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Clinical Trial Results:
A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Parallel-Group, Phase 2b Study of LY3009104 in Patients with Active Rheumatoid Arthritis on Background Methotrexate Therapy

Summary
EudraCT number	2010-022504-42
Trial protocol	GB HU
Global end of trial date	31 Mar 2014

Results information
Results version number	v2(current)
This version publication date	14 Oct 2017
First version publication date	26 Mar 2017
Other versions	v1
Version creation reason	Correction of full data set Revision Required

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

13854

ISRCTN number

US NCT number

NCT01185353

WHO universal trial number (UTN)

Other trial identifiers

Trial Alias: I4V-MC-JADA, Trial ID: 13854

Sponsor organisation name

Eli Lilly and Company

Sponsor organisation address

Lilly Corporate Center, Indianapolis, United States, 46285

Public contact

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

Scientific contact

Available Mon - Fri 9 AM - 5 PM EST, Eli Lilly and Company, 1 877-285-4559,

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

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

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

Analysis stage

Final

Date of interim/final analysis

31 Mar 2014

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

31 Mar 2014

Was the trial ended prematurely?

Main objective of the trial

The purpose of this trial is to evaluate the safety and efficacy of LY3009104 in participants with Rheumatoid Arthritis (RA).

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

Methotrexate (MTX) was administered orally as background therapy. Participants must have regularly used methotrexate (MTX) for at least 12 weeks, with treatment at a stable dose of 10 to 25 milligrams (mg) per week for at least 8 weeks prior to baseline.

Evidence for comparator

Actual start date of recruitment

13 Oct 2010

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 95

Country: Number of subjects enrolled

Hungary: 13

Country: Number of subjects enrolled

Czech Republic: 23

Country: Number of subjects enrolled

Mexico: 47

Country: Number of subjects enrolled

Poland: 33

Country: Number of subjects enrolled

Ukraine: 29

Country: Number of subjects enrolled

Croatia: 7

Country: Number of subjects enrolled

Romania: 11

Country: Number of subjects enrolled

India: 43

Worldwide total number of subjects

301

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

263

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

This study consisted of 4 parts and a follow-up up to 28 days post the last dose of study drug.

Period 1 title

Part A (Weeks 0 through 12)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

1 milligram (mg) LY3009104 QD - Part A

Arm description

Administered orally once daily (QD) for 12 weeks in Part A. Methotrexate (MTX) was administered orally as background therapy.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

LY3009104

Other name

Janus Kinase (JAK)1/JAK2, JAK 1/2 Inhibitor, INCB028050

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

1mg LY3009104 once daily for 12 weeks in Part A

2 mg LY3009104 QD - Parts A and B

Arm description

Administered orally QD for 24 weeks in Parts A and B. MTX was administered orally as background therapy.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

LY3009104

Other name

Janus Kinase (JAK)1/JAK2, JAK 1/2 Inhibitor, INCB028050

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

2 mg LY3009104 once daily for 24 weeks in Parts A and B

4 mg LY3009104 QD - Parts A and B

Arm description

Administered orally QD for 24 weeks in Parts A and B. MTX was administered orally as background therapy.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

LY3009104

Other name

Janus Kinase (JAK)1/JAK2, JAK 1/2 Inhibitor, INCB028050

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

4 mg LY3009104 once daily for 24 weeks in Parts A and B

8 mg LY3009104 QD - Parts A and B

Arm description

Administered orally QD for 24 weeks in Parts A and B. MTX was administered orally as background therapy.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

LY3009104

Other name

Janus Kinase (JAK)1/JAK2, JAK 1/2 Inhibitor, INCB028050

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

8 mg LY3009104 once daily for 24 weeks in Parts A and B

Placebo QD - Part A

Arm description

Placebo administered orally QD for 12 weeks in Part A. MTX was administered orally as background therapy.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Placebo daily for 12 weeks

Number of subjects in period 1	1 milligram (mg) LY3009104 QD - Part A	2 mg LY3009104 QD - Parts A and B	4 mg LY3009104 QD - Parts A and B	8 mg LY3009104 QD - Parts A and B	Placebo QD - Part A
Started	49	52	52	50	98
Received at least 1 dose of study drug	49	52	52	50	98
Completed	44	51	50	49	82
Not completed	5	1	2	1	16
Consent withdrawn by subject	2	-	-	-	3
Physician decision	-	-	1	-	2
Adverse event, non-fatal	1	1	1	1	5
Entry Criteria Not Met	-	-	-	-	4
Lack of efficacy	2	-	-	-	1
Protocol deviation	-	-	-	-	1

Period 2 title

Part B (Weeks 12 through 24)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

2 mg LY3009104 QD - Parts A and B

Arm description

Administered orally QD for 24 weeks in Parts A and B. MTX was administered orally as background therapy.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

LY3009104

Other name

Janus Kinase (JAK)1/JAK2, JAK 1/2 Inhibitor, INCB028050

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

2 mg LY3009104 once daily for 24 weeks in Parts A and B

4 mg LY3009104 QD - Parts A and B

Arm description

Administered orally QD for 24 weeks in Parts A and B. MTX was administered orally as background therapy.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

LY3009104

Other name

Janus Kinase (JAK)1/JAK2, JAK 1/2 Inhibitor, INCB028050

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

4 mg LY3009104 once daily for 24 weeks in Parts A and B

8 mg LY3009104 QD - Parts A and B

Arm description

Administered orally QD for 24 weeks in Parts A and B. MTX was administered orally as background therapy.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

LY3009104

Other name

Janus Kinase (JAK)1/JAK2, JAK 1/2 Inhibitor, INCB028050

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

8 mg LY3009104 once daily for 24 weeks in Parts A and B

2 mg LY3009104 BID - Part B

Arm description

Participants who received Placebo or 1 mg LY3009104 in Part A were re-randomized at Week 12 to receive 2 mg LY3009104 twice daily (BID) in Part B. MTX was administered orally as background therapy.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

LY3009104

Other name

Janus Kinase (JAK)1/JAK2, JAK 1/2 Inhibitor, INCB028050

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

2 mg LY3009104 twice daily for 12 weeks in Part B

4 mg LY3009104 QD - Part B

Arm description

Participants who received Placebo or 1 mg LY3009104 in Part A were re-randomized at Week 12 to receive 4 mg LY3009104 QD in Part B. MTX was administered orally as background therapy.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

LY3009104

Other name

Janus Kinase (JAK)1/JAK2, JAK 1/2 Inhibitor, INCB028050

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

4 mg LY3009104 once daily for 12 weeks in Part B

Number of subjects in period 2	2 mg LY3009104 QD - Parts A and B	4 mg LY3009104 QD - Parts A and B	8 mg LY3009104 QD - Parts A and B	2 mg LY3009104 BID - Part B	4 mg LY3009104 QD - Part B
Started	51	50	49	63	63
Completed	50	48	45	59	57
Not completed	1	2	4	4	6
Consent withdrawn by subject	-	1	2	3	4
Adverse event, non-fatal	-	1	-	1	-
Lost to follow-up	-	-	1	-	1
Entry Criteria Not Met	-	-	-	-	1
Lack of efficacy	1	-	1	-	-

Period 3 title

Part C (Weeks 24 through 76)

Is this the baseline period?

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

4 mg LY3009104 QD - Parts C and D

Arm description

Participants who received 2 mg LY3009104 QD or BID in Part B were re-assigned at Week 24 to 4 mg LY3009104 QD in Part C. Participants who received 4 mg LY3009104 QD in Part B continued to receive 4 mg LY3009104 QD in Part C. Participants who completed Part C continued to receive 4 mg LY3009104 QD in Part D. MTX was administered orally as background therapy.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

LY3009104

Other name

Janus Kinase (JAK)1/JAK2, JAK 1/2 Inhibitor, INCB028050

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

4 mg LY3009104 once daily for 52 weeks in Part C

4 to 8 mg LY3009104 QD - Part C and 4 mg LY3009104 QD - Part D

Arm description

Participants who received 2 mg LY3009104 QD or BID in Part B were re-assigned at Week 24 to 4 mg LY3009104 QD in Part C. Participants who received 4 mg LY3009104 QD in Part B continued to receive 4 mg LY3009104 QD in Part C. At Weeks 28 and 32, participants who met dose escalation criteria received 8 mg LY3009104 QD for the rest of Part C. Dose escalation criteria: ≥ 6 tender and 6 swollen joints based on the 28-joint count assessments and the clinical judgment of the investigator. Participants who completed Part C received 4 mg LY3009104 QD in Part D. MTX was administered orally as background therapy.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

LY3009104

Other name

Janus Kinase (JAK)1/JAK2, JAK 1/2 Inhibitor, INCB028050

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

4mg escalated to 8 mg LY3009104 once daily for 52 weeks in Part C

8 mg LY3009104 QD - Part C and 4 mg LY3009104 QD - Part D

Arm description

Participants who received 8 mg LY3009104 QD in Part B remained on 8 mg LY3009104 QD in Part C. Participants who completed Part C received 4 mg LY3009104 QD in Part D. MTX was administered orally as background therapy.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

LY3009104

Other name

Janus Kinase (JAK)1/JAK2, JAK 1/2 Inhibitor, INCB028050

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

8 mg LY3009104 once daily for 52 weeks in Part C

Number of subjects in period 3 ^[1]	4 mg LY3009104 QD - Parts C and D	4 to 8 mg LY3009104 QD - Part C and 4 mg LY3009104 QD - Part D	8 mg LY3009104 QD - Part C and 4 mg LY3009104 QD - Part D
Started	108	61	32
Completed	92	53	24
Not completed	16	8	8
Adverse event, serious fatal	-	-	1
Consent withdrawn by subject	6	2	2
Physician decision	-	-	1
Adverse event, non-fatal	8	2	2
Lost to follow-up	2	1	1
Entry Criteria Not Met	-	-	1
Reason missing	-	1	-
Lack of efficacy	-	2	-

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Participants who received 2mg LY3009104 QD or BID in Part B were reassigned at Wk 24 to receive 4 mg LY3009104 in Part C. Participants who received 4mg LY3009104 in Part B continued to received 4mg LY3009104 in Part C. At Wk 28 participants were assessed for dose escalation to receive 8 mg LY3009104 QD for the remainder of Part C. Participants who received 8 mg LY3009104 QD in Part B remained on 8 mg LY3009104 QD in Part C.

Period 4 title

Part D (Weeks 76 through 128)

Is this the baseline period?

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

4 mg LY3009104 QD - Parts C and D

Arm description

Participants who received 2 mg LY3009104 QD or BID in Part B were re-assigned at Week 24 to 4 mg LY3009104 QD in Part C. Participants who received 4 mg LY3009104 QD in Part B continued to receive 4 mg LY3009104 QD in Part C. Participants who completed Part C continued to receive 4 mg LY3009104 QD in Part D. MTX was administered orally as background therapy.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

LY3009104

Other name

Janus Kinase (JAK)1/JAK2, JAK 1/2 Inhibitor, INCB028050

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

4 mg LY3009104 once daily for 52 weeks in Part D

4 to 8 mg LY3009104 QD - Part C and 4 mg LY3009104 QD - Part D

Arm description

Participants who received 2 mg LY3009104 QD or BID in Part B were re-assigned at Week 24 to 4 mg LY3009104 QD in Part C. Participants who received 4 mg LY3009104 QD in Part B continued to receive 4 mg LY3009104 QD in Part C. At Weeks 28 and 32, participants who met dose escalation criteria received 8 mg LY3009104 QD for the rest of Part C. Dose escalation criteria: ≥ 6 tender and 6 swollen joints based on the 28-joint count assessments and the clinical judgment of the investigator. Participants who completed Part C received 4 mg LY3009104 QD in Part D. MTX was administered orally as background therapy.

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

LY3009104

Other name

Janus Kinase (JAK)1/JAK2, JAK 1/2 Inhibitor, INCB028050

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

4 mg LY3009104 once daily for 52 weeks in Part D

8 mg LY3009104 QD - Part C and 4 mg LY3009104 QD - Part D

Arm description

Arm type

Experimental

Investigational medicinal product name

Baricitinib

Investigational medicinal product code

LY3009104

Other name

Janus Kinase (JAK)1/JAK2, JAK 1/2 Inhibitor, INCB028050

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

4 mg LY3009104 once daily for 52 weeks in Part D

Number of subjects in period 4 ^[2]	4 mg LY3009104 QD - Parts C and D	4 to 8 mg LY3009104 QD - Part C and 4 mg LY3009104 QD - Part D	8 mg LY3009104 QD - Part C and 4 mg LY3009104 QD - Part D
Started	79	47	18
Completed	76	40	17
Not completed	3	7	1
Consent withdrawn by subject	1	2	1
Adverse event, non-fatal	1	2	-
Lost to follow-up	1	3	-

Notes
[2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Participants who completed Part C received 4 mg LY3009104 QD in Part D regardless of dose in Parts B and C.

