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Trial record 58 of 62 for:    Baricitinib

A Study in Participants With Rheumatoid Arthritis on Background Methotrexate Therapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01185353
Recruitment Status : Completed
First Posted : August 19, 2010
Results First Posted : April 21, 2017
Last Update Posted : June 16, 2017
Sponsor:
Collaborator:
Incyte Corporation
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Arthritis, Rheumatoid
Interventions Drug: LY3009104
Drug: Placebo
Drug: Methotrexate
Enrollment 301
Recruitment Details  
Pre-assignment Details This study consisted of 4 parts and a follow-up up to 28 days post the last dose of study drug.
Arm/Group Title 1 Milligrams (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 2 mg LY3009104 BID - Part B 4 mg LY3009104 QD - Part B 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
Hide Arm/Group Description

Administered orally once daily (QD) for 12 weeks in Part A.

Methotrexate (MTX) was administered orally as background therapy.

Administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

Administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

Administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

Placebo administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

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.

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.

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.

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 the 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.

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.

Period Title: Part A (Weeks 0 Through 12)
Started 49 52 52 50 98 0 0 0 0 0
Received at Least 1 Dose of Study Drug 49 52 52 50 98 0 0 0 0 0
Completed 44 51 50 49 82 0 0 0 0 0
Not Completed 5 1 2 1 16 0 0 0 0 0
Reason Not Completed
Adverse Event             1             1             1             1             5             0             0             0             0             0
Entry Criteria Not Met             0             0             0             0             4             0             0             0             0             0
Lack of Efficacy             2             0             0             0             1             0             0             0             0             0
Physician Decision             0             0             1             0             2             0             0             0             0             0
Protocol Violation             0             0             0             0             1             0             0             0             0             0
Withdrawal by Subject             2             0             0             0             3             0             0             0             0             0
Period Title: Part B (Weeks 12 Through 24)
Started 0 51 50 49 0 63 63 0 0 0
Completed 0 50 48 45 0 59 57 0 0 0
Not Completed 0 1 2 4 0 4 6 0 0 0
Reason Not Completed
Adverse Event             0             0             1             0             0             1             0             0             0             0
Lack of Efficacy             0             1             0             1             0             0             0             0             0             0
Lost to Follow-up             0             0             0             1             0             0             1             0             0             0
Withdrawal by Subject             0             0             1             2             0             3             4             0             0             0
Entry Criteria Not Met             0             0             0             0             0             0             1             0             0             0
Period Title: Part C (Weeks 24 Through 76)
Started 0 0 0 0 0 0 0 108 61 32
Completed 0 0 0 0 0 0 0 92 53 24
Not Completed 0 0 0 0 0 0 0 16 8 8
Reason Not Completed
Adverse Event             0             0             0             0             0             0             0             8             2             2
Withdrawal by Subject             0             0             0             0             0             0             0             6             2             2
Lost to Follow-up             0             0             0             0             0             0             0             2             1             1
Lack of Efficacy             0             0             0             0             0             0             0             0             2             0
Death             0             0             0             0             0             0             0             0             0             1
Entry Criteria Not Met             0             0             0             0             0             0             0             0             0             1
Physician Decision             0             0             0             0             0             0             0             0             0             1
Reason missing             0             0             0             0             0             0             0             0             1             0
Period Title: Part D (Weeks 76 Through 128)
Started 0 0 0 0 0 0 0 79 47 18
Completed 0 0 0 0 0 0 0 76 40 17
Not Completed 0 0 0 0 0 0 0 3 7 1
Reason Not Completed
Lost to Follow-up             0             0             0             0             0             0             0             1             3             0
Withdrawal by Subject             0             0             0             0             0             0             0             1             2             1
Adverse Event             0             0             0             0             0             0             0             1             2             0
Arm/Group Title 1 mg LY3009104 2 mg LY3009104 4 mg LY3009104 8 mg LY3009104 Placebo Total
Hide Arm/Group Description

Administered orally QD for initial 12 weeks (Part A) followed by randomization to either 4 mg QD or 2 mg BID for an additional 12 weeks (Part B). After 24 weeks of treatment, participants were eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally QD for 52 weeks. After 76 weeks of treatment, participants were eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally QD for 52 additional weeks.

MTX was administered orally as background therapy.

Administered orally QD for 24 weeks (Parts A and B). After 24 weeks of treatment, participants were eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally QD for 52 weeks. After 76 weeks of treatment, participants were eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally QD for 52 additional weeks.

MTX was administered orally as background therapy.

Administered orally QD for 24 weeks (Parts A and B). After 24 weeks of treatment, participants were eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally QD for 52 weeks. After 76 weeks of treatment, participants were eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally QD for 52 additional weeks.

MTX was administered orally as background therapy.

Administered orally QD for 24 weeks (Parts A and B). After 24 weeks of treatment, participants were eligible to participate in an open-label extension period (Part C). Part C: 8 mg administered orally QD for 52 weeks. After 76 weeks of treatment, participants were eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally QD for 52 additional weeks.

MTX was administered orally as background therapy.

Placebo administered orally QD for initial 12 weeks (Part A) followed by randomization to either 4 mg QD or 2 mg BID for an additional 12 weeks (Part B). After 24 weeks of treatment, participants were eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally QD for 52 weeks. After 76 weeks of treatment participants were eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally QD for 52 additional weeks.

MTX was administered orally as background therapy.

