Trial Outcomes & Findings for A Study in Participants With Rheumatoid Arthritis on Background Methotrexate Therapy (NCT NCT01185353)
NCT ID: NCT01185353
Last Updated: 2017-06-16
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
301 participants
Primary outcome timeframe
Baseline through Week 12
Results posted on
2017-06-16
Participant Flow
This study consisted of 4 parts and a follow-up up to 28 days post the last dose of study drug.
Participant milestones
| Measure |
1 Milligrams (mg) LY3009104 QD - Part A
Administered orally once daily (QD) for 12 weeks in Part A.
Methotrexate (MTX) was administered orally as background therapy.
|
2 mg LY3009104 QD - Parts A and B
Administered orally QD for 24 weeks in Parts A and B.
MTX was administered orally as background therapy.
|
4 mg LY3009104 QD - Parts A and B
Administered orally QD for 24 weeks in Parts A and B.
MTX was administered orally as background therapy.
|
8 mg LY3009104 QD - Parts A and B
Administered orally QD for 24 weeks in Parts A and B.
MTX was administered orally as background therapy.
|
Placebo QD - Part A
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
2 mg LY3009104 BID - Part B
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.
|
4 mg LY3009104 QD - Part B
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.
|
4 mg LY3009104 QD - Parts C and D
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.
|
4 to 8 mg LY3009104 QD - Part C and 4 mg LY3009104 QD - Part D
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.
|
8 mg LY3009104 QD - Part C and 4 mg LY3009104 QD - Part D
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.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part A (Weeks 0 Through 12)
STARTED
|
49
|
52
|
52
|
50
|
98
|
0
|
0
|
0
|
0
|
0
|
|
Part A (Weeks 0 Through 12)
Received at Least 1 Dose of Study Drug
|
49
|
52
|
52
|
50
|
98
|
0
|
0
|
0
|
0
|
0
|
|
Part A (Weeks 0 Through 12)
COMPLETED
|
44
|
51
|
50
|
49
|
82
|
0
|
0
|
0
|
0
|
0
|
|
Part A (Weeks 0 Through 12)
NOT COMPLETED
|
5
|
1
|
2
|
1
|
16
|
0
|
0
|
0
|
0
|
0
|
|
Part B (Weeks 12 Through 24)
STARTED
|
0
|
51
|
50
|
49
|
0
|
63
|
63
|
0
|
0
|
0
|
|
Part B (Weeks 12 Through 24)
COMPLETED
|
0
|
50
|
48
|
45
|
0
|
59
|
57
|
0
|
0
|
0
|
|
Part B (Weeks 12 Through 24)
NOT COMPLETED
|
0
|
1
|
2
|
4
|
0
|
4
|
6
|
0
|
0
|
0
|
|
Part C (Weeks 24 Through 76)
STARTED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
108
|
61
|
32
|
|
Part C (Weeks 24 Through 76)
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
92
|
53
|
24
|
|
Part C (Weeks 24 Through 76)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
16
|
8
|
8
|
|
Part D (Weeks 76 Through 128)
STARTED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
79
|
47
|
18
|
|
Part D (Weeks 76 Through 128)
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
76
|
40
|
17
|
|
Part D (Weeks 76 Through 128)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
3
|
7
|
1
|
Reasons for withdrawal
| Measure |
1 Milligrams (mg) LY3009104 QD - Part A
Administered orally once daily (QD) for 12 weeks in Part A.
Methotrexate (MTX) was administered orally as background therapy.
|
2 mg LY3009104 QD - Parts A and B
Administered orally QD for 24 weeks in Parts A and B.
MTX was administered orally as background therapy.
|
4 mg LY3009104 QD - Parts A and B
Administered orally QD for 24 weeks in Parts A and B.
MTX was administered orally as background therapy.
|
8 mg LY3009104 QD - Parts A and B
Administered orally QD for 24 weeks in Parts A and B.
MTX was administered orally as background therapy.
|
Placebo QD - Part A
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
2 mg LY3009104 BID - Part B
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.
|
4 mg LY3009104 QD - Part B
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.
|
4 mg LY3009104 QD - Parts C and D
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.
|
4 to 8 mg LY3009104 QD - Part C and 4 mg LY3009104 QD - Part D
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.
|
8 mg LY3009104 QD - Part C and 4 mg LY3009104 QD - Part D
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.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part A (Weeks 0 Through 12)
Adverse Event
|
1
|
1
|
1
|
1
|
5
|
0
|
0
|
0
|
0
|
0
|
|
Part A (Weeks 0 Through 12)
Entry Criteria Not Met
|
0
|
0
|
0
|
0
|
4
|
0
|
0
|
0
|
0
|
0
|
|
Part A (Weeks 0 Through 12)
Lack of Efficacy
|
2
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Part A (Weeks 0 Through 12)
Physician Decision
|
0
|
0
|
1
|
0
|
2
|
0
|
0
|
0
|
0
|
0
|
|
Part A (Weeks 0 Through 12)
Protocol Violation
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Part A (Weeks 0 Through 12)
Withdrawal by Subject
|
2
|
0
|
0
|
0
|
3
|
0
|
0
|
0
|
0
|
0
|
|
Part B (Weeks 12 Through 24)
Adverse Event
|
0
|
0
|
1
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Part B (Weeks 12 Through 24)
Lack of Efficacy
|
0
|
1
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Part B (Weeks 12 Through 24)
Lost to Follow-up
|
0
|
0
|
0
|
1
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Part B (Weeks 12 Through 24)
Withdrawal by Subject
|
0
|
0
|
1
|
2
|
0
|
3
|
4
|
0
|
0
|
0
|
|
Part B (Weeks 12 Through 24)
Entry Criteria Not Met
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Part C (Weeks 24 Through 76)
Adverse Event
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
8
|
2
|
2
|
|
Part C (Weeks 24 Through 76)
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
6
|
2
|
2
|
|
Part C (Weeks 24 Through 76)
Lost to Follow-up
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
2
|
1
|
1
|
|
Part C (Weeks 24 Through 76)
Lack of Efficacy
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
2
|
0
|
|
Part C (Weeks 24 Through 76)
Death
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Part C (Weeks 24 Through 76)
Entry Criteria Not Met
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Part C (Weeks 24 Through 76)
Physician Decision
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Part C (Weeks 24 Through 76)
Reason missing
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
|
Part D (Weeks 76 Through 128)
Lost to Follow-up
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
3
|
0
|
|
Part D (Weeks 76 Through 128)
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
2
|
1
|
|
Part D (Weeks 76 Through 128)
Adverse Event
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
2
|
0
|
Baseline Characteristics
All randomized participants who received at least one dose of study drug and had evaluable hsCRP data at baseline.
Baseline characteristics by cohort
| Measure |
1 mg LY3009104
n=49 Participants
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.
|
2 mg LY3009104
n=52 Participants
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.
|
4 mg LY3009104
n=52 Participants
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.
|
8 mg LY3009104
n=50 Participants
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
n=98 Participants
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
n=301 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
53.1 years
STANDARD_DEVIATION 11.07 • n=49 Participants
|
50.7 years
STANDARD_DEVIATION 13.12 • n=52 Participants
|
52.5 years
STANDARD_DEVIATION 10.42 • n=52 Participants
|
52.7 years
STANDARD_DEVIATION 10.91 • n=50 Participants
|
49.2 years
STANDARD_DEVIATION 12.15 • n=98 Participants
|
51.2 years
STANDARD_DEVIATION 11.71 • n=301 Participants
|
|
Sex: Female, Male
Female
|
42 Participants
n=49 Participants
|
44 Participants
n=52 Participants
|
37 Participants
n=52 Participants
|
41 Participants
n=50 Participants
|
85 Participants
n=98 Participants
|
249 Participants
n=301 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=49 Participants
|
8 Participants
n=52 Participants
|
15 Participants
n=52 Participants
|
9 Participants
n=50 Participants
|
13 Participants
n=98 Participants
|
52 Participants
n=301 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
10 Participants
n=49 Participants
|
7 Participants
n=52 Participants
|
12 Participants
n=52 Participants
|
11 Participants
n=50 Participants
|
16 Participants
n=98 Participants
|
56 Participants
n=301 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
36 Participants
n=49 Participants
|
41 Participants
n=52 Participants
|
36 Participants
n=52 Participants
|
36 Participants
n=50 Participants
|
78 Participants
n=98 Participants
|
227 Participants
n=301 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=49 Participants
|
4 Participants
n=52 Participants
|
4 Participants
n=52 Participants
|
3 Participants
n=50 Participants
|
4 Participants
n=98 Participants
|
18 Participants
n=301 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
4 Participants
n=49 Participants
|
3 Participants
n=52 Participants
|
3 Participants
n=52 Participants
|
2 Participants
n=50 Participants
|
7 Participants
n=98 Participants
|
19 Participants
n=301 Participants
|
|
Race (NIH/OMB)
Asian
|
8 Participants
n=49 Participants
|
8 Participants
n=52 Participants
|
7 Participants
n=52 Participants
|
9 Participants
n=50 Participants
|
15 Participants
n=98 Participants
|
47 Participants
n=301 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=49 Participants
|
0 Participants
n=52 Participants
|
0 Participants
n=52 Participants
|
0 Participants
n=50 Participants
|
0 Participants
n=98 Participants
|
0 Participants
n=301 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=49 Participants
|
1 Participants
n=52 Participants
|
2 Participants
n=52 Participants
|
2 Participants
n=50 Participants
|
6 Participants
n=98 Participants
|
11 Participants
n=301 Participants
|
|
Race (NIH/OMB)
White
|
37 Participants
n=49 Participants
|
40 Participants
n=52 Participants
|
40 Participants
n=52 Participants
|
37 Participants
n=50 Participants
|
70 Participants
n=98 Participants
|
224 Participants
n=301 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=49 Participants
|
0 Participants
n=52 Participants
|
0 Participants
n=52 Participants
|
0 Participants
n=50 Participants
|
0 Participants
n=98 Participants
|
0 Participants
n=301 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=49 Participants
|
0 Participants
n=52 Participants
|
0 Participants
n=52 Participants
