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Trial record 53 of 62 for:    Baricitinib

Oral Baricitinib (LY3009104)Treatment in Japanese Participants With Active Rheumatoid Arthritis on Background Methotrexate Therapy

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ClinicalTrials.gov Identifier: NCT01469013
Recruitment Status : Completed
First Posted : November 10, 2011
Results First Posted : November 1, 2018
Last Update Posted : September 20, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Arthritis, Rheumatoid
Interventions Drug: Placebo
Drug: Baricitinib
Drug: Methotrexate
Enrollment 145
Recruitment Details  
Pre-assignment Details Participants on background methotrexate therapy were assigned to a dose of 1, 2, 4, 8 mg baricitinib (LY3009104) or placebo capsule once daily in a double blind manner for 12 weeks followed by single blind treatment of 4 mg or 8 mg baricitinib (LY3009104) tablet once daily for 52 weeks extension period.
Arm/Group Title Part A: 1 mg Baricitinib (LY3009104) Part A: 2 mg Baricitinib (LY3009104) Part A: 4 mg Baricitinib (LY3009104) Part A: 8 mg Baricitinib (LY3009104) Part A: Placebo Part:1 mg Baricitinib(LY3009104) / 4 mg Baricitinib(LY3009104) Part B: 2 mg Baricitinib (LY3009104) / 4 mg Baricitinib (LY30 Part B: 4 mg Baricitinib (LY3009104) / 4 mg Baricitinib (LY30 Part B: Placebo /4 mg Baricitinib (LY3009104) Part B: 1 mg Baricitinib (LY3009104) / 8 mg Baricitinib (LY30 Part B: 2 mg Baricitinib (LY3009104) / 8 mg Baricitinib (LY300 Part B: 8 mg Baricitinib (LY3009104) / 8 mg Baricitinib (LY30 Part B: Placebo / 8 mg Baricitinib (LY3009104)
Hide Arm/Group Description Participants on background methotrexate therapy administered 1 x 1-mg baricitinib (LY3009104) capsule + 1 identical placebo capsule, orally once daily for 12 weeks. Participants on background methotrexate therapy administered 2 x 1-mg baricitinib (LY3009104) capsules orally once daily for 12 weeks. Participants on background methotrexate therapy administered 1 x 4-mg baricitinib (LY3009104) capsule +1 identical placebo capsule, orally once daily for 12 weeks. Participants on background methotrexate therapy administered 2 x 4-mg baricitinib (LY3009104) capsules orally once daily for 12 weeks. Participants on background methotrexate therapy administered 2 placebo capsules, orally once daily for 12 weeks. Participants on background methotrexate therapy who were administered 1 x 1-mg LY3009104 capsule +1 identical placebo capsule, orally once daily for 12 weeks in Part A received 4 mg LY3009104 and 1 placebo tablet orally once daily for 52 weeks in Part B. Participants on background methotrexate therapy who were administered 2 x 1-mg baricitinib (LY3009104) capsules orally once daily for 12 weeks in Part A received 4 mg baricitinib (LY3009104) and 1 placebo tablet orally once daily for 52 weeks in Part B. Participants on background methotrexate therapy who were administered 1 x 4-mg baricitinib (LY3009104) capsule + 1 identical placebo capsule, orally once daily for 12 weeks in Part A received 4 mg baricitinib (LY3009104) and 1 placebo tablet orally once daily for 52 weeks in Part B. Participants on background methotrexate therapy who were administered 2 placebo capsules orally once daily for 12 weeks in Part A received 4 mg baricitinib (LY3009104) and 1 placebo tablet orally once daily for 52 weeks in Part B. Participants on background methotrexate therapy who were administered 1 x 1-mg baricitinib (LY3009104) capsule + 1 identical placebo capsule orally once daily for 12 weeks in Part A received 2 x 4 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B. Participants on background methotrexate therapy who were administered 2 x 1-mg baricitinib (LY3009104) capsules orally once daily for 12 weeks in Part A received 2 x 4 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B. Participants on background methotrexate therapy who were administered 2 x 4-mg baricitinib (LY3009104) capsules orally once daily for 12 weeks in Part A received 2 x 4 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B. Participants on background methotrexate therapy who were administered 2 placebo capsules orally once daily for 12 weeks in Part A received 2 x 4 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B.
Period Title: Part A (Treatment Period)
Started 24 24 24 24 49 0 0 0 0 0 0 0 0
Received at Least 1 Dose of Study Drug 24 24 24 24 49 0 0 0 0 0 0 0 0
Completed 23 24 23 24 48 0 0 0 0 0 0 0 0
Not Completed 1 0 1 0 1 0 0 0 0 0 0 0 0
Reason Not Completed
Adverse Event             1             0             0             0             1             0             0             0             0             0             0             0             0
Withdrawal by Subject             0             0             1             0             0             0             0             0             0             0             0             0             0
Period Title: Part B (Extension Period)
Started 0 0 0 0 0 12 12 23 24 11 12 24 24
Received at Least 1 Dose of Study Drug 0 0 0 0 0 12 12 23 24 11 12 24 23 [1]
Completed 0 0 0 0 0 10 7 18 20 8 10 18 18
Not Completed 0 0 0 0 0 2 5 5 4 3 2 6 6
Reason Not Completed
Adverse Event             0             0             0             0             0             2             5             5             3             3             1             6             3
Withdrawal by Subject             0             0             0             0             0             0             0             0             1             0             1             0             3
[1]
1 participant discontinued prior to receiving study drug
Arm/Group Title Part A: 1 mg Baricitinib (LY3009104) Part A: 2 mg Baricitinib (LY3009104) Part A: 4 mg Baricitinib (LY3009104) Part A: 8 mg Baricitinib (LY3009104) Part A: Placebo Total
Hide Arm/Group Description Participants on background methotrexate therapy were administered 1 mg baricitinib (LY3009104) orally once daily for 12 weeks in Part A and received 4 mg or 8 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B. Participants on background methotrexate therapy were administered 2 mg baricitinib (LY3009104) orally once daily for 12 weeks in Part A and received 4 mg or 8 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B. Participants on background methotrexate therapy were administered 4 mg baricitinib (LY3009104) orally once daily for 12 weeks in Part A and received 4 mg or 8 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B. Participants on background methotrexate therapy were administered 8 mg baricitinib (LY3009104) orally once daily for 12 weeks in Part A and received 4 mg or 8 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B. Participants on background methotrexate therapy were administered placebo orally once daily for 12 weeks in Part A and received 4 mg or 8 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B. Total of all reporting groups
Overall Number of Baseline Participants 24 24 24 24 49 145
Hide Baseline Analysis Population Description
All randomized participants who received any amount of study treatment. All participants who completed Part A were re-randomized to 4 mg or 8 mg in Part B.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants 24 participants 24 participants 24 participants 49 participants 145 participants
52.7  (12.8) 56.1  (11.5) 57.5  (10.4) 53.6  (11.3) 51.1  (12.0) 53.6  (11.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 24 participants 24 participants 24 participants 49 participants 145 participants
Female 22 21 19 17 39 118
Male 2 3 5 7 10 27
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 24 participants 24 participants 24 participants 49 participants 145 participants
Hispanic or Latino 0 0 0 0 0 0
Not Hispanic or Latino 24 24 24 24 49 145
Unknown or Not Reported 0 0 0 0 0 0
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 24 participants 24 participants 24 participants 49 participants 145 participants
American Indian or Alaska Native 0 0 0 0 0 0
Asian 24 24 24 24 49 145
Native Hawaiian or Other Pacific Islander 0 0 0 0 0 0
Black or African American 0 0 0 0 0 0
White 0 0 0 0 0 0
More than one race 0 0 0 0 0 0
Unknown or Not Reported 0 0 0 0 0 0
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Japan Number Analyzed 24 participants 24 participants 24 participants 24 participants 49 participants 145 participants
24 24 24 24 49 145
1.Primary Outcome
Title Percentage of Participants in the 4 mg and 8 mg Dose Groups Who Achieved an American College of Rheumatology 20 (ACR20) Responder Index Response Baseline Through Week 12 .
