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

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01469013
• Collaborator: (none)
• Enrollment: 145
• Locations: 14
• Arms: 5
• Duration (Months): 25
• Patients Per Site: 10.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This is a Phase 2b, outpatient, randomized, double-blinded (with a single-blind extension), placebo-controlled, dose-ranging, parallel-group study of baricitinib (LY3009104) in Japanese participants with active rheumatoid arthritis (RA) on background methotrexate (MTX) therapy. Baricitinib will be orally administered once a day with background methotrexate [6 to 16 milligrams (mg)/week] therapy for 12 weeks in the double-blind treatment period (1, 2, 4 or 8 mg/day, or placebo), and for 52 weeks in the single-blind extension period (4 or 8 mg/day).

Condition or Disease	Intervention/Treatment	Phase
Arthritis, Rheumatoid	Drug: Placebo; Drug: Baricitinib; Drug: Baricitinib; Drug: Baricitinib; Drug: Methotrexate	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 145 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Parallel-Group, Phase 2 Study of Baricitinib (LY3009104) in Japanese Patients With Active Rheumatoid Arthritis on Background Methotrexate Therapy
• Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Nov 1, 2012
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo 2 placebo capsules administered orally once daily for 12 weeks. Participants who complete this treatment arm will be randomized in a 1:1 ratio to either the 4-mg baricitinib or 8-mg baricitinib arms. Participants rerandomized to 8-mg baricitinib arm at Week12 will switch to 4-mg baricitinib once a day after the approval of protocol amendment (d) and will receive that switched dose until Week 64. The dosage form changed from capsule in treatment period (up to Week 12) to tablet in extension period (Week 13 to 64) per protocol amendment (b).	Drug: Placebo; Other Names: Sugar pill ; Drug: Methotrexate; Administered orally as background therapy
Experimental: 1-mg Baricitinib (LY3009104) 1 x 1-mg baricitinib capsule + 1 identical placebo capsule, both administered orally once daily for 12 weeks. Participants who complete this treatment arm will be randomized in a 1:1 ratio to either the 4-mg baricitinib or 8-mg baricitinib arms. Participants rerandomized to 8-mg baricitinib arm at Week 12 will switch to 4-mg baricitinib once a day after the approval of protocol amendment (d) and will receive that switched dose until Week 64. The dosage form changed from capsule in treatment period (up to Week 12) to tablet in extension period (Week 13 to 64) per protocol amendment (b).	Drug: Placebo; Other Names: Sugar pill ; Drug: Baricitinib; Other Names: JAK1/JAK2 inhibitor JAK1 inhibitor JAK2 inhibitor NCB028050 LY3009104 ; Drug: Methotrexate; Administered orally as background therapy
Experimental: 2-mg Baricitinib (LY3009104) 2 x 1-mg baricitinib capsules administered orally once daily for 12 weeks. Participants who complete this treatment arm will be randomized in a 1:1 ratio to either the 4-mg baricitinib or 8-mg baricitinib arms. Participants rerandomized to 8-mg baricitinib arm at Week 12 will switch to 4-mg baricitinib once a day after the approval of protocol amendment (d) and will receive that switched dose until Week 64. The dosage form changed from capsule in treatment period (up to Week 12) to tablet in extension period (Week 13 to 64) per protocol amendment (b).	Drug: Baricitinib; Other Names: JAK1/JAK2 inhibitor JAK1 inhibitor JAK2 inhibitor NCB028050 LY3009104 ; Drug: Methotrexate; Administered orally as background therapy
Experimental: 4-mg Baricitinib (LY3009104) 1 x 4-mg baricitinib capsule + 1 identical placebo capsule, both administered orally once daily for 12 weeks. Participants who complete this 12-week period will remain on this treatment regimen in tablet form.	Drug: Placebo; Other Names: Sugar pill ; Drug: Baricitinib; Other Names: JAK1/JAK2 inhibitor JAK1 inhibitor JAK2 inhibitor NCB028050 LY3009104 ; Drug: Baricitinib; Other Names: JAK1/JAK2 inhibitor JAK1 inhibitor JAK2 inhibitor NCB028050 LY3009104 ; Drug: Methotrexate; Administered orally as background therapy
Experimental: 8-mg Baricitinib (LY3009104) 2 x 4-mg baricitinib capsules administered orally once daily for 12 weeks. Participants who complete this 12-week period will remain on this treatment regimen in tablet form. Participants taking 8-mg baricitinib tablet form will switch to 4-mg baricitinib once a day after the approval of protocol amendment (d) and will receive that switched dose until Week 64.	Drug: Baricitinib; Other Names: JAK1/JAK2 inhibitor JAK1 inhibitor JAK2 inhibitor NCB028050 LY3009104 ; Drug: Baricitinib; Other Names: JAK1/JAK2 inhibitor JAK1 inhibitor JAK2 inhibitor NCB028050 LY3009104 ; Drug: Methotrexate; Administered orally as background therapy