Total of all reporting groups
Overall Number of Baseline Participants 49 52 52 50 98 301
Hide Baseline Analysis Population Description
All randomized participants who received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 49 participants 52 participants 52 participants 50 participants 98 participants 301 participants
53.1  (11.07) 50.7  (13.12) 52.5  (10.42) 52.7  (10.91) 49.2  (12.15) 51.2  (11.71)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 49 participants 52 participants 52 participants 50 participants 98 participants 301 participants
Female
42
  85.7%
44
  84.6%
37
  71.2%
41
  82.0%
85
  86.7%
249
  82.7%
Male
7
  14.3%
8
  15.4%
15
  28.8%
9
  18.0%
13
  13.3%
52
  17.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 49 participants 52 participants 52 participants 50 participants 98 participants 301 participants
Hispanic or Latino
10
  20.4%
7
  13.5%
12
  23.1%
11
  22.0%
16
  16.3%
56
  18.6%
Not Hispanic or Latino
36
  73.5%
41
  78.8%
36
  69.2%
36
  72.0%
78
  79.6%
227
  75.4%
Unknown or Not Reported
3
   6.1%
4
   7.7%
4
   7.7%
3
   6.0%
4
   4.1%
18
   6.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 49 participants 52 participants 52 participants 50 participants 98 participants 301 participants
American Indian or Alaska Native
4
   8.2%
3
   5.8%
3
   5.8%
2
   4.0%
7
   7.1%
19
   6.3%
Asian
8
  16.3%
8
  15.4%
7
  13.5%
9
  18.0%
15
  15.3%
47
  15.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
1
   1.9%
2
   3.8%
2
   4.0%
6
   6.1%
11
   3.7%
White
37
  75.5%
40
  76.9%
40
  76.9%
37
  74.0%
70
  71.4%
224
  74.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 49 participants 52 participants 52 participants 50 participants 98 participants 301 participants
16 16 16 16 31 95
Hungary Number Analyzed 49 participants 52 participants 52 participants 50 participants 98 participants 301 participants
3 3 3 2 2 13
Czech Republic Number Analyzed 49 participants 52 participants 52 participants 50 participants 98 participants 301 participants
4 3 6 3 7 23
Mexico Number Analyzed 49 participants 52 participants 52 participants 50 participants 98 participants 301 participants
7 8 8 8 16 47
Poland Number Analyzed 49 participants 52 participants 52 participants 50 participants 98 participants 301 participants
4 5 6 7 11 33
Ukraine Number Analyzed 49 participants 52 participants 52 participants 50 participants 98 participants 301 participants
6 6 5 3 9 29
Croatia Number Analyzed 49 participants 52 participants 52 participants 50 participants 98 participants 301 participants
0 1 0 1 5 7
Romania Number Analyzed 49 participants 52 participants 52 participants 50 participants 98 participants 301 participants
2 2 1 3 3 11
India Number Analyzed 49 participants 52 participants 52 participants 50 participants 98 participants 301 participants
7 8 7 7 14 43
Duration of Rheumatoid Arthritis  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 49 participants 52 participants 52 participants 50 participants 98 participants 301 participants
5.45  (3.885) 5.53  (4.377) 5.28  (4.466) 6.63  (5.048) 5.40  (4.283) 5.62  (4.401)
Tender Joint Counts (TJC)   [1] 
Mean (Standard Deviation)
Unit of measure:  Number of joints
Number Analyzed 49 participants 52 participants 52 participants 50 participants 98 participants 301 participants
21.4  (10.90) 23.0  (12.60) 19.9  (12.71) 24.4  (13.76) 22.2  (12.06) 22.2  (12.38)
[1]
Measure 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.
Swollen Joint Counts (SJC)   [1] 
Mean (Standard Deviation)
Unit of measure:  Number of joints
Number Analyzed 49 participants 52 participants 52 participants 50 participants 98 participants 301 participants
15.2  (6.55) 17.0  (9.32) 14.8  (7.54) 16.1  (7.92) 15.8  (8.64) 15.8  (8.13)
[1]
Measure Description: 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.
High Sensitivity C-Reactive Protein (hsCRP)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Milligrams/liter (mg/L)
Number Analyzed 49 participants 52 participants 52 participants 50 participants 97 participants 300 participants
11.22  (12.410) 12.02  (22.111) 11.39  (16.941) 14.32  (15.602) 14.03  (23.527) 12.81  (19.402)
[1]
Measure Description: HsCRP is a laboratory analyte that is an indicator of inflammation. Decreases in hsCRP represent reductions in inflammation.
[2]
Measure Analysis Population Description: All randomized participants who received at least one dose of study drug and had evaluable hsCRP data at baseline.
Erythrocyte Sedimentation Rate (ESR)   [1] 
Mean (Standard Deviation)
Unit of measure:  Millimeters/hour (mm/hr)
Number Analyzed 49 participants 52 participants 52 participants 50 participants 98 participants 301 participants
38.2  (17.57) 36.5  (14.62) 35.4  (17.16) 43.3  (18.17) 39.9  (20.94) 38.8  (18.39)
[1]
Measure Description: ESR is a laboratory analyte that is an indicator of inflammation. Decreases represent reductions in inflammation.
1.Primary Outcome
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
Hide 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.
Time Frame Baseline through Week 12
Hide Outcome Measure Data
Hide Analysis Population 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).
Arm/Group Title 4 or 8 mg LY3009104 Placebo
Hide Arm/Group Description:

4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

Placebo administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 102 98
Measure Type: Number
Unit of Measure: percentage of participants
76 41
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 4 or 8 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments A priori p-value significance threshold: 1-sided ≤0.10
Method Regression, Logistic
Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 12 - Model Based Dose Response
Hide 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.
Time Frame Baseline through Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study drug in Part A. Participants who had missing components of the ACR20 index at Week 12 had these components imputed by LOCF.
Arm/Group Title 1 mg LY3009104 2 mg LY3009104 4 mg LY3009104 8 mg LY3009104 Placebo
Hide Arm/Group Description:

1 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

2 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

4 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

8 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

Placebo administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 49 52 52 50 98
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
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)
3.Secondary Outcome
Title Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24
Hide 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.
Time Frame Baseline through Weeks 2, 4, 8, 12, 16, 20, 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study drug in Parts A and B. Participants who had missing components of the ACR20 index at analysis time points had these components imputed by LOCF.
Arm/Group Title 1 mg LY3009104 2 mg LY3009104 4 mg LY3009104 8 mg LY3009104 Placebo
Hide Arm/Group Description:

1 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

2 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

4 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

8 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

Placebo administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 49 52 52 50 98
Measure Type: Number
Unit of Measure: percentage of participants
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 NA [1]  63 67 64 NA [2] 
Week 20 NA [1]  71 77 78 NA [2] 
Week 24 NA [1]  62 75 72 NA [2] 
[1]
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore percentage was not calculated.
[2]
Participants were not dosed with placebo after Week 12, therefore percentage was not calculated.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.045
Comments P-value is for Week 12. A priori p-value significance threshold: 1-sided ≤0.10.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 2 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.088
Comments P-value is for Week 12. A priori p-value significance threshold: 1-sided ≤0.10.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is for Week 12. A priori p-value significance threshold: 1-sided ≤0.10.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 8 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is for Week 12. A priori p-value significance threshold: 1-sided ≤0.10.
Method Fisher Exact
Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants Who Achieved an ACR20 Response Baseline Through Weeks 76 and 128
Hide 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.
Time Frame Baseline through Weeks 76 and 128
Hide Outcome Measure Data
Hide Analysis Population 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.
Arm/Group Title 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
Hide Arm/Group Description:

Received Placebo, or 1 mg, or 2 mg, or 4 mg LY3009104 in Part A.

Received 2 mg LY3009104 QD, or BID, or 4 mg LY3009104 QD in Part B.

Received 4 mg LY3009104 QD in Part C.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Received Placebo, or 1 mg, or 2 mg, or 4 mg LY3009104 in Part A.

Received 2 mg LY3009104 QD, or BID, or 4 mg LY3009104 QD in Part B.

Received 4 mg LY3009104 QD in Part C. During Part C, at Weeks 28 and 32, participants who met dose escalation criteria received 8 mg LY3009104 QD for the rest of the 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.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Received 8 mg LY3009104 QD in Parts A, B and C.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 108 61 32
Measure Type: Number
Unit of Measure: percentage of participants
Week 76 (n=108, 61, 32) 71 67 59
Week 128 (n=79, 47, 18) 77 57 72
5.Secondary Outcome
Title Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24
Hide 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.
Time Frame Baseline through Weeks 2, 4, 8, 12, 16, 20, 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study drug in Parts A and B. Participants who had missing components of the ACR50 index at analysis time points had these components imputed by LOCF.
Arm/Group Title 1 mg LY3009104 2 mg LY3009104 4 mg LY3009104 8 mg LY3009104 Placebo
Hide Arm/Group Description:

1 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

2 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

4 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

8 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

Placebo administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 49 52 52 50 98
Measure Type: Number
Unit of Measure: percentage of participants
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 NA [1]  19 38 44 NA [2] 
Week 20 NA [1]  27 46 48 NA [2] 
Week 24 NA [1]  19 46 54 NA [2] 
[1]
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore percentage was not calculated.
[2]
Participants were not dosed with placebo after Week 12, therefore percentage was not calculated.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments P-value is for Week 12. A priori p-value significance threshold: 1-sided ≤0.10.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 2 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.162
Comments P-value is for Week 12. A priori p-value significance threshold: 1-sided ≤0.10.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is for Week 12. A priori p-value significance threshold: 1-sided ≤0.10.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 8 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is for Week 12. A priori p-value significance threshold: 1-sided ≤0.10.
Method Fisher Exact
Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants Who Achieved an ACR50 Response Baseline Through Weeks 76 and 128
Hide 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.
Time Frame Baseline through Weeks 76 and 128
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received study drug in Parts C and D. Participants who had missing components of the ACR50 index at analysis time points had these components imputed by LOCF.
Arm/Group Title 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
Hide Arm/Group Description:

Received Placebo, or 1 mg, or 2 mg, or 4 mg LY3009104 in Part A.

Received 2 mg LY3009104 QD, or BID, or 4 mg LY3009104 QD in Part B.

Received 4 mg LY3009104 QD in Part C.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Received Placebo, or 1 mg, or 2 mg, or 4 mg LY3009104 in Part A.

Received 2 mg LY3009104 QD, or BID, or 4 mg LY3009104 QD in Part B.

Received 4 mg LY3009104 QD in Part C. During Part C, at Weeks 28 and 32, participants who met dose escalation criteria received 8 mg LY3009104 QD for the rest of the 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.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Received 8 mg LY3009104 QD in Parts A, B and C.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 108 61 32
Measure Type: Number
Unit of Measure: percentage of participants
Week 76 (n=108, 61, 32) 49 41 44
Week 128 (n=79, 47, 18) 58 30 44
7.Secondary Outcome
Title Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24
Hide 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.
Time Frame Baseline through Weeks 2, 4, 8, 12, 16, 20, 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study drug in Parts A and B. Participants who had missing components of the ACR70 index at analysis time points had these components imputed by LOCF.
Arm/Group Title 1 mg LY3009104 2 mg LY3009104 4 mg LY3009104 8 mg LY3009104 Placebo
Hide Arm/Group Description:

1 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

2 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

4 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

8 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

Placebo administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 49 52 52 50 98
Measure Type: Number
Unit of Measure: percentage of participants
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 NA [1]  8 23 30 NA [2] 
Week 20 NA [1]  10 21 26 NA [2] 
Week 24 NA [1]  10 27 24 NA [2] 
[1]
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore percentage was not calculated.
[2]
Participants were not dosed with placebo after Week 12, therefore percentage was not calculated.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.017
Comments P-value is for Week 12. A priori p-value significance threshold: 1-sided ≤0.10.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 2 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.109
Comments P-value is for Week 12. A priori p-value significance threshold: 1-sided ≤0.10.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is for Week 12. A priori p-value significance threshold: 1-sided ≤0.10.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 8 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is for Week 12. A priori p-value significance threshold: 1-sided ≤0.10.
Method Fisher Exact
Comments [Not Specified]
8.Secondary Outcome
Title Percentage of Participants Who Achieved an ACR70 Response Baseline Through Weeks 76 and 128
Hide 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.
Time Frame Baseline through Weeks 76 and 128
Hide Outcome Measure Data
Hide Analysis Population 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.
Arm/Group Title 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
Hide Arm/Group Description:

Received Placebo, or 1 mg, or 2 mg, or 4 mg LY3009104 in Part A.

Received 2 mg LY3009104 QD, or BID, or 4 mg LY3009104 QD in Part B.

Received 4 mg LY3009104 QD in Part C.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Received Placebo, or 1 mg, or 2 mg, or 4 mg LY3009104 in Part A.

Received 2 mg LY3009104 QD, or BID, or 4 mg LY3009104 QD in Part B.

Received 4 mg LY3009104 QD in Part C. During Part C, at Weeks 28 and 32, participants who met dose escalation criteria received 8 mg LY3009104 QD for the rest of the 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.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Received 8 mg LY3009104 QD in Parts A, B and C.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 108 61 32
Measure Type: Number
Unit of Measure: percentage of participants
Week 76 (n=108, 61, 32) 29 18 25
Week 128 (n=79, 47, 18) 28 17 22
9.Secondary Outcome
Title Percentage of Participants Who Achieved an ACR50 Response Baseline Through Week 12 - Model Based Dose Response
Hide 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.
Time Frame Baseline through Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study drug in Part A. Participants who had missing components of the ACR50 index at analysis time point had these components imputed by LOCF.
Arm/Group Title 1 mg LY3009104 2 mg LY3009104 4 mg LY3009104 8 mg LY3009104 Placebo
Hide Arm/Group Description:

1 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

2 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

4 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

8 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

Placebo administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 49 52 52 50 98
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
26.5
(16.0 to 39.2)
18.8
(9.9 to 29.7)
34.4
(23.1 to 46.7)
39.2
(27.1 to 52.2)
12.0
(6.5 to 18.8)
10.Secondary Outcome
Title ACR Percent Improvement (ACR-N)
Hide 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.
Time Frame Baseline through Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study drug in Part A. Participants who had missing components of the ACR-N at Week 12 had these components imputed by LOCF.
Arm/Group Title 1 mg LY3009104 2 mg LY3009104 4 mg LY3009104 8 mg LY3009104 Placebo
Hide Arm/Group Description:

1 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

2 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

4 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

8 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

Placebo administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 49 52 52 50 98
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of improvement
17.30
(7.57 to 28.22)
19.42
(8.74 to 29.25)
28.59
(17.67 to 40.83)
29.00
(17.67 to 41.47)
10.97
(-0.39 to 21.64)
11.Secondary Outcome
Title Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC)
Hide 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.
Time Frame Baseline, Weeks 12 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title 1 mg LY3009104 2 mg LY3009104 4 mg LY3009104 8 mg LY3009104 Placebo
Hide Arm/Group Description:

1 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

2 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

4 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

8 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

Placebo administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 49 52 51 50 98
Mean (Standard Deviation)
Unit of Measure: number of joints
TJC - Week 12 -8.4  (12.70) -11.3  (13.50) -12.2  (10.45) -14.7  (12.97) -7.6  (12.31)
TJC - Week 24 NA [1]   (NA) -12.4  (12.60) -14.0  (9.54) -17.5  (11.23) NA [2]   (NA)
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 NA [3]   (NA) -10.0  (8.16) -10.5  (6.42) -12.2  (7.29) NA [2]   (NA)
[1]
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore mean and standard deviation (SD) were not calculated.
[2]
Participants were not dosed with placebo after Week 12, therefore mean and SD were not calculated.
[3]
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore mean and SD were not calculated.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.480
Comments P-value is for TJC - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 2 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.064
Comments P-value is for TJC - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is for TJC - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 8 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments P-value is for TJC - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection 1 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.116
Comments P-value is for SJC - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection 2 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.201
Comments P-value is for SJC - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection 4 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is for SJC - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection 8 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments P-value is for SJC - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
12.Secondary Outcome
Title Mean Change From Baseline to Weeks 76 and 128 in TJC and SJC
Hide 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.
Time Frame Baseline, Weeks 76 and 128
Hide Outcome Measure Data
Hide Analysis Population 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.
Arm/Group Title 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
Hide Arm/Group Description:

Received Placebo, or 1 mg, or 2 mg, or 4 mg LY3009104 in Part A.

Received 2 mg LY3009104 QD, or BID, or 4 mg LY3009104 QD in Part B.

Received 4 mg LY3009104 QD in Part C.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Received Placebo, or 1 mg, or 2 mg, or 4 mg LY3009104 in Part A.

Received 2 mg LY3009104 QD, or BID, or 4 mg LY3009104 QD in Part B.