Baseline characteristics

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Reporting group title

Part A (Weeks 0 through 12)

Reporting group description

Reporting group values	Part A (Weeks 0 through 12)	Total
Number of subjects	301	301
Age categorical
Units: Subjects
In utero	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0
Newborns (0-27 days)	0	0
Infants and toddlers (28 days-23 months)	0	0
Children (2-11 years)	0	0
Adolescents (12-17 years)	0	0
Adults (18-64 years)	263	263
From 65-84 years	38	38
85 years and over	0	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	51.2 ( 11.71 )	-
Gender, Male/Female
Units: participants
Female	249	249
Male	52	52
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	56	56
Not Hispanic or Latino	227	227
Unknown or Not Reported	18	18
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	19	19
Asian	47	47
Native Hawaiian or Other Pacific Islander	0	0
Black or African American	11	11
White	224	224
More than one race	0	0
Unknown or Not Reported	0	0
Region of Enrollment
Units: Subjects
United States	95	95
Hungary	13	13
Czech Republic	23	23
Mexico	47	47
Poland	33	33
Ukraine	29	29
Croatia	7	7
Romania	11	11
India	43	43
Duration of Rheumatoid Arthritis
Units: years
arithmetic mean (standard deviation)	5.62 ( 4.401 )	-
Tender Joint Counts (TJC)
TJC 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.
Units: number of joints
arithmetic mean (standard deviation)	22.2 ( 12.38 )	-
Swollen Joint Counts (SJC)
SJC 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.
Units: number of joints
arithmetic mean (standard deviation)	15.8 ( 8.13 )	-
High Sensitivity C-Reactive Protein (hsCRP)
HsCRP is a laboratory analyte that is an indicator of inflammation. Decreases in hsCRP represent reductions in inflammation. Numbers of participants analyzed are 49, 52, 52, 50 for 1 mg, 2 mg, 4 mg, and 8 mg LY3009104 groups respectively, and 97 for placebo group.
Units: milligrams/liter (mg/L)
arithmetic mean (standard deviation)	12.81 ( 19.402 )	-
Erythrocyte Sedimentation Rate (ESR)
ESR is a laboratory analyte that is an indicator of inflammation. Decreases represent reductions in inflammation.
Units: millimeters/hour (mm/hr)
arithmetic mean (standard deviation)	38.8 ( 18.39 )	-

End points

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Reporting group title

1 milligram (mg) LY3009104 QD - Part A

Reporting group description

Administered orally once daily (QD) for 12 weeks in Part A. Methotrexate (MTX) was administered orally as background therapy.

Reporting group title

2 mg LY3009104 QD - Parts A and B

Reporting group description

Administered orally QD for 24 weeks in Parts A and B. MTX was administered orally as background therapy.

Reporting group title

4 mg LY3009104 QD - Parts A and B

Reporting group description

Administered orally QD for 24 weeks in Parts A and B. MTX was administered orally as background therapy.

Reporting group title

8 mg LY3009104 QD - Parts A and B

Reporting group description

Administered orally QD for 24 weeks in Parts A and B. MTX was administered orally as background therapy.

Reporting group title

Placebo QD - Part A

Reporting group description

Placebo administered orally QD for 12 weeks in Part A. MTX was administered orally as background therapy.

Reporting group title

2 mg LY3009104 QD - Parts A and B

Reporting group description

Administered orally QD for 24 weeks in Parts A and B. MTX was administered orally as background therapy.

Reporting group title

4 mg LY3009104 QD - Parts A and B

Reporting group description

Administered orally QD for 24 weeks in Parts A and B. MTX was administered orally as background therapy.

Reporting group title

8 mg LY3009104 QD - Parts A and B

Reporting group description

Administered orally QD for 24 weeks in Parts A and B. MTX was administered orally as background therapy.

Reporting group title

2 mg LY3009104 BID - Part B

Reporting group description

Participants who received Placebo or 1 mg LY3009104 in Part A were re-randomized at Week 12 to receive 2 mg LY3009104 twice daily (BID) in Part B. MTX was administered orally as background therapy.

Reporting group title

4 mg LY3009104 QD - Part B

Reporting group description

Participants who received Placebo or 1 mg LY3009104 in Part A were re-randomized at Week 12 to receive 4 mg LY3009104 QD in Part B. MTX was administered orally as background therapy.

Reporting group title

4 mg LY3009104 QD - Parts C and D

Reporting group description

Participants who received 2 mg LY3009104 QD or BID in Part B were re-assigned at Week 24 to 4 mg LY3009104 QD in Part C. Participants who received 4 mg LY3009104 QD in Part B continued to receive 4 mg LY3009104 QD in Part C. Participants who completed Part C continued to receive 4 mg LY3009104 QD in Part D. MTX was administered orally as background therapy.

Reporting group title

4 to 8 mg LY3009104 QD - Part C and 4 mg LY3009104 QD - Part D

Reporting group description

Participants who received 2 mg LY3009104 QD or BID in Part B were re-assigned at Week 24 to 4 mg LY3009104 QD in Part C. Participants who received 4 mg LY3009104 QD in Part B continued to receive 4 mg LY3009104 QD in Part C. At Weeks 28 and 32, participants who met dose escalation criteria received 8 mg LY3009104 QD for the rest of Part C. Dose escalation criteria: ≥ 6 tender and 6 swollen joints based on the 28-joint count assessments and the clinical judgment of the investigator. Participants who completed Part C received 4 mg LY3009104 QD in Part D. MTX was administered orally as background therapy.

Reporting group title

8 mg LY3009104 QD - Part C and 4 mg LY3009104 QD - Part D

Reporting group description

Reporting group title

4 mg LY3009104 QD - Parts C and D

Reporting group description

Participants who received 2 mg LY3009104 QD or BID in Part B were re-assigned at Week 24 to 4 mg LY3009104 QD in Part C. Participants who received 4 mg LY3009104 QD in Part B continued to receive 4 mg LY3009104 QD in Part C. Participants who completed Part C continued to receive 4 mg LY3009104 QD in Part D. MTX was administered orally as background therapy.

Reporting group title

4 to 8 mg LY3009104 QD - Part C and 4 mg LY3009104 QD - Part D

Reporting group description

Participants who received 2 mg LY3009104 QD or BID in Part B were re-assigned at Week 24 to 4 mg LY3009104 QD in Part C. Participants who received 4 mg LY3009104 QD in Part B continued to receive 4 mg LY3009104 QD in Part C. At Weeks 28 and 32, participants who met dose escalation criteria received 8 mg LY3009104 QD for the rest of Part C. Dose escalation criteria: ≥ 6 tender and 6 swollen joints based on the 28-joint count assessments and the clinical judgment of the investigator. Participants who completed Part C received 4 mg LY3009104 QD in Part D. MTX was administered orally as background therapy.

Reporting group title

8 mg LY3009104 QD - Part C and 4 mg LY3009104 QD - Part D

Reporting group description

Subject analysis set title

Combined 4mg and 8mg ACR20 Response Week 12

Subject analysis set type

Sub-group analysis

Subject analysis set description

All randomized participants who received placebo, 4 mg or 8 mg LY3009104 in Part A. Participants who had missing components of the ACR20 index at Week 12 had these components imputed by last observation carried forward (LOCF).

Subject analysis set title

4mg ACR20 Response Weeks (Wks) 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D. Participants who had missing components of the ACR20 index at analysis time points had these components imputed by LOCF.

Subject analysis set title

4-8mg ACR20 Response Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D. Participants who had missing components of the ACR20 index at analysis time points had these components imputed by LOCF.

Subject analysis set title

8mg ACR20 Response Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D. Participants who had missing components of the ACR20 index at analysis time points had these components imputed by LOCF.

Subject analysis set title

4mg ACR70 Response Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D. Participants who had missing components of the ACR70 index at analysis time points had these components imputed by LOCF.

Subject analysis set title

4-8mg ACR70 Response Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D. Participants who had missing components of the ACR70 index at analysis time points had these components imputed by LOCF.

Subject analysis set title

8mg ACR70 Response Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D. Participants who had missing components of the ACR70 index at analysis time points had these components imputed by LOCF.

Subject analysis set title

4mg Mean Change TJC and SJC From Baseline To Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D and had TJC and SJC evaluated at analysis time points. LOCF was used to impute missing post-baseline values.

Subject analysis set title

4-8mg Mean Change TJC and SJC From Baseline To Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D and had TJC and SJC evaluated at analysis time points. LOCF was used to impute missing post-baseline values.

Subject analysis set title

8mg Mean Change TJC and SJC From Baseline To Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D and had TJC and SJC evaluated at analysis time points. LOCF was used to impute missing post-baseline values.

Subject analysis set title

4mg Mean Change HAQ-DI From Baseline To Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D and had HAQ-DI evaluated at analysis time points. LOCF was used to impute missing post-baseline values

Subject analysis set title

4-8mg Mean Change HAQ-DI From Baseline To Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D and had HAQ-DI evaluated at analysis time points. LOCF was used to impute missing post-baseline values.

Subject analysis set title

8mg Mean Change HAQ-DI From Baseline To Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D and had HAQ-DI evaluated at analysis time points. LOCF was used to impute missing post-baseline values.

Subject analysis set title

4mg Mean Change hsCRP From Baseline To Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D and had hsCRP evaluated at analysis time points. LOCF was used to impute missing post-baseline values.

Subject analysis set title

4-8mg Mean Change hsCRP From Baseline To Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D and had hsCRP evaluated at analysis time points. LOCF was used to impute missing post-baseline values.

Subject analysis set title

8mg Mean Change hsCRP From Baseline To Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D and had hsCRP evaluated at analysis time points. LOCF was used to impute missing post-baseline values.

Subject analysis set title

4mg DA Assessment Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D and had physician's and participant's assessments of disease activity and pain evaluated at analysis time points. LOCF was used to impute missing post-baseline values.

Subject analysis set title

4-8mg DA Assessment Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

8mg DA Assessment Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

2mg LY3009104 PK Assessment for AUC Part A

Subject analysis set type

Sub-group analysis

Subject analysis set description

All randomized participants who received at least 1 dose of LY3009104 with evaluable LY3009104 PK data.

Subject analysis set title

4mg LY3009104 PK Assessment for AUC Part A

Subject analysis set type

Sub-group analysis

Subject analysis set description

All randomized participants who received at least 1 dose of LY3009104 with evaluable LY3009104 PK data.

Subject analysis set title

8mg LY3009104 PK Assessment for AUC Part A

Subject analysis set type

Sub-group analysis

Subject analysis set description

All randomized participants who received at least 1 dose of LY3009104 with evaluable LY3009104 PK data.

Subject analysis set title

4mg Percentage Participants Meeting Low DA Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D and had DAS28-CRP evaluated at analysis time points.

Subject analysis set title

4-8mg Percentage Participants Meeting Low DA Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D and had DAS28-CRP evaluated at analysis time points.

Subject analysis set title

8mg Percentage Participants Meeting Low DA Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D and had DAS28-CRP evaluated at analysis time points.

Subject analysis set title

4mg EULAR28 Response Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D and had EULAR28 evaluated at analysis time points. LOCF was used to impute missing post-baseline values.

Subject analysis set title

4-8mg EULAR28 Response Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D and had EULAR28 evaluated at analysis time points. LOCF was used to impute missing post-baseline values.

Subject analysis set title

8mg EULAR28 Response Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D and had EULAR28 evaluated at analysis time points. LOCF was used to impute missing post-baseline values.

Subject analysis set title

4mg Mean Change ESR From Baseline To Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D and had ESR evaluated at analysis time points. LOCF was used to impute missing post-baseline values.

Subject analysis set title

4-8mg Mean Change ESR From Baseline To Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D and had ESR evaluated at analysis time points. LOCF was used to impute missing post-baseline values.

Subject analysis set title

8mg Mean Change ESR From Baseline To Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D and had ESR evaluated at analysis time points. LOCF was used to impute missing post-baseline values.

Subject analysis set title

2mg LY3009104 PK Assessment for Cmax Part A

Subject analysis set type

Sub-group analysis

Subject analysis set description

All randomized participants who received at least 1 dose of LY3009104 with evaluable LY3009104 PK data.

Subject analysis set title

4mg LY3009104 PK Assessment for Cmax Part A

Subject analysis set type

Sub-group analysis

Subject analysis set description

All randomized participants who received at least 1 dose of LY3009104 with evaluable LY3009104 PK data.

Subject analysis set title

8mg LY3009104 PK Assessment for Cmax Part A

Subject analysis set type

Sub-group analysis

Subject analysis set description

All randomized participants who received at least 1 dose of LY3009104 with evaluable LY3009104 PK data.

Subject analysis set title

4mg Mean Change DAS28-CRP From Baseline To Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D and had DAS28-CRP evaluated at analysis time points. LOCF was used to impute missing post-baseline values.

Subject analysis set title

4-8mg Mean Change DAS28-CRP From Baseline To Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D and had DAS28-CRP evaluated at analysis time points. LOCF was used to impute missing post-baseline values.

Subject analysis set title

8mg Mean Change DAS28-CRP From Baseline To Wks 76 and 128

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants who received study drug in Parts C and D and had DAS28-CRP evaluated at analysis time points. LOCF was used to impute missing post-baseline values.

Primary: Percentage of Participants in the 4 mg and 8 mg Dose Groups Who Achieved an American College of Rheumatology 20 (ACR20) Responder Index Response Baseline through Week 12

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End point title

Percentage of Participants in the 4 mg and 8 mg Dose Groups Who Achieved an American College of Rheumatology 20 (ACR20) Responder Index Response Baseline through Week 12 ^[1]

End point description

ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (assessment of participant’s physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time point are treated as non-responders. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants analyzed) * 100.

End point type

Primary

End point timeframe

Baseline through Week 12

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All randomized participants who received placebo, 4 mg or 8 mg LY3009104in Part A. Participants for the 4mg and 8mg reporting groups were combined and number of participants analyzed is 102. Participants who had missing components of the ACR20 index at Week 12 had these components imputed by last observation carried forward (LOCF).

End point values	Placebo QD - Part A	Combined 4mg and 8mg ACR20 Response Week 12
Number of subjects analysed	98	102
Units: percentage of participants
number (not applicable)	41	76

Statistical Analysis for Primary Endpoint

Comparison groups

Placebo QD - Part A v Combined 4mg and 8mg ACR20 Response Week 12

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[2]

Method

Regression, Logistic

Confidence interval

Notes
[2] - A priori p-value significance threshold: 1-sided ≤0.10

Secondary: Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline through Week 12 - Model Based Dose Response

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End point title

Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline through Week 12 - Model Based Dose Response

End point description

ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant’s physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time point are treated as non-responders. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants analyzed) * 100. Data presented are model-based Bayesian posterior mean response rates with 95% credible interval.

End point type

Secondary

End point timeframe

Baseline through Week 12

End point values	1 milligram (mg) LY3009104 QD - Part A	2 mg LY3009104 QD - Parts A and B	4 mg LY3009104 QD - Parts A and B	8 mg LY3009104 QD - Parts A and B	Placebo QD - Part A
Number of subjects analysed	49	52	52	50	98
Units: percentage of participants
number (confidence interval 95%)	54.6 (42.2 to 67.1)	55.2 (42.3 to 67.6)	74.3 (63.1 to 84.1)	77.2 (65.9 to 86.7)	42.1 (32.9 to 51.6)

No statistical analyses for this end point

Secondary: Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline through Week 24

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End point title

Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline through Week 24

End point description

ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant’s physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants treated) * 100. Participants were not dosed with 1 mg LY3009104 after Week 12; percentage was not calculated. 9999=Data Not Available (N/A).