Hide Description ACR20 responders are participants with at least 20% improvement from baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: Health Assessment Questionnaire-Disability Index (HAQ-DI) which measured participants perceived degree of difficulty performing daily activities, C-reactive Protein (CRP) and erythrocyte sedimentation rate (ESR), Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS) , Patient's Global Assessment of Disease Activity-VAS (PtGADA-VAS), and Physician's Global Assessment of Disease Activity-VAS (PhGA-VAS). Missing values were imputed using Non-Responder Imputation (NRI), where non-responders were participants who discontinued the study prior to the completion of Part A. Percentage of participants achieving ACR20 response = (number of ACR20 responders) /(number of participants treated) * 100.
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of 4 mg, 8 mg baricitinib (LY3009104) or placebo in Part A as per protocol for combined analysis .
Arm/Group Title Part A: Combined 4 mg and 8 mg Baricitinib (LY3009104) Part A: Placebo
Hide Arm/Group Description:
Participants on background methotrexate therapy administered 1- 4 mg baricitinib (LY3009104) capsule +1 identical placebo capsule or 2 x 4-mg baricitinib (LY3009104) capsules, orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 placebo capsules, orally once daily for 12 weeks.
Overall Number of Participants Analyzed 48 49
Measure Type: Number
Unit of Measure: percentage of participants
77 31
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part A: Combined 4 mg and 8 mg Baricitinib (LY3009104), Part A: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants Who Achieved an ACR20 Response at 64 Weeks
Hide Description ACR20 responders are participants with at least 20% improvement from baseline for TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI which measured participants perceived degree of difficulty performing daily activities, CRP and ESR, PAAP-VAS, PtGADA-VAS, or PhGA-VAS. Missing values were imputed using NRI, where non-responders were participants who discontinued the study prior to the completion of Part B. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants treated) * 100.
Time Frame Baseline up to 64 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any amount of study drug in Part B.
Arm/Group Title Combined 4 mg Baricitinib (LY3009104) (Part B) Combined 8 mg Baricitinib (LY3009104) (Part B)
Hide Arm/Group Description:
Participants on background methotrexate therapy who were administered 1 mg, 2 mg, 4 mg baricitinib (LY3009104) capsule or placebo capsule, orally once daily for 12 weeks in Part A received 4 mg baricitinib (LY3009104) and 1 placebo tablet orally once daily for 52 weeks in Part B.
Participants on background methotrexate therapy who were administered 1 mg, 2 mg, 8 mg baricitinib (LY3009104) capsule or placebo capsule, orally once daily for 12 weeks in Part A received 2 x 4 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B.
Overall Number of Participants Analyzed 71 70
Measure Type: Number
Unit of Measure: percentage of participants
66 73
3.Secondary Outcome
Title Percentage of Participants Who Achieved an ACR70 Response at 12 Weeks (Part A)
Hide Description ACR70 responders were participants with at least 70% improvement from baseline for TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, or PhGA-VAS. Missing values were imputed using NRI, where non-responders were participants who discontinued the study prior to the completion of Part A. Percentage of participants achieving ACR70 response=(number of ACR70 responders / number of participants treated) * 100.
Time Frame Baseline up to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any study drug in Part A.
Arm/Group Title 1 mg Baricitinib (LY3009104) 2 mg Baricitinib (LY3009104) 4 mg Baricitinib (LY3009104) 8 mg Baricitinib (LY3009104) Placebo
Hide Arm/Group Description:
Participants on background methotrexate therapy administered 1 x 1-mg baricitinib (LY3009104) capsule + 1 identical placebo capsule, orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 x 1-mg baricitinib (LY3009104) capsules orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 1 x 4-mg baricitinib (LY3009104) capsule +1 identical placebo capsule, orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 x 4-mg baricitinib (LY3009104) capsules orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 placebo capsules, orally once daily for 12 weeks.
Overall Number of Participants Analyzed 24 24 24 24 49
Measure Type: Number
Unit of Measure: percentage of participants
13 29 29 21 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1 mg Baricitinib (LY3009104), 2 mg Baricitinib (LY3009104), 4 mg Baricitinib (LY3009104), 8 mg Baricitinib (LY3009104), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments [Not Specified]
Method Cochran-Armitage trend test
Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants Who Achieved an ACR70 Response at 64 Weeks (Part B)
Hide Description ACR70 responders were participants with at least 70% improvement from baseline for TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, or PhGA-VAS. Missing values were imputed using NRI, where non-responders were participants who discontinued the study prior to the completion of Part B. Percentage of participants achieving ACR70 response=(number of ACR70 responders) / (number of participants treated) * 100.
Time Frame Baseline up to 64 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any study drug in Part B.
Arm/Group Title Combined 4 mg Baricitinib (LY3009104) Combined 8 mg Baricitinib (LY3009104)
Hide Arm/Group Description:
Participants on background methotrexate therapy who were administered 1 mg, 2 mg, 4 mg baricitinib (LY3009104) capsule or identical placebo capsule, orally once daily for 12 weeks in Part A received 4 mg baricitinib (LY3009104) and 1 placebo tablet orally once daily for 52 weeks in Part B.
Participants on background methotrexate therapy who were administered 1 mg, 2 mg, 8 mg baricitinib (LY3009104) capsules orally once daily for 12 weeks in Part A received 2 x 4 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B.
Overall Number of Participants Analyzed 71 70
Measure Type: Number
Unit of Measure: percentage of participants
37 34
5.Secondary Outcome
Title Mean Change From Baseline to Week 12 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP)
Hide Description DAS modified included the DAS28 that consisted of a composite score of the following variables: tender joint count out of 28 (TJC28), swollen joint count out of 28 (SJC28), CRP [milligrams per liter (mg/L)], and PtGADA on a 0 to 100 millimeter (mm) VAS (0mm=no arthritis activity to 100 mm= extremely active arthritis). DAS28 calculated as: DAS28−CRP = 0.56(square root of TJC28)+0.28(square root of SJC28)+0.36[ln(CRP +1)]+0.014(VAS)+0.96. A decrease in DAS28-CRP indicated an improvement in participant's condition.
Time Frame Baseline, 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received any study drug in Part A and had DAS28-CRP evaluated at analysis time points. The last non-missing post-baseline value in Part A was used.