Received 4 mg LY3009104 QD in Part C. During Part C, at Weeks 28 and 32, participants who met dose escalation criteria received 8 mg LY3009104 QD for the rest of the 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.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Received 8 mg LY3009104 QD in Parts A, B and C.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 108 61 32
Mean (Standard Deviation)
Unit of Measure: units on a scale
TJC - Week 76 (n=108, 61, 32) -15.7  (11.26) -16.0  (13.37) -18.1  (12.06)
TJC - Week 128 (n=79, 47, 18) -16.4  (11.01) -15.3  (12.56) -14.0  (13.68)
SJC - Week 76 (n=108, 61, 32) -11.6  (6.40) -12.9  (7.80) -12.4  (7.67)
SJC - Week 128 (n=79, 47, 18) -11.4  (6.81) -12.4  (8.01) -11.6  (6.23)
13.Secondary Outcome
Title Mean Change From Baseline to Weeks 12 and 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
Hide 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.
Time Frame Baseline, Weeks 12 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study drug in Parts A and B and had HAQ-DI evaluated at analysis time points. LOCF was used to impute missing post-baseline values.
Arm/Group Title 1 mg LY3009104 2 mg LY3009104 4 mg LY3009104 8 mg LY3009104 Placebo
Hide Arm/Group Description:

1 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

2 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

4 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

8 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

Placebo administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 49 52 51 50 98
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 12 -0.35  (0.528) -0.18  (0.524) -0.33  (0.459) -0.39  (0.497) -0.10  (0.406)
Week 24 NA [1]   (NA) -0.18  (0.505) -0.32  (0.506) -0.44  (0.529) NA [2]   (NA)
[1]
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore mean and SD were not calculated.
[2]
Participants were not dosed with placebo after Week 12, therefore mean and SD were not calculated.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments P-value is for Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 2 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.167
Comments P-value is for Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is for Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 8 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments P-value is for Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
14.Secondary Outcome
Title Mean Change From Baseline to Weeks 76 and 128 in HAQ-DI Score
Hide 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.
Time Frame Baseline, Weeks 76 and 128
Hide Outcome Measure Data
Hide Analysis Population 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.
Arm/Group Title 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
Hide Arm/Group Description:

Received Placebo, or 1 mg, or 2 mg, or 4 mg LY3009104 in Part A.

Received 2 mg LY3009104 QD, or BID, or 4 mg LY3009104 QD in Part B.

Received 4 mg LY3009104 QD in Part C.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Received Placebo, or 1 mg, or 2 mg, or 4 mg LY3009104 in Part A.

Received 2 mg LY3009104 QD, or BID, or 4 mg LY3009104 QD in Part B.

Received 4 mg LY3009104 QD in Part C. During Part C, at Weeks 28 and 32, participants who met dose escalation criteria received 8 mg LY3009104 QD for the rest of the 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.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Received 8 mg LY3009104 QD in Parts A, B and C.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 108 61 32
Mean (Standard Deviation)
Unit of Measure: units on a scale
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) -0.30  (0.66)
15.Secondary Outcome
Title Mean Change From Baseline to Weeks 12 and 24 in High-Sensitivity C-Reactive Protein (hsCRP)
Hide Description hsCRP is a laboratory analyte that is an indicator of inflammation. Decreases in hsCRP represent reductions in inflammation.
Time Frame Baseline, Weeks 12 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study drug in Parts A and B and had hsCRP evaluated at analysis time points. LOCF was used to impute missing post-baseline values.
Arm/Group Title 1 mg LY3009104 2 mg LY3009104 4 mg LY3009104 8 mg LY3009104 Placebo
Hide Arm/Group Description:

1 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

2 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

4 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

8 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

Placebo administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 49 52 51 50 97
Mean (Standard Deviation)
Unit of Measure: mg/L
Week 12 -6.14  (10.236) -3.39  (19.409) -7.06  (16.945) -2.32  (32.582) 1.50  (34.107)
Week 24 NA [1]   (NA) -4.76  (18.695) -4.95  (19.819) -7.61  (17.548) NA [2]   (NA)
[1]
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore mean and SD were not calculated.
[2]
Participants were not dosed with placebo after Week 12, therefore mean and SD were not calculated.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.016
Comments P-value is for Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 2 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.108
Comments P-value is for Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments P-value is for Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 8 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.368
Comments P-value is for Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
16.Secondary Outcome
Title Mean Change From Baseline to Weeks 76 and 128 in hsCRP
Hide Description hsCRP is a laboratory analyte that is an indicator of inflammation. Decreases in hsCRP represent reductions in inflammation.
Time Frame Baseline, Weeks 76 and 128
Hide Outcome Measure Data
Hide Analysis Population 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.
Arm/Group Title 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
Hide Arm/Group Description:

Received Placebo, or 1 mg, or 2 mg, or 4 mg LY3009104 in Part A.

Received 2 mg LY3009104 QD, or BID, or 4 mg LY3009104 QD in Part B.

Received 4 mg LY3009104 QD in Part C.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Received Placebo, or 1 mg, or 2 mg, or 4 mg LY3009104 in Part A.

Received 2 mg LY3009104 QD, or BID, or 4 mg LY3009104 QD in Part B.