End point type

Secondary

End point timeframe

Baseline through Weeks 2, 4, 8, 12, 16, 20, 24

End point values	1 milligram (mg) LY3009104 QD - Part A	2 mg LY3009104 QD - Parts A and B	4 mg LY3009104 QD - Parts A and B	8 mg LY3009104 QD - Parts A and B	Placebo QD - Part A
Number of subjects analysed	49 ^[3]	52	52	50	98 ^[4]
Units: percentage of participants
number (not applicable)
Week 2	29	21	42	44	11
Week 4	43	37	60	54	24
Week 8	43	42	67	72	36
Week 12	57	54	75	78	41
Week 16	9999	63	67	64	9999
Week 20	9999	71	77	78	9999
Week 24	9999	62	75	72	9999

Notes
[3] - Participants were not dosed with 1 mg LY3009104 after Week 12; percentage was not calculated.
[4] - Participants were not dosed with placebo after Week 12; percentage was not calculated.

No statistical analyses for this end point

Secondary: Percentage of Participants Who Achieved an ACR20 Response Baseline through Weeks 76 and 128

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End point title

Percentage of Participants Who Achieved an ACR20 Response Baseline through Weeks 76 and 128

End point description

ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant’s physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants analyzed) * 100.

End point type

Secondary

End point timeframe

Baseline through Weeks 76 and 128

End point values	4mg ACR20 Response Weeks (Wks) 76 and 128	4-8mg ACR20 Response Wks 76 and 128	8mg ACR20 Response Wks 76 and 128
Number of subjects analysed	108	61	32
Units: percentage of participants
number (not applicable)
Week 76 (n=108, 61, 32)	71	67	59
Week 128 (n=79, 47, 18)	77	57	72

No statistical analyses for this end point

Secondary: Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline through Week 24

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End point title

Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline through Week 24

End point description

ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR50 Responder is a participant who had ≥50% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥50% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant’s physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR50 response = (number of ACR50 responders) / (number of participants analyzed) * 100. Participants were not dosed with 1 mg LY3009104 after Week 12; percentage was not calculated. 9999=Data Not Available (N/A).

End point type

Secondary

End point timeframe

Baseline through Weeks 2, 4, 8, 12, 16, 20, 24

End point values	1 milligram (mg) LY3009104 QD - Part A	2 mg LY3009104 QD - Parts A and B	4 mg LY3009104 QD - Parts A and B	8 mg LY3009104 QD - Parts A and B	Placebo QD - Part A
Number of subjects analysed	49 ^[5]	52	52	50	98 ^[6]
Units: percentage of participants
number (not applicable)
Week 2	0	4	21	4	2
Week 4	10	10	29	22	3
Week 8	16	10	33	36	7
Week 12	31	17	35	40	10
Week 16	9999	19	38	44	9999
Week 20	9999	27	46	48	9999
Week 24	9999	19	46	54	9999

Notes
[5] - Participants were not dosed with 1 mg LY3009104 after Week 12; percentage was not calculated.
[6] - Participants were not dosed with Placebo LY3009104 after Week 12; percentage was not calculated.

No statistical analyses for this end point

Secondary: Percentage of Participants Who Achieved an ACR50 Response Baseline through Weeks 76 and 128

Top of page

End point title

Percentage of Participants Who Achieved an ACR50 Response Baseline through Weeks 76 and 128

End point description

End point type

Secondary

End point timeframe

Baseline through Weeks 76 and 128

End point values	4 mg LY3009104 QD - Parts C and D	4 to 8 mg LY3009104 QD - Part C and 4 mg LY3009104 QD - Part D	8 mg LY3009104 QD - Part C and 4 mg LY3009104 QD - Part D
Number of subjects analysed	108	61	32
Units: percentage of participants
number (not applicable)
Week 76 (n=108, 61, 32)	49	41	44
Week 128 (n=79, 47, 18)	58	30	44

No statistical analyses for this end point

Secondary: Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline through Week 24

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End point title

Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline through Week 24

End point description

ACR70 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR70 Responder is a participant who had ≥70% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥70% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant’s physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR70 response = (number of ACR70 responders) / (number of participants analyzed) * 100. Participants were not dosed with 1 mg LY3009104 after Week 12; percentage was not calculated. 9999=Data Not Available (N/A).

End point type

Secondary

End point timeframe

Baseline through Weeks 2, 4, 8, 12, 16, 20, 24

End point values	1 milligram (mg) LY3009104 QD - Part A	2 mg LY3009104 QD - Parts A and B	4 mg LY3009104 QD - Parts A and B	8 mg LY3009104 QD - Parts A and B	Placebo QD - Part A
Number of subjects analysed	49 ^[7]	52	52	50	98 ^[8]
Units: percentage of participants
number (not applicable)
Week 2	0	2	12	0	0
Week 4	2	4	10	6	0
Week 8	4	4	15	22	0
Week 12	12	8	23	20	2
Week 16	9999	8	23	30	9999
Week 20	9999	10	21	26	9999
Week 24	9999	10	27	24	9999

Notes
[7] - Participants were not dosed with 1 mg LY3009104 after Week 12; percentage was not calculated.
[8] - Participants were not dosed with placebo after Week 12; percentage was not calculated.

No statistical analyses for this end point

Secondary: Percentage of Participants Who Achieved an ACR70 Response Baseline through Weeks 76 and 128

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End point title

Percentage of Participants Who Achieved an ACR70 Response Baseline through Weeks 76 and 128

End point description

End point type

Secondary

End point timeframe

Baseline through Weeks 76 and 128

End point values	4mg ACR70 Response Wks 76 and 128	4-8mg ACR70 Response Wks 76 and 128	8mg ACR70 Response Wks 76 and 128
Number of subjects analysed	108	61	32
Units: percentage of participants
number (not applicable)
Week 76 (n=108, 61, 32)	29	18	25
Week 128 (n=79, 47, 18)	28	17	22

No statistical analyses for this end point

Secondary: Percentage of Participants Who Achieved an ACR50 Response Baseline through Week 12 - Model Based Dose Response

Top of page

End point title

Percentage of Participants Who Achieved an ACR50 Response Baseline through Week 12 - Model Based Dose Response

End point description

ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR50 Responder is a participant who had ≥50% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥50% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant’s physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time point are treated as non-responders. Percentage of participants achieving ACR50 response = (number of ACR50 responders) / (number of participants analyzed) * 100. Data presented are model-based Bayesian posterior mean response rates with 95% credible interval.

End point type

Secondary

End point timeframe

Baseline through Week 12

End point values	1 milligram (mg) LY3009104 QD - Part A	2 mg LY3009104 QD - Parts A and B	4 mg LY3009104 QD - Parts A and B	8 mg LY3009104 QD - Parts A and B	Placebo QD - Part A
Number of subjects analysed	49	52	52	50	98
Units: percentage of participants
number (confidence interval 95%)	26.5 (16 to 39.2)	18.8 (9.9 to 29.7)	34.4 (23.1 to 46.7)	39.2 (27.1 to 52.2)	12 (6.5 to 18.8)

No statistical analyses for this end point

Secondary: ACR Percent Improvement (ACR-N)

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End point title

ACR 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 a) % of improvement in TJC, b) % of improvement in SJC, and c) third highest percentage of improvement 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 a range of -100 to 100 to minimize impact of outliers (greater scores indicate greater % improvement) and negative scores indicate a decline. Data presented are model-based Bayesian posterior mean response rates with 95% credible interval.

End point type

Secondary

End point timeframe

Baseline through Week 12

End point values	1 milligram (mg) LY3009104 QD - Part A	2 mg LY3009104 QD - Parts A and B	4 mg LY3009104 QD - Parts A and B	8 mg LY3009104 QD - Parts A and B	Placebo QD - Part A
Number of subjects analysed	49	52	52	50	98
Units: percentage of improvement
number (confidence interval 95%)	17.3 (7.57 to 28.22)	19.42 (8.74 to 29.25)	28.59 (17.67 to 40.83)	29 (17.67 to 41.47)	10.97 (-0.39 to 21.64)

No statistical analyses for this end point

Secondary: Mean Change from Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC)

Top of page

End point title

Mean Change from Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC)

End point description

TJC 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. SJC 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. Participants were not dosed with 1 mg LY3009104 after Week 12; mean and standard deviation (SD) were not calculated. 9999=Data Not Available (N/A). All randomized participants who received study drug in Parts A and B and had TJC and SJC evaluated at analysis time points. LOCF was used to impute missing post-baseline values

End point type

Secondary

End point timeframe

Baseline, Weeks 12 and 24

End point values	1 milligram (mg) LY3009104 QD - Part A	2 mg LY3009104 QD - Parts A and B	4 mg LY3009104 QD - Parts A and B	8 mg LY3009104 QD - Parts A and B	Placebo QD - Part A
Number of subjects analysed	49 ^[9]	52	51	50	98 ^[10]
Units: number of joints
arithmetic mean (standard deviation)
TJC - Week 12	-8.4 ( 12.7 )	-11.3 ( 13.5 )	-12.2 ( 10.45 )	-14.7 ( 12.97 )	-7.6 ( 12.31 )
TJC - Week 24	9999 ( 9999 )	-12.4 ( 12.6 )	-14 ( 9.54 )	-17.5 ( 11.23 )	9999 ( 9999 )
SJC - Week 12	-8.1 ( 7.24 )	-8.9 ( 9.03 )	-9.6 ( 6.49 )	-10.4 ( 8.88 )	-6.7 ( 7.97 )
SJC - Week 24	9999 ( 9999 )	-10 ( 8.16 )	-10.5 ( 6.42 )	-12.2 ( 7.29 )	9999 ( 9999 )

Notes
[9] - Participants were not dosed with 1 mg LY3009104 after Week 12; mean and SD were not calculated.
[10] - Participants were not dosed with placebo after Week 12; mean and SD were not calculated.

No statistical analyses for this end point

Secondary: Mean Change from Baseline to Weeks 76 and 128 in TJC and SJC

Top of page

End point title

Mean Change from Baseline to Weeks 76 and 128 in TJC and SJC

End point description

End point type

Secondary

End point timeframe

Baseline, Weeks 76 and 128

End point values	4mg Mean Change TJC and SJC From Baseline To Wks 76 and 128	4-8mg Mean Change TJC and SJC From Baseline To Wks 76 and 128	8mg Mean Change TJC and SJC From Baseline To Wks 76 and 128
Number of subjects analysed	108	61	32
Units: units on a scale
arithmetic mean (standard deviation)
TJC - Week 76 (n=108, 61, 32)	-15.7 ( 11.26 )	-16 ( 13.37 )	-18.1 ( 12.06 )
TJC - Week 128 (n=79, 47, 18)	-16.4 ( 11.01 )	-15.3 ( 12.56 )	-14 ( 13.68 )
SJC - Week 76 (n=108, 61, 32)	-11.6 ( 6.4 )	-12.9 ( 7.8 )	-12.4 ( 7.67 )
SJC - Week 128 (n=79, 47, 18)	-11.4 ( 6.81 )	-12.4 ( 8.01 )	-11.6 ( 6.23 )

No statistical analyses for this end point

Secondary: Mean Change from Baseline to Weeks 12 and 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score

Top of page

End point title

Mean Change from Baseline to Weeks 12 and 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score

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 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition. Participants were not dosed with 1 mg LY3009104 after Week 12; mean and SD were not calculated. 9999=Data Not Available (N/A).

End point type

Secondary

End point timeframe

Baseline, Weeks 12 and 24

End point values	1 milligram (mg) LY3009104 QD - Part A	2 mg LY3009104 QD - Parts A and B	4 mg LY3009104 QD - Parts A and B	8 mg LY3009104 QD - Parts A and B	Placebo QD - Part A
Number of subjects analysed	49 ^[11]	52	51 ^[12]	50	98 ^[13]
Units: units on a scale
arithmetic mean (standard deviation)
Week 12	-0.35 ( 0.528 )	-0.18 ( 0.524 )	-0.33 ( 0.459 )	-0.39 ( 0.497 )	-0.1 ( 0.406 )
Week 24	9999 ( 9999 )	-0.18 ( 0.505 )	-0.32 ( 0.506 )	-0.44 ( 0.529 )	9999 ( 9999 )

Notes
[11] - Participants were not dosed with 1 mg LY3009104 after Week 12; mean and SD were not calculated.
[12] - Participants who received study drug in Parts A and B and had evaluable HAQ-DI data.
[13] - Participants were not dosed with placebo after Week 12; mean and SD were not calculated.

No statistical analyses for this end point

Secondary: Mean Change from Baseline to Weeks 76 and 128 in HAQ-DI Score

Top of page

End point title

Mean Change from Baseline to Weeks 76 and 128 in HAQ-DI Score

End point description

End point type

Secondary

End point timeframe

Baseline, Weeks 76 and 128

End point values	4mg Mean Change HAQ-DI From Baseline To Wks 76 and 128	4-8mg Mean Change HAQ-DI From Baseline To Wks 76 and 128	8mg Mean Change HAQ-DI From Baseline To Wks 76 and 128
Number of subjects analysed	108	61	32
Units: units on a scale
arithmetic mean (standard deviation)
Week 76 (n=108, 61, 32)	-0.34 ( 0.58 )	-0.29 ( 0.53 )	-0.55 ( 0.58 )
Week 128 (n=79, 47, 18)	-0.31 ( 0.61 )	-0.22 ( 0.56 )	-0.3 ( 0.66 )

No statistical analyses for this end point

Secondary: Mean Change from Baseline to Weeks 12 and 24 in High-Sensitivity C-Reactive Protein (hsCRP)

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End point title

Mean Change from Baseline to Weeks 12 and 24 in High-Sensitivity C-Reactive Protein (hsCRP)

End point description

hsCRP is a laboratory analyte that is an indicator of inflammation. Decreases in hsCRP represent reductions in inflammation. Participants were not dosed with 1 mg LY3009104 after Week 12; mean and SD were not calculated. 9999=Data Not Available (N/A).