|
0 Participants
n=50 Participants
|
0 Participants
n=98 Participants
|
0 Participants
n=301 Participants
|
|
Region of Enrollment
United States
|
16 participants
n=49 Participants
|
16 participants
n=52 Participants
|
16 participants
n=52 Participants
|
16 participants
n=50 Participants
|
31 participants
n=98 Participants
|
95 participants
n=301 Participants
|
|
Region of Enrollment
Hungary
|
3 participants
n=49 Participants
|
3 participants
n=52 Participants
|
3 participants
n=52 Participants
|
2 participants
n=50 Participants
|
2 participants
n=98 Participants
|
13 participants
n=301 Participants
|
|
Region of Enrollment
Czech Republic
|
4 participants
n=49 Participants
|
3 participants
n=52 Participants
|
6 participants
n=52 Participants
|
3 participants
n=50 Participants
|
7 participants
n=98 Participants
|
23 participants
n=301 Participants
|
|
Region of Enrollment
Mexico
|
7 participants
n=49 Participants
|
8 participants
n=52 Participants
|
8 participants
n=52 Participants
|
8 participants
n=50 Participants
|
16 participants
n=98 Participants
|
47 participants
n=301 Participants
|
|
Region of Enrollment
Poland
|
4 participants
n=49 Participants
|
5 participants
n=52 Participants
|
6 participants
n=52 Participants
|
7 participants
n=50 Participants
|
11 participants
n=98 Participants
|
33 participants
n=301 Participants
|
|
Region of Enrollment
Ukraine
|
6 participants
n=49 Participants
|
6 participants
n=52 Participants
|
5 participants
n=52 Participants
|
3 participants
n=50 Participants
|
9 participants
n=98 Participants
|
29 participants
n=301 Participants
|
|
Region of Enrollment
Croatia
|
0 participants
n=49 Participants
|
1 participants
n=52 Participants
|
0 participants
n=52 Participants
|
1 participants
n=50 Participants
|
5 participants
n=98 Participants
|
7 participants
n=301 Participants
|
|
Region of Enrollment
Romania
|
2 participants
n=49 Participants
|
2 participants
n=52 Participants
|
1 participants
n=52 Participants
|
3 participants
n=50 Participants
|
3 participants
n=98 Participants
|
11 participants
n=301 Participants
|
|
Region of Enrollment
India
|
7 participants
n=49 Participants
|
8 participants
n=52 Participants
|
7 participants
n=52 Participants
|
7 participants
n=50 Participants
|
14 participants
n=98 Participants
|
43 participants
n=301 Participants
|
|
Duration of Rheumatoid Arthritis
|
5.45 years
STANDARD_DEVIATION 3.885 • n=49 Participants
|
5.53 years
STANDARD_DEVIATION 4.377 • n=52 Participants
|
5.28 years
STANDARD_DEVIATION 4.466 • n=52 Participants
|
6.63 years
STANDARD_DEVIATION 5.048 • n=50 Participants
|
5.40 years
STANDARD_DEVIATION 4.283 • n=98 Participants
|
5.62 years
STANDARD_DEVIATION 4.401 • n=301 Participants
|
|
Tender Joint Counts (TJC)
|
21.4 number of joints
STANDARD_DEVIATION 10.90 • n=49 Participants
|
23.0 number of joints
STANDARD_DEVIATION 12.60 • n=52 Participants
|
19.9 number of joints
STANDARD_DEVIATION 12.71 • n=52 Participants
|
24.4 number of joints
STANDARD_DEVIATION 13.76 • n=50 Participants
|
22.2 number of joints
STANDARD_DEVIATION 12.06 • n=98 Participants
|
22.2 number of joints
STANDARD_DEVIATION 12.38 • n=301 Participants
|
|
Swollen Joint Counts (SJC)
|
15.2 number of joints
STANDARD_DEVIATION 6.55 • n=49 Participants
|
17.0 number of joints
STANDARD_DEVIATION 9.32 • n=52 Participants
|
14.8 number of joints
STANDARD_DEVIATION 7.54 • n=52 Participants
|
16.1 number of joints
STANDARD_DEVIATION 7.92 • n=50 Participants
|
15.8 number of joints
STANDARD_DEVIATION 8.64 • n=98 Participants
|
15.8 number of joints
STANDARD_DEVIATION 8.13 • n=301 Participants
|
|
High Sensitivity C-Reactive Protein (hsCRP)
|
11.22 milligrams/liter (mg/L)
STANDARD_DEVIATION 12.410 • n=49 Participants • All randomized participants who received at least one dose of study drug and had evaluable hsCRP data at baseline.
|
12.02 milligrams/liter (mg/L)
STANDARD_DEVIATION 22.111 • n=52 Participants • All randomized participants who received at least one dose of study drug and had evaluable hsCRP data at baseline.
|
11.39 milligrams/liter (mg/L)
STANDARD_DEVIATION 16.941 • n=52 Participants • All randomized participants who received at least one dose of study drug and had evaluable hsCRP data at baseline.
|
14.32 milligrams/liter (mg/L)
STANDARD_DEVIATION 15.602 • n=50 Participants • All randomized participants who received at least one dose of study drug and had evaluable hsCRP data at baseline.
|
14.03 milligrams/liter (mg/L)
STANDARD_DEVIATION 23.527 • n=97 Participants • All randomized participants who received at least one dose of study drug and had evaluable hsCRP data at baseline.
|
12.81 milligrams/liter (mg/L)
STANDARD_DEVIATION 19.402 • n=300 Participants • All randomized participants who received at least one dose of study drug and had evaluable hsCRP data at baseline.
|
|
Erythrocyte Sedimentation Rate (ESR)
|
38.2 millimeters/hour (mm/hr)
STANDARD_DEVIATION 17.57 • n=49 Participants
|
36.5 millimeters/hour (mm/hr)
STANDARD_DEVIATION 14.62 • n=52 Participants
|
35.4 millimeters/hour (mm/hr)
STANDARD_DEVIATION 17.16 • n=52 Participants
|
43.3 millimeters/hour (mm/hr)
STANDARD_DEVIATION 18.17 • n=50 Participants
|
39.9 millimeters/hour (mm/hr)
STANDARD_DEVIATION 20.94 • n=98 Participants
|
38.8 millimeters/hour (mm/hr)
STANDARD_DEVIATION 18.39 • n=301 Participants
|
PRIMARY outcome
Timeframe: Baseline through Week 12Population: 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).
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.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=102 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=98 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
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
|
76 percentage of participants
|
41 percentage of participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline through Week 12Population: 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.
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.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=49 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=52 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=52 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
n=50 Participants
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=98 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 12 - Model Based Dose Response
|
54.6 percentage of participants
Interval 42.2 to 67.1
|
55.2 percentage of participants
Interval 42.3 to 67.6
|
74.3 percentage of participants
Interval 63.1 to 84.1
|
77.2 percentage of participants
Interval 65.9 to 86.7
|
42.1 percentage of participants
Interval 32.9 to 51.6
|
SECONDARY outcome
Timeframe: Baseline through Weeks 2, 4, 8, 12, 16, 20, 24Population: 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.
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.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=49 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=52 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=52 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
n=50 Participants
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=98 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24
Week 4
|
43 percentage of participants
|
37 percentage of participants
|
60 percentage of participants
|
54 percentage of participants
|
24 percentage of participants
|
|
Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24
Week 8
|
43 percentage of participants
|
42 percentage of participants
|
67 percentage of participants
|
72 percentage of participants
|
36 percentage of participants
|
|
Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24
Week 16
|
NA percentage of participants
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore percentage was not calculated.
|
63 percentage of participants
|
67 percentage of participants
|
64 percentage of participants
|
NA percentage of participants
Participants were not dosed with placebo after Week 12, therefore percentage was not calculated.
|
|
Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24
Week 24
|
NA percentage of participants
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore percentage was not calculated.
|
62 percentage of participants
|
75 percentage of participants
|
72 percentage of participants
|
NA percentage of participants
Participants were not dosed with placebo after Week 12, therefore percentage was not calculated.
|
|
Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24
Week 2
|
29 percentage of participants
|
21 percentage of participants
|
42 percentage of participants
|
44 percentage of participants
|
11 percentage of participants
|
|
Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24
Week 20
|
NA percentage of participants
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore percentage was not calculated.
|
71 percentage of participants
|
77 percentage of participants
|
78 percentage of participants
|
NA percentage of participants
Participants were not dosed with placebo after Week 12, therefore percentage was not calculated.
|
|
Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24
Week 12
|
57 percentage of participants
|
54 percentage of participants
|
75 percentage of participants
|
78 percentage of participants
|
41 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline through Weeks 76 and 128Population: 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.
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.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=108 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=61 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=32 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Achieved an ACR20 Response Baseline Through Weeks 76 and 128
Week 76 (n=108, 61, 32)
|
71 percentage of participants
|
67 percentage of participants
|
59 percentage of participants
|
—
|
—
|
|
Percentage of Participants Who Achieved an ACR20 Response Baseline Through Weeks 76 and 128
Week 128 (n=79, 47, 18)
|
77 percentage of participants
|
57 percentage of participants
|
72 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline through Weeks 2, 4, 8, 12, 16, 20, 24Population: 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.