Outcome Measures

Primary Outcome Measures

1. 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 . [12 weeks]

   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.

Secondary Outcome Measures

1. Percentage of Participants Who Achieved an ACR20 Response at 64 Weeks [Baseline up to 64 weeks]

   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.

2. Percentage of Participants Who Achieved an ACR70 Response at 12 Weeks (Part A) [Baseline up to 12 weeks]

   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.

3. Percentage of Participants Who Achieved an ACR70 Response at 64 Weeks (Part B) [Baseline up to 64 weeks]

   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.

4. Mean Change From Baseline to Week 12 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP) [Baseline, 12 weeks]

   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.

5. Mean Change From Baseline to Week 64 in DAS Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP) [Baseline, 64 weeks]

   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.

6. Percentage of Participants Who Achieved an European League Against Rheumatism Rating of 28-Joint Arthritic Condition (EULAR28) Response at 12 Weeks (Part A) [Baseline up to 12 weeks]

   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.

7. Percentage of Participants Who Achieved an EULAR28 Response at 64 Weeks (Part B) [Baseline up to 64 weeks]

   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.

8. Mean Change in Simplified Disease Activity Index (SDAI) Responses up to 12 Weeks (Part A) [Baseline up to 12 weeks]

   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.

9. Mean Change in SDAI Responses up to 64 Weeks (Part B) [Baseline, 64 weeks]

   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.

10. Mean Change in Health Assessment Questionnaire - Disability Index (HAQ-DI) Responses up to 12 Weeks (Part A) [Baseline, 12 weeks]

    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.

11. Mean Change in HAQ-DI Responses up to 64 Weeks (Part B) [Baseline, 64 weeks]

    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.

12. Mean Value of ACR-N Response (Part A) [Baseline up to 12 weeks]

    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.

13. Mean Value of ACR-N Response (Part B) [Baseline up to 64 weeks]

    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.

14. Percentage of Participants Who Achieved a DAS28 Remission at 12 Weeks (Part A) [Baseline up to 12 weeks]

    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.

15. Percentage of Participants Who Achieved a DAS28 Remission at 64 Weeks (Part B) [Baseline up to 64 weeks]

    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.

16. Percentage of Participants Who Achieved an SDAI Remission at 12 Weeks (Part A) [Baseline up to 12 weeks]

    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

17. Percentage of Participants Who Achieved an SDAI Remission at 64 Weeks (Part B) [Baseline up to 64 weeks]

    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

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

    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.

19. PK: Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104 [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.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Ambulatory males or females between the ages of 20 and 75 years, inclusive, at time of study entry

• Diagnosis of adult-onset RA (of at least 6 months duration but not longer than 15 years prior to screening) according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Responder Index classification criteria for RA

• Have active RA defined as at least 6 swollen and at least 6 tender joints based on the 66/68 joint count

• Regular use of MTX for at least 12 weeks, and treatment at a stable dose of 6 to 16 mg/week (2 or 3 times a week) for at least 8 weeks prior to the treatment period. The dose of MTX should remain stable throughout the study, but may be adjusted for safety reasons.