Received 4 mg LY3009104 QD in Part C. During Part C, at Weeks 28 and 32, participants who met dose escalation criteria received 8 mg LY3009104 QD for the rest of the 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.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Received 8 mg LY3009104 QD in Parts A, B and C.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 108 61 32
Mean (Standard Deviation)
Unit of Measure: mg/L
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)
17.Secondary Outcome
Title Mean Change From Baseline to Weeks 12 and 24 in Erythrocyte Sedimentation Rate (ESR)
Hide Description ESR is a laboratory analyte that is an indicator of inflammation. Decreases represent reductions in inflammation.
Time Frame Baseline, Weeks 12 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study drug in Parts A and B and had ESR evaluated at analysis time points.
Arm/Group Title 1 mg LY3009104 2 mg LY3009104 4 mg LY3009104 8 mg LY3009104 Placebo
Hide Arm/Group Description:

1 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

2 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

4 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

8 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

Placebo administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 44 51 50 49 83
Mean (Standard Deviation)
Unit of Measure: mm/hr
Week 12 (n=44, 51, 50, 49, 83) -11.6  (14.45) -6.4  (16.81) -11.5  (17.28) -13.9  (22.42) -6.0  (19.49)
Week 24 (n=0, 50, 48, 45, 0) NA [1]   (NA) -6.9  (13.89) -9.2  (19.00) -13.7  (21.62) NA [2]   (NA)
[1]
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore mean and SD were not calculated.
[2]
Participants were not dosed with placebo after Week 12, therefore mean and SD were not calculated.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.039
Comments P-value is for Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 2 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.458
Comments P-value is for Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments P-value is for Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 8 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.029
Comments P-value is for Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
18.Secondary Outcome
Title Mean Change From Baseline to Weeks 76 and 128 in ESR
Hide Description ESR is a laboratory analyte that is an indicator of inflammation. Decreases represent reductions in inflammation.
Time Frame Baseline, Weeks 76 and 128
Hide Outcome Measure Data
Hide Analysis Population 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.
Arm/Group Title 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
Hide Arm/Group Description:

Received Placebo, or 1 mg, or 2 mg, or 4 mg LY3009104 in Part A.

Received 2 mg LY3009104 QD, or BID, or 4 mg LY3009104 QD in Part B.

Received 4 mg LY3009104 QD in Part C.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Received Placebo, or 1 mg, or 2 mg, or 4 mg LY3009104 in Part A.

Received 2 mg LY3009104 QD, or BID, or 4 mg LY3009104 QD in Part B.

Received 4 mg LY3009104 QD in Part C. During Part C, at Weeks 28 and 32, participants who met dose escalation criteria received 8 mg LY3009104 QD for the rest of the 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.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Received 8 mg LY3009104 QD in Parts A, B and C.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 108 61 32
Mean (Standard Deviation)
Unit of Measure: mm/hr
Week 76 (n=108, 61, 32) -13.0  (18.84) -7.4  (26.28) -8.9  (23.12)
Week 128 (n=79, 47, 18) -16.0  (18.74) -8.5  (23.11) -15.5  (23.07)
19.Secondary Outcome
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
Hide 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).
Time Frame Baseline, Weeks 12 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study drug in Parts A and B and had physician's and participant’s assessments of disease activity and participant’s pain evaluated at analysis time points. LOCF was used to impute missing post-baseline values.
Arm/Group Title 1 mg LY3009104 2 mg LY3009104 4 mg LY3009104 8 mg LY3009104 Placebo
Hide Arm/Group Description:

1 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

2 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

4 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

8 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

Placebo administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 49 52 51 50 98
Mean (Standard Deviation)
Unit of Measure: units on a scale
Physician's Assessment of DA - Week 12 -23.9  (18.49) -25.0  (20.81) -30.4  (18.75) -33.5  (19.49) -19.0  (21.40)
Physician's Assessment of DA - Week 24 NA [1]   (NA) -27.8  (21.13) -35.5  (17.72) -37.8  (18.73) NA [2]   (NA)
Patient's Assessment of DA - Week 12 -24.9  (27.26) -16.2  (22.43) -25.4  (21.61) -29.8  (21.20) -10.3  (22.02)
Patient's Assessment of DA - Week 24 NA [1]   (NA) -16.9  (24.96) -30.2  (21.85) -30.0  (20.90) NA [2]   (NA)
Patient's Assessment of Pain - Week 12 -22.8  (27.39) -14.2  (17.82) -25.0  (19.22) -25.3  (20.31) -8.8  (22.77)
Patient's Assessment of Pain - Week 24 NA [1]   (NA) -14.7  (20.57) -27.3  (22.11) -26.9  (19.22) NA [2]   (NA)
[1]
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore mean and SD were not calculated.
[2]
Participants were not dosed with placebo after Week 12, therefore mean and SD were not calculated.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.217
Comments P-value is for Physician's Assessment of DA - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 2 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.092
Comments P-value is for Physician's Assessment of DA - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is for Physician's Assessment of DA - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 8 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is for Physician's Assessment of DA - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection 1 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is for Patient's Assessment of DA - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection 2 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.072
Comments P-value is for Patient's Assessment of DA - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection 4 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is for Patient's Assessment of DA - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection 8 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is for Patient's Assessment of DA - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection 1 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is for Patient's Assessment of Pain - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection 2 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.082
Comments P-value is for Patient's Assessment of Pain - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection 4 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is for Patient's Assessment of Pain - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection 8 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is for Patient's Assessment of Pain - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
20.Secondary Outcome
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
Hide 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).
Time Frame Baseline, Weeks 76 and 128
Hide Outcome Measure Data
Hide Analysis Population 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.
Arm/Group Title 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
Hide Arm/Group Description:

Received Placebo, or 1 mg, or 2 mg, or 4 mg LY3009104 in Part A.

Received 2 mg LY3009104 QD, or BID, or 4 mg LY3009104 QD in Part B.

Received 4 mg LY3009104 QD in Part C.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Received Placebo, or 1 mg, or 2 mg, or 4 mg LY3009104 in Part A.

