FLEX O: A Rheumatoid Arthritis Study in Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01202760
• Collaborator: (none)
• Enrollment: 1,004
• Locations: 213
• Arms: 3
• Duration (Months): 30
• Patients Per Site: 4.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The primary purpose of this study is to help answer if LY2127399 is safe and effective in the treatment of rheumatoid arthritis with or without background disease-modifying anti-rheumatic drug (DMARD) therapy.

This study is comprised of 2 periods:

Period 1 - 24-week blinded treatment

Period 2 - 48-week post-treatment follow-up

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: LY2127399; Drug: Placebo	Phase 3

Detailed Description

In consideration of disease severity, all participants were assessed for non-response at Week 16. A total of 66 joints were examined for swelling, and a total of 66 joint were examined for tenderness. For participants who had at least 5 swollen and 5 tender joints at baseline, Week 16 non-responders (NRs) were defined as participants with <20% improvement from baseline in both tender joint counts and swollen joint counts. For participants who did not have at least 5 swollen and 5 tender joints at baseline, Week 16 NRs were defined as participants who had at least 2 additional tender and 2 additional swollen joints from baseline. All Week 16 NRs and all participants who discontinued study treatment at any time, for any reason, were defined as NRs starting at that timepoint and going forward for all American College of Rheumatology (ACR) imputed analyses, including the Week 24 endpoint.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1004 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of LY2127399 in Patients With Rheumatoid Arthritis (RA) With or Without Background Disease-Modifying Anti-rheumatic Drug (DMARD) Therapy (FLEX O)
• Study Start Date: Jan 1, 2011
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Jul 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 120 mg LY2127399 LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240-mg (2 SC injections of 120 mg each) loading dose of LY2127399 when initiating treatment. During the Treatment Period, for blinding purposes, participants alternated injections of LY2127399 and injections of Placebo every 2 weeks. After 16 weeks, non-responders received 90 mg of LY2127399 every 2 weeks for the rest of the 24-week Treatment Period.	Drug: LY2127399; Other Names: Tabalumab ; Drug: Placebo
Experimental: 90 mg LY2127399 LY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180-mg (2 SC injections of 90 mg each) loading dose of LY2127399 when initiating treatment. After 16 weeks, non-responders continued to receive 90 mg of LY2127399 every 2 weeks for the rest of the 24-week Treatment Period.	Drug: LY2127399; Other Names: Tabalumab
Placebo Comparator: Placebo Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections of Placebo when initiating treatment. After 16 weeks, non-responders received 90 milligrams (mg) of LY2127399 every 2 weeks for the rest of the 24-week Treatment Period.	Drug: LY2127399; Other Names: Tabalumab ; Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With American College of Rheumatology 20% (ACR20) Response [Up to 24 weeks]

   ACR20 Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis. ACR20 Responder: had >=20% improvement from baseline in both 68 tender and 66 swollen joint counts and >=20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and C-reactive protein (CRP). Percentage of participants achieving ACR20 response=(number of ACR20 responders/number of participants treated)*100. All non-responders at Week 16 as well as all participants who discontinued study treatment at any time, for any reason, were defined as non-responders starting at that timepoint and going forward, including Week 24 endpoint.

Secondary Outcome Measures

1. Percentage of Participants With American College of Rheumatology 50% (ACR50) and 70% (ACR70) Responses [Up to 24 weeks]

   ACR Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis. ACR50 Responder: had >=50% improvement from baseline in both 68 tender joint (TJ) and 66 swollen joint (SJ) counts and >=50% improvement in at least 3/5 criteria: participant's (Pt's) and physician's global assessment of disease activity, HAQ-DI (measured Pts' perceived degree of difficulty performing daily activities), joint pain, and CRP. Percentage of Pt achieving ACR50 response=(number (No) of ACR50 responders/No of Pts treated)*100. ACR70 Responder: had >=70% improvement from baseline in both TJ and SJ counts and >=70% improvement in at least 3 of same 5 criteria for ACR50. Percentage of Pts achieving ACR70 response=(No of ACR70 responders/No of Pts treated)*100. All non-responders at Week 16 as well as all Pts who discontinued study treatment at any time, for any reason, were defined as non-responders starting at that timepoint and going forward, including Week 24 endpoint.