• For participants receiving corticosteroids, they must be on a dose not to exceed 10 mg of prednisone daily (or equivalent) and have been on the same dosing regimen for at least 6 weeks prior to the treatment period

• Have C-Reactive Protein (CRP) measurement > 0.5 milligrams/deciliter (mg/dL) or Erythrocyte Sedimentation Rate (ESR) > 28 millimeters/hour (mm/hr). The CRP and ESR may be repeated once during the screening period at the discretion of the investigator, and the repeat results may be accepted for study eligibility purposes

Exclusion Criteria:

• Use of nonsteroidal anti-inflammatories (NSAIDs) for less than 4 weeks prior to the treatment period. If on NSAIDs, must be on a stable dose of the drug for at least 4 weeks prior to the treatment period and must remain on a stable dose throughout the study

• Received prior treatment with an oral Janus Kinase (JAK) inhibitor regardless of when they received it

• Have a diagnosis of Felty's syndrome

• Evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies

• Have hepatitis C virus (HCV; positive for anti-hepatitis C antibody with confirmed presence of HCV)

• Positive for hepatitis B surface antigen (HBsAg+), OR negative for hepatitis B surface antigen (HBsAg-), but positive for hepatitis B core antibody (HBcAb+) and/or positive for hepatitis B surface antibody (HBsAb+) with positive Hepatitis B virus (HBV)-deoxyribonucleic acid (DNA) [≥2.1 Log copy/mL by Polymerase Chain Reaction (PCR) method] detected in the serum

• Have a positive result of the QuantiFERON®-tuberculosis (TB) Gold test (QFT-G) or a purified protein derivative (PPD) test

• Have estimated Glomerular Filtration Rate (GFR) from serum creatinine using the Modification of Diet in Renal Disease (MDRD) method of <50 milliliter/minute (mL/min)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Chiba		Japan	260-8712
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fukuoka		Japan	812-0025
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hiroshima		Japan	730-0017
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hokkaido		Japan	063-0811
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hyogo		Japan	673-1462
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ibaragi		Japan	316-0035
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kagoshima		Japan	890-0067
8	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kanagawa		Japan	252-0392
9	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nagasaki		Japan	857-1165
10	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Oita		Japan	870-0823
11	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Okayama		Japan	700-8607
12	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Osaka		Japan	586-8521
13	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tokyo		Japan	130-0013
14	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Toyama		Japan	933-0874

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01469013
• Other Study ID Numbers: 14116; I4V-JE-JADN
• First Posted: Nov 10, 2011
• Last Update Posted: Sep 20, 2019
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Methotrexate

Study Results

Participant Flow

Pre-assignment Detail	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)
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
Period Title: Part A (Treatment 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
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

Baseline Characteristics

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
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 Participants	24	24	24	24	49	145
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	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 (Count of Participants)
Female	22 91.7%	21 87.5%	19 79.2%	17 70.8%	39 79.6%	118 81.4%
Male	2 8.3%	3 12.5%	5 20.8%	7 29.2%	10 20.4%	27 18.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	24 100%	24 100%	24 100%	24 100%	49 100%	145 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	24 100%	24 100%	24 100%	24 100%	49 100%	145 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Japan	24 100%	24 100%	24 100%	24 100%	49 100%	145 100%

Outcome Measures

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 .
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

Outcome Measure Data

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
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.
Measure Participants	48	49
Number [percentage of participants]	77 320.8%	31 129.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: Combined 4 mg and 8 mg Baricitinib (LY3009104), Part A: Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments

2. Secondary Outcome

Title	Percentage of Participants Who Achieved an ACR20 Response at 64 Weeks
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

Outcome Measure Data

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)
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.
Measure Participants	71	70
Number [percentage of participants]	66 275%	73 304.2%

3. Secondary Outcome

Title	Percentage of Participants Who Achieved an ACR70 Response at 12 Weeks (Part A)
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

Outcome Measure Data

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
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.
Measure Participants	24	24	24	24	49
Number [percentage of participants]	13 54.2%	29 120.8%	29 120.8%	21 87.5%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: Combined 4 mg and 8 mg Baricitinib (LY3009104), Part A: Placebo, 4 mg Baricitinib (LY3009104), 8 mg Baricitinib (LY3009104), Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments
	Method	Cochran-Armitage trend test
	Comments