End point type

Secondary

End point timeframe

Baseline, Weeks 12 and 24

End point values	1 milligram (mg) LY3009104 QD - Part A	2 mg LY3009104 QD - Parts A and B	4 mg LY3009104 QD - Parts A and B	8 mg LY3009104 QD - Parts A and B	Placebo QD - Part A
Number of subjects analysed	49 ^[14]	52	51 ^[15]	50	97 ^[16]
Units: mg/L
arithmetic mean (standard deviation)
Week 12	-6.14 ( 10.236 )	-3.39 ( 19.409 )	-7.06 ( 16.945 )	-2.32 ( 32.582 )	1.5 ( 34.107 )
Week 24	9999 ( 9999 )	-4.76 ( 19.819 )	-4.95 ( 19.819 )	-7.61 ( 17.548 )	9999 ( 9999 )

Notes
[14] - Participants were not dosed with 1 mg LY3009104 after Week 12; mean and SD were not calculated.
[15] - Participants who received study drug in Parts A and B and had evaluable hsCRP data.
[16] - Participants were not dosed with placebo after Week 12, therefore mean and SD were not calculated.

No statistical analyses for this end point

Secondary: Mean Change from Baseline to Weeks 76 and 128 in hsCRP

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End point title

Mean Change from Baseline to Weeks 76 and 128 in hsCRP

End point description

hsCRP is a laboratory analyte that is an indicator of inflammation. Decreases in hsCRP represent reductions in inflammation.

End point type

Secondary

End point timeframe

Baseline, Weeks 76 and 128

End point values	4mg Mean Change hsCRP From Baseline To Wks 76 and 128	4-8mg Mean Change hsCRP From Baseline To Wks 76 and 128	8mg Mean Change hsCRP From Baseline To Wks 76 and 128
Number of subjects analysed	108	61	32
Units: mg/L
arithmetic mean (standard deviation)
Week 76 (n=108, 61, 32)	-3.9 ( 22.43 )	-3.3 ( 14.28 )	-2.9 ( 25.36 )
Week 128 (n=79, 47, 18)	-6.8 ( 13.66 )	-2.9 ( 21.88 )	-8.2 ( 12.33 )

No statistical analyses for this end point

Secondary: Mean Change from Baseline to Weeks 12 and 24 in Erythrocyte Sedimentation Rate (ESR)

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End point title

Mean Change from Baseline to Weeks 12 and 24 in Erythrocyte Sedimentation Rate (ESR)

End point description

ESR is a laboratory analyte that is an indicator of inflammation. Decreases represent reductions in inflammation. Participants were not dosed with 1 mg LY3009104 after Week 12; mean and SD were not calculated. 9999=Data Not Available (N/A).

End point type

Secondary

End point timeframe

Baseline, Weeks 12 and 24

End point values	1 milligram (mg) LY3009104 QD - Part A	2 mg LY3009104 QD - Parts A and B	4 mg LY3009104 QD - Parts A and B	8 mg LY3009104 QD - Parts A and B	Placebo QD - Part A
Number of subjects analysed	44 ^[17]	51 ^[18]	50 ^[19]	49 ^[20]	83 ^[21]
Units: mm/hr
arithmetic mean (standard deviation)
Week 12 (n=44, 51, 50, 49, 83)	-11.6 ( 14.45 )	-6.4 ( 16.81 )	-11.5 ( 17.28 )	13.9 ( 22.42 )	-6 ( 19.49 )
Week 24 (n=0, 50, 48, 45, 0)	9999 ( 9999 )	-6.9 ( 13.89 )	-9.2 ( 19 )	-13.7 ( 21.62 )	9999 ( 9999 )

Notes
[17] - Participants were not dosed with 1 mg LY3009104 after Week 12; mean and SD were not calculated.
[18] - Participants who received study drug in Parts A and B and had evaluable ESR data.
[19] - Participants who received study drug in Parts A and B and had evaluable ESR data.
[20] - Participants who received study drug in Parts A and B and had evaluable ESR data.
[21] - Participants were not dosed with 1 mg LY3009104 after Week 12; mean and SD were not calculated.

No statistical analyses for this end point

Secondary: Mean Change from Baseline to Weeks 76 and 128 in ESR

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End point title

Mean Change from Baseline to Weeks 76 and 128 in ESR

End point description

ESR is a laboratory analyte that is an indicator of inflammation. Decreases represent reductions in inflammation.

End point type

Secondary

End point timeframe

Baseline, Weeks 76 and 128

End point values	4mg Mean Change ESR From Baseline To Wks 76 and 128	4-8mg Mean Change ESR From Baseline To Wks 76 and 128	8mg Mean Change ESR From Baseline To Wks 76 and 128
Number of subjects analysed	108 ^[22]	61 ^[23]	32 ^[24]
Units: mm/hr
arithmetic mean (standard deviation)
Week 76 (n=108, 61, 32)	-13 ( 18.84 )	-7.4 ( 26.28 )	-8.9 ( 23.12 )
Week 128 (n=79, 47, 18)	-16 ( 18.74 )	-8.5 ( 23.11 )	-15.5 ( 23.07 )

Notes
[22] - Participants who received study drug Parts C and D and had evaluable ESR data.
[23] - Participants who received study drug Parts C and D and had evaluable ESR data.
[24] - Participants who received study drug Parts C and D and had evaluable ESR data.

No statistical analyses for this end point

Secondary: Mean Change from Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain

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End point title

Mean Change from Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain

End point description

Physician's and Patient's Assessments of Disease Activity (DA) assessed using a visual analog scale (VAS) that ranged from 0 to 100 millimeters (mm), where 0 indicated no arthritis activity and 100 indicated extremely active arthritis. Patient's assessment of pain due to arthritis was also assessed using a VAS that ranged from 0 (no pain) to 100 mm (worst possible pain). Participants were not dosed with 1 mg LY3009104 after Week 12; mean and SD were not calculated. 9999=Data Not Available (N/A).

End point type

Secondary

End point timeframe

Baseline, Weeks 12 and 24

End point values	1 milligram (mg) LY3009104 QD - Part A	2 mg LY3009104 QD - Parts A and B	4 mg LY3009104 QD - Parts A and B	8 mg LY3009104 QD - Parts A and B	Placebo QD - Part A
Number of subjects analysed	49 ^[25]	52	51 ^[26]	50	98 ^[27]
Units: units on a scale
arithmetic mean (standard deviation)
Physician's Assessment of DA - Week 12	-23.9 ( 18.49 )	-25 ( 20.81 )	-30.4 ( 18.75 )	-33.5 ( 19.49 )	-19 ( 21.4 )
Physician's Assessment of DA - Week 24	9999 ( 9999 )	-27.8 ( 21.13 )	-35.5 ( 17.72 )	-37.8 ( 18.73 )	9999 ( 9999 )
Patient's Assessment of DA - Week 12	-24.9 ( 27.26 )	-16.2 ( 22.43 )	-25.4 ( 21.61 )	-29.8 ( 21.2 )	-10.3 ( 22.02 )
Patient's Assessment of DA - Week 24	9999 ( 9999 )	-16.9 ( 24.96 )	-30.2 ( 21.85 )	-30 ( 20.9 )	9999 ( 9999 )
Patient's Assessment of Pain - Week 12	-22.8 ( 27.39 )	-14.2 ( 17.82 )	-25 ( 19.22 )	-25.3 ( 20.31 )	-8.8 ( 22.77 )
Patient's Assessment of Pain - Week 24	9999 ( 9999 )	-14.7 ( 20.57 )	-27.3 ( 22.11 )	-26.9 ( 19.22 )	9999 ( 9999 )

Notes
[25] - Participants were not dosed with 1 mg LY3009104 after Week 12; mean and SD were not calculated.
[26] - Participants who received study drug in Parts A and B and had evaluable DA assessment data,
[27] - Participants were not dosed with placebo after Week 12; mean and SD were not calculated.

No statistical analyses for this end point

Secondary: Mean Change from Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain

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End point title

Mean Change from Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain

End point description

Physician's and Patient's assessments of DA assessed using a VAS that ranged from 0 to 100 mm, where 0 indicated no arthritis activity and 100 indicated extremely active arthritis. Patient's assessment of pain due to arthritis assessed using a VAS that ranged from 0 (no pain) to 100 mm (worst possible pain).

End point type

Secondary

End point timeframe

Baseline, Weeks 76 and 128

End point values	4mg DA Assessment Wks 76 and 128	4-8mg DA Assessment Wks 76 and 128	8mg DA Assessment Wks 76 and 128
Number of subjects analysed	108	61	32
Units: units on a scale
arithmetic mean (standard deviation)
Physician Assessment of DA-Week 76 (n=108, 61, 32)	-40.3 ( 19.15 )	-32.3 ( 23.37 )	-40.5 ( 21.44 )
Physician Assessment of DA-Week 128 (n=79, 47, 18)	-39.5 ( 20.32 )	-31 ( 25.54 )	-34 ( 27.51 )
Patient Assessment of DA-Week 76 (n=108, 61, 32)	-27.5 ( 26.49 )	-27.5 ( 25.52 )	-27.6 ( 24.11 )
Patient Assessment of DA-Week 128 (n=79, 47, 18)	-27.9 ( 27.4 )	-19.3 ( 29.72 )	-27.6 ( 25.17 )
Patient Assessment of Pain-Week 76 (n=108, 61, 32)	-25.1 ( 24.1 )	-27.3 ( 24.24 )	-23.4 ( 23.49 )
Patient Assessment of Pain-Week 128 (n=79, 47, 18)	-24.2 ( 24.35 )	-18 ( 28.85 )	-22.3 ( 22.99 )

No statistical analyses for this end point

Secondary: Mean Change from Baseline to Weeks 12 and 24 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP)

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End point title

Mean Change from Baseline to Weeks 12 and 24 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP 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-28 (TJC28), swollen joint count-28 (SJC28), CRP (mg/L), and Patient's Global Assessment of Disease Activity using VAS (patient's global VAS). DAS28-CRP=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.36*natural log(CRP+1)+0.014*patient's global VAS+0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity, and remission was DAS28-CRP <2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition. Participants were not dosed with 1 mg LY3009104 after Week 12; mean and SD were not calculated. 9999=Data Not Available (N/A).

End point type

Secondary

End point timeframe

Baseline, Weeks 12 and 24

End point values	1 milligram (mg) LY3009104 QD - Part A	2 mg LY3009104 QD - Parts A and B	4 mg LY3009104 QD - Parts A and B	8 mg LY3009104 QD - Parts A and B	Placebo QD - Part A
Number of subjects analysed	49 ^[28]	52	50 ^[29]	50	93 ^[30]
Units: units on a scale
arithmetic mean (standard deviation)
Week 12	-1.47 ( 1.299 )	-1.4 ( 1.21 )	-2.09 ( 1.22 )	-2.15 ( 1.273 )	-0.98 ( 1.141 )
Week 24	9999 ( 9999 )	-1.53 ( 1.187 )	-2.25 ( 1.054 )	-2.47 ( 1.28 )	9999 ( 9999 )

Notes
[28] - Participants were not dosed with 1 mg LY3009104 after Week 12; mean and SD were not calculated.
[29] - Participants who received drug in Parts A and B and had evaluable DAS28-CRP data.
[30] - Participants were not dosed with placebo after Week 12; mean and SD were not calculated.

No statistical analyses for this end point

Secondary: Mean Change from Baseline to Weeks 76 and 128 in DAS28-CRP

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End point title

Mean Change from Baseline to Weeks 76 and 128 in 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 (mg/L), and Patient's Global Assessment of Disease Activity using visual analog scale (VAS) (patient's global VAS). DAS28-CRP=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.36*natural log(CRP+1)+0.014*patient's 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.

End point type

Secondary

End point timeframe

Baseline, Weeks 76 and 128

End point values	4mg Mean Change DAS28-CRP From Baseline To Wks 76 and 128	4-8mg Mean Change DAS28-CRP From Baseline To Wks 76 and 128	8mg Mean Change DAS28-CRP From Baseline To Wks 76 and 128
Number of subjects analysed	107 ^[31]	61 ^[32]	31 ^[33]
Units: units on a scale
arithmetic mean (standard deviation)
Week 76 (n=107, 61, 31)	-2.47 ( 1.23 )	-2.16 ( 1.28 )	-2.68 ( 1.12 )
Week 128 (n=79, 47, 18)	-2.56 ( 1.16 )	-2.02 ( 1.23 )	-2.35 ( 1.4 )

Notes
[31] - Participants who received study drug in Parts C and D and had evaluable DAS28-CRP data.
[32] - Participants who received study drug in Parts C and D and had evaluable DAS28-CRP data.
[33] - Participants who received study drug in Parts C and D and had evaluable DAS28-CRP data.

No statistical analyses for this end point

Secondary: Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-Joint Count (EULAR28) Baseline through Weeks 12 and 24

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End point title

Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-Joint Count (EULAR28) Baseline through Weeks 12 and 24

End point description

EULAR28 categorizes clinical response based upon improvement since baseline in DAS modified to include the 28-joint count (DAS28) and post-baseline DAS28. DAS28 consists of a composite score of the following variables: TJC28, SJC28, CRP, and Patient's Global Assessment of their Disease Activity (patient's global VAS). DAS28 scores range from 1.0-9.4. EULAR28 categories include: No Response (improvement in DAS28 of ≤0.6 units or post-baseline DAS28 score >5.1 with improvement by ≤1.2 units), Moderate Response (post-baseline DAS28 ≤5.1 with improvement by >0.6 units but ≤1.2 units or post-baseline DAS28 score >3.2 with improvement by >1.2 units), and Good Response (post-baseline DAS28 score ≤3.2 with improvement by >1.2 units). Participants were not dosed with 1 mg LY3009104 after Week 12; percentage was not calculated. 9999=Data Not Available (N/A).