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.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=49 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=52 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=52 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
n=50 Participants
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=98 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24
Week 8
|
16 percentage of participants
|
10 percentage of participants
|
33 percentage of participants
|
36 percentage of participants
|
7 percentage of participants
|
|
Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24
Week 2
|
0 percentage of participants
|
4 percentage of participants
|
21 percentage of participants
|
4 percentage of participants
|
2 percentage of participants
|
|
Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24
Week 4
|
10 percentage of participants
|
10 percentage of participants
|
29 percentage of participants
|
22 percentage of participants
|
3 percentage of participants
|
|
Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24
Week 12
|
31 percentage of participants
|
17 percentage of participants
|
35 percentage of participants
|
40 percentage of participants
|
10 percentage of participants
|
|
Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24
Week 16
|
NA percentage of participants
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore percentage was not calculated.
|
19 percentage of participants
|
38 percentage of participants
|
44 percentage of participants
|
NA percentage of participants
Participants were not dosed with placebo after Week 12, therefore percentage was not calculated.
|
|
Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24
Week 24
|
NA percentage of participants
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore percentage was not calculated.
|
19 percentage of participants
|
46 percentage of participants
|
54 percentage of participants
|
NA percentage of participants
Participants were not dosed with placebo after Week 12, therefore percentage was not calculated.
|
|
Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24
Week 20
|
NA percentage of participants
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore percentage was not calculated.
|
27 percentage of participants
|
46 percentage of participants
|
48 percentage of participants
|
NA percentage of participants
Participants were not dosed with placebo after Week 12, therefore percentage was not calculated.
|
SECONDARY outcome
Timeframe: Baseline through Weeks 76 and 128Population: 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.
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.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=108 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=61 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=32 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Achieved an ACR50 Response Baseline Through Weeks 76 and 128
Week 128 (n=79, 47, 18)
|
58 percentage of participants
|
30 percentage of participants
|
44 percentage of participants
|
—
|
—
|
|
Percentage of Participants Who Achieved an ACR50 Response Baseline Through Weeks 76 and 128
Week 76 (n=108, 61, 32)
|
49 percentage of participants
|
41 percentage of participants
|
44 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline through Weeks 2, 4, 8, 12, 16, 20, 24Population: 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.
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.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=49 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=52 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=52 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
n=50 Participants
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=98 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24
Week 20
|
NA percentage of participants
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore percentage was not calculated.
|
10 percentage of participants
|
21 percentage of participants
|
26 percentage of participants
|
NA percentage of participants
Participants were not dosed with placebo after Week 12, therefore percentage was not calculated.
|
|
Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24
Week 2
|
0 percentage of participants
|
2 percentage of participants
|
12 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24
Week 4
|
2 percentage of participants
|
4 percentage of participants
|
10 percentage of participants
|
6 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24
Week 12
|
12 percentage of participants
|
8 percentage of participants
|
23 percentage of participants
|
20 percentage of participants
|
2 percentage of participants
|
|
Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24
Week 24
|
NA percentage of participants
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore percentage was not calculated.
|
10 percentage of participants
|
27 percentage of participants
|
24 percentage of participants
|
NA percentage of participants
Participants were not dosed with placebo after Week 12, therefore percentage was not calculated.
|
|
Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24
Week 16
|
NA percentage of participants
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore percentage was not calculated.
|
8 percentage of participants
|
23 percentage of participants
|
30 percentage of participants
|
NA percentage of participants
Participants were not dosed with placebo after Week 12, therefore percentage was not calculated.
|
|
Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24
Week 8
|
4 percentage of participants
|
4 percentage of participants
|
15 percentage of participants
|
22 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline through Weeks 76 and 128Population: 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.
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.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=108 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=61 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=32 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Achieved an ACR70 Response Baseline Through Weeks 76 and 128
Week 128 (n=79, 47, 18)
|
28 percentage of participants
|
17 percentage of participants
|
22 percentage of participants
|
—
|
—
|
|
Percentage of Participants Who Achieved an ACR70 Response Baseline Through Weeks 76 and 128
Week 76 (n=108, 61, 32)
|
29 percentage of participants
|
18 percentage of participants
|
25 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline through Week 12Population: 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.
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.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=49 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=52 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=52 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
n=50 Participants
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=98 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
Percentage of Participants Who Achieved an ACR50 Response Baseline Through Week 12 - Model Based Dose Response
|
26.5 percentage of participants
Interval 16.0 to 39.2
|
18.8 percentage of participants
Interval 9.9 to 29.7
|
34.4 percentage of participants
Interval 23.1 to 46.7
|
39.2 percentage of participants
Interval 27.1 to 52.2
|
12.0 percentage of participants
Interval 6.5 to 18.8
|
SECONDARY outcome
Timeframe: Baseline through Week 12Population: 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.
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.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=49 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=52 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=52 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
n=50 Participants
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=98 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
ACR Percent Improvement (ACR-N)
|
17.30 percentage of improvement
Interval 7.57 to 28.22
|
19.42 percentage of improvement
Interval 8.74 to 29.25
|
28.59 percentage of improvement
Interval 17.67 to 40.83
|
29.00 percentage of improvement
Interval 17.67 to 41.47
|
10.97 percentage of improvement
Interval -0.39 to 21.64
|
SECONDARY outcome
Timeframe: Baseline, Weeks 12 and 24Population: 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
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.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=49 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=52 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=51 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
n=50 Participants
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=98 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC)
TJC - Week 24
|
NA number of joints
Standard Deviation NA
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore mean and standard deviation (SD) were not calculated.
|
-12.4 number of joints
Standard Deviation 12.60
|
-14.0 number of joints
Standard Deviation 9.54
|
-17.5 number of joints
Standard Deviation 11.23
|
NA number of joints
Standard Deviation NA
Participants were not dosed with placebo after Week 12, therefore mean and SD were not calculated.
|
|
Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC)
SJC - Week 12
|
-8.1 number of joints
Standard Deviation 7.24
|
-8.9 number of joints
Standard Deviation 9.03
|
-9.6 number of joints
Standard Deviation 6.49
|
-10.4 number of joints
Standard Deviation 8.88
|
-6.7 number of joints
Standard Deviation 7.97
|
|
Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC)
SJC - Week 24
|
NA number of joints
Standard Deviation NA
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore mean and SD were not calculated.
|
-10.0 number of joints
Standard Deviation 8.16
|
-10.5 number of joints
Standard Deviation 6.42
|
-12.2 number of joints
Standard Deviation 7.29
|
NA number of joints
Standard Deviation NA
Participants were not dosed with placebo after Week 12, therefore mean and SD were not calculated.
|
|
Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC)
TJC - Week 12
|
-8.4 number of joints
Standard Deviation 12.70
|
-11.3 number of joints
Standard Deviation 13.50
|
-12.2 number of joints
Standard Deviation 10.45
|
-14.7 number of joints
Standard Deviation 12.97
|
-7.6 number of joints
Standard Deviation 12.31
|
SECONDARY outcome
Timeframe: Baseline, Weeks 76 and 128Population: 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.
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.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=108 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=61 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=32 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
Mean Change From Baseline to Weeks 76 and 128 in TJC and SJC
TJC - Week 76 (n=108, 61, 32)
|
-15.7 units on a scale
Standard Deviation 11.26
|
-16.0 units on a scale
Standard Deviation 13.37
|
-18.1 units on a scale
Standard Deviation 12.06
|
—
|
—
|
|
Mean Change From Baseline to Weeks 76 and 128 in TJC and SJC
SJC - Week 76 (n=108, 61, 32)
|
-11.6 units on a scale
Standard Deviation 6.40
|
-12.9 units on a scale
Standard Deviation 7.80
|
-12.4 units on a scale
Standard Deviation 7.67
|
—
|
—
|
|
Mean Change From Baseline to Weeks 76 and 128 in TJC and SJC
SJC - Week 128 (n=79, 47, 18)
|
-11.4 units on a scale
Standard Deviation 6.81
|
-12.4 units on a scale
Standard Deviation 8.01
|
-11.6 units on a scale
Standard Deviation 6.23
|
—
|
—
|
|
Mean Change From Baseline to Weeks 76 and 128 in TJC and SJC
TJC - Week 128 (n=79, 47, 18)
|
-16.4 units on a scale
Standard Deviation 11.01
|
-15.3 units on a scale
Standard Deviation 12.56
|
-14.0 units on a scale
Standard Deviation 13.68
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 12 and 24Population: 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.
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.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=49 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=52 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=51 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
n=50 Participants
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=98 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
Mean Change From Baseline to Weeks 12 and 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
Week 12
|
-0.35 units on a scale
Standard Deviation 0.528
|
-0.18 units on a scale
Standard Deviation 0.524
|
-0.33 units on a scale
Standard Deviation 0.459
|
-0.39 units on a scale
Standard Deviation 0.497
|
-0.10 units on a scale
Standard Deviation 0.406
|
|
Mean Change From Baseline to Weeks 12 and 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
Week 24
|
NA units on a scale
Standard Deviation NA
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore mean and SD were not calculated.
|
-0.18 units on a scale
Standard Deviation 0.505
|
-0.32 units on a scale
Standard Deviation 0.506
|
-0.44 units on a scale
Standard Deviation 0.529
|
NA units on a scale
Standard Deviation NA
Participants were not dosed with placebo after Week 12, therefore mean and SD were not calculated.
|
SECONDARY outcome
Timeframe: Baseline, Weeks 76 and 128Population: 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.