2. Mean Percent Improvement in American College of Rheumatology Percent Improvement (ACR-N) [Up to 24 weeks]

   ACR-N is a continuous measure of clinical, laboratory, and functional outcomes in rheumatoid arthritis that characterizes percentage of improvement in disease activity from baseline based on ACR core set. Percentage of improvement was truncated to range of -100 to 100 to minimize impact of outliers (greater values indicate greater percent improvement). This index was calculated as minimum of a) percentage of improvement in TJ count, b) percentage of improvement in SJ count, or c) third highest percentage of improvement of remaining 5 ACR core criteria: If >=3 components of the 5 ACR core criteria were missing, then c) was set to missing; if any of 3 components a), b), or c) were missing, then ACR-N was set to missing. Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with treatment, region, tumor necrosis factor-inadequate responder treatment history, and disease-modifying anti-rheumatic drug (DMARD) background as fixed factors and baseline as a covariate.

3. Change From Baseline to 24 Weeks in Tender Joint Count (68 Joint Count) [Baseline, up to 24 weeks]

   Tender joint count is the number of tender and painful joints determined for each participant by examination of 68 joints. Joints were assessed by pressure and joint manipulation on physical examination. Participants were asked for pain sensations on these manipulations and watched for spontaneous pain reactions. Any positive response on pressure, movement, or both is translated into a single tender-versus-nontender dichotomy. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.

4. Change From Baseline to 24 Weeks in Swollen Joint Count (66 Joint Count) [Baseline, up to 24 weeks]

   Swollen joint count is the number of swollen joints determined for each participant by examination of 66 joints. Joints were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.

5. Change From Baseline to 24 Weeks in Participant's Assessment of Pain (Visual Analog Scale) [Baseline, up to 24 weeks]

   Participant's assessment of their current arthritis pain using a visual analog scale (VAS) ranged from 0 millimeters (mm) (no pain) to 100 mm (worst possible pain). A decrease in pain score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.

6. Change From Baseline to 24 Weeks in Participant's Global Assessment of Disease Activity (Visual Analog Scale) [Baseline, up to 24 weeks]

   Participant's assessment of their current arthritis disease activity using a visual analog scale (VAS) ranged from 0 millimeters (mm) (no arthritis activity) to 100 mm (extremely active arthritis). A decrease in disease activity score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.

7. Change From Baseline to 24 Weeks in Physician's Global Assessment of Disease Activity (Visual Analog Scale) [Baseline, up to 24 weeks]

   Physician's assessment of the participant's current arthritis disease activity using a visual analog scale (VAS) ranged from 0 millimeters (mm) (no arthritis activity) to 100 mm (extremely active arthritis). A decrease in disease activity score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.

8. Change From Baseline to 24 Weeks in Disease Activity Score (Based on 28 Joint Count)-C-Reactive Protein (DAS28-CRP) [Baseline, up to 24 weeks]

   Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP) (milligrams per liter), and participant global assessment of disease activity using visual analog scale (VAS) (participant global VAS). DAS28-CRP was calculated using following formula: DAS28-CRP=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.36*natural log(CRP+1)+0.014*participant global VAS+0.96. Scores ranged 1.0-9.4, where lower scores indicated less disease activity and remission is DAS28-CRP <2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.

9. Change From Baseline to 24 Weeks in Health Assessment Questionnaire-Disability Index (HAQ-DI) [Baseline, up to 24 weeks]

   The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty [0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area, which ranged from 0 (no disability) to 3 (severe disability), were averaged to calculate HAQ-DI. A decrease in HAQ-DI score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.