Arm/Group Title 1 mg Baricitinib (LY3009104) 2 mg Baricitinib (LY3009104) 4 mg Baricitinib (LY3009104) 8 mg Baricitinib (LY3009104) Placebo
Hide Arm/Group Description:
Participants on background methotrexate therapy administered 1 x 1-mg baricitinib (LY3009104) capsule + 1 identical placebo capsule, orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 x 1-mg baricitinib (LY3009104) capsules orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 1 x 4-mg baricitinib (LY3009104) capsule +1 identical placebo capsule, orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 x 4-mg baricitinib (LY3009104) capsules orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 placebo capsules, orally once daily for 12 weeks.
Overall Number of Participants Analyzed 24 24 24 24 49
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.52  (0.970) -2.02  (1.072) -2.09  (1.105) -1.96  (0.947) -0.60  (1.204)
6.Secondary Outcome
Title Mean Change From Baseline to Week 64 in DAS Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP)
Hide Description DAS modified included the 28 diarthroidal joint count (DAS28) that consisted of a composite score of the following variables: TJC28, SJC28, CRP (mg/L), and PtGADA on a 0 to 100 mm VAS (0mm=no arthritis activity to 100 mm= extremely active arthritis). DAS28 calculated as: DAS28−CRP = 0.56(square root of TJC28)+0.28(square root of SJC28)+0.36[ln(CRP +1)]+0.014(VAS)+0.96. A decrease in DAS28-CRP indicated an improvement in participant's condition.
Time Frame Baseline, 64 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received any study drug in Part B and had DAS28-CRP evaluated at analysis time points. The last non-missing post-baseline value in Part B was used.
Arm/Group Title Combined 4 mg Baricitinib (LY3009104) Combined 8 mg Baricitinib (LY3009104)
Hide Arm/Group Description:
Participants on background methotrexate therapy who were administered 1 mg, 2 mg, 4 mg baricitinib (LY3009104) capsule or identical placebo capsule, orally once daily for 12 weeks in Part A received 4 mg baricitinib (LY3009104) and 1 placebo tablet orally once daily for 52 weeks in Part B.
Participants on background methotrexate therapy who were administered 1 mg, 2 mg, 8 mg baricitinib (LY3009104) capsules orally once daily for 12 weeks in Part A received 2 x 4 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B.
Overall Number of Participants Analyzed 71 70
Mean (Standard Deviation)
Unit of Measure: units on a scale
-2.44  (1.152) -2.48  (1.109)
7.Secondary Outcome
Title Percentage of Participants Who Achieved an European League Against Rheumatism Rating of 28-Joint Arthritic Condition (EULAR28) Response at 12 Weeks (Part A)
Hide Description EULAR Responder Index based on 28 joint counts categorizes clinical response based on improvement from baseline in DAS28-CRP. DAS28-CRP scores range from 1.0-9.4, where lower scores indicated less disease activity. High disease activity: DAS28-CRP >5.1, low disease activity: DAS28-CRP ≤3.2, and remission: DAS28-CRP <2.6. Participants are categorized as EULAR responders or non-responders based on improvement of DAS28-CRP scores from baseline. EULAR DAS28-CRP responder index defines a good (absolute: ≤3.2 and >1.2 improvement from baseline), moderate (absolute: >3.2 and ≤5.1 and >0.6 and ≤1.2 improvement from baseline), or no response (absolute: >5.1 and ≤0.6 improvement from baseline). Percentage of participants calculated as = (number of good +moderate responders) / (number of participants treated) * 100.
Time Frame Baseline up to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any amount of study drug in Part A.
Arm/Group Title 1 mg Baricitinib (LY3009104) 2 mg Baricitinib (LY3009104) 4 mg Baricitinib (LY3009104) 8 mg Baricitinib (LY3009104) Placebo
Hide Arm/Group Description:
Participants on background methotrexate therapy administered 1 x 1-mg baricitinib (LY3009104) capsule + 1 identical placebo capsule, orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 x 1-mg baricitinib (LY3009104) capsules orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 1 x 4-mg baricitinib (LY3009104) capsule +1 identical placebo capsule, orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 x 4-mg baricitinib (LY3009104) capsules orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 placebo capsules, orally once daily for 12 weeks.
Overall Number of Participants Analyzed 24 24 24 24 49
Measure Type: Number
Unit of Measure: percentage of participants
83 88 92 92 47
8.Secondary Outcome
Title Percentage of Participants Who Achieved an EULAR28 Response at 64 Weeks (Part B)
Hide Description EULAR Responder Index based on 28 joint counts categorizes clinical response based on improvement from baseline in DAS28-CRP. DAS28-CRP scores range from 1.0-9.4, where lower scores indicated less disease activity. High disease activity: DAS28-CRP >5.1, low disease activity: DAS28-CRP <3.2, and remission: DAS28-CRP <2.6. Participants are categorized as EULAR responders or non-responders based on improvement of DAS28-CRP scores from baseline. EULAR DAS28-CRP Responder Index defines a good (absolute: ≤3.2 and >1.2 improvement from baseline), moderate (absolute: >3.2 and ≤5.1 and >0.6 and ≤1.2 improvement from baseline), or no response (absolute: >5.1 and ≤0.6 improvement from baseline). Percentage of participants calculated as = (number of good +moderate responders) / (number of participants treated) * 100.
Time Frame Baseline up to 64 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any amount of study drug in Part B.
Arm/Group Title Combined 4 mg Baricitinib (LY3009104) Combined 8 mg Baricitinib (LY3009104)
Hide Arm/Group Description:
Participants on background methotrexate therapy who were administered 1 mg, 2 mg, 4 mg baricitinib (LY3009104) capsule or identical placebo capsule, orally once daily for 12 weeks in Part A received 4 mg baricitinib (LY3009104) and 1 placebo tablet orally once daily for 52 weeks in Part B.
Participants on background methotrexate therapy who were administered 1 mg, 2 mg, 8 mg baricitinib (LY3009104) capsules orally once daily for 12 weeks in Part A received 2 x 4 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B.
Overall Number of Participants Analyzed 71 70
Measure Type: Number
Unit of Measure: percentage of participants
94 94
9.Secondary Outcome
Title Mean Change in Simplified Disease Activity Index (SDAI) Responses up to 12 Weeks (Part A)
Hide Description The SDAI is the numerical sum of 5 outcome parameters: TJC28, SJC28, patient and physician global assessment of disease activity and CRP. The equation used to calculate the SDAI:SDAI=SJC28+TJC28+PtGADA-VAS+PhGA-VAS+CRP where PtGADA-VAS=PtGADA-VAS / 10 and PhGA-VAS=PhGA-VAS / 10, with lower values indicating fewer symptoms.
Time Frame Baseline up to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any amount of study drug in Part A and had SDAI data at analysis time points. The last non-missing post-baseline value in Part A was used.