End point type

Secondary

End point timeframe

Baseline through Weeks 12 and 24

End point values	1 milligram (mg) LY3009104 QD - Part A	2 mg LY3009104 QD - Parts A and B	4 mg LY3009104 QD - Parts A and B	8 mg LY3009104 QD - Parts A and B	Placebo QD - Part A
Number of subjects analysed	49 ^[34]	52	52	50	98 ^[35]
Units: percentage of participants
number (not applicable)
Good Response - Week 12	22	17	46	40	16
Moderate Response - Week 12	43	63	31	46	35
No Response - Week 12	35	19	23	14	49
Good Response - Week 24	9999	25	42	46	9999
Moderate Response - Week 24	9999	52	42	32	9999
No Response - Week 24	9999	23	15	22	9999

Notes
[34] - Participants were not dosed with 1 mg LY3009104 after Week 12; percentage was not calculated.
[35] - Participants were not dosed with placebo after Week 12; percentage was not calculated.

No statistical analyses for this end point

Secondary: Percentage of Responders According to EULAR28 Baseline through Weeks 76 and 128

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End point title

Percentage of Responders According to EULAR28 Baseline through Weeks 76 and 128

End point description

EULAR28 categorizes clinical response based upon improvement since baseline in Disease Activity Score modified to include the 28-joint count (DAS28) and post-baseline DAS28. DAS28 consists of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP, and Patient's Global Assessment of their Disease Activity (patient's global VAS). DAS28 scores range from 1.0-9.4. EULAR28 categories include: No Response (improvement in DAS28 of ≤0.6 units or post-baseline DAS28 score >5.1 with improvement by ≤1.2 units), Moderate Response (post-baseline DAS28 ≤5.1 with improvement by >0.6 units but ≤1.2 units or post-baseline DAS28 score >3.2 with improvement by >1.2 units), and Good Response (post-baseline DAS28 score ≤3.2 with improvement by >1.2 units). All participants who received study drug in Parts C and D and had EULAR28 evaluated at analysis time points. LOCF was used to impute missing post-baseline values.

End point type

Secondary

End point timeframe

Baseline, Weeks 76 and 128

End point values	4mg EULAR28 Response Wks 76 and 128	4-8mg EULAR28 Response Wks 76 and 128	8mg EULAR28 Response Wks 76 and 128
Number of subjects analysed	107	61	31
Units: percentage of participants
number (not applicable)
Good Response - Week 76 (n=107, 61, 31)	64	41	55
Moderate Response - Week 76 (n=107, 61, 31)	27	46	39
No Response - Week 76 (n=107, 61, 31)	8	13	6
Good Response - Week 128 (n=79, 47, 18)	65	40	56
Moderate Response - Week 128 (n=79, 47, 18)	30	40	28
No Response - Week 128 (n=79, 47, 18)	5	19	17

No statistical analyses for this end point

Secondary: Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline through Weeks 12 and 24

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End point title

Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline through Weeks 12 and 24

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 Patient's Global Assessment of Disease Activity using VAS (patient's global VAS). Scores ranged from 1.0-9.4, where lower scores indicated less disease activity. DAS28 scores ≤3.2 are considered as low disease activity, and scores <2.6 are considered as remission. Participants who discontinue before analysis time points are treated as non-responders. Participants were not dosed with 1 mg LY3009104 after Week 12; percentage was not calculated. 9999=Data Not Available (N/A).

End point type

Secondary

End point timeframe

Baseline through Weeks 12 and 24

End point values	1 milligram (mg) LY3009104 QD - Part A	2 mg LY3009104 QD - Parts A and B	4 mg LY3009104 QD - Parts A and B	8 mg LY3009104 QD - Parts A and B	Placebo QD - Part A
Number of subjects analysed	49 ^[36]	52	52	50	98 ^[37]
Units: percentage of participants
number (not applicable)
Low Disease Activity - Week 12	22	23	48	40	19
Remission - Week 12	14	15	37	22	4
Low Disease Activity - Week 24	9999	31	50	46	9999
Remission - Week 24	9999	15	33	36	9999

Notes
[36] - Participants were not dosed with 1 mg LY3009104 after Week 12; percentage was not calculated.
[37] - Participants were not dosed with placebo after Week 12; percentage was not calculated.

No statistical analyses for this end point

Secondary: Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline through Weeks 76 and 128

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End point title

Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline through Weeks 76 and 128

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 (mg/L), and Patient's Global Assessment of Disease Activity using VAS (patient's global VAS). Scores ranged from 1.0-9.4, where lower scores indicated less disease activity. DAS28 scores ≤3.2 are considered as low disease activity, and scores <2.6 are considered as remission. Participants who discontinue before analysis time points are treated as non-responders.

End point type

Secondary

End point timeframe

Baseline through Weeks 76 and 128

End point values	4mg Percentage Participants Meeting Low DA Wks 76 and 128	4-8mg Percentage Participants Meeting Low DA Wks 76 and 128	8mg Percentage Participants Meeting Low DA Wks 76 and 128
Number of subjects analysed	108	61	32
Units: percentage of participants
number (not applicable)
Low Disease activity - Week 76 (n=108, 61, 32)	58	38	44
Remission - Week 76 (n=108, 61, 32)	52	21	22
Low Disease activity - Week 128 (n=79, 47, 18)	59	36	56
Remission - Week 128 (n=79, 47, 18)	47	26	39

No statistical analyses for this end point

Secondary: Mean Change from Baseline through Week 12 in Duration (Minutes) of Morning Stiffness

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End point title

Mean Change from Baseline through Week 12 in Duration (Minutes) of Morning Stiffness

End point description

The Investigator asked participants about the duration of their morning stiffness (in minutes) in and around the joints and recorded the duration. The Investigator asked the participants about duration of morning stiffness on the day prior to the study visit to capture actual symptoms. If morning stiffness duration was longer than 12 hours (720 minutes), it was truncated to 720 minutes for statistical presentations and analyses.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12

End point values	1 milligram (mg) LY3009104 QD - Part A	2 mg LY3009104 QD - Parts A and B	4 mg LY3009104 QD - Parts A and B	8 mg LY3009104 QD - Parts A and B	Placebo QD - Part A
Number of subjects analysed	48 ^[38]	51 ^[39]	50 ^[40]	50	97 ^[41]
Units: minutes
arithmetic mean (standard deviation)
Week 4 (n=47, 50, 50, 50, 94)	-34.1 ( 70.49 )	-27 ( 46.49 )	-57.4 ( 149 )	-25.5 ( 126.13 )	-22.5 ( 63.61 )
Week 8 (n=46, 50, 50, 50, 86)	-41.2 ( 85.45 )	-31.1 ( 45.8 )	-67.8 ( 138.02 )	-53.8 ( 101.76 )	-25.5 ( 67.39 )
Week 12 (n=48, 51, 50, 50, 97)	-49.5 ( 72.8 )	-30.7 ( 47.41 )	-75 ( 142.04 )	-62.7 ( 88.27 )	-33.9 ( 97.79 )

Notes
[38] - Participants who received study drug in Part A and had evaluable morning stiffness data.
[39] - Participants who received study drug in Part A and had evaluable morning stiffness data.
[40] - Participants who received study drug in Part A and had evaluable morning stiffness data.
[41] - Participants who received study drug in Part A and had evaluable morning stiffness data.

No statistical analyses for this end point

Secondary: Mean Change from Baseline to Week 12 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores

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End point title

Mean Change from Baseline to Week 12 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores

End point description

The 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 also emotional problems, general health, mental health, social functioning and vitality) and 2 component scores (PCS and MCS). The PCS score consisted of physical functioning, bodily pain, role-physical, and general health scales. The MCS score consisted of social functioning, vitality, mental health, and role-emotional scales. Both PCS and MCS range from 0-100 with higher scores indicating better health or functioning.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	1 milligram (mg) LY3009104 QD - Part A	2 mg LY3009104 QD - Parts A and B	4 mg LY3009104 QD - Parts A and B	8 mg LY3009104 QD - Parts A and B	Placebo QD - Part A
Number of subjects analysed	48 ^[42]	51 ^[43]	51 ^[44]	50	97 ^[45]
Units: units on a scale
arithmetic mean (standard deviation)
PCS	6.66 ( 8.074 )	4.15 ( 7.68 )	7.07 ( 7.378 )	7 ( 9.054 )	3.22 ( 6.733 )
MCS	2.54 ( 11.983 )	1.89 ( 6.869 )	2.39 ( 7.898 )	3.03 ( 10.675 )	0.88 ( 10.437 )

Notes
[42] - Participants who received study drug in Part A and had evaluable SF-36 data.
[43] - Participants who received study drug in Part A and had evaluable SF-36 data.
[44] - Participants who received study drug in Part A and had evaluable SF-36 data.
[45] - Participants who received study drug in Part A and had evaluable SF-36 data.

No statistical analyses for this end point

Secondary: Mean Change from Baseline to Week 12 in Brief Pain Inventory Modified Short Form (BPI-SF Modified) Worst-Pain-in-the-Past-24-hours Item Score

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End point title

Mean Change from Baseline to Week 12 in Brief Pain Inventory Modified Short Form (BPI-SF Modified) Worst-Pain-in-the-Past-24-hours Item Score

End point description

The BPI-sf modified is a self-administered questionnaire developed for the rapid assessment of pain. The BPI-sf modified provides information on the intensity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The questionnaire asks questions about pain relief, pain quality, and the participant's perception of the cause of pain. The BPI-sf modified uses a numeric rating scale from 0 (“No pain”) to 10 (“Pain as bad as you can imagine”). Since pain can be quite variable over a day, the BPI-sf modified asked participants to rate their pain at the time of responding to the questionnaire (right now), and also at its worst, least and average over the last 24 hours.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	1 milligram (mg) LY3009104 QD - Part A	2 mg LY3009104 QD - Parts A and B	4 mg LY3009104 QD - Parts A and B	8 mg LY3009104 QD - Parts A and B	Placebo QD - Part A
Number of subjects analysed	48 ^[46]	51 ^[47]	51 ^[48]	50	97 ^[49]
Units: units on a scale
arithmetic mean (standard deviation)	-1.35 ( 2.547 )	-0.67 ( 2.132 )	-1.41 ( 1.813 )	-1.54 ( 2.131 )	-0.35 ( 2.136 )

Notes
[46] - Participants who received study drug and had evaluable BPI-sf worst-pain-in-the past-24-hours data.
[47] - Participants who received study drug and had evaluable BPI-sf worst-pain-in-the past-24-hours data.
[48] - Participants who received study drug and had evaluable BPI-sf worst-pain-in-the past-24-hours data.
[49] - Participants who received study drug and had evaluable BPI-sf worst-pain-in-the past-24-hours data.

No statistical analyses for this end point

Secondary: Mean Change from Baseline to Week 12 in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Score

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End point title

Mean Change from Baseline to Week 12 in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Score

End point description

The FACIT-F Scale is a brief 13-item, symptom-specific questionnaire that specifically assesses the participant self-reported severity of fatigue and its impact upon daily activities and functioning. The FACIT-F uses a numeric rating scale of 0 (“Not at all”) to 4 (“Very much”) for each item to assess fatigue and its impact in the past 7 days. Total scores range from 0 to 52, with higher scores indicating less fatigue.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	1 milligram (mg) LY3009104 QD - Part A	2 mg LY3009104 QD - Parts A and B	4 mg LY3009104 QD - Parts A and B	8 mg LY3009104 QD - Parts A and B	Placebo QD - Part A
Number of subjects analysed	48 ^[50]	51 ^[51]	51 ^[52]	50	97 ^[53]
Units: units on a scale
arithmetic mean (standard deviation)	4.48 ( 10.492 )	3.8 ( 9.152 )	4.41 ( 8.631 )	4.11 ( 9.971 )	2.02 ( 8.941 )

Notes
[50] - Participants who received study drug in Part A and had evaluable FACIT-F at Week 12 data.
[51] - Participants who received study drug in Part A and had evaluable FACIT-F at Week 12 data.
[52] - Participants who received study drug in Part A and had evaluable FACIT-F at Week 12 data.
[53] - Participants who received study drug in Part A and had evaluable FACIT-F at Week 12 data.

No statistical analyses for this end point

Secondary: Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104

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End point title

Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104 ^[54]

End point description

End point type

Secondary

End point timeframe

Baseline through 24 weeks

Notes
[54] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All randomized participants who received at least 1 dose of LY3009104 with evaluable LY3009104 PK data. Participants receiving placebo will not have PK data.

End point values	1 milligram (mg) LY3009104 QD - Part A	2mg LY3009104 PK Assessment for Cmax Part A	4mg LY3009104 PK Assessment for Cmax Part A	8mg LY3009104 PK Assessment for Cmax Part A
Number of subjects analysed	47 ^[55]	91 ^[56]	91 ^[57]	50
Units: nanomoles/Liter (nmol/L)
geometric mean (geometric coefficient of variation)	36.5 ( 36.1 )	59.1 ( 21.3 )	119 ( 20.5 )	241 ( 22.9 )

Notes
[55] - Participants who received at least 1 dose of LY3009104 with evaluable LY3009104 PK data.
[56] - Participants who received at least 1 dose of LY3009104 with evaluable LY3009104 PK data.
[57] - Participants who received at least 1 dose of LY3009104 with evaluable LY3009104 PK data.

No statistical analyses for this end point

Secondary: Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of LY3009104

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End point title

Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of LY3009104 ^[58]

End point description

End point type

Secondary

End point timeframe

Baseline through 24 weeks

Notes
[58] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All randomized participants who received at least 1 dose of LY3009104 with evaluable LY3009104 PK data. Participants receiving placebo will not have PK data.