10. Time to American College of Rheumatology 20% (ACR20) Response [Baseline through 24 weeks]

    ACR20 Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis. ACR20 Responder: had >= 20% improvement from baseline in both 68 tender and 66 swollen joint counts and >=20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and C-reactive protein (CRP). The Kaplan-Meier estimator was used to summarize time to ACR20 response over the Treatment Period (24 weeks). The time to American College of Rheumatology 20% (ACR20) response (in weeks) is calculated as: (Date of the first postbaseline visit during the Treatment Period meeting ACR20 response criteria - Date of first injection of study treatment + 1) / 7.

11. Probability of an ACR20 Response by 24 Weeks [Baseline through 24 weeks]

    ACR20 Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis. ACR20 Responder: had >= 20% improvement from baseline in both 68 tender and 66 swollen joint counts and >=20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and C-reactive protein (CRP). The Kaplan-Meier estimator was used to summarize time to ACR20 response over the Treatment Period (24 weeks). The time to American College of Rheumatology 20% (ACR20) response (in weeks) is calculated as: (Date of the first postbaseline visit during the Treatment Period meeting ACR20 response criteria - Date of first injection of study treatment + 1) / 7.

12. Percentage of Participants With DAS28-Based European League Against Rheumatism (EULAR) Response [Up to 24 weeks]

    EULAR Responder index based on 28 joint count categorizes clinical response based on improvement since baseline in DAS28-CRP. Participants are categorized as EULAR responders or non-responders based on improvement of DAS28-CRP scores from baseline. EULAR28 responder is defined as either DAS28-CRP <=5.1 and DAS28-CRP change <-0.6; or DAS28-CRP >5.1 and DAS28-CRP change <-1.2. EULAR28 responder index is defined as good response: DAS28-CRP <=3.2 and DAS28-CRP change <-1.2; moderate response: DAS28-CRP change <-1.2 except cases defined in good response; or DAS28-CRP <=5.1 and DAS28-CRP change <-0.6 and >-1.2. EULAR Remission is defined as a DAS28-CRP score of <2.6.

13. Change From Baseline to 24 Weeks in Medical Outcomes Study 36-Item Short Form (SF-36) Health Status Survey Domain and Summary Scores [Baseline, up to 24 weeks]

    The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, and 2 component scores (mental [MCS] and physical health [PCS]). Domain scores calculated by summing each item for each domain and transforming scores into 0-100 scale; higher scores indicated better health status. MCS score consisted of social functioning, vitality, mental health, and role-emotional scales. PCS score consisted of physical functioning, bodily pain, role-physical, and general health scales. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.

14. Change From Baseline in C-reactive Protein (CRP) up to Week 24 Endpoint [Baseline, up to 24 weeks]

    CRP is an indicator of inflammation. A negative change indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.

15. Change From Baseline to 24 Weeks in Absolute CD3-CD20+ B-cell Counts [Baseline, up to 24 weeks]

    Cell-surface marker cluster designation (CD) 3 negative, CD20 positive (CD3-CD20+) defines total mature B cells. B-lymphocyte antigen CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all mature B cells. Baseline B-cell count is determined by calculating the average of the 2 pretreatment B-cell counts obtained once during Days -28 through -7 and on Day 0. A positive or negative change indicated an increase or decrease, respectively in B-cell count. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.

16. Change From Baseline to 24 Weeks in Serum Immunoglobulin (Ig) Levels [Baseline, up to 24 weeks]

    Immunoglobulins, or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Change from baseline serum immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) levels are reported. A negative change indicated a decrease in immunoglobulin levels. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.

17. Population Pharmacokinetics (PK) [Baseline through 24 weeks]

    Population estimate of constant clearance as determined by population pharmacokinetics (PK) analysis. A 2-compartment model was used in PK modeling.