Arm/Group Title 1 mg Baricitinib (LY3009104) 2 mg Baricitinib (LY3009104) 4 mg Baricitinib (LY3009104) 8 mg Baricitinib (LY3009104) Placebo
Hide Arm/Group Description:
Participants on background methotrexate therapy administered 1 x 1-mg baricitinib (LY3009104) capsule + 1 identical placebo capsule, orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 x 1-mg baricitinib (LY3009104) capsules orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 1 x 4-mg baricitinib (LY3009104) capsule +1 identical placebo capsule, orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 x 4-mg baricitinib (LY3009104) capsules orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 placebo capsules, orally once daily for 12 weeks.
Overall Number of Participants Analyzed 24 24 24 24 49
Mean (Standard Deviation)
Unit of Measure: units on a scale
-13.11  (8.918) -16.85  (9.517) -18.17  (9.202) -18.02  (8.293) -4.54  (13.113)
10.Secondary Outcome
Title Mean Change in SDAI Responses up to 64 Weeks (Part B)
Hide Description

The SDAI is the numerical sum of 5 outcome parameters: TJC28, SJC28, PtGADA, PhGA, and CRP. The equation used to calculate the SDAI:

SDAI=SJC28+TJC28+PtGADA-VAS+PhGA-VAS+CRP where PtGADA-VAS=PtGADA -VAS/ 10 and PhGA-VAS=PhGA-VAS/ 10, with lower values indicating fewer symptoms.

Time Frame Baseline, 64 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any amount of study drug in Part B and had data for SDAI at analysis time points. The last non-missing post-baseline value in Part B was used.
Arm/Group Title Combined 4 mg Baricitinib (LY3009104) Combined 8 mg Baricitinib (LY3009104)
Hide Arm/Group Description:
Participants on background methotrexate therapy who were administered 1 mg, 2 mg, 4 mg baricitinib (LY3009104) capsule or identical placebo capsule, orally once daily for 12 weeks in Part A received 4 mg baricitinib (LY3009104) and 1 placebo tablet orally once daily for 52 weeks in Part B.
Participants on background methotrexate therapy who were administered 1 mg, 2 mg, 8 mg baricitinib (LY3009104) capsules orally once daily for 12 weeks in Part A received 2 x 4 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B.
Overall Number of Participants Analyzed 71 70
Mean (Standard Deviation)
Unit of Measure: units on a scale
-20.42  (9.671) -21.33  (10.318)
11.Secondary Outcome
Title Mean Change in Health Assessment Questionnaire - Disability Index (HAQ-DI) Responses up to 12 Weeks (Part A)
Hide Description HAQ-DI was a participant-reported questionnaire that consisted of 24 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the week using response categories: without any difficulty (0), with some difficulty (1), with much difficulty (2), and unable to do (3). The highest score for any question in a category was the score of that category unless special aids or devices or help from another person was required. Answers for at least 6 of the 8 domains were required. Otherwise, HAQ-DI score was considered missing. The HAQ-DI score was the sum of the category scores divided by the number of categories scored, with a possible scores range from 0 to 3, 0 being without any difficulty and 3 being unable to do.
Time Frame Baseline, 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any amount of study drug in Part A and had HAQ-DI evaluated at analysis time points. The last non-missing post-baseline value in Part A was used.
Arm/Group Title 1 mg Baricitinib (LY3009104) 2 mg Baricitinib (LY3009104) 4 mg Baricitinib (LY3009104) 8 mg Baricitinib (LY3009104) Placebo
Hide Arm/Group Description:
Participants on background methotrexate therapy administered 1 x 1-mg baricitinib (LY3009104) capsule + 1 identical placebo capsule, orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 x 1-mg baricitinib (LY3009104) capsules orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 1 x 4-mg baricitinib (LY3009104) capsule +1 identical placebo capsule, orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 x 4-mg baricitinib (LY3009104) capsules orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 placebo capsules, orally once daily for 12 weeks.
Overall Number of Participants Analyzed 24 24 24 24 49
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.302  (0.3336) -0.396  (0.4759) -0.469  (0.3463) -0.422  (0.3646) -0.077  (0.3552)
12.Secondary Outcome
Title Mean Change in HAQ-DI Responses up to 64 Weeks (Part B)
Hide Description HAQ-DI was a participant-reported questionnaire that consisted of 24 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the week using response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). The highest score for any question in a category was the score of that category unless special aids or devices or help from another person was required. Answers for at least 6 of the 8 domains were required. Otherwise, HAQ-DI score was considered missing. The HAQ-DI score was the sum of the category scores divided by the number of categories scored, with a possible scores range from 0 to 3, 0 being without any difficulty and 3 being unable to do.
Time Frame Baseline, 64 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any amount of study drug in Part B and had HAQ-DI evaluated at analysis time points. The last non-missing post-baseline value in Part B was used.
Arm/Group Title Combined 4 mg Baricitinib (LY3009104) Combined 8 mg Baricitinib (LY3009104)
Hide Arm/Group Description:
Participants on background methotrexate therapy who were administered 1 mg, 2 mg, 4 mg baricitinib (LY3009104) capsule or identical placebo capsule, orally once daily for 12 weeks in Part A received 4 mg baricitinib (LY3009104) and 1 placebo tablet orally once daily for 52 weeks in Part B.
Participants on background methotrexate therapy who were administered 1 mg, 2 mg, 8 mg baricitinib (LY3009104) capsules orally once daily for 12 weeks in Part A received 2 x 4 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B.
Overall Number of Participants Analyzed 71 70
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.498  (0.4779) -0.568  (0.6203)
13.Secondary Outcome
Title Mean Value of ACR-N Response (Part A)
Hide Description The ACR-N Response Index is a continuous measure of clinical, laboratory, and functional measures in RA to characterize the percentage of improvement from baseline in RA disease activity. This index is defined as the lowest of either: a) percent change in TJC, b) percent change in SJC, or c) median percent change of the remaining 5 ACR core criteria (HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, or PhGA-VAS). A participant with an ACR-N of "X" has improvement of at least "X%" in tender and swollen joints and a median improvement of at least "X%" in the 5 remaining ACR core criteria. Since ACR-N is a continuous measure, the mean values are reported instead of the originally registered percentage of participants.
Time Frame Baseline up to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any study drug in Part A and had baseline and at least one post baseline ACR-N response measure. LOCF was used to impute missing post-baseline values.
Arm/Group Title 1 mg Baricitinib (LY3009104) 2 mg Baricitinib (LY3009104) 4 mg Baricitinib (LY3009104) 8 mg Baricitinib (LY3009104) Placebo
Hide Arm/Group Description:
Participants on background methotrexate therapy administered 1 x 1-mg baricitinib (LY3009104) capsule + 1 identical placebo capsule, orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 x 1-mg baricitinib (LY3009104) capsules orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 1 x 4-mg baricitinib (LY3009104) capsule +1 identical placebo capsule, orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 x 4-mg baricitinib (LY3009104) 4 capsules orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 placebo capsules, orally once daily for 12 weeks.