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.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=108 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=61 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=32 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
Mean Change From Baseline to Weeks 76 and 128 in HAQ-DI Score
Week 76 (n=108, 61, 32)
|
-0.34 units on a scale
Standard Deviation 0.58
|
-0.29 units on a scale
Standard Deviation 0.53
|
-0.55 units on a scale
Standard Deviation 0.58
|
—
|
—
|
|
Mean Change From Baseline to Weeks 76 and 128 in HAQ-DI Score
Week 128 (n=79, 47, 18)
|
-0.31 units on a scale
Standard Deviation 0.61
|
-0.22 units on a scale
Standard Deviation 0.56
|
-0.30 units on a scale
Standard Deviation 0.66
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 12 and 24Population: 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.
hsCRP is a laboratory analyte that is an indicator of inflammation. Decreases in hsCRP represent reductions in inflammation.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=49 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=52 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=51 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
n=50 Participants
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=97 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
Mean Change From Baseline to Weeks 12 and 24 in High-Sensitivity C-Reactive Protein (hsCRP)
Week 12
|
-6.14 mg/L
Standard Deviation 10.236
|
-3.39 mg/L
Standard Deviation 19.409
|
-7.06 mg/L
Standard Deviation 16.945
|
-2.32 mg/L
Standard Deviation 32.582
|
1.50 mg/L
Standard Deviation 34.107
|
|
Mean Change From Baseline to Weeks 12 and 24 in High-Sensitivity C-Reactive Protein (hsCRP)
Week 24
|
NA mg/L
Standard Deviation NA
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore mean and SD were not calculated.
|
-4.76 mg/L
Standard Deviation 18.695
|
-4.95 mg/L
Standard Deviation 19.819
|
-7.61 mg/L
Standard Deviation 17.548
|
NA mg/L
Standard Deviation NA
Participants were not dosed with placebo after Week 12, therefore mean and SD were not calculated.
|
SECONDARY outcome
Timeframe: Baseline, Weeks 76 and 128Population: 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.
hsCRP is a laboratory analyte that is an indicator of inflammation. Decreases in hsCRP represent reductions in inflammation.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=108 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=61 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=32 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
Mean Change From Baseline to Weeks 76 and 128 in hsCRP
Week 76 (n=108, 61, 32)
|
-3.9 mg/L
Standard Deviation 22.43
|
-3.3 mg/L
Standard Deviation 14.28
|
-2.9 mg/L
Standard Deviation 25.36
|
—
|
—
|
|
Mean Change From Baseline to Weeks 76 and 128 in hsCRP
Week 128 (n=79, 47, 18)
|
-6.8 mg/L
Standard Deviation 13.66
|
-2.9 mg/L
Standard Deviation 21.88
|
-8.2 mg/L
Standard Deviation 12.33
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 12 and 24Population: All randomized participants who received study drug in Parts A and B and had ESR evaluated at analysis time points.
ESR is a laboratory analyte that is an indicator of inflammation. Decreases represent reductions in inflammation.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=44 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=51 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=50 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
n=49 Participants
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=83 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
Mean Change From Baseline to Weeks 12 and 24 in Erythrocyte Sedimentation Rate (ESR)
Week 24 (n=0, 50, 48, 45, 0)
|
NA mm/hr
Standard Deviation NA
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore mean and SD were not calculated.
|
-6.9 mm/hr
Standard Deviation 13.89
|
-9.2 mm/hr
Standard Deviation 19.00
|
-13.7 mm/hr
Standard Deviation 21.62
|
NA mm/hr
Standard Deviation NA
Participants were not dosed with placebo after Week 12, therefore mean and SD were not calculated.
|
|
Mean Change From Baseline to Weeks 12 and 24 in Erythrocyte Sedimentation Rate (ESR)
Week 12 (n=44, 51, 50, 49, 83)
|
-11.6 mm/hr
Standard Deviation 14.45
|
-6.4 mm/hr
Standard Deviation 16.81
|
-11.5 mm/hr
Standard Deviation 17.28
|
-13.9 mm/hr
Standard Deviation 22.42
|
-6.0 mm/hr
Standard Deviation 19.49
|
SECONDARY outcome
Timeframe: Baseline, Weeks 76 and 128Population: 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.
ESR is a laboratory analyte that is an indicator of inflammation. Decreases represent reductions in inflammation.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=108 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=61 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=32 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
Mean Change From Baseline to Weeks 76 and 128 in ESR
Week 128 (n=79, 47, 18)
|
-16.0 mm/hr
Standard Deviation 18.74
|
-8.5 mm/hr
Standard Deviation 23.11
|
-15.5 mm/hr
Standard Deviation 23.07
|
—
|
—
|
|
Mean Change From Baseline to Weeks 76 and 128 in ESR
Week 76 (n=108, 61, 32)
|
-13.0 mm/hr
Standard Deviation 18.84
|
-7.4 mm/hr
Standard Deviation 26.28
|
-8.9 mm/hr
Standard Deviation 23.12
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 12 and 24Population: 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.
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).
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=49 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=52 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=51 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
n=50 Participants
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=98 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
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
Physician's Assessment of DA - Week 24
|
NA units on a scale
Standard Deviation NA
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore mean and SD were not calculated.
|
-27.8 units on a scale
Standard Deviation 21.13
|
-35.5 units on a scale
Standard Deviation 17.72
|
-37.8 units on a scale
Standard Deviation 18.73
|
NA units on a scale
Standard Deviation NA
Participants were not dosed with placebo after Week 12, therefore mean and SD were not calculated.
|
|
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
Patient's Assessment of DA - Week 12
|
-24.9 units on a scale
Standard Deviation 27.26
|
-16.2 units on a scale
Standard Deviation 22.43
|
-25.4 units on a scale
Standard Deviation 21.61
|
-29.8 units on a scale
Standard Deviation 21.20
|
-10.3 units on a scale
Standard Deviation 22.02
|
|
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
Patient's Assessment of DA - Week 24
|
NA units on a scale
Standard Deviation NA
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore mean and SD were not calculated.
|
-16.9 units on a scale
Standard Deviation 24.96
|
-30.2 units on a scale
Standard Deviation 21.85
|
-30.0 units on a scale
Standard Deviation 20.90
|
NA units on a scale
Standard Deviation NA
Participants were not dosed with placebo after Week 12, therefore mean and SD were not calculated.
|
|
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
Patient's Assessment of Pain - Week 24
|
NA units on a scale
Standard Deviation NA
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore mean and SD were not calculated.
|
-14.7 units on a scale
Standard Deviation 20.57
|
-27.3 units on a scale
Standard Deviation 22.11
|
-26.9 units on a scale
Standard Deviation 19.22
|
NA units on a scale
Standard Deviation NA
Participants were not dosed with placebo after Week 12, therefore mean and SD were not calculated.
|
|
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
Patient's Assessment of Pain - Week 12
|
-22.8 units on a scale
Standard Deviation 27.39
|
-14.2 units on a scale
Standard Deviation 17.82
|
-25.0 units on a scale
Standard Deviation 19.22
|
-25.3 units on a scale
Standard Deviation 20.31
|
-8.8 units on a scale
Standard Deviation 22.77
|
|
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
Physician's Assessment of DA - Week 12
|
-23.9 units on a scale
Standard Deviation 18.49
|
-25.0 units on a scale
Standard Deviation 20.81
|
-30.4 units on a scale
Standard Deviation 18.75
|
-33.5 units on a scale
Standard Deviation 19.49
|
-19.0 units on a scale
Standard Deviation 21.40
|
SECONDARY outcome
Timeframe: Baseline, Weeks 76 and 128Population: 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.
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).
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=108 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=61 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=32 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
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
Physician Assessment of DA-Week 76 (n=108, 61, 32)
|
-40.3 units on a scale
Standard Deviation 19.15
|
-32.3 units on a scale
Standard Deviation 23.37
|
-40.5 units on a scale
Standard Deviation 21.44
|
—
|
—
|
|
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
Physician Assessment of DA-Week 128 (n=79, 47, 18)
|
-39.5 units on a scale
Standard Deviation 20.32
|
-31.0 units on a scale
Standard Deviation 25.54
|
-34.0 units on a scale
Standard Deviation 27.51
|
—
|
—
|
|
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
Patient Assessment of DA-Week 76 (n=108, 61, 32)
|
-27.5 units on a scale
Standard Deviation 26.49
|
-27.5 units on a scale
Standard Deviation 25.52
|
-27.6 units on a scale
Standard Deviation 24.11
|
—
|
—
|
|
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
Patient Assessment of DA-Week 128 (n=79, 47, 18)
|
-27.9 units on a scale
Standard Deviation 27.40
|
-19.3 units on a scale
Standard Deviation 29.72
|
-27.6 units on a scale
Standard Deviation 25.17
|
—
|
—
|
|
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
Patient Assessment of Pain-Week 76 (n=108, 61, 32)
|
-25.1 units on a scale
Standard Deviation 24.10
|
-27.3 units on a scale
Standard Deviation 24.24
|
-23.4 units on a scale
Standard Deviation 23.49
|
—
|
—
|
|
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
Patient Assessment of Pain-Week 128 (n=79, 47, 18)
|
-24.2 units on a scale
Standard Deviation 24.35
|
-18.0 units on a scale
Standard Deviation 28.85
|
-22.3 units on a scale
Standard Deviation 22.99
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 12 and 24Population: 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.
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.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=49 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=52 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=50 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
n=50 Participants
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=93 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
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)
Week 12
|
-1.47 units on a scale
Standard Deviation 1.299
|
-1.40 units on a scale
Standard Deviation 1.210
|
-2.09 units on a scale
Standard Deviation 1.220
|
-2.15 units on a scale
Standard Deviation 1.273
|
-0.98 units on a scale
Standard Deviation 1.141
|
|
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)
Week 24
|
NA units on a scale
Standard Deviation NA
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore mean and SD were not calculated.
|
-1.53 units on a scale
Standard Deviation 1.187
|
-2.25 units on a scale
Standard Deviation 1.054
|
-2.47 units on a scale
Standard Deviation 1.280
|
NA units on a scale
Standard Deviation NA
Participants were not dosed with placebo after Week 12, therefore mean and SD were not calculated.
|
SECONDARY outcome
Timeframe: Baseline, Weeks 76 and 128Population: 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.