18. Percentage of Participants Developing Anti-LY2127399 Antibodies [Baseline through 24 weeks]

    LY2127399 anti-drug antibodies (ADA) were assessed at baseline, 1, 4, 16, and 24 weeks. Percentage of participants (Pts) with ADA=(number of Pts with treatment-emergent ADA/number of Pts assessed)*100. Pts with treatment-emergent ADA were Pts who had any sample from baseline up to and through Week 24 that was a 4-fold increase (2-dilution increase) in immunogenicity titer over baseline titer, or Pts who tested negative at baseline and positive post-baseline (at titer of ≥1:20).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of Rheumatoid Arthritis (RA) of more than 6 months and less than 15 years

• Global Assessment of Disease Activity visual analog scale (VAS) greater than or equal to 20/100 millimeters (mm)

• If on one or more conventional disease-modifying anti-rheumatic Drugs (DMARDs) at randomization, must have been on a stable dose for at least 8 weeks prior to study start.

• Women must not be pregnant, breastfeeding, or become pregnant during the study

Exclusion Criteria:

• Use of unstable doses of non-steroidal inflammatory drugs (NSAIDS) in the past 6 weeks

• Steroid injection or intravenous (IV) infusion in the last 6 weeks

• Use of more than 10 milligrams per day (mg/day) of oral steroids in the last 6 weeks

• Use of biologic DMARD concurrently or recently

• History of a serious reaction to other biological DMARDs

• Use of an oral calcineurin inhibitor (for example, cyclosporin or tacrolimus) in the last 8 weeks

• Surgery on a joint or other major surgery less than 2 months prior to study start, or plans to have joint surgery or major surgery during the study

• Active fibromyalgia, juvenile chronic arthritis, spondyloarthropathy, Crohn's disease, ulcerative colitis, psoriatic arthritis, or other systemic inflammatory condition except RA

• Cervical cancer or squamous skin cancer within the past 3 years, or other cancer within the past 5 years

• Received a live vaccine within the past 12 weeks (for example, vaccines for measles, mumps, rubella, and chicken pox, and nasal-spray flu vaccines)

• Hepatitis or human immunodeficiency virus (HIV)

• A serious bacterial infection (for example, pneumonia or cellulitis) within 3 months or a serious bone or joint infection within 6 months

• Symptoms of herpes zoster or herpes simplex within the last month

• Active or latent tuberculosis (TB)