4. Secondary Outcome

Title	Percentage of Participants Who Achieved an ACR70 Response at 64 Weeks (Part B)
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

Outcome Measure Data

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)
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.
Measure Participants	71	70
Number [percentage of participants]	37 154.2%	34 141.7%

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)
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

Outcome Measure Data

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
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.
Measure Participants	24	24	24	24	49
Mean (Standard Deviation) [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)
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

Outcome Measure Data

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)
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.
Measure Participants	71	70
Mean (Standard Deviation) [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)
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

Outcome Measure Data

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
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.
Measure Participants	24	24	24	24	49
Number [percentage of participants]	83 345.8%	88 366.7%	92 383.3%	92 383.3%	47 95.9%

8. Secondary Outcome

Title	Percentage of Participants Who Achieved an EULAR28 Response at 64 Weeks (Part B)
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

Outcome Measure Data

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)
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.
Measure Participants	71	70
Number [percentage of participants]	94 391.7%	94 391.7%

9. Secondary Outcome

Title	Mean Change in Simplified Disease Activity Index (SDAI) Responses up to 12 Weeks (Part A)
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

Outcome Measure Data

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
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.
Measure Participants	24	24	24	24	49
Mean (Standard Deviation) [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)
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

Outcome Measure Data

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)
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.
Measure Participants	71	70
Mean (Standard Deviation) [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)
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

Outcome Measure Data

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
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.
Measure Participants	24	24	24	24	49
Mean (Standard Deviation) [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)
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

Outcome Measure Data

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)
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.
Measure Participants	71	70
Mean (Standard Deviation) [units on a scale]	-0.498 (0.4779)	-0.568 (0.6203)

13. Secondary Outcome

Title	Mean Value of ACR-N Response (Part A)
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

Outcome Measure Data

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
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.
Measure Participants	23	24	23	24	48
Mean (Standard Deviation) [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)
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

Outcome Measure Data

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)
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.
Measure Participants	55	54
Mean (Standard Deviation) [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)
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

Outcome Measure Data

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
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.
Measure Participants	24	24	24	24	49
Number [percentage of participants]	33 137.5%	33 137.5%	42 175%	50 208.3%	22 44.9%

16. Secondary Outcome

Title	Percentage of Participants Who Achieved a DAS28 Remission at 64 Weeks (Part B)
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

Outcome Measure Data

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)
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.
Measure Participants	71	70
Number [percentage of participants]	66 275%	66 275%

17. Secondary Outcome

Title	Percentage of Participants Who Achieved an SDAI Remission at 12 Weeks (Part A)
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

Outcome Measure Data

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
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.
Measure Participants	24	24	24	24	49
Number [percentage of participants]	4 16.7%	29 120.8%	17 70.8%	17 70.8%	8 16.3%

18. Secondary Outcome

Title	Percentage of Participants Who Achieved an SDAI Remission at 64 Weeks (Part B)
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

Outcome Measure Data

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)
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.
Measure Participants	71	70
Number [percentage of participants]	39 162.5%	39 162.5%

19. Secondary Outcome

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

Outcome Measure Data

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)
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.
Measure Participants	24	24	48	47
Geometric Mean (Geometric Coefficient of Variation) [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
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.

Outcome Measure Data

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)
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.
Measure Participants	24	24	48	47
Geometric Mean (Geometric Coefficient of Variation) [nM]	35.7 (20.9)	73.5 (22.5)	147 (20.6)	278 (21.7)