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.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=107 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=61 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=31 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
Mean Change From Baseline to Weeks 76 and 128 in DAS28-CRP
Week 76 (n=107, 61, 31)
|
-2.47 units on a scale
Standard Deviation 1.23
|
-2.16 units on a scale
Standard Deviation 1.28
|
-2.68 units on a scale
Standard Deviation 1.12
|
—
|
—
|
|
Mean Change From Baseline to Weeks 76 and 128 in DAS28-CRP
Week 128 (n=79, 47, 18)
|
-2.56 units on a scale
Standard Deviation 1.16
|
-2.02 units on a scale
Standard Deviation 1.23
|
-2.35 units on a scale
Standard Deviation 1.40
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline through Weeks 12 and 24Population: All randomized participants who received study drug in Parts A and B and had EULAR28 evaluated at analysis time points.
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).
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=49 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=52 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=52 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
n=50 Participants
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=98 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24
Good Response - Week 12
|
22 percentage of participants
|
17 percentage of participants
|
46 percentage of participants
|
40 percentage of participants
|
16 percentage of participants
|
|
Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24
Moderate Response - Week 12
|
43 percentage of participants
|
63 percentage of participants
|
31 percentage of participants
|
46 percentage of participants
|
35 percentage of participants
|
|
Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24
No Response - Week 12
|
35 percentage of participants
|
19 percentage of participants
|
23 percentage of participants
|
14 percentage of participants
|
49 percentage of participants
|
|
Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24
No Response - Week 24
|
NA percentage of participants
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore percentage was not calculated.
|
23 percentage of participants
|
15 percentage of participants
|
22 percentage of participants
|
NA percentage of participants
Participants were not dosed with placebo after Week 12, therefore percentage was not calculated.
|
|
Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24
Good Response - Week 24
|
NA percentage of participants
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore percentage was not calculated.
|
25 percentage of participants
|
42 percentage of participants
|
46 percentage of participants
|
NA percentage of participants
Participants were not dosed with placebo after Week 12, therefore percentage was not calculated.
|
|
Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24
Moderate Response - Week 24
|
NA percentage of participants
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore percentage was not calculated.
|
52 percentage of participants
|
42 percentage of participants
|
32 percentage of participants
|
NA percentage of participants
Participants were not dosed with placebo after Week 12, therefore percentage was not calculated.
|
SECONDARY outcome
Timeframe: Baseline, Weeks 76 and 128Population: 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.
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).
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=107 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=61 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=31 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128
Moderate Response - Week 76 (n=107, 61, 31)
|
27 percentage of participants
|
46 percentage of participants
|
39 percentage of participants
|
—
|
—
|
|
Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128
No Response - Week 76 (n=107, 61, 31)
|
8 percentage of participants
|
13 percentage of participants
|
6 percentage of participants
|
—
|
—
|
|
Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128
Good Response - Week 128 (n=79, 47, 18)
|
65 percentage of participants
|
40 percentage of participants
|
56 percentage of participants
|
—
|
—
|
|
Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128
Moderate Response - Week 128 (n=79, 47, 18)
|
30 percentage of participants
|
40 percentage of participants
|
28 percentage of participants
|
—
|
—
|
|
Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128
No Response - Week 128 (n=79, 47, 18)
|
5 percentage of participants
|
19 percentage of participants
|
17 percentage of participants
|
—
|
—
|
|
Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128
Good Response - Week 76 (n=107, 61, 31)
|
64 percentage of participants
|
41 percentage of participants
|
55 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline through Weeks 12 and 24Population: All randomized participants who received study drug in Parts A and B and had DAS28-CRP evaluated at analysis time points.
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.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=49 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=52 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=52 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
n=50 Participants
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=98 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24
Low Disease Activity - Week 24
|
NA percentage of participants
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore percentage was not calculated.
|
31 percentage of participants
|
50 percentage of participants
|
46 percentage of participants
|
NA percentage of participants
Participants were not dosed with placebo after Week 12, therefore percentage was not calculated.
|
|
Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24
Low Disease Activity - Week 12
|
22 percentage of participants
|
23 percentage of participants
|
48 percentage of participants
|
40 percentage of participants
|
19 percentage of participants
|
|
Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24
Remission - Week 12
|
14 percentage of participants
|
15 percentage of participants
|
37 percentage of participants
|
22 percentage of participants
|
4 percentage of participants
|
|
Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24
Remission - Week 24
|
NA percentage of participants
Participants were not dosed with 1 mg LY3009104 after Week 12, therefore percentage was not calculated.
|
15 percentage of participants
|
33 percentage of participants
|
36 percentage of participants
|
NA percentage of participants
Participants were not dosed with placebo after Week 12, therefore percentage was not calculated.
|
SECONDARY outcome
Timeframe: Baseline through Weeks 76 and 128Population: All participants who received study drug in Parts C and D and had DAS28-CRP evaluated at analysis time points.
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.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=108 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=61 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=32 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 76 and 128
Low Disease activity - Week 76 (n=108, 61, 32)
|
58 percentage of participants
|
38 percentage of participants
|
44 percentage of participants
|
—
|
—
|
|
Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 76 and 128
Remission - Week 76 (n=108, 61, 32)
|
52 percentage of participants
|
21 percentage of participants
|
22 percentage of participants
|
—
|
—
|
|
Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 76 and 128
Low Disease activity - Week 128 (n=79, 47, 18)
|
59 percentage of participants
|
36 percentage of participants
|
56 percentage of participants
|
—
|
—
|
|
Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 76 and 128
Remission - Week 128 (n=79, 47, 18)
|
47 percentage of participants
|
26 percentage of participants
|
39 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 4, 8, 12Population: 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.
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.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=48 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=51 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=50 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
n=50 Participants
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=97 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
Mean Change From Baseline Through Week 12 in Duration (Minutes) of Morning Stiffness
Week 4 (n=47, 50, 50, 50, 94)
|
-34.1 minutes
Standard Deviation 70.49
|
-27.0 minutes
Standard Deviation 46.49
|
-57.4 minutes
Standard Deviation 149.00
|
-25.5 minutes
Standard Deviation 126.13
|
-22.5 minutes
Standard Deviation 63.61
|
|
Mean Change From Baseline Through Week 12 in Duration (Minutes) of Morning Stiffness
Week 8 (n=46, 50, 50, 50, 86)
|
-41.2 minutes
Standard Deviation 85.45
|
-31.1 minutes
Standard Deviation 45.80
|
-67.8 minutes
Standard Deviation 138.02
|
-53.8 minutes
Standard Deviation 101.76
|
-25.5 minutes
Standard Deviation 67.39
|
|
Mean Change From Baseline Through Week 12 in Duration (Minutes) of Morning Stiffness
Week 12 (n=48, 51, 50, 50, 97)
|
-49.5 minutes
Standard Deviation 72.80
|
-30.7 minutes
Standard Deviation 47.41
|
-75.0 minutes
Standard Deviation 142.04
|
-62.7 minutes
Standard Deviation 88.27
|
-33.9 minutes
Standard Deviation 91.79
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: 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.
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.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=48 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=51 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=51 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
n=50 Participants
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=97 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
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
PCS
|
6.66 units on a scale
Standard Deviation 8.074
|
4.15 units on a scale
Standard Deviation 7.680
|
7.07 units on a scale
Standard Deviation 7.378
|
7.00 units on a scale
Standard Deviation 9.054
|
3.22 units on a scale
Standard Deviation 6.733
|
|
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
MCS
|
2.54 units on a scale
Standard Deviation 11.983
|
1.89 units on a scale
Standard Deviation 6.869
|
2.39 units on a scale
Standard Deviation 7.898
|
3.03 units on a scale
Standard Deviation 10.675
|
0.88 units on a scale
Standard Deviation 10.437
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: 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.
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.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=48 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=51 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=51 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
n=50 Participants
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=97 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
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
|
-1.35 units on a scale
Standard Deviation 2.547
|
-0.67 units on a scale
Standard Deviation 2.132
|
-1.41 units on a scale
Standard Deviation 1.813
|
-1.54 units on a scale
Standard Deviation 2.131
|
-0.35 units on a scale
Standard Deviation 2.136
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: All randomized participants who received study drug in Part A and had FACIT-F evaluated at Week 12. LOCF was used to impute missing post-baseline values.
The FACIT-F Scale is a brief 13-item, symptom-specific questionnaire that specifically assesses the participant self-reported severity of fatigue and its impact upon daily activities and functioning. The FACIT-F uses a numeric rating scale of 0 ("Not at all") to 4 ("Very much") for each item to assess fatigue and its impact in the past 7 days. Total scores range from 0 to 52, with higher scores indicating less fatigue.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=48 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=51 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=51 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
n=50 Participants
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=97 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
Mean Change From Baseline to Week 12 in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Score
|
4.48 units on a scale
Standard Deviation 10.492
|
3.80 units on a scale
Standard Deviation 9.152
|
4.41 units on a scale
Standard Deviation 8.631
|
4.11 units on a scale
Standard Deviation 9.971
|
2.02 units on a scale
Standard Deviation 8.941
|
SECONDARY outcome
Timeframe: Baseline through 24 weeksPopulation: All randomized participants who received at least 1 dose of LY3009104 with evaluable LY3009104 PK data.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=47 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=91 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=91 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
n=50 Participants
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104
|
36.5 nanomoles/Liter (nmol/L)
Geometric Coefficient of Variation 36.1
|
59.1 nanomoles/Liter (nmol/L)
Geometric Coefficient of Variation 21.3
|
119.0 nanomoles/Liter (nmol/L)
Geometric Coefficient of Variation 20.5
|
241.0 nanomoles/Liter (nmol/L)
Geometric Coefficient of Variation 22.9
|
—
|
SECONDARY outcome
Timeframe: Baseline through 24 weeksPopulation: All randomized participants who received at least 1 dose of LY3009104 with evaluable LY3009104 PK data.