• Current symptoms of a serious disorder or illness

• Use of an investigational drug within the last month

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.	Birmingham	Alabama	United States	35216
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.	Paradise Valley	Arizona	United States	85253
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.	Peoria	Arizona	United States	85381
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.	Phoenix	Arizona	United States	85018
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.	Scottsdale	Arizona	United States	85251
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.	Tucson	Arizona	United States	85704
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.	Hot Springs	Arkansas	United States	71913
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.	Little Rock	Arkansas	United States	72205
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.	San Diego	California	United States	92103
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.	Torrance	California	United States	90505
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.	Tustin	California	United States	92780
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.	Whittier	California	United States	90606
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.	Wildomar	California	United States	92595
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.	Colorado Springs	Colorado	United States	80910
15	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.	Lewes	Delaware	United States	19958
16	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.	Aventura	Florida	United States	33180
17	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.	DeBary	Florida	United States	32713
18	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.	Palm Harbor	Florida	United States	34684
19	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.	Pinellas Park	Florida	United States	33781
20	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.	Saint Petersburg	Florida	United States	33716
21	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.	Tamarac	Florida	United States	33321
22	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.	Venice	Florida	United States	34292
23	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.	Zephyrhills	Florida	United States	33542
24	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.	Decatur	Georgia	United States	30033
25	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.	Gainesville	Georgia	United States	30501
26	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.	Lawrenceville	Georgia	United States	30045
27	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.	Marietta	Georgia	United States	30060
28	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.	Savannah	Georgia	United States	31405
29	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.	Eagle	Idaho	United States	83616
30	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.	Morton Grove	Illinois	United States	60053
31	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.	Rockford	Illinois	United States	61103
32	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.	Indianapolis	Indiana	United States	46227
33	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.	Wichita	Kansas	United States	67208
34	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.	Cumberland	Maryland	United States	21502
35	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.	Hyannis	Massachusetts	United States	02601
36	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.	Worcester	Massachusetts	United States	01605
37	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.	Bingham Farms	Michigan	United States	48025
38	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.	Saint Clair Shores	Michigan	United States	48081
39	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.	Flowood	Mississippi	United States	39232
40	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.	Jackson	Mississippi	United States	39202
41	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.	Saint Louis	Missouri	United States	63131
42	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.	Lincoln	Nebraska	United States	68516
43	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.	Omaha	Nebraska	United States	68134
44	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.	Las Vegas	Nevada	United States	89123
45	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.	Albuquerque	New Mexico	United States	87108
46	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.	Brooklyn	New York	United States	11201
47	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.	Roslyn	New York	United States	11576
48	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.	Syracuse	New York	United States	13210
49	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.	Charlotte	North Carolina	United States	28210
50	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.	Hickory	North Carolina	United States	28601
51	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.	Raleigh	North Carolina	United States	27609
52	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.	Cincinnati	Ohio	United States	45242
53	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.	Oklahoma City	Oklahoma	United States	73103
54	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.	Tulsa	Oklahoma	United States	74135
55	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.	Bend	Oregon	United States	97701
56	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.	Bethlehem	Pennsylvania	United States	18017
57	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.	Limerick	Pennsylvania	United States	19468
58	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.	Philadelphia	Pennsylvania	United States	19152
59	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.	Pottstown	Pennsylvania	United States	19464
60	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.	Columbia	South Carolina	United States	29204
61	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.	Greenville	South Carolina	United States	29601
62	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.	Greer	South Carolina	United States	29650
63	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.	Myrtle Beach	South Carolina	United States	29572
64	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.	North Charleston	South Carolina	United States	29406
65	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.	Knoxville	Tennessee	United States	37909
66	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.	Memphis	Tennessee	United States	38119
67	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.	Nashville	Tennessee	United States	37205
68	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.	Austin	Texas	United States	78731
69	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.	Dallas	Texas	United States	75231
70	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.	Lake Jackson	Texas	United States	77566
71	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.	Lubbock	Texas	United States	79424
72	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.	Mesquite	Texas	United States	75150
73	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.	Nassau Bay	Texas	United States	77058
74	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.	North Richland Hills	Texas	United States	76180
75	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.	San Antonio	Texas	United States	78217
76	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.	Sugar Land	Texas	United States	77478
77	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.	Spokane	Washington	United States	99204
78	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.	Buenos Aires		Argentina	C1280AEB
79	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.	Córdoba		Argentina	X5016KEH
80	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.	Mar Del Plata		Argentina	B7600FZN
81	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.	Rosario		Argentina	2000
82	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.	San Juan		Argentina	5400
83	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.	Tucuman		Argentina	4000
84	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.	Kogarah	New South Wales	Australia	04266-010
85	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.	Herston	Queensland	Australia	4029
86	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.	Malvern East		Australia	3145
87	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.	Burgas		Bulgaria	8000
88	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.	Pleven		Bulgaria	5800
89	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.	Plovdiv		Bulgaria	4003
90	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.	Rousse		Bulgaria	7002
91	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.	Sevlievo		Bulgaria	5400
92	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.	Sofia		Bulgaria	1784
93	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.	Varna		Bulgaria	9000
94	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.	Bogota		Colombia
95	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.	Medellin		Colombia
96	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.	Opatija		Croatia	51410
97	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.	Rijeka		Croatia	HR-51000
98	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.	Split		Croatia	21000
99	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.	Budapest		Hungary	1036