Overall Number of Participants Analyzed 23 24 23 24 48
Mean (Standard Deviation)
Unit of Measure: percentage of responders
28.76  (38.65) 42.48  (39.52) 45.17  (33.75) 25.58  (130.02) -9.98  (58.10)
14.Secondary Outcome
Title Mean Value of ACR-N Response (Part B)
Hide Description The ACR-N Response Index is a continuous measure of clinical, laboratory, and functional measures in RA to characterize the percentage of improvement from baseline in RA disease activity. This index is defined as the lowest of either: a) percent change in TJC, b) percent change in SJC, or c) median percent change of the remaining 5 ACR core criteria (HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, or PhGA-VAS). A participant with an ACR-N of "X" has improvement of at least "X%" in tender and swollen joints and a median improvement of at least "X%" in the 5 remaining ACR core criteria. Since ACR-N is a continuous measure, the mean values are reported instead of the originally registered percentage of participants.
Time Frame Baseline up to 64 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any study drug in Part B and had baseline and at least one post baseline ACR-N response measure. LOCF was used to impute missing post-baseline values.
Arm/Group Title Combined 4 mg Baricitinib (LY3009104) Combined 8 mg Baricitinib (LY3009104)
Hide Arm/Group Description:
Participants on background methotrexate therapy who were administered 1 mg, 2 mg, 4 mg baricitinib (LY3009104) capsule or identical placebo capsule, orally once daily for 12 weeks in Part A received 4 mg baricitinib (LY3009104) and 1 placebo tablet orally once daily for 52 weeks in Part B.
Participants on background methotrexate therapy who were administered 1 mg, 2 mg, 8 mg baricitinib (LY3009104) capsules orally once daily for 12 weeks in Part A received 2 x 4 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B.
Overall Number of Participants Analyzed 55 54
Mean (Standard Deviation)
Unit of Measure: percentage of responders
61.14  (30.70) 61.07  (33.22)
15.Secondary Outcome
Title Percentage of Participants Who Achieved a DAS28 Remission at 12 Weeks (Part A)
Hide Description DAS modified included the DAS28 that consisted of a composite score of the following variables: TJC28, SJC28, CRP (mg/L), and PtGADA on a 0 to 100 mm VAS: 0 mm (no arthritis activity) to 100 mm (extremely active arthritis). DAS28 calculated as: DAS28−CRP = 0.56(square root of TJC28)+0.28(square root of SJC28)+0.36[ln(CRP +1)]+0.014(VAS)+0.96. For remission, DAS28 is <2.6. Percentage of participants = (number of participants with DAS28 remission) / (number of participants treated) * 100.
Time Frame Baseline up to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any amount of study treatment in Part A.
Arm/Group Title 1 mg Baricitinib (LY3009104) 2 mg Baricitinib (LY3009104) 4 mg Baricitinib (LY3009104) 8 mg Baricitinib (LY3009104) Placebo
Hide Arm/Group Description:
Participants on background methotrexate therapy administered 1 x 1-mg baricitinib (LY3009104) capsule + 1 identical placebo capsule, orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 x 1-mg baricitinib (LY3009104) capsules orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 1 x 4-mg baricitinib (LY3009104) capsule +1 identical placebo capsule, orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 x 4-mg baricitinib (LY3009104) capsules orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 placebo capsules, orally once daily for 12 weeks.
Overall Number of Participants Analyzed 24 24 24 24 49
Measure Type: Number
Unit of Measure: percentage of participants
33 33 42 50 22
16.Secondary Outcome
Title Percentage of Participants Who Achieved a DAS28 Remission at 64 Weeks (Part B)
Hide Description DAS modified included the DAS28 that consisted of a composite score of the following variables: TJC28, SJC28, CRP (mg/L), and PtGADA-VAS on a 0 to 100 mm VAS: 0 mm (no arthritis activity) to 100 mm (extremely active arthritis). DAS28 calculated as: DAS28−CRP = 0.56(sqrt of TJC28)+0.28(sqrt of SJC28)+0.36[ln(CRP +1)]+0.014(VAS)+0.96. For remission, DAS28 is <2.6. Percentage of participants = (number of participants with DAS 28 remission) / (number of participants treated) * 100.
Time Frame Baseline up to 64 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any amount of study drug in Part B.
Arm/Group Title Combined 4 mg Baricitinib (LY3009104) Combined 8 mg Baricitinib (LY3009104)
Hide Arm/Group Description:
Participants on background methotrexate therapy who were administered 1 mg, 2 mg, 4 mg baricitinib (LY3009104) capsule or identical placebo capsule, orally once daily for 12 weeks in Part A received 4 mg baricitinib (LY3009104) and 1 placebo tablet orally once daily for 52 weeks in Part B.
Participants on background methotrexate therapy who were administered 1 mg, 2 mg, 8 mg baricitinib (LY3009104) capsules orally once daily for 12 weeks in Part A received 2 x 4 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B.
Overall Number of Participants Analyzed 71 70
Measure Type: Number
Unit of Measure: percentage of participants
66 66
17.Secondary Outcome
Title Percentage of Participants Who Achieved an SDAI Remission at 12 Weeks (Part A)
Hide Description

The SDAI is the numerical sum of 5 outcome parameters: TJC28, SJC28, PtGADA, PhGA and CRP. The equation used to calculate the SDAI:

SDAI=SJC28+TJC28+PtGADA-VAS+PhGA-VAS+CRP where PtGADA-VAS=PtGADA -VAS/ 10 and PhGA-VAS=PhGA-VAS / 10. Definition of remission is SDAI ≤ 3.3. Percentage of participants = (number of responders) / (number of participants treated) * 100

Time Frame Baseline up to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any amount of study drug in Part A.
Arm/Group Title 1 mg Baricitinib (LY3009104) 2 mg Baricitinib (LY3009104) 4 mg Baricitinib (LY3009104) 8 mg Baricitinib (LY3009104) Placebo
Hide Arm/Group Description:
Participants on background methotrexate therapy administered 1 x 1-mg baricitinib (LY3009104) capsule + 1 identical placebo capsule, orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 x 1-mg baricitinib (LY3009104) capsules orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 1 x 4-mg baricitinib (LY3009104) capsule +1 identical placebo capsule, orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 x 4-mg baricitinib (LY3009104) capsules orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 placebo capsules, orally once daily for 12 weeks.
Overall Number of Participants Analyzed 24 24 24 24 49
Measure Type: Number
Unit of Measure: percentage of participants
4 29 17 17 8
18.Secondary Outcome
Title Percentage of Participants Who Achieved an SDAI Remission at 64 Weeks (Part B)
Hide Description

The SDAI is the numerical sum of 5 outcome parameters: TJC28, SJC28, PtGADA, PhGA, and CRP. The equation used to calculate the SDAI:

SDAI=SJC28+TJC28+PtGADA-VAS+PhGA-VAS+CRP where PtGADA-VAS=PtGADA-VAS / 10 and PhGA-VAS=PhGA-VAS / 10. Definition of remission is SDAI ≤ 3.3. Percentage of participants = (number of responders) / (number of participants treated) * 100

Time Frame Baseline up to 64 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any amount of study drug in Part B.
Arm/Group Title Combined 4 mg Baricitinib (LY3009104) Combined 8 mg Baricitinib (LY3009104)
Hide Arm/Group Description:
Participants on background methotrexate therapy who were administered 1 mg, 2 mg, 4 mg baricitinib (LY3009104) capsule or identical placebo capsule, orally once daily for 12 weeks in Part A received 4 mg baricitinib (LY3009104) and 1 placebo tablet orally once daily for 52 weeks in Part B.