Outcome measures
| Measure |
4 or 8 mg LY3009104
n=47 Participants
4 or 8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
n=91 Participants
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104
n=91 Participants
4 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
8 mg LY3009104
n=50 Participants
8 mg LY3009104 administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|
|
Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of LY3009104
|
333 nanomoles*hour/Liter (nmol*h/L)
Geometric Coefficient of Variation 61.7
|
541 nanomoles*hour/Liter (nmol*h/L)
Geometric Coefficient of Variation 38.0
|
1060 nanomoles*hour/Liter (nmol*h/L)
Geometric Coefficient of Variation 37.0
|
2190 nanomoles*hour/Liter (nmol*h/L)
Geometric Coefficient of Variation 45.6
|
—
|
SECONDARY outcome
Timeframe: Baseline, 12 weeksPopulation: Zero participants were analyzed. Assessment of ENSEMBLE Minimum Data Set 1.0 was not collected at Week 12 and therefore results are not reported for outcome measure.
Outcome measures
Outcome data not reported
Adverse Events
1 mg LY3009104 QD - Part A
Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths
2 mg LY3009104 QD - Part A
Serious events: 3 serious events
Other events: 13 other events
Deaths: 0 deaths
4 mg LY3009104 QD - Part A
Serious events: 2 serious events
Other events: 13 other events
Deaths: 0 deaths
8 mg LY3009104 QD - Part A
Serious events: 1 serious events
Other events: 15 other events
Deaths: 0 deaths
Placebo QD - Part A
Serious events: 3 serious events
Other events: 18 other events
Deaths: 0 deaths
2 mg LY3009104 BID Crossover- Part B
Serious events: 2 serious events
Other events: 15 other events
Deaths: 0 deaths
4 mg LY3009104 QD Crossover- Part B
Serious events: 1 serious events
Other events: 10 other events
Deaths: 0 deaths
2 mg LY3009104 QD - Part B
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
4 mg LY3009104 QD - Part B
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
8 mg LY3009104 QD - Part B
Serious events: 3 serious events
Other events: 18 other events
Deaths: 0 deaths
4 mg LY3009104 QD - Part C
Serious events: 16 serious events
Other events: 35 other events
Deaths: 0 deaths
4 to 8 mg LY3009104 QD Pre-Rescue - Part C
Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths
4 to 8 mg LY3009104 QD Post-Rescue - Part C
Serious events: 6 serious events
Other events: 25 other events
Deaths: 0 deaths
8 mg LY3009104 QD - Part C
Serious events: 6 serious events
Other events: 16 other events
Deaths: 0 deaths
4 mg LY3009104 QD - Part D
Serious events: 5 serious events
Other events: 24 other events
Deaths: 0 deaths
4 mg LY3009104 QD (4 to 8 mg Rescue)- Part D
Serious events: 3 serious events
Other events: 13 other events
Deaths: 0 deaths
8/4 mg LY3009104 QD - Part D
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Follow-Up
Serious events: 2 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
1 mg LY3009104 QD - Part A
n=49 participants at risk
Administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
2 mg LY3009104 QD - Part A
n=52 participants at risk
Administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104 QD - Part A
n=52 participants at risk
Administered orally QD for 12 weeks in Pat A.
MTX was administered orally as background therapy.
|
8 mg LY3009104 QD - Part A
n=50 participants at risk
Administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo QD - Part A
n=98 participants at risk
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
2 mg LY3009104 BID Crossover- Part B
n=63 participants at risk
Participants who received Placebo or 1 mg LY3009104 in Part A were re-randomized at Week 12 to receive 2 mg LY3009104 BID in Part B.
MTX was administered orally as background therapy.
|
4 mg LY3009104 QD Crossover- Part B
n=63 participants at risk
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.
|
2 mg LY3009104 QD - Part B
n=51 participants at risk
Participants who received 2 mg LY3009104 QD in Part A continued to receive 2 mg LY3009104 QD in Part B.
MTX was administered orally as background therapy.
|
4 mg LY3009104 QD - Part B
n=50 participants at risk
Participants who received 4 mg LY3009104 QD in Part A continued to receive 4 mg LY3009104 QD in Part B.
MTX was administered orally as background therapy.
|
8 mg LY3009104 QD - Part B
n=49 participants at risk
Participants who received 8 mg LY3009104 QD in Part A continued to receive 8 mg LY3009104 QD in Part B.
MTX was administered orally as background therapy.
|
4 mg LY3009104 QD - Part C
n=108 participants at risk
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.
MTX was administered orally as background therapy.
|
4 to 8 mg LY3009104 QD Pre-Rescue - Part C
n=61 participants at risk
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.
During Part C, at Weeks 28 and 32, participants who met dose escalation criteria received 8 mg LY3009104 QD (rescue treatment) for the rest of the Part C.
MTX was administered orally as background therapy.
Adverse events were collected from Week 24 until predose of 8 mg LY3009104 QD.
|
4 to 8 mg LY3009104 QD Post-Rescue - Part C
n=61 participants at risk
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.
During Part C, at Weeks 28 and 32, participants who met dose escalation criteria received 8 mg LY3009104 QD (rescue treatment) for the rest of the Part C.
MTX was administered orally as background therapy.
Adverse events were collected from predose of 8 mg LY3009104 QD until Week 76.
|
8 mg LY3009104 QD - Part C
n=32 participants at risk
Participants who received 8 mg LY3009104 QD in Part B remained on 8 mg LY3009104 QD in Part C.
MTX was administered orally as background therapy.
|
4 mg LY3009104 QD - Part D
n=79 participants at risk
Participants who received 4 mg LY3009104 QD in Part C continued to receive 4 mg LY3009104 QD in Part D.
MTX was administered orally as background therapy.
|
4 mg LY3009104 QD (4 to 8 mg Rescue)- Part D
n=47 participants at risk
Participants who received 8 mg LY3009104 QD rescue treatment in Part C received 4 mg LY3009104 QD in Part D.
MTX was administered orally as background therapy.
|
8/4 mg LY3009104 QD - Part D
n=18 participants at risk
Participants who received 8 mg LY3009104 QD in Part C received 4 mg LY3009104 QD in Part D.
MTX was administered orally as background therapy.
|
Follow-Up
n=159 participants at risk
Up to 28 days post the last dose of study drug.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.93%
1/108 • Number of events 1
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Blood and lymphatic system disorders
Microcytic anaemia
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
1.0%
1/98 • Number of events 1
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Blood and lymphatic system disorders
Normochromic normocytic anaemia
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
1.6%
1/61 • Number of events 1
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
2.0%
1/50 • Number of events 1
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
3.1%
1/32 • Number of events 1
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Eye disorders
Cataract
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.93%
1/108 • Number of events 1
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Eye disorders
Ulcerative keratitis
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
3.1%
1/32 • Number of events 1
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Gastrointestinal disorders
Coeliac disease
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
1.0%
1/98 • Number of events 1
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
1.6%
1/61 • Number of events 1
|
3.1%
1/32 • Number of events 1
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
1.6%
1/61 • Number of events 1
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Gastrointestinal disorders
Large intestinal obstruction
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
1.3%
1/79 • Number of events 1
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Gastrointestinal disorders
Large intestinal stenosis
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
1.3%
1/79 • Number of events 1
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
1.3%
1/79 • Number of events 1
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
General disorders
Pyrexia
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
1.6%
1/63 • Number of events 1
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
1.6%
1/63 • Number of events 1
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
1.3%
1/79 • Number of events 1
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Infections and infestations
Acute hepatitis b
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
3.1%
1/32 • Number of events 1
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Infections and infestations
Bronchitis
|
0.00%
0/49
|
1.9%
1/52 • Number of events 1
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.93%
1/108 • Number of events 1
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
2.1%
1/47 • Number of events 1
|
0.00%
0/18
|
0.00%
0/159
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
1.6%
1/61 • Number of events 1
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Infections and infestations
Helicobacter gastritis
|
0.00%
0/49
|
0.00%
0/52
|
1.9%
1/52 • Number of events 1
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
2.0%
1/49 • Number of events 1
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Infections and infestations
Herpes simplex
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
1.6%
1/61 • Number of events 2
|
0.00%
0/32
|
1.3%
1/79 • Number of events 1
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
3.7%
4/108 • Number of events 4
|
0.00%
0/61
|
0.00%
0/61
|
3.1%
1/32 • Number of events 1
|
1.3%
1/79 • Number of events 1
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Infections and infestations
Pneumonia
|
0.00%
0/49
|
1.9%
1/52 • Number of events 1
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
4.3%
2/47 • Number of events 2
|
0.00%
0/18
|
0.00%
0/159
|
|
Infections and infestations
Pneumonia bacterial
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
2.0%
1/49 • Number of events 1
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
1.6%
1/61 • Number of events 1
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Injury, poisoning and procedural complications
Head injury
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.93%
1/108 • Number of events 1
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Injury, poisoning and procedural complications
Jaw fracture
|
0.00%
0/49
|
1.9%
1/52 • Number of events 1
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
1.6%
1/61 • Number of events 1
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.93%
1/108 • Number of events 1
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Injury, poisoning and procedural complications
Scar
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.93%
1/108 • Number of events 1
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
1.9%
2/108 • Number of events 2
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.93%
1/108 • Number of events 1
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.93%
1/108 • Number of events 1
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Investigations
Glomerular filtration rate decreased
|
0.00%
0/49
|
0.00%
0/52
|
1.9%
1/52 • Number of events 1
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.63%
1/159 • Number of events 1
|
|
Investigations
Transaminases increased
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.93%
1/108 • Number of events 1
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.93%
1/108 • Number of events 1
|
0.00%
0/61
|
0.00%
0/61
|
3.1%
1/32 • Number of events 1
|
0.00%
0/79
|
2.1%
1/47 • Number of events 1
|
0.00%
0/18
|
0.00%
0/159
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
1.0%
1/98 • Number of events 1
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.93%
1/108 • Number of events 1
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Musculoskeletal and connective tissue disorders
Diastasis recti abdominis
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
1.3%
1/79 • Number of events 1
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
1.6%
1/61 • Number of events 1
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.93%
1/108 • Number of events 1
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
1.3%
1/79 • Number of events 1
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
1.6%
1/63 • Number of events 1
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Nervous system disorders
Carotid artery stenosis
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.93%
1/108 • Number of events 1
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Nervous system disorders
Presyncope
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
3.1%
1/32 • Number of events 1
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Nervous system disorders
Syncope
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
2.1%
1/47 • Number of events 1
|
0.00%
0/18
|
0.00%
0/159
|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
0.00%
0/42
|
0.00%
0/44
|
0.00%
0/37
|
0.00%
0/41
|
0.00%
0/85
|
0.00%
0/56
|
0.00%
0/54
|
0.00%
0/43
|
0.00%
0/35
|
0.00%
0/40
|
0.00%
0/87
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/28
|
0.00%
0/62
|
0.00%
0/40
|
0.00%
0/17
|
0.77%
1/130 • Number of events 1
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
0.00%
0/42
|
0.00%
0/44
|
0.00%
0/37
|
0.00%
0/41
|
0.00%
0/85
|
0.00%
0/56
|
0.00%
0/54
|
0.00%
0/43
|
0.00%
0/35
|
0.00%
0/40
|
0.00%
0/87
|
0.00%
0/52
|
1.9%
1/52 • Number of events 1
|
0.00%
0/28
|
0.00%
0/62
|
0.00%
0/40
|
0.00%
0/17
|
0.00%
0/130
|
|
Psychiatric disorders
Major depression
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
2.1%
1/47 • Number of events 1
|
0.00%
0/18
|
0.00%
0/159
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
1.0%
1/98 • Number of events 1
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
2.0%
1/49 • Number of events 1
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/49
|
1.9%
1/52 • Number of events 1
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
1.6%
1/61 • Number of events 1
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.93%
1/108 • Number of events 1
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
Other adverse events
| Measure |
1 mg LY3009104 QD - Part A
n=49 participants at risk
Administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
2 mg LY3009104 QD - Part A
n=52 participants at risk
Administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
4 mg LY3009104 QD - Part A
n=52 participants at risk
Administered orally QD for 12 weeks in Pat A.