End point values	1 milligram (mg) LY3009104 QD - Part A	2mg LY3009104 PK Assessment for AUC Part A	4mg LY3009104 PK Assessment for AUC Part A	8mg LY3009104 PK Assessment for AUC Part A
Number of subjects analysed	47 ^[59]	91 ^[60]	91 ^[61]	50
Units: nanomoleshour/Liter (nmolh/L)
geometric mean (geometric coefficient of variation)	333 ( 61.7 )	541 ( 38 )	1060 ( 37 )	2190 ( 45.6 )

Notes
[59] - Participants who received at least 1 dose of LY3009104 with evaluable LY3009104 PK data.
[60] - Participants who received at least 1 dose of LY3009104 with evaluable LY3009104 PK data.
[61] - Participants who received at least 1 dose of LY3009104 with evaluable LY3009104 PK data.

No statistical analyses for this end point

Secondary: Mean Change from Baseline through Week 12 in the Ensemble Minimum Data Set 1.0

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End point title

Mean Change from Baseline through Week 12 in the Ensemble Minimum Data Set 1.0

End point description

Zero participants were analyzed. Assessment of Ensemble Minimum Data Set 1.0 was not collected at Week 12 and therefore results are not reported for outcome measure.

End point type

Secondary

End point timeframe

Baseline, 12 weeks

End point values	1 milligram (mg) LY3009104 QD - Part A	2 mg LY3009104 QD - Parts A and B	4 mg LY3009104 QD - Parts A and B	8 mg LY3009104 QD - Parts A and B	Placebo QD - Part A
Number of subjects analysed	0 ^[62]	0 ^[63]	0 ^[64]	0 ^[65]	0 ^[66]
Units: number
number (not applicable)

Notes
[62] - Zero participants were analyzed. Assessment of Ensemble Minimum Data Set 1.0 was not collected.
[63] - Zero participants were analyzed. Assessment of Ensemble Minimum Data Set 1.0 was not collected.
[64] - Zero participants were analyzed. Assessment of Ensemble Minimum Data Set 1.0 was not collected.
[65] - Zero participants were analyzed. Assessment of Ensemble Minimum Data Set 1.0 was not collected.
[66] - Zero participants were analyzed. Assessment of Ensemble Minimum Data Set 1.0 was not collected.

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Entire Study

Adverse event reporting additional description

I4V-MC-JADA

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

16.1

Reporting group title

1 mg LY3009104 once daily Weeks 0-12

Reporting group description

Reporting group title

2 mg LY3009104 once daily Weeks 0-12

Reporting group description

Reporting group title

4 mg LY3009104 once daily Weeks 0-12

Reporting group description

Reporting group title

8 mg LY3009104 once daily Weeks 0-12

Reporting group description

Reporting group title

Placebo once daily Weeks 0-12

Reporting group description

Reporting group title

2 mg LY3009104 twice daily crossover Weeks 12-24

Reporting group description

Reporting group title

4 mg LY3009104 once daily crossover Weeks 12-24

Reporting group description

Reporting group title

2 mg LY3009104 once daily Weeks 12-24

Reporting group description

Reporting group title

4 mg LY3009104 once daily Weeks 12-24

Reporting group description

Reporting group title

8 mg LY3009104 once daily Weeks 12-24

Reporting group description

Reporting group title

4/4 mg LY3009104 once daily Weeks 24-76

Reporting group description

Reporting group title

4:8/4 mg LY3009104 once daily pre-rescue Weeks 24-76

Reporting group description

Reporting group title

4:8/4 mg LY3009104 once daily post-rescue Weeks 24-76

Reporting group description

Reporting group title

8/4 mg LY3009104 once daily Weeks 24-76

Reporting group description

Reporting group title

4/4 mg LY3009104 once daily Weeks 76-128

Reporting group description

Reporting group title

4:8/4 mg LY3009104 once daily Weeks 76-128

Reporting group description

Reporting group title

8/4 mg LY3009104 once daily Weeks 76-128

Reporting group description

Reporting group title

Follow-up

Reporting group description

1 mg LY3009104 once daily Weeks 0-12

2 mg LY3009104 once daily Weeks 0-12

4 mg LY3009104 once daily Weeks 0-12

8 mg LY3009104 once daily Weeks 0-12

Placebo once daily Weeks 0-12

2 mg LY3009104 twice daily crossover Weeks 12-24

4 mg LY3009104 once daily crossover Weeks 12-24

2 mg LY3009104 once daily Weeks 12-24

4 mg LY3009104 once daily Weeks 12-24

8 mg LY3009104 once daily Weeks 12-24

4/4 mg LY3009104 once daily Weeks 24-76

4:8/4 mg LY3009104 once daily pre-rescue Weeks 24-76

4:8/4 mg LY3009104 once daily post-rescue Weeks 24-76

8/4 mg LY3009104 once daily Weeks 24-76

4/4 mg LY3009104 once daily Weeks 76-128

4:8/4 mg LY3009104 once daily Weeks 76-128

8/4 mg LY3009104 once daily Weeks 76-128

Follow-up

Total subjects affected by serious adverse events

subjects affected / exposed

0 / 49 (0.00%)

3 / 52 (5.77%)

2 / 52 (3.85%)

1 / 50 (2.00%)

3 / 98 (3.06%)

2 / 63 (3.17%)

1 / 63 (1.59%)

0 / 51 (0.00%)

0 / 50 (0.00%)

3 / 49 (6.12%)

16 / 108 (14.81%)

1 / 61 (1.64%)

6 / 61 (9.84%)

6 / 32 (18.75%)

5 / 79 (6.33%)

3 / 47 (6.38%)

0 / 18 (0.00%)

2 / 159 (1.26%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

basal cell carcinoma

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

1 / 63 (1.59%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pregnancy, puerperium and perinatal conditions

abortion spontaneous

alternative dictionary used: MedDRA 16.1

subjects affected / exposed ^[1]

0 / 42 (0.00%)

0 / 44 (0.00%)

0 / 37 (0.00%)

0 / 41 (0.00%)

0 / 85 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

0 / 40 (0.00%)

0 / 87 (0.00%)

0 / 52 (0.00%)

0 / 28 (0.00%)

0 / 62 (0.00%)

0 / 40 (0.00%)

0 / 17 (0.00%)

1 / 130 (0.77%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

pregnancy

alternative dictionary used: MedDRA 16.1

subjects affected / exposed ^[2]

0 / 42 (0.00%)

0 / 44 (0.00%)

0 / 37 (0.00%)

0 / 41 (0.00%)

0 / 85 (0.00%)

0 / 56 (0.00%)

0 / 54 (0.00%)

0 / 43 (0.00%)

0 / 35 (0.00%)

0 / 40 (0.00%)

0 / 87 (0.00%)

0 / 52 (0.00%)

1 / 52 (1.92%)

0 / 28 (0.00%)

0 / 62 (0.00%)

0 / 40 (0.00%)

0 / 17 (0.00%)

0 / 130 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

non-cardiac chest pain

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

0 / 32 (0.00%)

1 / 79 (1.27%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pyrexia

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

1 / 63 (1.59%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

asthma

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

1 / 52 (1.92%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pneumothorax

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

1 / 61 (1.64%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

major depression

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

1 / 47 (2.13%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

alanine aminotransferase increased

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

2 / 108 (1.85%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

aspartate aminotransferase increased

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

1 / 108 (0.93%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

blood creatine phosphokinase increased

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

1 / 108 (0.93%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

glomerular filtration rate decreased

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

1 / 52 (1.92%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hepatic enzyme increased

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

1 / 159 (0.63%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

transaminases increased

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

1 / 108 (0.93%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

fall

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

1 / 61 (1.64%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (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 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

1 / 108 (0.93%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

jaw fracture

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

1 / 52 (1.92%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

rib fracture

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

1 / 61 (1.64%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

road traffic accident

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

1 / 108 (0.93%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

scar

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

1 / 108 (0.93%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

myocardial infarction

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

1 / 32 (3.13%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (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

Nervous system disorders

carotid artery stenosis

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

1 / 108 (0.93%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

presyncope

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

1 / 32 (3.13%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (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 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

1 / 47 (2.13%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

anaemia

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

1 / 108 (0.93%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

microcytic anaemia

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

1 / 98 (1.02%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

normochromic normocytic anaemia

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

1 / 61 (1.64%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (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 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

1 / 50 (2.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Eye disorders

cataract

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

1 / 108 (0.93%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ulcerative keratitis

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

1 / 32 (3.13%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

coeliac disease

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

1 / 98 (1.02%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

colitis

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

1 / 61 (1.64%)

1 / 32 (3.13%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

gastritis

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

1 / 61 (1.64%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

large intestinal obstruction

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

0 / 32 (0.00%)

1 / 79 (1.27%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

large intestinal stenosis

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

0 / 32 (0.00%)

1 / 79 (1.27%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

cholecystitis

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

1 / 63 (1.59%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cholelithiasis

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

0 / 32 (0.00%)

1 / 79 (1.27%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Skin and subcutaneous tissue disorders

angioedema

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

1 / 108 (0.93%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (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

haematuria

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

1 / 98 (1.02%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

renal failure

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

1 / 49 (2.04%)

0 / 108 (0.00%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

arthritis

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

1 / 108 (0.93%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

diastasis recti abdominis

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

0 / 32 (0.00%)

1 / 79 (1.27%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (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 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

1 / 61 (1.64%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

neck pain

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

1 / 108 (0.93%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (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 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

0 / 32 (0.00%)

1 / 79 (1.27%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (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

acute hepatitis b

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

1 / 32 (3.13%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

bronchitis

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

1 / 52 (1.92%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

gastroenteritis

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

1 / 108 (0.93%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

1 / 47 (2.13%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

gastroenteritis viral

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

1 / 61 (1.64%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

helicobacter gastritis

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

1 / 52 (1.92%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

1 / 49 (2.04%)

0 / 108 (0.00%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (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

herpes simplex

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

1 / 61 (1.64%)

0 / 32 (0.00%)

1 / 79 (1.27%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

herpes zoster

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

4 / 108 (3.70%)

0 / 61 (0.00%)

1 / 32 (3.13%)

1 / 79 (1.27%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

3 / 4

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pneumonia

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

1 / 52 (1.92%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

2 / 47 (4.26%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

pneumonia bacterial

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

1 / 49 (2.04%)

0 / 108 (0.00%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

dehydration

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

0 / 98 (0.00%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

1 / 108 (0.93%)

0 / 61 (0.00%)

1 / 32 (3.13%)

0 / 79 (0.00%)

1 / 47 (2.13%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hyperglycaemia

alternative dictionary used: MedDRA 16.1

subjects affected / exposed

0 / 49 (0.00%)

0 / 52 (0.00%)

0 / 50 (0.00%)

1 / 98 (1.02%)

0 / 63 (0.00%)

0 / 51 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 108 (0.00%)

0 / 61 (0.00%)

0 / 32 (0.00%)

0 / 79 (0.00%)

0 / 47 (0.00%)

0 / 18 (0.00%)

0 / 159 (0.00%)

occurrences causally related to treatment / all

0 / 0

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.