Participants on background methotrexate therapy who were administered 1 mg, 2 mg, 8 mg baricitinib (LY3009104) capsules orally once daily for 12 weeks in Part A received 2 x 4 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B.
Overall Number of Participants Analyzed 71 70
Measure Type: Number
Unit of Measure: percentage of participants
39 39
19.Secondary Outcome
Title Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve at a Dosing Interval at Steady State (AUCtau,ss) of LY3009104
Hide Description Steady state is achieved when the rate of drug input is equal to the rate of drug elimination. The AUC(tau,ss) at 1 dosing interval is the average concentration of the drug at steady state multiplied by the time of the dosing interval.
Time Frame Weeks (Wks) 0, 8, 12, or 20: Predose, 15 to 30 minutes and 1 to 3 hours postdose; Wks 2 or 4 and 15 or 16: Predose; Wks 28, 40, 52, or 64: random single sample.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any study drug and had evaluable data for AUC(tau,ss).
Arm/Group Title 1 mg Baricitinib (LY3009104) 2 mg Baricitinib (LY3009104) 4 mg Baricitinib (LY3009104) 8 mg Baricitinib (LY3009104)
Hide Arm/Group Description:
Participants on background methotrexate therapy administered 1 x 1-mg baricitinib (LY3009104) capsule + 1 identical placebo capsule, orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 x 1-mg baricitinib (LY3009104) capsules orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 1 x 4-mg baricitinib (LY3009104) capsule +1 identical placebo capsule, orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 x 4-mg baricitinib (LY3009104) capsules orally once daily for 12 weeks.
Overall Number of Participants Analyzed 24 24 48 47
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanomoles*hour (nM*h)
237
(28.8%)
525
(21%)
1020
(32.5%)
1900
(24.1%)
20.Secondary Outcome
Title PK: Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104
Hide Description [Not Specified]
Time Frame Wks 0, 8, 12, or 20: Predose, 15 to 30 minutes and 1 to 3 hours postdose; Wks 2 or 4 and 15 or 16: Predose; Wks 28, 40, 52, or 64: random single sample.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any study drug and had evaluable Cmax data.
Arm/Group Title 1 mg Baricitinib (LY3009104) 2 mg Baricitinib (LY3009104) 4 mg Baricitinib (LY3009104) 8 mg Baricitinib (LY3009104)
Hide Arm/Group Description:
Participants on background methotrexate therapy administered 1 x 1-mg baricitinib (LY3009104) capsule + 1 identical placebo capsule, orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 x 1-mg baricitinib (LY3009104) capsules orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 1 x 4-mg baricitinib (LY3009104) capsule +1 identical placebo capsule, orally once daily for 12 weeks.
Participants on background methotrexate therapy administered 2 x 4-mg baricitinib (LY3009104) capsules orally once daily for 12 weeks.
Overall Number of Participants Analyzed 24 24 48 47
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nM
35.7
(20.9%)
73.5
(22.5%)
147
(20.6%)
278
(21.7%)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo 1 mg Baricitinib (LY3009104) 2 mg Baricitinib (LY3009104) 4 mg Baricitinib (LY3009104) 8 mg Baricitinib (LY3009104) Placebo / 4 mg Baricitinib (LY3009104) 1 mg Baricitinib (LY3009104) / 4mg Baricitinib (LY3009104) 2 mg Baricitinib (LY3009104) / 4 mg Baricitinib (LY3009104) 4 mg Baricitinib (LY3009104) / 4 mg Baricitinib (LY3009104) Placebo /8 mg Baricitinib (LY3009104) 1 mg Baricitinib (LY3009104) / 8 mg Baricitinib (LY3009104) 2 mg Baricitinib (LY3009104) / 8 mg Baricitinib (LY3009104) 8 mg Baricitinib (LY3009104) / 8 mg Baricitinib (LY3009104)
Hide Arm/Group Description Participants on background methotrexate therapy administered 2 placebo capsules, orally once daily for 12 weeks. Participants on background methotrexate therapy administered 1 x 1-mg baricitinib (LY3009104) capsule + 1 identical placebo capsule, orally once daily for 12 weeks. Participants on background methotrexate therapy administered 2 x 1-mg baricitinib (LY3009104) capsules orally once daily for 12 weeks. Participants on background methotrexate therapy administered 1 x 4-mg baricitinib (LY3009104) capsule +1 identical placebo capsule, orally once daily for 12 weeks. Participants on background methotrexate therapy administered 2 x 4-mg baricitinib (LY3009104) capsules orally once daily for 12 weeks. Participants on background methotrexate therapy who were administered placebo capsule, orally once daily for 12 weeks in Part A received 4 mg baricitinib (LY3009104) and 1 placebo tablet orally once daily for 52 weeks in Part B. Participants on background methotrexate therapy who were administered 1 mg baricitinib (LY3009104) capsule, orally once daily for 12 weeks in Part A received 4 mg baricitinib (LY3009104) and 1 placebo tablet orally once daily for 52 weeks in Part B. Participants on background methotrexate therapy who were administered 2 mg baricitinib (LY3009104) capsule, orally once daily for 12 weeks in Part A received 4 mg baricitinib (LY3009104) and 1 placebo tablet orally once daily for 52 weeks in Part B. Participants on background methotrexate therapy who were administered 4 mg baricitinib (LY3009104) capsule, orally once daily for 12 weeks in Part A received 4 mg baricitinib (LY3009104) and 1 placebo tablet orally once daily for 52 weeks in Part B. Participants on background methotrexate therapy who were administered placebo capsule, orally once daily for 12 weeks in Part A received 2 x 4 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B. Participants on background methotrexate therapy who were administered 1 mg baricitinib (LY3009104) capsule, orally once daily for 12 weeks in Part A received 2 x 4 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B. Participants on background methotrexate therapy who were administered 2 mg baricitinib (LY3009104) capsule, orally once daily for 12 weeks in Part A received 2 x 4 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B. Participants on background methotrexate therapy who were administered 8 mg baricitinib (LY3009104) capsule, orally once daily for 12 weeks in Part A received 2 x 4 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B.