MTX was administered orally as background therapy.
|
8 mg LY3009104 QD - Part A
n=50 participants at risk
Administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
Placebo QD - Part A
n=98 participants at risk
Placebo administered orally QD for 12 weeks in Part A.
MTX was administered orally as background therapy.
|
2 mg LY3009104 BID Crossover- Part B
n=63 participants at risk
Participants who received Placebo or 1 mg LY3009104 in Part A were re-randomized at Week 12 to receive 2 mg LY3009104 BID in Part B.
MTX was administered orally as background therapy.
|
4 mg LY3009104 QD Crossover- Part B
n=63 participants at risk
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.
|
2 mg LY3009104 QD - Part B
n=51 participants at risk
Participants who received 2 mg LY3009104 QD in Part A continued to receive 2 mg LY3009104 QD in Part B.
MTX was administered orally as background therapy.
|
4 mg LY3009104 QD - Part B
n=50 participants at risk
Participants who received 4 mg LY3009104 QD in Part A continued to receive 4 mg LY3009104 QD in Part B.
MTX was administered orally as background therapy.
|
8 mg LY3009104 QD - Part B
n=49 participants at risk
Participants who received 8 mg LY3009104 QD in Part A continued to receive 8 mg LY3009104 QD in Part B.
MTX was administered orally as background therapy.
|
4 mg LY3009104 QD - Part C
n=108 participants at risk
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.
MTX was administered orally as background therapy.
|
4 to 8 mg LY3009104 QD Pre-Rescue - Part C
n=61 participants at risk
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.
During Part C, at Weeks 28 and 32, participants who met dose escalation criteria received 8 mg LY3009104 QD (rescue treatment) for the rest of the Part C.
MTX was administered orally as background therapy.
Adverse events were collected from Week 24 until predose of 8 mg LY3009104 QD.
|
4 to 8 mg LY3009104 QD Post-Rescue - Part C
n=61 participants at risk
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.
During Part C, at Weeks 28 and 32, participants who met dose escalation criteria received 8 mg LY3009104 QD (rescue treatment) for the rest of the Part C.
MTX was administered orally as background therapy.
Adverse events were collected from predose of 8 mg LY3009104 QD until Week 76.
|
8 mg LY3009104 QD - Part C
n=32 participants at risk
Participants who received 8 mg LY3009104 QD in Part B remained on 8 mg LY3009104 QD in Part C.
MTX was administered orally as background therapy.
|
4 mg LY3009104 QD - Part D
n=79 participants at risk
Participants who received 4 mg LY3009104 QD in Part C continued to receive 4 mg LY3009104 QD in Part D.
MTX was administered orally as background therapy.
|
4 mg LY3009104 QD (4 to 8 mg Rescue)- Part D
n=47 participants at risk
Participants who received 8 mg LY3009104 QD rescue treatment in Part C received 4 mg LY3009104 QD in Part D.
MTX was administered orally as background therapy.
|
8/4 mg LY3009104 QD - Part D
n=18 participants at risk
Participants who received 8 mg LY3009104 QD in Part C received 4 mg LY3009104 QD in Part D.
MTX was administered orally as background therapy.
|
Follow-Up
n=159 participants at risk
Up to 28 days post the last dose of study drug.
MTX was administered orally as background therapy.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/49
|
0.00%
0/52
|
3.8%
2/52 • Number of events 2
|
0.00%
0/50
|
0.00%
0/98
|
1.6%
1/63 • Number of events 1
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
2.0%
1/49 • Number of events 1
|
0.00%
0/108
|
1.6%
1/61 • Number of events 1
|
0.00%
0/61
|
6.2%
2/32 • Number of events 2
|
1.3%
1/79 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
0.00%
0/18
|
0.00%
0/159
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
4.0%
2/50 • Number of events 2
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
2.0%
1/49 • Number of events 1
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
5.6%
1/18 • Number of events 2
|
0.00%
0/159
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
1.6%
1/63 • Number of events 1
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
2.0%
1/49 • Number of events 1
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
3.1%
1/32 • Number of events 1
|
1.3%
1/79 • Number of events 1
|
0.00%
0/47
|
5.6%
1/18 • Number of events 1
|
0.00%
0/159
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/49
|
1.9%
1/52 • Number of events 1
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
5.6%
1/18 • Number of events 1
|
0.00%
0/159
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/49
|
1.9%
1/52 • Number of events 1
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
2.0%
1/51 • Number of events 1
|
0.00%
0/50
|
2.0%
1/49 • Number of events 1
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
3.1%
1/32 • Number of events 1
|
0.00%
0/79
|
2.1%
1/47 • Number of events 1
|
5.6%
1/18 • Number of events 1
|
0.00%
0/159
|
|
Gastrointestinal disorders
Acquired oesophageal web
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
5.6%
1/18 • Number of events 1
|
0.00%
0/159
|
|
Gastrointestinal disorders
Dyspepsia
|
4.1%
2/49 • Number of events 2
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
1.6%
1/63 • Number of events 2
|
0.00%
0/51
|
0.00%
0/50
|
2.0%
1/49 • Number of events 1
|
0.00%
0/108
|
0.00%
0/61
|
1.6%
1/61 • Number of events 1
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
1.0%
1/98 • Number of events 1
|
0.00%
0/63
|
0.00%
0/63
|
2.0%
1/51 • Number of events 1
|
2.0%
1/50 • Number of events 1
|
0.00%
0/49
|
0.93%
1/108 • Number of events 1
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
5.6%
1/18 • Number of events 1
|
0.00%
0/159
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
2.1%
1/47 • Number of events 1
|
5.6%
1/18 • Number of events 1
|
0.00%
0/159
|
|
Gastrointestinal disorders
Irritable bowel syndrome
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
6.2%
2/32 • Number of events 2
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Gastrointestinal disorders
Oesophagitis
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
5.6%
1/18 • Number of events 1
|
0.00%
0/159
|
|
General disorders
Oedema peripheral
|
4.1%
2/49 • Number of events 2
|
1.9%
1/52 • Number of events 1
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
1.6%
1/63 • Number of events 1
|
0.00%
0/63
|
0.00%
0/51
|
2.0%
1/50 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
0.00%
0/108
|
0.00%
0/61
|
1.6%
1/61 • Number of events 2
|
3.1%
1/32 • Number of events 1
|
0.00%
0/79
|
2.1%
1/47 • Number of events 1
|
0.00%
0/18
|
0.63%
1/159 • Number of events 1
|
|
General disorders
Pyrexia
|
2.0%
1/49 • Number of events 1
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
4.1%
2/49 • Number of events 2
|
0.00%
0/108
|
0.00%
0/61
|
1.6%
1/61 • Number of events 1
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Infections and infestations
Bronchitis
|
2.0%
1/49 • Number of events 1
|
1.9%
1/52 • Number of events 1
|
3.8%
2/52 • Number of events 2
|
2.0%
1/50 • Number of events 1
|
3.1%
3/98 • Number of events 3
|
1.6%
1/63 • Number of events 1
|
3.2%
2/63 • Number of events 2
|
3.9%
2/51 • Number of events 2
|
0.00%
0/50
|
0.00%
0/49
|
8.3%
9/108 • Number of events 9
|
0.00%
0/61
|
4.9%
3/61 • Number of events 3
|
15.6%
5/32 • Number of events 5
|
3.8%
3/79 • Number of events 3
|
4.3%
2/47 • Number of events 2
|
5.6%
1/18 • Number of events 1
|
0.63%
1/159 • Number of events 1
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/49
|
0.00%
0/52
|
3.8%
2/52 • Number of events 2
|
2.0%
1/50 • Number of events 1
|
2.0%
2/98 • Number of events 3
|
1.6%
1/63 • Number of events 1
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
4.1%
2/49 • Number of events 2
|
1.9%
2/108 • Number of events 2
|
0.00%
0/61
|
6.6%
4/61 • Number of events 4
|
3.1%
1/32 • Number of events 1
|
8.9%
7/79 • Number of events 9
|
4.3%
2/47 • Number of events 2
|
11.1%
2/18 • Number of events 3
|
0.00%
0/159
|
|
Infections and infestations
Pharyngitis
|
2.0%