Frequency threshold for reporting non-serious adverse events: 4%

Non-serious adverse events	1 mg LY3009104 once daily Weeks 0-12	2 mg LY3009104 once daily Weeks 0-12	4 mg LY3009104 once daily Weeks 0-12	8 mg LY3009104 once daily Weeks 0-12	Placebo once daily Weeks 0-12	2 mg LY3009104 twice daily crossover Weeks 12-24	4 mg LY3009104 once daily crossover Weeks 12-24	2 mg LY3009104 once daily Weeks 12-24	4 mg LY3009104 once daily Weeks 12-24	8 mg LY3009104 once daily Weeks 12-24	4/4 mg LY3009104 once daily Weeks 24-76	4:8/4 mg LY3009104 once daily pre-rescue Weeks 24-76	4:8/4 mg LY3009104 once daily post-rescue Weeks 24-76	8/4 mg LY3009104 once daily Weeks 24-76	4/4 mg LY3009104 once daily Weeks 76-128	4:8/4 mg LY3009104 once daily Weeks 76-128	8/4 mg LY3009104 once daily Weeks 76-128	Follow-up
Total subjects affected by non serious adverse events
subjects affected / exposed	15 / 49 (30.61%)	13 / 52 (25.00%)	13 / 52 (25.00%)	15 / 50 (30.00%)	18 / 98 (18.37%)	15 / 63 (23.81%)	10 / 63 (15.87%)	12 / 51 (23.53%)	10 / 50 (20.00%)	18 / 49 (36.73%)	35 / 108 (32.41%)	7 / 61 (11.48%)	25 / 61 (40.98%)	16 / 32 (50.00%)	24 / 79 (30.38%)	13 / 47 (27.66%)	10 / 18 (55.56%)	5 / 159 (3.14%)
Investigations
alanine aminotransferase increased
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 49 (0.00%)	1 / 52 (1.92%)	0 / 52 (0.00%)	1 / 50 (2.00%)	3 / 98 (3.06%)	0 / 63 (0.00%)	0 / 63 (0.00%)	1 / 51 (1.96%)	1 / 50 (2.00%)	1 / 49 (2.04%)	1 / 108 (0.93%)	0 / 61 (0.00%)	0 / 61 (0.00%)	0 / 32 (0.00%)	1 / 79 (1.27%)	3 / 47 (6.38%)	0 / 18 (0.00%)	0 / 159 (0.00%)
occurrences all number	0	1	0	3	3	0	0	1	1	1	1	0	0	0	1	4	0	0
blood cholesterol increased
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	2 / 49 (4.08%)	1 / 52 (1.92%)	2 / 52 (3.85%)	2 / 50 (4.00%)	2 / 98 (2.04%)	3 / 63 (4.76%)	1 / 63 (1.59%)	0 / 51 (0.00%)	1 / 50 (2.00%)	3 / 49 (6.12%)	3 / 108 (2.78%)	0 / 61 (0.00%)	0 / 61 (0.00%)	0 / 32 (0.00%)	4 / 79 (5.06%)	0 / 47 (0.00%)	0 / 18 (0.00%)	0 / 159 (0.00%)
occurrences all number	2	1	2	2	2	3	1	0	1	4	4	0	0	0	4	0	0	0
blood creatine phosphokinase increased
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	2 / 49 (4.08%)	0 / 52 (0.00%)	2 / 52 (3.85%)	1 / 50 (2.00%)	1 / 98 (1.02%)	1 / 63 (1.59%)	0 / 63 (0.00%)	2 / 51 (3.92%)	1 / 50 (2.00%)	2 / 49 (4.08%)	1 / 108 (0.93%)	1 / 61 (1.64%)	2 / 61 (3.28%)	0 / 32 (0.00%)	1 / 79 (1.27%)	0 / 47 (0.00%)	0 / 18 (0.00%)	0 / 159 (0.00%)
occurrences all number	2	0	2	1	1	1	0	2	1	2	1	1	2	0	1	0	0	0
low density lipoprotein increased
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 49 (0.00%)	0 / 52 (0.00%)	1 / 52 (1.92%)	1 / 50 (2.00%)	2 / 98 (2.04%)	4 / 63 (6.35%)	1 / 63 (1.59%)	1 / 51 (1.96%)	1 / 50 (2.00%)	3 / 49 (6.12%)	0 / 108 (0.00%)	0 / 61 (0.00%)	0 / 61 (0.00%)	0 / 32 (0.00%)	3 / 79 (3.80%)	0 / 47 (0.00%)	0 / 18 (0.00%)	0 / 159 (0.00%)
occurrences all number	0	0	1	1	2	4	1	1	1	3	0	0	0	0	3	0	0	0
weight increased
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 49 (0.00%)	0 / 52 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)	0 / 98 (0.00%)	0 / 63 (0.00%)	0 / 63 (0.00%)	0 / 51 (0.00%)	0 / 50 (0.00%)	0 / 49 (0.00%)	0 / 108 (0.00%)	0 / 61 (0.00%)	3 / 61 (4.92%)	0 / 32 (0.00%)	1 / 79 (1.27%)	1 / 47 (2.13%)	0 / 18 (0.00%)	0 / 159 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	3	0	1	1	0	0
Vascular disorders
hypertension
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 49 (0.00%)	0 / 52 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)	1 / 98 (1.02%)	0 / 63 (0.00%)	0 / 63 (0.00%)	1 / 51 (1.96%)	4 / 50 (8.00%)	1 / 49 (2.04%)	1 / 108 (0.93%)	0 / 61 (0.00%)	0 / 61 (0.00%)	0 / 32 (0.00%)	0 / 79 (0.00%)	0 / 47 (0.00%)	0 / 18 (0.00%)	0 / 159 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	5	1	1	0	0	0	0	0	0	0
Surgical and medical procedures
spinal laminectomy
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 49 (0.00%)	0 / 52 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)	0 / 98 (0.00%)	0 / 63 (0.00%)	0 / 63 (0.00%)	0 / 51 (0.00%)	0 / 50 (0.00%)	0 / 49 (0.00%)	0 / 108 (0.00%)	0 / 61 (0.00%)	0 / 61 (0.00%)	0 / 32 (0.00%)	0 / 79 (0.00%)	0 / 47 (0.00%)	1 / 18 (5.56%)	0 / 159 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Nervous system disorders
dizziness
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 49 (0.00%)	1 / 52 (1.92%)	0 / 52 (0.00%)	1 / 50 (2.00%)	0 / 98 (0.00%)	0 / 63 (0.00%)	0 / 63 (0.00%)	0 / 51 (0.00%)	0 / 50 (0.00%)	0 / 49 (0.00%)	1 / 108 (0.93%)	0 / 61 (0.00%)	0 / 61 (0.00%)	2 / 32 (6.25%)	0 / 79 (0.00%)	1 / 47 (2.13%)	1 / 18 (5.56%)	0 / 159 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0	0	1	0	0	2	0	1	1	0
headache
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	2 / 49 (4.08%)	1 / 52 (1.92%)	1 / 52 (1.92%)	2 / 50 (4.00%)	2 / 98 (2.04%)	2 / 63 (3.17%)	1 / 63 (1.59%)	1 / 51 (1.96%)	0 / 50 (0.00%)	0 / 49 (0.00%)	1 / 108 (0.93%)	1 / 61 (1.64%)	0 / 61 (0.00%)	0 / 32 (0.00%)	0 / 79 (0.00%)	0 / 47 (0.00%)	0 / 18 (0.00%)	0 / 159 (0.00%)
occurrences all number	2	1	1	3	2	2	1	1	0	0	1	1	0	0	0	0	0	0
syncope
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 49 (0.00%)	0 / 52 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)	1 / 98 (1.02%)	0 / 63 (0.00%)	0 / 63 (0.00%)	0 / 51 (0.00%)	0 / 50 (0.00%)	0 / 49 (0.00%)	0 / 108 (0.00%)	0 / 61 (0.00%)	0 / 61 (0.00%)	0 / 32 (0.00%)	0 / 79 (0.00%)	0 / 47 (0.00%)	1 / 18 (5.56%)	0 / 159 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0
Blood and lymphatic system disorders
anaemia
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 49 (0.00%)	0 / 52 (0.00%)	2 / 52 (3.85%)	0 / 50 (0.00%)	0 / 98 (0.00%)	1 / 63 (1.59%)	0 / 63 (0.00%)	0 / 51 (0.00%)	0 / 50 (0.00%)	1 / 49 (2.04%)	0 / 108 (0.00%)	1 / 61 (1.64%)	0 / 61 (0.00%)	2 / 32 (6.25%)	1 / 79 (1.27%)	1 / 47 (2.13%)	0 / 18 (0.00%)	0 / 159 (0.00%)
occurrences all number	0	0	2	0	0	1	0	0	0	1	0	1	0	2	1	1	0	0
leukopenia
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 49 (0.00%)	0 / 52 (0.00%)	0 / 52 (0.00%)	2 / 50 (4.00%)	0 / 98 (0.00%)	0 / 63 (0.00%)	0 / 63 (0.00%)	0 / 51 (0.00%)	0 / 50 (0.00%)	1 / 49 (2.04%)	0 / 108 (0.00%)	0 / 61 (0.00%)	0 / 61 (0.00%)	0 / 32 (0.00%)	0 / 79 (0.00%)	0 / 47 (0.00%)	1 / 18 (5.56%)	0 / 159 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	1	0	0	0	0	0	0	2	0
neutropenia
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 49 (0.00%)	0 / 52 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)	0 / 98 (0.00%)	1 / 63 (1.59%)	0 / 63 (0.00%)	0 / 51 (0.00%)	0 / 50 (0.00%)	1 / 49 (2.04%)	0 / 108 (0.00%)	0 / 61 (0.00%)	0 / 61 (0.00%)	1 / 32 (3.13%)	1 / 79 (1.27%)	0 / 47 (0.00%)	1 / 18 (5.56%)	0 / 159 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	1	0	0	0	1	1	0	1	0
General disorders and administration site conditions
oedema peripheral
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	2 / 49 (4.08%)	1 / 52 (1.92%)	0 / 52 (0.00%)	0 / 50 (0.00%)	0 / 98 (0.00%)	1 / 63 (1.59%)	0 / 63 (0.00%)	0 / 51 (0.00%)	1 / 50 (2.00%)	1 / 49 (2.04%)	0 / 108 (0.00%)	0 / 61 (0.00%)	1 / 61 (1.64%)	1 / 32 (3.13%)	0 / 79 (0.00%)	1 / 47 (2.13%)	0 / 18 (0.00%)	1 / 159 (0.63%)
occurrences all number	2	1	0	0	0	1	0	0	1	1	0	0	2	1	0	1	0	1
pyrexia
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	1 / 49 (2.04%)	0 / 52 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)	0 / 98 (0.00%)	0 / 63 (0.00%)	0 / 63 (0.00%)	0 / 51 (0.00%)	0 / 50 (0.00%)	2 / 49 (4.08%)	0 / 108 (0.00%)	0 / 61 (0.00%)	1 / 61 (1.64%)	0 / 32 (0.00%)	0 / 79 (0.00%)	0 / 47 (0.00%)	0 / 18 (0.00%)	0 / 159 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	2	0	0	1	0	0	0	0	0
Gastrointestinal disorders
abdominal discomfort
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 49 (0.00%)	1 / 52 (1.92%)	0 / 52 (0.00%)	0 / 50 (0.00%)	0 / 98 (0.00%)	0 / 63 (0.00%)	0 / 63 (0.00%)	0 / 51 (0.00%)	0 / 50 (0.00%)	0 / 49 (0.00%)	0 / 108 (0.00%)	0 / 61 (0.00%)	0 / 61 (0.00%)	0 / 32 (0.00%)	0 / 79 (0.00%)	0 / 47 (0.00%)	1 / 18 (5.56%)	0 / 159 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
abdominal pain
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 49 (0.00%)	1 / 52 (1.92%)	0 / 52 (0.00%)	0 / 50 (0.00%)	0 / 98 (0.00%)	0 / 63 (0.00%)	0 / 63 (0.00%)	1 / 51 (1.96%)	0 / 50 (0.00%)	1 / 49 (2.04%)	0 / 108 (0.00%)	0 / 61 (0.00%)	0 / 61 (0.00%)	1 / 32 (3.13%)	0 / 79 (0.00%)	1 / 47 (2.13%)	1 / 18 (5.56%)	0 / 159 (0.00%)
occurrences all number	0	1	0	0	0	0	0	1	0	1	0	0	0	1	0	1	1	0
acquired oesophageal web
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 49 (0.00%)	0 / 52 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)	0 / 98 (0.00%)	0 / 63 (0.00%)	0 / 63 (0.00%)	0 / 51 (0.00%)	0 / 50 (0.00%)	0 / 49 (0.00%)	0 / 108 (0.00%)	0 / 61 (0.00%)	0 / 61 (0.00%)	0 / 32 (0.00%)	0 / 79 (0.00%)	0 / 47 (0.00%)	1 / 18 (5.56%)	0 / 159 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
dyspepsia
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	2 / 49 (4.08%)	0 / 52 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)	0 / 98 (0.00%)	0 / 63 (0.00%)	1 / 63 (1.59%)	0 / 51 (0.00%)	0 / 50 (0.00%)	1 / 49 (2.04%)	0 / 108 (0.00%)	0 / 61 (0.00%)	1 / 61 (1.64%)	0 / 32 (0.00%)	0 / 79 (0.00%)	0 / 47 (0.00%)	0 / 18 (0.00%)	0 / 159 (0.00%)
occurrences all number	2	0	0	0	0	0	2	0	0	1	0	0	1	0	0	0	0	0
gastritis
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 49 (0.00%)	0 / 52 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)	1 / 98 (1.02%)	0 / 63 (0.00%)	0 / 63 (0.00%)	1 / 51 (1.96%)	1 / 50 (2.00%)	0 / 49 (0.00%)	1 / 108 (0.93%)	0 / 61 (0.00%)	0 / 61 (0.00%)	0 / 32 (0.00%)	0 / 79 (0.00%)	0 / 47 (0.00%)	1 / 18 (5.56%)	0 / 159 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	1	0	1	0	0	0	0	0	1	0
haemorrhoids
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 49 (0.00%)	0 / 52 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)	0 / 98 (0.00%)	0 / 63 (0.00%)	0 / 63 (0.00%)	0 / 51 (0.00%)	0 / 50 (0.00%)	0 / 49 (0.00%)	0 / 108 (0.00%)	0 / 61 (0.00%)	0 / 61 (0.00%)	0 / 32 (0.00%)	0 / 79 (0.00%)	1 / 47 (2.13%)	1 / 18 (5.56%)	0 / 159 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0
irritable bowel syndrome
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 49 (0.00%)	0 / 52 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)	0 / 98 (0.00%)	0 / 63 (0.00%)	0 / 63 (0.00%)	0 / 51 (0.00%)	0 / 50 (0.00%)	0 / 49 (0.00%)	0 / 108 (0.00%)	0 / 61 (0.00%)	0 / 61 (0.00%)	2 / 32 (6.25%)	0 / 79 (0.00%)	0 / 47 (0.00%)	0 / 18 (0.00%)	0 / 159 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0
oesophagitis
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 49 (0.00%)	0 / 52 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)	0 / 98 (0.00%)	0 / 63 (0.00%)	0 / 63 (0.00%)	0 / 51 (0.00%)	0 / 50 (0.00%)	0 / 49 (0.00%)	0 / 108 (0.00%)	0 / 61 (0.00%)	0 / 61 (0.00%)	0 / 32 (0.00%)	0 / 79 (0.00%)	0 / 47 (0.00%)	1 / 18 (5.56%)	0 / 159 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Respiratory, thoracic and mediastinal disorders
oropharyngeal pain
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 49 (0.00%)	1 / 52 (1.92%)	0 / 52 (0.00%)	0 / 50 (0.00%)	0 / 98 (0.00%)	0 / 63 (0.00%)	0 / 63 (0.00%)	0 / 51 (0.00%)	0 / 50 (0.00%)	2 / 49 (4.08%)	0 / 108 (0.00%)	0 / 61 (0.00%)	0 / 61 (0.00%)	1 / 32 (3.13%)	0 / 79 (0.00%)	0 / 47 (0.00%)	0 / 18 (0.00%)	0 / 159 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	2	0	0	0	1	0	0	0	0
sinus congestion
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 49 (0.00%)	0 / 52 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)	0 / 98 (0.00%)	0 / 63 (0.00%)	1 / 63 (1.59%)	0 / 51 (0.00%)	0 / 50 (0.00%)	0 / 49 (0.00%)	0 / 108 (0.00%)	0 / 61 (0.00%)	1 / 61 (1.64%)	0 / 32 (0.00%)	1 / 79 (1.27%)	0 / 47 (0.00%)	1 / 18 (5.56%)	0 / 159 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	1	0	1	0	1	0
Skin and subcutaneous tissue disorders
rash
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	1 / 49 (2.04%)	1 / 52 (1.92%)	0 / 52 (0.00%)	0 / 50 (0.00%)	1 / 98 (1.02%)	0 / 63 (0.00%)	1 / 63 (1.59%)	0 / 51 (0.00%)	0 / 50 (0.00%)	0 / 49 (0.00%)	0 / 108 (0.00%)	1 / 61 (1.64%)	0 / 61 (0.00%)	0 / 32 (0.00%)	1 / 79 (1.27%)	0 / 47 (0.00%)	1 / 18 (5.56%)	1 / 159 (0.63%)
occurrences all number	1	1	0	0	1	0	1	0	0	0	0	1	0	0	1	0	1	1
Musculoskeletal and connective tissue disorders
back pain
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 49 (0.00%)	0 / 52 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)	0 / 98 (0.00%)	1 / 63 (1.59%)	0 / 63 (0.00%)	0 / 51 (0.00%)	0 / 50 (0.00%)	0 / 49 (0.00%)	1 / 108 (0.93%)	0 / 61 (0.00%)	0 / 61 (0.00%)	2 / 32 (6.25%)	1 / 79 (1.27%)	0 / 47 (0.00%)	1 / 18 (5.56%)	0 / 159 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	1	0	0	2	1	0	1	0
Infections and infestations
bronchitis
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	1 / 49 (2.04%)	1 / 52 (1.92%)	2 / 52 (3.85%)	1 / 50 (2.00%)	3 / 98 (3.06%)	1 / 63 (1.59%)	2 / 63 (3.17%)	2 / 51 (3.92%)	0 / 50 (0.00%)	0 / 49 (0.00%)	9 / 108 (8.33%)	0 / 61 (0.00%)	3 / 61 (4.92%)	5 / 32 (15.63%)	3 / 79 (3.80%)	2 / 47 (4.26%)	1 / 18 (5.56%)	1 / 159 (0.63%)
occurrences all number	1	1	2	1	3	1	2	2	0	0	9	0	3	5	3	2	1	1
nasopharyngitis
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 49 (0.00%)	0 / 52 (0.00%)	2 / 52 (3.85%)	1 / 50 (2.00%)	2 / 98 (2.04%)	1 / 63 (1.59%)	0 / 63 (0.00%)	0 / 51 (0.00%)	0 / 50 (0.00%)	2 / 49 (4.08%)	2 / 108 (1.85%)	0 / 61 (0.00%)	4 / 61 (6.56%)	1 / 32 (3.13%)	7 / 79 (8.86%)	2 / 47 (4.26%)	2 / 18 (11.11%)	0 / 159 (0.00%)
occurrences all number	0	0	2	1	3	1	0	0	0	2	2	0	4	1	9	2	3	0
pharyngitis
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	1 / 49 (2.04%)	1 / 52 (1.92%)	3 / 52 (5.77%)	0 / 50 (0.00%)	0 / 98 (0.00%)	0 / 63 (0.00%)	0 / 63 (0.00%)	2 / 51 (3.92%)	0 / 50 (0.00%)	0 / 49 (0.00%)	1 / 108 (0.93%)	1 / 61 (1.64%)	1 / 61 (1.64%)	2 / 32 (6.25%)	2 / 79 (2.53%)	1 / 47 (2.13%)	0 / 18 (0.00%)	0 / 159 (0.00%)
occurrences all number	1	1	3	0	0	0	0	2	0	0	1	1	1	3	2	1	0	0
tooth abscess
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 49 (0.00%)	0 / 52 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)	0 / 98 (0.00%)	0 / 63 (0.00%)	0 / 63 (0.00%)	0 / 51 (0.00%)	0 / 50 (0.00%)	0 / 49 (0.00%)	0 / 108 (0.00%)	0 / 61 (0.00%)	1 / 61 (1.64%)	0 / 32 (0.00%)	0 / 79 (0.00%)	1 / 47 (2.13%)	1 / 18 (5.56%)	0 / 159 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	1	0
upper respiratory tract infection
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 49 (0.00%)	1 / 52 (1.92%)	1 / 52 (1.92%)	1 / 50 (2.00%)	2 / 98 (2.04%)	2 / 63 (3.17%)	4 / 63 (6.35%)	2 / 51 (3.92%)	1 / 50 (2.00%)	2 / 49 (4.08%)	9 / 108 (8.33%)	1 / 61 (1.64%)	6 / 61 (9.84%)	1 / 32 (3.13%)	3 / 79 (3.80%)	2 / 47 (4.26%)	1 / 18 (5.56%)	0 / 159 (0.00%)
occurrences all number	0	1	1	1	2	2	4	2	1	2	10	1	8	1	5	3	1	0
urinary tract infection
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	2 / 49 (4.08%)	2 / 52 (3.85%)	2 / 52 (3.85%)	2 / 50 (4.00%)	4 / 98 (4.08%)	1 / 63 (1.59%)	1 / 63 (1.59%)	2 / 51 (3.92%)	1 / 50 (2.00%)	2 / 49 (4.08%)	12 / 108 (11.11%)	1 / 61 (1.64%)	5 / 61 (8.20%)	3 / 32 (9.38%)	3 / 79 (3.80%)	1 / 47 (2.13%)	0 / 18 (0.00%)	2 / 159 (1.26%)
occurrences all number	2	2	2	2	4	1	1	2	1	2	15	1	6	3	4	1	0	2
Metabolism and nutrition disorders
dyslipidaemia
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 49 (0.00%)	1 / 52 (1.92%)	0 / 52 (0.00%)	1 / 50 (2.00%)	0 / 98 (0.00%)	0 / 63 (0.00%)	0 / 63 (0.00%)	0 / 51 (0.00%)	0 / 50 (0.00%)	0 / 49 (0.00%)	0 / 108 (0.00%)	0 / 61 (0.00%)	2 / 61 (3.28%)	2 / 32 (6.25%)	4 / 79 (5.06%)	0 / 47 (0.00%)	0 / 18 (0.00%)	0 / 159 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0	0	0	0	2	2	4	0	0	0
hypercholesterolaemia
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	2 / 49 (4.08%)	2 / 52 (3.85%)	0 / 52 (0.00%)	2 / 50 (4.00%)	2 / 98 (2.04%)	1 / 63 (1.59%)	0 / 63 (0.00%)	0 / 51 (0.00%)	0 / 50 (0.00%)	4 / 49 (8.16%)	1 / 108 (0.93%)	1 / 61 (1.64%)	1 / 61 (1.64%)	0 / 32 (0.00%)	1 / 79 (1.27%)	0 / 47 (0.00%)	1 / 18 (5.56%)	0 / 159 (0.00%)
occurrences all number	2	2	0	2	2	1	0	0	0	4	1	1	1	0	1	0	1	0