Received 2 mg LY3009104 QD, or BID, or 4 mg LY3009104 QD in Part B.

Received 4 mg LY3009104 QD in Part C. During Part C, at Weeks 28 and 32, participants who met dose escalation criteria received 8 mg LY3009104 QD for the rest of the 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.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Received 8 mg LY3009104 QD in Parts A, B and C.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 108 61 32
Mean (Standard Deviation)
Unit of Measure: units on a scale
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) -31.0  (25.54) -34.0  (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  (27.40) -19.3  (29.72) -27.6  (25.17)
Patient Assessment of Pain-Week 76 (n=108, 61, 32) -25.1  (24.10) -27.3  (24.24) -23.4  (23.49)
Patient Assessment of Pain-Week 128 (n=79, 47, 18) -24.2  (24.35) -18.0  (28.85) -22.3  (22.99)
21.Secondary Outcome
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)
Hide 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.
Time Frame Baseline, Weeks 12 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study drug in Parts A and B and had DAS28-CRP evaluated at analysis time points. LOCF was used to impute missing post-baseline values.
Arm/Group Title 1 mg LY3009104 2 mg LY3009104 4 mg LY3009104 8 mg LY3009104 Placebo
Hide Arm/Group Description:

1 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

2 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

4 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

8 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

Placebo administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 49 52 50 50 93
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 12 -1.47  (1.299) -1.40  (1.210) -2.09  (1.220) -2.15  (1.273) -0.98  (1.141)
Week 24 NA [1]   (NA) -1.53  (1.187) -2.25  (1.054) -2.47  (1.280) NA [2]   (NA)
[1]
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore mean and SD were not calculated.
[2]
Participants were not dosed with placebo after Week 12, therefore mean and SD were not calculated.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.024
Comments P-value is for Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 2 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.030
Comments P-value is for Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is for Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 8 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is for Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
22.Secondary Outcome
Title Mean Change From Baseline to Weeks 76 and 128 in DAS28-CRP
Hide 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.
Time Frame Baseline, Weeks 76 and 128
Hide Outcome Measure Data
Hide Analysis Population 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.
Arm/Group Title 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
Hide Arm/Group Description:

Received Placebo, or 1 mg, or 2 mg, or 4 mg LY3009104 in Part A.

Received 2 mg LY3009104 QD, or BID, or 4 mg LY3009104 QD in Part B.

Received 4 mg LY3009104 QD in Part C.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Received Placebo, or 1 mg, or 2 mg, or 4 mg LY3009104 in Part A.

Received 2 mg LY3009104 QD, or BID, or 4 mg LY3009104 QD in Part B.

Received 4 mg LY3009104 QD in Part C. During Part C, at Weeks 28 and 32, participants who met dose escalation criteria received 8 mg LY3009104 QD for the rest of the 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.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Received 8 mg LY3009104 QD in Parts A, B and C.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 107 61 31
Mean (Standard Deviation)
Unit of Measure: units on a scale
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  (1.40)
23.Secondary Outcome
Title Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24
Hide 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).
Time Frame Baseline through Weeks 12 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study drug in Parts A and B and had EULAR28 evaluated at analysis time points.
Arm/Group Title 1 mg LY3009104 2 mg LY3009104 4 mg LY3009104 8 mg LY3009104 Placebo
Hide Arm/Group Description:

1 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

2 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

4 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

8 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

Placebo administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 49 52 52 50 98
Measure Type: Number
Unit of Measure: percentage of participants
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 NA [1]  25 42 46 NA [2] 
Moderate Response - Week 24 NA [1]  52 42 32 NA [2] 
No Response - Week 24 NA [1]  23 15 22 NA [2] 
[1]
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore percentage was not calculated.
[2]
Participants were not dosed with placebo after Week 12, therefore percentage was not calculated.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.120
Comments P-value is for comparison of the superiority of the LY3009104 dose level vs. placebo for the ordinal levels of response - Week 12. A priori p-value significance threshold: 1-sided ≤0.10.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 2 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments P-value is for comparison of the superiority of the LY3009104 dose level vs. placebo for the ordinal levels of response - Week 12. A priori p-value significance threshold: 1-sided ≤0.10.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is for comparison of the superiority of the LY3009104 dose level vs. placebo for the ordinal levels of response - Week 12. A priori p-value significance threshold: 1-sided ≤0.10.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 8 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is for comparison of the superiority of the LY3009104 dose level vs. placebo for the ordinal levels of response - Week 12. A priori p-value significance threshold: 1-sided ≤0.10.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
24.Secondary Outcome
Title Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128
Hide 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).
Time Frame Baseline, Weeks 76 and 128
Hide Outcome Measure Data
Hide Analysis Population 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.
Arm/Group Title 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
Hide Arm/Group Description:

Received Placebo, or 1 mg, or 2 mg, or 4 mg LY3009104 in Part A.

Received 2 mg LY3009104 QD, or BID, or 4 mg LY3009104 QD in Part B.

Received 4 mg LY3009104 QD in Part C.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Received Placebo, or 1 mg, or 2 mg, or 4 mg LY3009104 in Part A.

Received 2 mg LY3009104 QD, or BID, or 4 mg LY3009104 QD in Part B.

Received 4 mg LY3009104 QD in Part C. During Part C, at Weeks 28 and 32, participants who met dose escalation criteria received 8 mg LY3009104 QD for the rest of the 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.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Received 8 mg LY3009104 QD in Parts A, B and C.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 107 61 31
Measure Type: Number
Unit of Measure: percentage of participants
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
25.Secondary Outcome
Title Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24
Hide 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.
Time Frame Baseline through Weeks 12 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study drug in Parts A and B and had DAS28-CRP evaluated at analysis time points.
Arm/Group Title 1 mg LY3009104 2 mg LY3009104 4 mg LY3009104 8 mg LY3009104 Placebo
Hide Arm/Group Description:

1 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

2 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

4 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

8 mg LY3009104 administered orally QD for 24 weeks in Parts A and B.