All-Cause Mortality
Placebo 1 mg Baricitinib (LY3009104) 2 mg Baricitinib (LY3009104) 4 mg Baricitinib (LY3009104) 8 mg Baricitinib (LY3009104) Placebo / 4 mg Baricitinib (LY3009104) 1 mg Baricitinib (LY3009104) / 4mg Baricitinib (LY3009104) 2 mg Baricitinib (LY3009104) / 4 mg Baricitinib (LY3009104) 4 mg Baricitinib (LY3009104) / 4 mg Baricitinib (LY3009104) Placebo /8 mg Baricitinib (LY3009104) 1 mg Baricitinib (LY3009104) / 8 mg Baricitinib (LY3009104) 2 mg Baricitinib (LY3009104) / 8 mg Baricitinib (LY3009104) 8 mg Baricitinib (LY3009104) / 8 mg Baricitinib (LY3009104)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo 1 mg Baricitinib (LY3009104) 2 mg Baricitinib (LY3009104) 4 mg Baricitinib (LY3009104) 8 mg Baricitinib (LY3009104) Placebo / 4 mg Baricitinib (LY3009104) 1 mg Baricitinib (LY3009104) / 4mg Baricitinib (LY3009104) 2 mg Baricitinib (LY3009104) / 4 mg Baricitinib (LY3009104) 4 mg Baricitinib (LY3009104) / 4 mg Baricitinib (LY3009104) Placebo /8 mg Baricitinib (LY3009104) 1 mg Baricitinib (LY3009104) / 8 mg Baricitinib (LY3009104) 2 mg Baricitinib (LY3009104) / 8 mg Baricitinib (LY3009104) 8 mg Baricitinib (LY3009104) / 8 mg Baricitinib (LY3009104)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/49 (2.04%)      0/24 (0.00%)      1/24 (4.17%)      0/24 (0.00%)      1/24 (4.17%)      1/24 (4.17%)      1/12 (8.33%)      3/12 (25.00%)      3/23 (13.04%)      2/23 (8.70%)      2/11 (18.18%)      2/12 (16.67%)      6/24 (25.00%)    
Cardiac disorders                           
Angina pectoris  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 1/24 (4.17%)  1
Myocardial infarction  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 1/24 (4.17%)  1
Ear and labyrinth disorders                           
Meniere's disease  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Eye disorders                           
Cataract  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 1/12 (8.33%)  1 1/24 (4.17%)  1
Gastrointestinal disorders                           
Large intestine polyp  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 1/12 (8.33%)  1 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 1/24 (4.17%)  1
Pancreatitis acute  1  0/49 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 1/12 (8.33%)  1 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Hepatobiliary disorders                           
Cholecystitis  1  1/49 (2.04%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Infections and infestations                           
Gastroenteritis  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Herpes zoster  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 1/12 (8.33%)  1 0/23 (0.00%)  0 0/23 (0.00%)  0 1/11 (9.09%)  1 0/12 (0.00%)  0 1/24 (4.17%)  1
Pneumocystis jirovecii pneumonia  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 1/12 (8.33%)  1 0/24 (0.00%)  0
Pneumonia  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Injury, poisoning and procedural complications                           
Clavicle fracture  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 1/12 (8.33%)  1 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Fall  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 1/12 (8.33%)  1 0/23 (0.00%)  0 1/23 (4.35%)  1 1/11 (9.09%)  1 0/12 (0.00%)  0 0/24 (0.00%)  0
Forearm fracture  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Ulna fracture  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/11 (9.09%)  1 0/12 (0.00%)  0 0/24 (0.00%)  0
Investigations                           
Blood creatine phosphokinase increased  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/11 (9.09%)  1 0/12 (0.00%)  0 0/24 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                           
Rectal cancer  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Nervous system disorders                           
Cerebral haemorrhage  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/11 (9.09%)  1 0/12 (0.00%)  0 0/24 (0.00%)  0
Viith nerve paralysis  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 1/24 (4.17%)  1
Respiratory, thoracic and mediastinal disorders                           
Interstitial lung disease  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 1/24 (4.17%)  1
Vascular disorders                           
Deep vein thrombosis  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Placebo 1 mg Baricitinib (LY3009104) 2 mg Baricitinib (LY3009104) 4 mg Baricitinib (LY3009104) 8 mg Baricitinib (LY3009104) Placebo / 4 mg Baricitinib (LY3009104) 1 mg Baricitinib (LY3009104) / 4mg Baricitinib (LY3009104) 2 mg Baricitinib (LY3009104) / 4 mg Baricitinib (LY3009104) 4 mg Baricitinib (LY3009104) / 4 mg Baricitinib (LY3009104) Placebo /8 mg Baricitinib (LY3009104) 1 mg Baricitinib (LY3009104) / 8 mg Baricitinib (LY3009104) 2 mg Baricitinib (LY3009104) / 8 mg Baricitinib (LY3009104) 8 mg Baricitinib (LY3009104) / 8 mg Baricitinib (LY3009104)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   26/49 (53.06%)      11/24 (45.83%)      12/24 (50.00%)      13/24 (54.17%)      17/24 (70.83%)      21/24 (87.50%)      11/12 (91.67%)      11/12 (91.67%)      22/23 (95.65%)      23/23 (100.00%)      11/11 (100.00%)      12/12 (100.00%)      23/24 (95.83%)    
Blood and lymphatic system disorders                           
Anaemia  1  0/49 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 1/24 (4.17%)  1 1/24 (4.17%)  1 0/24 (0.00%)  0 0/12 (0.00%)  0 1/12 (8.33%)  1 1/23 (4.35%)  2 1/23 (4.35%)  1 0/11 (0.00%)  0 0/12 (0.00%)  0 1/24 (4.17%)  1
Haemorrhagic anaemia  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  2 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Iron deficiency anaemia  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/11 (9.09%)  1 1/12 (8.33%)  1 0/24 (0.00%)  0
Leukopenia  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 2/24 (8.33%)  2 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 3/23 (13.04%)  4 0/11 (0.00%)  0 0/12 (0.00%)  0 1/24 (4.17%)  1
Lymphopenia  1  1/49 (2.04%)  1 0/24 (0.00%)  0 1/24 (4.17%)  1 1/24 (4.17%)  1 1/24 (4.17%)  1 1/24 (4.17%)  1 1/12 (8.33%)  1 0/12 (0.00%)  0 3/23 (13.04%)  4 3/23 (13.04%)  4 1/11 (9.09%)  1 1/12 (8.33%)  1 0/24 (0.00%)  0
Pancytopenia  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 1/12 (8.33%)  1 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Cardiac disorders                           
Arrhythmia  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Bradycardia  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 1/12 (8.33%)  1 0/24 (0.00%)  0
Sinus tachycardia  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Ventricular extrasystoles  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Congenital, familial and genetic disorders                           
Birth mark  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 1/24 (4.17%)  1
Ear and labyrinth disorders                           
Deafness neurosensory  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Tinnitus  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Vertigo  1  1/49 (2.04%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Endocrine disorders                           
Thyroid mass  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Thyroiditis  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 1/12 (8.33%)  1 0/24 (0.00%)  0
Thyroiditis chronic  1  0/49 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Eye disorders                           
Cataract  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Conjunctivitis  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 1/24 (4.17%)  1
Dry eye  1  1/49 (2.04%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 2/24 (8.33%)  2 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Gastrointestinal disorders                           
Abdominal discomfort  1  1/49 (2.04%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/12 (0.00%)  0 1/23 (4.35%)  1 1/23 (4.35%)  1 1/11 (9.09%)  1 0/12 (0.00%)  0 1/24 (4.17%)  1
Abdominal distension  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 1/12 (8.33%)  1 0/24 (0.00%)  0
Abdominal pain  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  2 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/11 (9.09%)  1 1/12 (8.33%)  1 0/24 (0.00%)  0
Abdominal pain upper  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 1/24 (4.17%)  1 1/12 (8.33%)  2 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Aphthous stomatitis  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Cheilitis  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Constipation  1  1/49 (2.04%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 2/24 (8.33%)  2 2/12 (16.67%)  2 1/12 (8.33%)  1 0/23 (0.00%)  0 2/23 (8.70%)  2 1/11 (9.09%)  1 1/12 (8.33%)  1 1/24 (4.17%)  1