100	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.	Debrecen		Hungary	4032
101	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.	Kiskunhalas		Hungary	6400
102	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.	Nyiregyhaza		Hungary	4400
103	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.	Satoraljaujhely		Hungary	3980
104	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.	Szikszo		Hungary	3800
105	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.	Veszprem		Hungary	8200
106	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.	Ahmedabad		India	3800015
107	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.	Bangalore		India	5600092
108	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.	Chennai		India	600100
109	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.	Hyderabaad		India	500033
110	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.	Jaipur		India	302023
111	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.	Mysore		India	570023
112	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.	Nellore		India	524003
113	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.	New Delhi		India	110 076
114	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.	Secunderabad		India	500 003
115	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.	Surat		India	560092
116	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.	Aichi		Japan	460-0001
117	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	820-8505
118	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.	Gunma		Japan	370-0053
119	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
120	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	650-0017
121	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
122	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
123	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.	Kumamoto		Japan	861-8520
124	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.	Mie		Japan	514-1101
125	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.	Miyagi		Japan	982-0032
126	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.	Nagano		Japan	390-8601
127	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	857-1195
128	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.	Nara		Japan	634-0007
129	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.	Ohita		Japan	874-0011
130	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	712-8044
131	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
132	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.	Saga		Japan	843-0393
133	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.	Saitama		Japan	337-0012
134	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.	Sapporo-Shi		Japan	060-8648
135	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.	Shizuoka		Japan	420-8623
136	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	185-0012
137	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.	Tomakomai		Japan	053-8567
138	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.	Busan		Korea, Republic of	602-715
139	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.	Daegu		Korea, Republic of	700-721
140	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.	Seoul		Korea, Republic of	134-727
141	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.	Alytus		Lithuania	62114
142	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.	Kaunas		Lithuania	49475
143	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.	Klaipedos		Lithuania	92288
144	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.	Siauliai		Lithuania	73231
145	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.	Vilnius		Lithuania	LT-08661
146	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.	Batu Caves		Malaysia	68100
147	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.	Kuantan Pahang		Malaysia	25100
148	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.	Perak		Malaysia	30990
149	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.	Sarawak		Malaysia	93586
150	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.	Aguascalientes		Mexico	20203
151	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.	Chihuahua		Mexico	31000
152	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.	Guadalajara		Mexico	44690
153	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.	Mexicali		Mexico	21100
154	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.	Mexico City		Mexico	06100
155	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.	Monterrey		Mexico	64000
156	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.	Morelia		Mexico	58070
157	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.	Queretaro		Mexico	76000
158	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.	San Luis Potosi		Mexico	78200
159	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.	Tijuana		Mexico	22010
160	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.	Tlalpan		Mexico	14080
161	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.	Hamilton		New Zealand	3204
162	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.	Rotorua		New Zealand	3010
163	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.	Tauranga		New Zealand	3140
164	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.	Timaru		New Zealand
165	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.	Bydgoszcz		Poland	85-168
166	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.	Elblag		Poland	82-300
167	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.	Gdynia		Poland	81-384
168	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.	Krakow		Poland	30-510
169	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.	Lublin		Poland	20-607
170	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.	Torun		Poland	87-100
171	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.	Warsaw		Poland	01-192
172	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.	Brasov		Romania	500365
173	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.	Cluj-Napoca		Romania	400130
174	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.	Iasi		Romania	700656
175	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.	Ploiesti		Romania	100337
176	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.	Barnaul		Russian Federation	656038
177	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.	Kemerovo		Russian Federation	650066
178	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.	Kursk		Russian Federation	305007
179	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.	Moscow		Russian Federation	111539
180	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.	Nizhny Novgorod		Russian Federation	603005
181	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.	Novosibirsk		Russian Federation	630047
182	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.	Ryazan		Russian Federation	390026
183	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.	Saint Petersburg		Russian Federation	197022
184	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.	Stavropol		Russian Federation	355017
185	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.	Bratislava		Slovakia	84231
186	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.	Piestany		Slovakia	921 12
187	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.	Benoni		South Africa	1500
188	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.	Bloemfontein		South Africa	9301
189	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.	Breyten		South Africa	2330
190	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.	Cape Town		South Africa	7925
191	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.	Durban		South Africa	4092
192	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.	Limpopo		South Africa	0380
193	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.	Pretoria		South Africa	0184
194	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.	Somerset West		South Africa	7130
195	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.	Stellenbosch		South Africa	7600
196	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.	Westville		South Africa	3630
197	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.	Colombo		Sri Lanka
198	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.	Galle		Sri Lanka
199	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.	Kalubowila		Sri Lanka
200	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.	Nugegoda		Sri Lanka
201	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.	Keelong		Taiwan	333
202	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.	Kuei Shan Hsiang		Taiwan	33305
203	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.	Taichung		Taiwan	407
204	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.	Taipei		Taiwan	112
205	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.	Dnipropetrovsk		Ukraine	49008
206	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.	Donetsk		Ukraine	83045
207	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.	Kharkiv		Ukraine	61178
208	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.	Kiev		Ukraine	04114
209	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.	Kyiv		Ukraine	03151
210	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.	Odesa		Ukraine	65026
211	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.	Poltava		Ukraine	36038
212	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.	Simferopol		Ukraine	95017
213	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.	Vinnytsya		Ukraine	21018