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Were there any global substantial amendments to the protocol? Yes

23 May 2011

Amendment I4V-MC-JADA(a): An open-label extension period (referred to as Part C of the study) was added as an optional extension of the study for patients who completed 24 weeks of treatment and met enrollment criteria. The open-label extension period was added to collect additional safety data, and to examine the effect of long-term administration of LY3009104 on efficacy measures. o New secondary and exploratory objectives were added to evaluate the safety and tolerability of long-term administration of LY3009104, and to examine the effects of long-term administration of LY3009104 on patient-reported outcomes. o Blinding information was clarified throughout the document to distinguish the double-blind period (Part A and Part B) and the open-label extension period (Part C). o Additional inclusion and exclusion criteria applicable to Part C of the study were added. Inclusion and exclusion criteria for Parts A and B were revised. o Study design for Part C was provided. Study design for Parts A and B was updated. o Use of concomitant medications during Part C of the study was added. o The study schedule (Attachment 1 of the protocol amendment) of Parts A and B was updated. A study schedule was added to include assessments of Part C of the study. o Treatment assignment for Part C of the study and dose escalation process during the open-label extension period were added.

29 Jun 2012

Amendment I4V-MC-JADA(b) - An additional open-label extension period (referred to as Part D of the study) was added as an optional extension of the study for patients who completed 76 weeks of treatment and met enrollment criteria. This additional extension would allow for further evaluation of longer-term administration in patients who may have been receiving therapeutic benefit of 4 mg LY3009104 once daily and assist in characterization of the safety and tolerability profile of LY3009104. All patients who entered Part D would receive 4 mg LY3009104 once daily. o Secondary and exploratory objectives were updated to reflect the addition of Part D. o Blinding information was updated to reflect the addition of Part D. o Additional inclusion and exclusion criteria applicable to Part D of the study were added. o Study design for Part D was provided. o Use of concomitant medications was updated to reflect the addition of Part D of the study. o A study schedule was added to include assessments of Part D of the study. o Treatment assignment for Part D of the study was added. • Statistical methods were revised to reflect the addition of Part D. • In general, changes were made to clarify study procedures and to keep consistency throughout the protocol. • Editorial revisions with no impact on protocol design or implementation also were made.

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Parallel-Group, Phase 2b Study of LY3009104 in Patients with Active Rheumatoid Arthritis on Background Methotrexate Therapy

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants in the 4 mg and 8 mg Dose Groups Who Achieved an American College of Rheumatology 20 (ACR20) Responder Index Response Baseline through Week 12

Primary: Percentage of Participants in the 4 mg and 8 mg Dose Groups Who Achieved an American College of Rheumatology 20 (ACR20) Responder Index Response Baseline through Week 12

Secondary: Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline through Week 12 - Model Based Dose Response

Secondary: Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline through Week 12 - Model Based Dose Response

Secondary: Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline through Week 24

Secondary: Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline through Week 24

Secondary: Percentage of Participants Who Achieved an ACR20 Response Baseline through Weeks 76 and 128

Secondary: Percentage of Participants Who Achieved an ACR20 Response Baseline through Weeks 76 and 128

Secondary: Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline through Week 24

Secondary: Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline through Week 24

Secondary: Percentage of Participants Who Achieved an ACR50 Response Baseline through Weeks 76 and 128

Secondary: Percentage of Participants Who Achieved an ACR50 Response Baseline through Weeks 76 and 128

Secondary: Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline through Week 24

Secondary: Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline through Week 24

Secondary: Percentage of Participants Who Achieved an ACR70 Response Baseline through Weeks 76 and 128

Secondary: Percentage of Participants Who Achieved an ACR70 Response Baseline through Weeks 76 and 128

Secondary: Percentage of Participants Who Achieved an ACR50 Response Baseline through Week 12 - Model Based Dose Response

Secondary: Percentage of Participants Who Achieved an ACR50 Response Baseline through Week 12 - Model Based Dose Response

Secondary: ACR Percent Improvement (ACR-N)

Secondary: ACR Percent Improvement (ACR-N)

Secondary: Mean Change from Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC)

Secondary: Mean Change from Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC)

Secondary: Mean Change from Baseline to Weeks 76 and 128 in TJC and SJC

Secondary: Mean Change from Baseline to Weeks 76 and 128 in TJC and SJC

Secondary: Mean Change from Baseline to Weeks 12 and 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score

Secondary: Mean Change from Baseline to Weeks 12 and 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score

Secondary: Mean Change from Baseline to Weeks 76 and 128 in HAQ-DI Score

Secondary: Mean Change from Baseline to Weeks 76 and 128 in HAQ-DI Score

Secondary: Mean Change from Baseline to Weeks 12 and 24 in High-Sensitivity C-Reactive Protein (hsCRP)

Secondary: Mean Change from Baseline to Weeks 12 and 24 in High-Sensitivity C-Reactive Protein (hsCRP)

Secondary: Mean Change from Baseline to Weeks 76 and 128 in hsCRP

Secondary: Mean Change from Baseline to Weeks 76 and 128 in hsCRP

Secondary: Mean Change from Baseline to Weeks 12 and 24 in Erythrocyte Sedimentation Rate (ESR)

Secondary: Mean Change from Baseline to Weeks 12 and 24 in Erythrocyte Sedimentation Rate (ESR)

Secondary: Mean Change from Baseline to Weeks 76 and 128 in ESR

Secondary: Mean Change from Baseline to Weeks 76 and 128 in ESR

Secondary: Mean Change from Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain

Secondary: Mean Change from Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain

Secondary: Mean Change from Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain

Secondary: Mean Change from Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain

Secondary: Mean Change from Baseline to Weeks 12 and 24 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP)

Secondary: Mean Change from Baseline to Weeks 12 and 24 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP)

Secondary: Mean Change from Baseline to Weeks 76 and 128 in DAS28-CRP

Secondary: Mean Change from Baseline to Weeks 76 and 128 in DAS28-CRP

Secondary: Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-Joint Count (EULAR28) Baseline through Weeks 12 and 24

Secondary: Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-Joint Count (EULAR28) Baseline through Weeks 12 and 24

Secondary: Percentage of Responders According to EULAR28 Baseline through Weeks 76 and 128

Secondary: Percentage of Responders According to EULAR28 Baseline through Weeks 76 and 128

Secondary: Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline through Weeks 12 and 24

Secondary: Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline through Weeks 12 and 24

Secondary: Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline through Weeks 76 and 128

Secondary: Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline through Weeks 76 and 128

Secondary: Mean Change from Baseline through Week 12 in Duration (Minutes) of Morning Stiffness

Secondary: Mean Change from Baseline through Week 12 in Duration (Minutes) of Morning Stiffness

Secondary: Mean Change from Baseline to Week 12 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores

Secondary: Mean Change from Baseline to Week 12 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores

Secondary: Mean Change from Baseline to Week 12 in Brief Pain Inventory Modified Short Form (BPI-SF Modified) Worst-Pain-in-the-Past-24-hours Item Score

Secondary: Mean Change from Baseline to Week 12 in Brief Pain Inventory Modified Short Form (BPI-SF Modified) Worst-Pain-in-the-Past-24-hours Item Score

Secondary: Mean Change from Baseline to Week 12 in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Score

Secondary: Mean Change from Baseline to Week 12 in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Score

Secondary: Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104

Secondary: Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104

Secondary: Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of LY3009104

Secondary: Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of LY3009104

Secondary: Mean Change from Baseline through Week 12 in the Ensemble Minimum Data Set 1.0

Secondary: Mean Change from Baseline through Week 12 in the Ensemble Minimum Data Set 1.0

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Clinical Trial Results:
A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Parallel-Group, Phase 2b Study of LY3009104 in Patients with Active Rheumatoid Arthritis on Background Methotrexate Therapy