Dental caries  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0 2/11 (18.18%)  2 0/12 (0.00%)  0 0/24 (0.00%)  0
Diarrhoea  1  0/49 (0.00%)  0 1/24 (4.17%)  1 1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 2/23 (8.70%)  2 1/23 (4.35%)  1 0/11 (0.00%)  0 1/12 (8.33%)  1 0/24 (0.00%)  0
Dry mouth  1  1/49 (2.04%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Duodenal ulcer  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Dyspepsia  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/12 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Food poisoning  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Gastric polyps  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Gastric ulcer  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0 0/11 (0.00%)  0 1/12 (8.33%)  1 0/24 (0.00%)  0
Gastritis  1  0/49 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 3/23 (13.04%)  3 0/11 (0.00%)  0 0/12 (0.00%)  0 1/24 (4.17%)  1
Gastritis atrophic  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0 0/11 (0.00%)  0 1/12 (8.33%)  1 0/24 (0.00%)  0
Gastritis erosive  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/12 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Gastrooesophageal reflux disease  1  1/49 (2.04%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1 0/11 (0.00%)  0 0/12 (0.00%)  0 1/24 (4.17%)  1
Hyperchlorhydria  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 1/12 (8.33%)  1 0/24 (0.00%)  0
Mouth ulceration  1  1/49 (2.04%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 1/24 (4.17%)  1
Nausea  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 2/24 (8.33%)  2 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/11 (9.09%)  1 2/12 (16.67%)  2 0/24 (0.00%)  0
Pancreatitis chronic  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 1/12 (8.33%)  1 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Periodontal disease  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/11 (9.09%)  1 0/12 (0.00%)  0 0/24 (0.00%)  0
Stomatitis  1  0/49 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 1/24 (4.17%)  1 0/24 (0.00%)  0 3/24 (12.50%)  3 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1 0/11 (0.00%)  0 0/12 (0.00%)  0 2/24 (8.33%)  4
Vomiting  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0 1/11 (9.09%)  1 0/12 (0.00%)  0 0/24 (0.00%)  0
General disorders                           
Chest discomfort  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Chest pain  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 1/24 (4.17%)  1
Fatigue  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Malaise  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/11 (9.09%)  1 0/12 (0.00%)  0 0/24 (0.00%)  0
Mass  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/11 (9.09%)  1 0/12 (0.00%)  0 0/24 (0.00%)  0
Oedema  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Oedema peripheral  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1 1/11 (9.09%)  1 0/12 (0.00%)  0 0/24 (0.00%)  0
Pyrexia  1  2/49 (4.08%)  2 1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Hepatobiliary disorders                           
Cholelithiasis  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Gallbladder polyp  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Hepatic cyst  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Hepatic function abnormal  1  0/49 (0.00%)  0 0/24 (0.00%)  0 3/24 (12.50%)  3 0/24 (0.00%)  0 3/24 (12.50%)  3 1/24 (4.17%)  2 2/12 (16.67%)  2 1/12 (8.33%)  1 3/23 (13.04%)  4 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 2/24 (8.33%)  2
Hepatic steatosis  1  0/49 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Liver injury  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Immune system disorders                           
Allergy to arthropod sting  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/11 (9.09%)  1 0/12 (0.00%)  0 0/24 (0.00%)  0
Seasonal allergy  1  1/49 (2.04%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Infections and infestations                           
Acute tonsillitis  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/12 (0.00%)  0 2/23 (8.70%)  2 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Appendicitis  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Bacteriuria  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 1/12 (8.33%)  1 0/24 (0.00%)  0
Bronchitis  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 1/12 (8.33%)  1 0/12 (0.00%)  0 1/23 (4.35%)  2 0/23 (0.00%)  0 0/11 (0.00%)  0 1/12 (8.33%)  1 1/24 (4.17%)  1
Cellulitis  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Chronic sinusitis  1  0/49 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Cystitis  1  2/49 (4.08%)  2 0/24 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 1/23 (4.35%)  1 1/23 (4.35%)  1 1/11 (9.09%)  1 1/12 (8.33%)  1 2/24 (8.33%)  2
Diverticulitis  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 1/24 (4.17%)  1
Eczema impetiginous  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Empyema  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/11 (9.09%)  1 0/12 (0.00%)  0 0/24 (0.00%)  0
Enteritis infectious  1  0/49 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/11 (9.09%)  1 0/12 (0.00%)  0 0/24 (0.00%)  0
Enterocolitis bacterial  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Folliculitis  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Fungal paronychia  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Fungal skin infection  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Furuncle  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 1/24 (4.17%)  1
Gastroenteritis  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 1/23 (4.35%)  1 1/23 (4.35%)  1 0/11 (0.00%)  0 1/12 (8.33%)  1 1/24 (4.17%)  2
Gastroenteritis norovirus  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Gastroenteritis viral  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  2 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Genital herpes  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 1/24 (4.17%)  1
Gingivitis  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 1/24 (4.17%)  1
Helicobacter infection  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 1/12 (8.33%)  1 0/24 (0.00%)  0
Herpes simplex  1  0/49 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Herpes virus infection  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 1/12 (8.33%)  1 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Herpes zoster  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 2/12 (16.67%)  2 1/23 (4.35%)  1 1/23 (4.35%)  1 1/11 (9.09%)  1 0/12 (0.00%)  0 2/24 (8.33%)  2
Influenza  1  1/49 (2.04%)  1 1/24 (4.17%)  1 0/24 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/12 (0.00%)  0 1/23 (4.35%)  1 1/23 (4.35%)  1 0/11 (0.00%)  0 1/12 (8.33%)  1 1/24 (4.17%)  1
Molluscum contagiosum  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Nasopharyngitis  1  6/49 (12.24%)  7 2/24 (8.33%)  2 2/24 (8.33%)  2 2/24 (8.33%)  2 2/24 (8.33%)  2 4/24 (16.67%)  4 5/12 (41.67%)  6 6/12 (50.00%)  6 7/23 (30.43%)  8 9/23 (39.13%)  15 1/11 (9.09%)  1 1/12 (8.33%)  2 5/24 (20.83%)  9
Oesophageal candidiasis  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 1/12 (8.33%)  1 0/24 (0.00%)  0
Oral candidiasis  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 1/12 (8.33%)  1 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Oral herpes  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/12 (0.00%)  0 1/23 (4.35%)  1 1/23 (4.35%)  1 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Paronychia  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 2/23 (8.70%)  2 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Periodontitis  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 1/24 (4.17%)  1
Pertussis  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 2/24 (8.33%)  2 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Pharyngitis  1  1/49 (2.04%)  1 1/24 (4.17%)  1 1/24 (4.17%)  1 0/24 (0.00%)  0 2/24 (8.33%)  2 2/24 (8.33%)  6 0/12 (0.00%)  0 0/12 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0 0/11 (0.00%)  0 1/12 (8.33%)  1 2/24 (8.33%)  2
Pneumonia  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1 0/11 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0
Pulpitis dental  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/11 (9.09%)  1 0/12 (0.00%)  0 1/24 (4.17%)  1
Rhinitis  1  0/49 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0