Adverse Events

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)
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 (%)	# 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	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
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%)		0/24 (0%)		1/24 (4.2%)		0/24 (0%)		1/24 (4.2%)		1/24 (4.2%)		1/12 (8.3%)		3/12 (25%)		3/23 (13%)		2/23 (8.7%)		2/11 (18.2%)		2/12 (16.7%)		6/24 (25%)
Cardiac disorders
Angina pectoris	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Myocardial infarction	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Ear and labyrinth disorders
Meniere's disease	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Eye disorders
Cataract	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	1/24 (4.2%)	1
Gastrointestinal disorders
Large intestine polyp	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Pancreatitis acute	0/49 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Hepatobiliary disorders
Cholecystitis	1/49 (2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Infections and infestations
Gastroenteritis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Herpes zoster	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/23 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	1/24 (4.2%)	1
Pneumocystis jirovecii pneumonia	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/24 (0%)	0
Pneumonia	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Injury, poisoning and procedural complications
Clavicle fracture	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Fall	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/23 (0%)	0	1/23 (4.3%)	1	1/11 (9.1%)	1	0/12 (0%)	0	0/24 (0%)	0
Forearm fracture	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Ulna fracture	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/24 (0%)	0
Investigations
Blood creatine phosphokinase increased	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/24 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal cancer	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Nervous system disorders
Cerebral haemorrhage	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/24 (0%)	0
Viith nerve paralysis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Vascular disorders
Deep vein thrombosis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Other (Not Including 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	26/49 (53.1%)		11/24 (45.8%)		12/24 (50%)		13/24 (54.2%)		17/24 (70.8%)		21/24 (87.5%)		11/12 (91.7%)		11/12 (91.7%)		22/23 (95.7%)		23/23 (100%)		11/11 (100%)		12/12 (100%)		23/24 (95.8%)
Blood and lymphatic system disorders
Anaemia	0/49 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	1/24 (4.2%)	1	1/24 (4.2%)	1	0/24 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	1/23 (4.3%)	2	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Haemorrhagic anaemia	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	2	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Iron deficiency anaemia	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	1/12 (8.3%)	1	0/24 (0%)	0
Leukopenia	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	2/24 (8.3%)	2	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	3/23 (13%)	4	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Lymphopenia	1/49 (2%)	1	0/24 (0%)	0	1/24 (4.2%)	1	1/24 (4.2%)	1	1/24 (4.2%)	1	1/24 (4.2%)	1	1/12 (8.3%)	1	0/12 (0%)	0	3/23 (13%)	4	3/23 (13%)	4	1/11 (9.1%)	1	1/12 (8.3%)	1	0/24 (0%)	0
Pancytopenia	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Cardiac disorders
Arrhythmia	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Bradycardia	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/24 (0%)	0
Sinus tachycardia	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Ventricular extrasystoles	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Congenital, familial and genetic disorders
Birth mark	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Ear and labyrinth disorders
Deafness neurosensory	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Tinnitus	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Vertigo	1/49 (2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Endocrine disorders
Thyroid mass	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Thyroiditis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/24 (0%)	0
Thyroiditis chronic	0/49 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Eye disorders
Cataract	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Conjunctivitis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Dry eye	1/49 (2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	2/24 (8.3%)	2	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Gastrointestinal disorders
Abdominal discomfort	1/49 (2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	1/23 (4.3%)	1	1/11 (9.1%)	1	0/12 (0%)	0	1/24 (4.2%)	1
Abdominal distension	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/24 (0%)	0
Abdominal pain	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	2	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	1/12 (8.3%)	1	0/24 (0%)	0
Abdominal pain upper	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	1/24 (4.2%)	1	1/12 (8.3%)	2	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Aphthous stomatitis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Cheilitis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Constipation	1/49 (2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	2/24 (8.3%)	2	2/12 (16.7%)	2	1/12 (8.3%)	1	0/23 (0%)	0	2/23 (8.7%)	2	1/11 (9.1%)	1	1/12 (8.3%)	1	1/24 (4.2%)	1
Dental caries	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	2/11 (18.2%)	2	0/12 (0%)	0	0/24 (0%)	0
Diarrhoea	0/49 (0%)	0	1/24 (4.2%)	1	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	2/23 (8.7%)	2	1/23 (4.3%)	1	0/11 (0%)	0	1/12 (8.3%)	1	0/24 (0%)	0
Dry mouth	1/49 (2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Duodenal ulcer	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Dyspepsia	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Food poisoning	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Gastric polyps	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Gastric ulcer	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/24 (0%)	0