MTX was administered orally as background therapy.

Placebo administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 49 52 52 50 98
Measure Type: Number
Unit of Measure: percentage of participants
Low Disease Activity - Week 12 22 23 48 40 19
Remission - Week 12 14 15 37 22 4
Low Disease Activity - Week 24 NA [1]  31 50 46 NA [2] 
Remission - Week 24 NA [1]  15 33 36 NA [2] 
[1]
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore percentage was not calculated.
[2]
Participants were not dosed with placebo after Week 12, therefore percentage was not calculated.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.409
Comments P-value is for Low Disease Activity - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 2 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.371
Comments P-value is for Low Disease Activity - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is for Low Disease Activity - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 8 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments P-value is for Low Disease Activity - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection 1 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.033
Comments P-value is for Remission - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection 2 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.019
Comments P-value is for Remission - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection 4 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is for Remission - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection 8 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments P-value is for Remission - Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method Fisher Exact
Comments [Not Specified]
26.Secondary Outcome
Title Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 76 and 128
Hide 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.
Time Frame Baseline through Weeks 76 and 128
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received study drug in Parts C and D and had DAS28-CRP evaluated at analysis time points.
Arm/Group Title 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
Hide Arm/Group Description:

Received Placebo, or 1 mg, or 2 mg, or 4 mg LY3009104 in Part A.

Received 2 mg LY3009104 QD, or BID, or 4 mg LY3009104 QD in Part B.

Received 4 mg LY3009104 QD in Part C.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Received Placebo, or 1 mg, or 2 mg, or 4 mg LY3009104 in Part A.

Received 2 mg LY3009104 QD, or BID, or 4 mg LY3009104 QD in Part B.

Received 4 mg LY3009104 QD in Part C. During Part C, at Weeks 28 and 32, participants who met dose escalation criteria received 8 mg LY3009104 QD for the rest of the 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.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Received 8 mg LY3009104 QD in Parts A, B and C.

Received 4 mg LY3009104 QD in Part D.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 108 61 32
Measure Type: Number
Unit of Measure: percentage of participants
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
27.Secondary Outcome
Title Mean Change From Baseline Through Week 12 in Duration (Minutes) of Morning Stiffness
Hide 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.
Time Frame Baseline, Weeks 4, 8, 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study drug in Part A and had morning stiffness evaluated at analysis time points. LOCF was used to impute missing post-baseline values for Week 12 analysis.
Arm/Group Title 1 mg LY3009104 2 mg LY3009104 4 mg LY3009104 8 mg LY3009104 Placebo
Hide Arm/Group Description:

1 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

2 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

4 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

8 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

Placebo administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 48 51 50 50 97
Mean (Standard Deviation)
Unit of Measure: minutes
Week 4 (n=47, 50, 50, 50, 94) -34.1  (70.49) -27.0  (46.49) -57.4  (149.00) -25.5  (126.13) -22.5  (63.61)
Week 8 (n=46, 50, 50, 50, 86) -41.2  (85.45) -31.1  (45.80) -67.8  (138.02) -53.8  (101.76) -25.5  (67.39)
Week 12 (n=48, 51, 50, 50, 97) -49.5  (72.80) -30.7  (47.41) -75.0  (142.04) -62.7  (88.27) -33.9  (91.79)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015
Comments P-value is for Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 2 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.073
Comments P-value is for Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is for Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 8 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is for Week 12. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
28.Secondary Outcome
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
Hide 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.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study drug in Part A and had SF-36 evaluated at analysis time point. LOCF was used to impute missing post-baseline values.
Arm/Group Title 1 mg LY3009104 2 mg LY3009104 4 mg LY3009104 8 mg LY3009104 Placebo
Hide Arm/Group Description:

1 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

2 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

4 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

8 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

Placebo administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 48 51 51 50 97
Mean (Standard Deviation)
Unit of Measure: units on a scale
PCS 6.66  (8.074) 4.15  (7.680) 7.07  (7.378) 7.00  (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)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.021
Comments P-value is for PCS. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 2 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.194
Comments P-value is for PCS. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is for PCS. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 8 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments P-value is for PCS. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection 1 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.449
Comments P-value is for MCS. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection 2 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.578
Comments P-value is for MCS. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection 4 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.140
Comments P-value is for MCS. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection 8 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.266
Comments P-value is for MCS. A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
29.Secondary Outcome
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
Hide 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.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study drug and had BPI-sf worst-pain-in-the past-24-hours item evaluated at Week 12. LOCF was used to impute missing post-baseline values.
Arm/Group Title 1 mg LY3009104 2 mg LY3009104 4 mg LY3009104 8 mg LY3009104 Placebo
Hide Arm/Group Description:

1 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

2 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

4 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

8 mg LY3009104 administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

Placebo administered orally QD for 12 weeks in Part A.

MTX was administered orally as background therapy.

Overall Number of Participants Analyzed 48 51 51 50 97
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.35  (2.547) -0.67  (2.132) -1.41  (1.813) -1.54  (2.131) -0.35  (2.136)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method ANCOVA
Comments A priori p-value significance threshold: 2-sided ≤0.10.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 2 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.135
Comments A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 8 mg LY3009104, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments A priori p-value significance threshold: 2-sided ≤0.10.
Method ANCOVA
Comments [Not Specified]