%)	0 / 168 (0.00%)
occurrences all number	4	0	0	0	2	1	0	2	0	0	0	2	0	0	0	0	0	0	0

Notes
[6] - 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.
[7] - 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.
[8] - 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.
[9] - 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.
[10] - 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.
[11] - 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? No

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 Methotrexate Therapy (FLEX M)

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% response (ACR20) at Week 24

Primary: Percentage of participants with American College of Rheumatology 20% response (ACR20) at Week 24

Primary: Change from baseline to Week 52 in van der Heijde modified Total Sharp Score (mTSS)

Primary: Change from baseline to Week 52 in van der Heijde modified Total Sharp Score (mTSS)

Primary: Change from baseline to Week 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI)

Primary: Change from baseline to Week 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI)

Secondary: Change from baseline in Disease Activity Score based on 28 joint count and C-Reactive Protein Level (DAS28-CRP)

Secondary: Change from baseline in Disease Activity Score based on 28 joint count and C-Reactive Protein Level (DAS28-CRP)

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 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey domain scores and summary scores

Secondary: Change from baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey domain scores and summary scores

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 in Brief Fatigue Inventory (BFI) individual items and impact score

Secondary: Change from baseline in Brief Fatigue Inventory (BFI) individual items and impact score

Secondary: Change from baseline in Brief Pain Inventory Short Form (BPI-SF) individual items and interference scores

Secondary: Change from baseline in Brief Pain Inventory Short Form (BPI-SF) individual items and interference scores

Secondary: Change from baseline in duration of morning stiffness (minutes)

Secondary: Change from baseline in duration of morning stiffness (minutes)

Secondary: Percentage of participants with change from baseline in mTSS less than or equal to (≤) 0

Secondary: Percentage of participants with change from baseline in mTSS less than or equal to (≤) 0

Secondary: Percentage of participants with Major Clinical Response (MCR) during 52 weeks

Secondary: Percentage of participants with Major Clinical Response (MCR) during 52 weeks

Secondary: Change from baseline to week 52 in B cell subset counts

Secondary: Change from baseline to week 52 in B cell subset counts

Secondary: Population Pharmacokinetics (PK): Constant Clearance

Secondary: Population Pharmacokinetics (PK): Constant Clearance

Secondary: Percentage of participants developing anti-LY2127399 antibodies

Secondary: Percentage of participants developing anti-LY2127399 antibodies

Secondary: Percentage of participants with No structural progression at Week 52

Secondary: Percentage of participants with No structural progression at Week 52

Secondary: Change from baseline to Week 24 in mTSS

Secondary: Change from baseline to Week 24 in mTSS

Secondary: Change from baseline in serum immunoglobulin (Ig) levels

Secondary: Change from baseline in serum immunoglobulin (Ig) levels

Secondary: Change from baseline in joint space narrowing score and bone erosions score (components of mTSS)

Secondary: Change from baseline in joint space narrowing score and bone erosions score (components of mTSS)

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

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

Secondary: Change from baseline in Tender Joint Count (68 joint count)

Secondary: Change from baseline in Tender Joint Count (68 joint count)

Secondary: Change from baseline in Swollen Joint Count (66 joint count)

Secondary: Change from baseline in Swollen Joint Count (66 joint count)

Secondary: Change from baseline in Participant's Assessment of Pain [Visual Analog Scale (VAS)]

Secondary: Change from baseline in Participant's Assessment of Pain [Visual Analog Scale (VAS)]

Secondary: Change from baseline in Participant's Global Assessment of Disease Activity (VAS)

Secondary: Change from baseline in Participant's Global Assessment of Disease Activity (VAS)

Secondary: Change from baseline in Physician's Global Assessment of Disease Activity (VAS)

Secondary: Change from baseline in Physician's Global Assessment of Disease Activity (VAS)

Secondary: Change from baseline to Week 52 in HAQ-DI

Secondary: Change from baseline to Week 52 in HAQ-DI

Secondary: Change from baseline to week 52 in absolute B cell counts

Secondary: Change from baseline to week 52 in absolute B cell counts

Secondary: Time to ACR20 response

Secondary: Time to ACR20 response

Secondary: Percentage of participants with ACR20 at Week 52

Secondary: Percentage of participants with ACR20 at Week 52

Secondary: Change from baseline in CRP

Secondary: Change from baseline in CRP

Other pre-specified: Number of participants who died during post-Treatment follow-Up period

Other pre-specified: Number of participants who died during post-Treatment follow-Up period

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 Methotrexate Therapy (FLEX M)