Gastritis	0/49 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	3/23 (13%)	3	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Gastritis atrophic	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/24 (0%)	0
Gastritis erosive	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Gastrooesophageal reflux disease	1/49 (2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Hyperchlorhydria	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/24 (0%)	0
Mouth ulceration	1/49 (2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Nausea	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	2/24 (8.3%)	2	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	2/12 (16.7%)	2	0/24 (0%)	0
Pancreatitis chronic	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Periodontal disease	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/24 (0%)	0
Stomatitis	0/49 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	1/24 (4.2%)	1	0/24 (0%)	0	3/24 (12.5%)	3	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	2/24 (8.3%)	4
Vomiting	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/24 (0%)	0
General disorders
Chest discomfort	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Chest pain	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Fatigue	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Malaise	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/24 (0%)	0
Mass	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/24 (0%)	0
Oedema	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Oedema peripheral	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	1/11 (9.1%)	1	0/12 (0%)	0	0/24 (0%)	0
Pyrexia	2/49 (4.1%)	2	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Hepatobiliary disorders
Cholelithiasis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Gallbladder polyp	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Hepatic cyst	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Hepatic function abnormal	0/49 (0%)	0	0/24 (0%)	0	3/24 (12.5%)	3	0/24 (0%)	0	3/24 (12.5%)	3	1/24 (4.2%)	2	2/12 (16.7%)	2	1/12 (8.3%)	1	3/23 (13%)	4	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	2/24 (8.3%)	2
Hepatic steatosis	0/49 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Liver injury	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Immune system disorders
Allergy to arthropod sting	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/24 (0%)	0
Seasonal allergy	1/49 (2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Infections and infestations
Acute tonsillitis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	2/23 (8.7%)	2	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Appendicitis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Bacteriuria	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/24 (0%)	0
Bronchitis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	1/12 (8.3%)	1	0/12 (0%)	0	1/23 (4.3%)	2	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	1/24 (4.2%)	1
Cellulitis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Chronic sinusitis	0/49 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Cystitis	2/49 (4.1%)	2	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	1/23 (4.3%)	1	1/11 (9.1%)	1	1/12 (8.3%)	1	2/24 (8.3%)	2
Diverticulitis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Eczema impetiginous	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Empyema	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/24 (0%)	0
Enteritis infectious	0/49 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/24 (0%)	0
Enterocolitis bacterial	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Folliculitis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Fungal paronychia	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Fungal skin infection	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Furuncle	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Gastroenteritis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	1/23 (4.3%)	1	0/11 (0%)	0	1/12 (8.3%)	1	1/24 (4.2%)	2
Gastroenteritis norovirus	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Gastroenteritis viral	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	2	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Genital herpes	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Gingivitis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Helicobacter infection	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/24 (0%)	0
Herpes simplex	0/49 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Herpes virus infection	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Herpes zoster	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1	2/12 (16.7%)	2	1/23 (4.3%)	1	1/23 (4.3%)	1	1/11 (9.1%)	1	0/12 (0%)	0	2/24 (8.3%)	2
Influenza	1/49 (2%)	1	1/24 (4.2%)	1	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	1/23 (4.3%)	1	1/23 (4.3%)	1	0/11 (0%)	0	1/12 (8.3%)	1	1/24 (4.2%)	1
Molluscum contagiosum	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Nasopharyngitis	6/49 (12.2%)	7	2/24 (8.3%)	2	2/24 (8.3%)	2	2/24 (8.3%)	2	2/24 (8.3%)	2	4/24 (16.7%)	4	5/12 (41.7%)	6	6/12 (50%)	6	7/23 (30.4%)	8	9/23 (39.1%)	15	1/11 (9.1%)	1	1/12 (8.3%)	2	5/24 (20.8%)	9
Oesophageal candidiasis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/24 (0%)	0
Oral candidiasis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Oral herpes	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	1/23 (4.3%)	1	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Paronychia	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	2/23 (8.7%)	2	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Periodontitis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Pertussis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	2/24 (8.3%)	2	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Pharyngitis	1/49 (2%)	1	1/24 (4.2%)	1	1/24 (4.2%)	1	0/24 (0%)	0	2/24 (8.3%)	2	2/24 (8.3%)	6	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	2/24 (8.3%)	2
Pneumonia	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Pulpitis dental	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	1/24 (4.2%)	1