1/49 • Number of events 1
|
1.9%
1/52 • Number of events 1
|
5.8%
3/52 • Number of events 3
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
3.9%
2/51 • Number of events 2
|
0.00%
0/50
|
0.00%
0/49
|
0.93%
1/108 • Number of events 1
|
1.6%
1/61 • Number of events 1
|
1.6%
1/61 • Number of events 1
|
6.2%
2/32 • Number of events 3
|
2.5%
2/79 • Number of events 2
|
2.1%
1/47 • Number of events 1
|
0.00%
0/18
|
0.00%
0/159
|
|
Infections and infestations
Tooth abscess
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
1.6%
1/61 • Number of events 1
|
0.00%
0/32
|
0.00%
0/79
|
2.1%
1/47 • Number of events 1
|
5.6%
1/18 • Number of events 1
|
0.00%
0/159
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/49
|
1.9%
1/52 • Number of events 1
|
1.9%
1/52 • Number of events 1
|
2.0%
1/50 • Number of events 1
|
2.0%
2/98 • Number of events 2
|
3.2%
2/63 • Number of events 2
|
6.3%
4/63 • Number of events 4
|
3.9%
2/51 • Number of events 2
|
2.0%
1/50 • Number of events 1
|
4.1%
2/49 • Number of events 2
|
8.3%
9/108 • Number of events 10
|
1.6%
1/61 • Number of events 1
|
9.8%
6/61 • Number of events 8
|
3.1%
1/32 • Number of events 1
|
3.8%
3/79 • Number of events 5
|
4.3%
2/47 • Number of events 3
|
5.6%
1/18 • Number of events 1
|
0.00%
0/159
|
|
Infections and infestations
Urinary tract infection
|
4.1%
2/49 • Number of events 2
|
3.8%
2/52 • Number of events 2
|
3.8%
2/52 • Number of events 2
|
4.0%
2/50 • Number of events 2
|
4.1%
4/98 • Number of events 4
|
1.6%
1/63 • Number of events 1
|
1.6%
1/63 • Number of events 1
|
3.9%
2/51 • Number of events 2
|
2.0%
1/50 • Number of events 1
|
4.1%
2/49 • Number of events 2
|
11.1%
12/108 • Number of events 15
|
1.6%
1/61 • Number of events 1
|
8.2%
5/61 • Number of events 6
|
9.4%
3/32 • Number of events 3
|
3.8%
3/79 • Number of events 4
|
2.1%
1/47 • Number of events 1
|
0.00%
0/18
|
1.3%
2/159 • Number of events 2
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/49
|
1.9%
1/52 • Number of events 1
|
0.00%
0/52
|
2.0%
1/50 • Number of events 3
|
3.1%
3/98 • Number of events 3
|
0.00%
0/63
|
0.00%
0/63
|
2.0%
1/51 • Number of events 1
|
2.0%
1/50 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
0.93%
1/108 • Number of events 1
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
1.3%
1/79 • Number of events 1
|
6.4%
3/47 • Number of events 4
|
0.00%
0/18
|
0.00%
0/159
|
|
Investigations
Blood cholesterol increased
|
4.1%
2/49 • Number of events 2
|
1.9%
1/52 • Number of events 1
|
3.8%
2/52 • Number of events 2
|
4.0%
2/50 • Number of events 2
|
2.0%
2/98 • Number of events 2
|
4.8%
3/63 • Number of events 3
|
1.6%
1/63 • Number of events 1
|
0.00%
0/51
|
2.0%
1/50 • Number of events 1
|
6.1%
3/49 • Number of events 4
|
2.8%
3/108 • Number of events 4
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
5.1%
4/79 • Number of events 4
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Investigations
Blood creatine phosphokinase increased
|
4.1%
2/49 • Number of events 2
|
0.00%
0/52
|
3.8%
2/52 • Number of events 2
|
2.0%
1/50 • Number of events 1
|
1.0%
1/98 • Number of events 1
|
1.6%
1/63 • Number of events 1
|
0.00%
0/63
|
3.9%
2/51 • Number of events 2
|
2.0%
1/50 • Number of events 1
|
4.1%
2/49 • Number of events 2
|
0.93%
1/108 • Number of events 1
|
1.6%
1/61 • Number of events 1
|
3.3%
2/61 • Number of events 2
|
0.00%
0/32
|
1.3%
1/79 • Number of events 1
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Investigations
Low density lipoprotein increased
|
0.00%
0/49
|
0.00%
0/52
|
1.9%
1/52 • Number of events 1
|
2.0%
1/50 • Number of events 1
|
2.0%
2/98 • Number of events 2
|
6.3%
4/63 • Number of events 4
|
1.6%
1/63 • Number of events 1
|
2.0%
1/51 • Number of events 1
|
2.0%
1/50 • Number of events 1
|
6.1%
3/49 • Number of events 3
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
3.8%
3/79 • Number of events 3
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Investigations
Weight increased
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
4.9%
3/61 • Number of events 3
|
0.00%
0/32
|
1.3%
1/79 • Number of events 1
|
2.1%
1/47 • Number of events 1
|
0.00%
0/18
|
0.00%
0/159
|
|
Metabolism and nutrition disorders
Dyslipidaemia
|
0.00%
0/49
|
1.9%
1/52 • Number of events 1
|
0.00%
0/52
|
2.0%
1/50 • Number of events 1
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
3.3%
2/61 • Number of events 2
|
6.2%
2/32 • Number of events 2
|
5.1%
4/79 • Number of events 4
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
4.1%
2/49 • Number of events 2
|
3.8%
2/52 • Number of events 2
|
0.00%
0/52
|
4.0%
2/50 • Number of events 2
|
2.0%
2/98 • Number of events 2
|
1.6%
1/63 • Number of events 1
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
8.2%
4/49 • Number of events 4
|
0.93%
1/108 • Number of events 1
|
1.6%
1/61 • Number of events 1
|
1.6%
1/61 • Number of events 1
|
0.00%
0/32
|
1.3%
1/79 • Number of events 1
|
0.00%
0/47
|
5.6%
1/18 • Number of events 1
|
0.00%
0/159
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
1.6%
1/63 • Number of events 1
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.93%
1/108 • Number of events 1
|
0.00%
0/61
|
0.00%
0/61
|
6.2%
2/32 • Number of events 2
|
1.3%
1/79 • Number of events 1
|
0.00%
0/47
|
5.6%
1/18 • Number of events 1
|
0.00%
0/159
|
|
Nervous system disorders
Dizziness
|
0.00%
0/49
|
1.9%
1/52 • Number of events 1
|
0.00%
0/52
|
2.0%
1/50 • Number of events 1
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.93%
1/108 • Number of events 1
|
0.00%
0/61
|
0.00%
0/61
|
6.2%
2/32 • Number of events 2
|
0.00%
0/79
|
2.1%
1/47 • Number of events 1
|
5.6%
1/18 • Number of events 1
|
0.00%
0/159
|
|
Nervous system disorders
Headache
|
4.1%
2/49 • Number of events 2
|
1.9%
1/52 • Number of events 1
|
1.9%
1/52 • Number of events 1
|
4.0%
2/50 • Number of events 3
|
2.0%
2/98 • Number of events 2
|
3.2%
2/63 • Number of events 2
|
1.6%
1/63 • Number of events 1
|
2.0%
1/51 • Number of events 1
|
0.00%
0/50
|
0.00%
0/49
|
0.93%
1/108 • Number of events 1
|
1.6%
1/61 • Number of events 1
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Nervous system disorders
Syncope
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
1.0%
1/98 • Number of events 1
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
5.6%
1/18 • Number of events 1
|
0.00%
0/159
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/49
|
1.9%
1/52 • Number of events 1
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
4.1%
2/49 • Number of events 2
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
3.1%
1/32 • Number of events 1
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
1.6%
1/63 • Number of events 1
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
1.6%
1/61 • Number of events 1
|
0.00%
0/32
|
1.3%
1/79 • Number of events 1
|
0.00%
0/47
|
5.6%
1/18 • Number of events 1
|
0.00%
0/159
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.0%
1/49 • Number of events 1
|
1.9%
1/52 • Number of events 1
|
0.00%
0/52
|
0.00%
0/50
|
1.0%
1/98 • Number of events 1
|
0.00%
0/63
|
1.6%
1/63 • Number of events 1
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
1.6%
1/61 • Number of events 1
|
0.00%
0/61
|
0.00%
0/32
|
1.3%
1/79 • Number of events 1
|
0.00%
0/47
|
5.6%
1/18 • Number of events 1
|
0.63%
1/159 • Number of events 1
|
|
Surgical and medical procedures
Spinal laminectomy
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/63
|
0.00%
0/63
|
0.00%
0/51
|
0.00%
0/50
|
0.00%
0/49
|
0.00%
0/108
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
5.6%
1/18 • Number of events 1
|
0.00%
0/159
|
|
Vascular disorders
Hypertension
|
0.00%
0/49
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/50
|
1.0%
1/98 • Number of events 1
|
0.00%
0/63
|
0.00%
0/63
|
2.0%
1/51 • Number of events 1
|
8.0%
4/50 • Number of events 5
|
2.0%
1/49 • Number of events 1
|
0.93%
1/108 • Number of events 1
|
0.00%
0/61
|
0.00%
0/61
|
0.00%
0/32
|
0.00%
0/79
|
0.00%
0/47
|
0.00%
0/18
|
0.00%
0/159
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60