Rhinitis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Sinusitis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Skin candida	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Skin infection	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Tinea pedis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Tinea versicolour	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Tonsillitis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Upper respiratory tract infection	1/49 (2%)	1	1/24 (4.2%)	2	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	2/23 (8.7%)	2	1/23 (4.3%)	1	1/11 (9.1%)	1	0/12 (0%)	0	1/24 (4.2%)	1
Urinary tract infection	1/49 (2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Viral infection	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Viral rash	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Vulval abscess	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Injury, poisoning and procedural complications
Arthropod bite	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Arthropod sting	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/24 (0%)	0
Chillblains	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Contusion	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	2/24 (8.3%)	2
Fall	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/24 (0%)	0
Foot fracture	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Humerus fracture	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Laceration	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	2/12 (16.7%)	2	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Ligament sprain	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Lip injury	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/24 (0%)	0
Rib fracture	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Sternal fracture	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Thermal burn	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Tooth fracture	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/24 (0%)	0
Investigations
Alanine aminotransferase increased	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	1/23 (4.3%)	1	2/23 (8.7%)	2	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Aspartate aminotransferase increased	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	1/23 (4.3%)	1	2/23 (8.7%)	2	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Blood cholesterol increased	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Blood creatine phosphokinase increased	2/49 (4.1%)	2	0/24 (0%)	0	0/24 (0%)	0	2/24 (8.3%)	2	3/24 (12.5%)	3	4/24 (16.7%)	4	1/12 (8.3%)	1	0/12 (0%)	0	3/23 (13%)	3	4/23 (17.4%)	5	2/11 (18.2%)	2	2/12 (16.7%)	3	2/24 (8.3%)	2
Blood creatinine increased	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	2	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Catheterisation cardiac	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Cell marker increased	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	2/24 (8.3%)	2	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	1/11 (9.1%)	1	1/12 (8.3%)	1	1/24 (4.2%)	1
Colonoscopy	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Electrocardiogram st-t segment abnormal	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Endoscopy	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Eosinophil count increased	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Glomerular filtration rate decreased	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Hepatic enzyme abnormal	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Lipids abnormal	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Liver function test abnormal	0/49 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	2/24 (8.3%)	2	2/24 (8.3%)	2	0/24 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Low density lipoprotein increased	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Lymphocyte count decreased	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	1/24 (4.2%)	2	1/12 (8.3%)	1	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Oesophagogastroduodenoscopy	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Transaminases increased	1/49 (2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Weight decreased	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Weight increased	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	2	0/24 (0%)	0
Metabolism and nutrition disorders
Dyslipidaemia	0/49 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/24 (0%)	0
Hypercholesterolaemia	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	3/24 (12.5%)	3	1/24 (4.2%)	1	0/12 (0%)	0	1/12 (8.3%)	1	3/23 (13%)	3	2/23 (8.7%)	2	1/11 (9.1%)	1	0/12 (0%)	0	3/24 (12.5%)	3
Hyperlipidaemia	1/49 (2%)	1	1/24 (4.2%)	1	1/24 (4.2%)	1	0/24 (0%)	0	1/24 (4.2%)	1	1/24 (4.2%)	1	1/12 (8.3%)	1	0/12 (0%)	0	1/23 (4.3%)	1	3/23 (13%)	3	2/11 (18.2%)	2	1/12 (8.3%)	1	3/24 (12.5%)	3
Hypoglycaemia	0/49 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	1/49 (2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Intervertebral disc degeneration	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Intervertebral disc protrusion	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	1/12 (8.3%)	1	0/24 (0%)	0
Lumbar spinal stenosis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Muscle spasms	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	1/23 (4.3%)	1	1/11 (9.1%)	1	0/12 (0%)	0	1/24 (4.2%)	1
Myalgia	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Osteoarthritis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Osteoporosis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	1/12 (8.3%)	1	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Pain in extremity	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Spinal column stenosis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Spinal osteoarthritis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	2/24 (8.3%)	2	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pyogenic granuloma	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Skin papilloma	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Uterine leiomyoma	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/23 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/24 (0%)	0
Nervous system disorders
Cubital tunnel syndrome	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/24 (0%)	0
Dizziness	0/49 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Dizziness postural	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Headache	1/49 (2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	2/24 (8.3%)	2	1/12 (8.3%)	1	1/12 (8.3%)	1	1/23 (4.3%)	1	1/23 (4.3%)	1	1/11 (9.1%)	1	0/12 (0%)	0	1/24 (4.2%)	1
Hyposmia	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Intercostal neuralgia	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Migraine	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Neuropathy peripheral	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Sciatica	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1	1/12 (8.3%)	1	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Syncope	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Visual field defect	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Psychiatric disorders
Anxiety disorder	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Dysphoria	0/49 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Head banging	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Insomnia	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	3/24 (12.5%)	3	0/12 (0%)	0	1/12 (8.3%)	1	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Renal and urinary disorders
Hypertonic bladder	1/49 (2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Leukocyturia	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/24 (0%)	0
Nephrolithiasis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Pollakiuria	1/49 (2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Renal cyst	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Renal impairment	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	1/12 (8.3%)	1	1/24 (4.2%)	1
Reproductive system and breast disorders
Dysmenorrhoea	0/39 (0%)	0	0/22 (0%)	0	0/21 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/21 (0%)	0	1/10 (10%)	1	0/9 (0%)	0	0/18 (0%)	0	0/17 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/17 (0%)	0
Menstrual disorder	1/39 (2.6%)	1	0/22 (0%)	0	0/21 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/21 (0%)	0	0/10 (0%)	0	0/9 (0%)	0	0/18 (0%)	0	0/17 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/17 (0%)	0
Ovarian cyst	0/39 (0%)	0	0/22 (0%)	0	0/21 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/21 (0%)	0	0/10 (0%)	0	1/9 (11.1%)	1	0/18 (0%)	0	1/17 (5.9%)	1	0/11 (0%)	0	0/12 (0%)	0	0/17 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	1/49 (2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	2	1/12 (8.3%)	1	0/12 (0%)	0	1/23 (4.3%)	2	2/23 (8.7%)	2	0/11 (0%)	0	1/12 (8.3%)	1	0/24 (0%)	0
Hyperventilation	1/49 (2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Interstitial lung disease	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Nasal congestion	0/49 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Oropharyngeal pain	0/49 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Rhinorrhoea	1/49 (2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Upper respiratory tract inflammation	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	1/23 (4.3%)	1	1/23 (4.3%)	1	2/11 (18.2%)	3	1/12 (8.3%)	1	0/24 (0%)	0
Skin and subcutaneous tissue disorders
Acne	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Acne cystic	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	2
Angioedema	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Dermal cyst	0/49 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Dermatitis contact	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Drug eruption	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Eczema	1/49 (2%)	1	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	1/23 (4.3%)	3	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Eczema asteatotic	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Erythema	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Haemorrhage subcutaneous	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Hyperkeratosis	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/24 (0%)	0
Miliaria	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Photosensitivity reaction	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/24 (0%)	0
Pruritus	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	1/23 (4.3%)	1	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Rash	0/49 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	1/11 (9.1%)	1	0/12 (0%)	0	0/24 (0%)	0
Toxic skin eruption	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Urticaria	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	1/24 (4.2%)	1	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Xanthoma	0/49 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/24 (0%)	0
Surgical and medical procedures
Cholecystectomy	1/49 (2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Coronary angioplasty	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Drug delivery device implantation	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
External fixation of fracture	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Gastrointestinal endoscopic therapy	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/24 (4.2%)	1
Internal fixation of fracture	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Intraocular lens implant	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	1/24 (4.2%)	2
Medical device removal	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Open reduction of fracture	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Removal of foreign body	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/24 (0%)	0
Tooth extraction	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	2/23 (8.7%)	2	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Wound treatment	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	2	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Vascular disorders
Hypertension	0/49 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/23 (0%)	0	1/23 (4.3%)	1	1/11 (9.1%)	1	0/12 (0%)	0	1/24 (4.2%)	1
Phlebitis	0/49 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	3	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0
Varicose vein	0/49 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0	0/12 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/24 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.