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: NCT01202760
• Other Study ID Numbers: 12978; H9B-MC-BCDO; CTRI/2011/07/001867
• First Posted: Sep 16, 2010
• Last Update Posted: Apr 25, 2018
• Last Verified: Mar 1, 2018

• Keywords provided by Eli Lilly and Company: Rheumatoid Arthritis
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid

Study Results

Participant Flow

Arm/Group Title	120 mg LY2127399	90 mg LY2127399	Placebo
Arm/Group Description	LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240-mg (2 SC injections of 120 mg each) loading dose of LY2127399 when initiating treatment. During the Treatment Period, for blinding purposes, participants alternated injections of LY2127399 and injections of Placebo every 2 weeks. After 16 weeks, non-responders received 90 mg of LY2127399 every 2 weeks for the rest of the 24-week Treatment Period.	LY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180-mg (2 SC injections of 90 mg each) loading dose of LY2127399 when initiating treatment. After 16 weeks, non-responders continued to receive 90 mg of LY2127399 every 2 weeks for the rest of the 24-week Treatment Period.	Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections of Placebo when initiating treatment. After 16 weeks, non-responders received 90 milligrams (mg) of LY2127399 every 2 weeks for the rest of the 24-week Treatment Period.
Period Title: Overall Study
STARTED	379	374	251
Received at Least One Dose of Study Drug	379	371	250
COMPLETED	332	322	216
NOT COMPLETED	47	52	35

Baseline Characteristics

Arm/Group Title	120 mg LY2127399	90 mg LY2127399	Placebo	Total
Arm/Group Description	LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240-mg (2 SC injections of 120 mg each) loading dose of LY2127399 when initiating treatment. During the Treatment Period, for blinding purposes, participants alternated injections of LY2127399 and injections of Placebo every 2 weeks. After 16 weeks, non-responders received 90 mg of LY2127399 every 2 weeks for the rest of the 24-week Treatment Period.	LY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180-mg (2 SC injections of 90 mg each) loading dose of LY2127399 when initiating treatment. After 16 weeks, non-responders continued to receive 90 mg of LY2127399 every 2 weeks for the rest of the 24-week Treatment Period.	Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections of Placebo when initiating treatment. After 16 weeks, non-responders received 90 milligrams (mg) of LY2127399 every 2 weeks for the rest of the 24-week Treatment Period.	Total of all reporting groups
Overall Participants	379	374	251	1004
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.4 (11.2)	50.6 (12.2)	51.0 (12.0)	51.4 (11.8)
Sex: Female, Male (Count of Participants)
Female	293 77.3%	295 78.9%	209 83.3%	797 79.4%
Male	86 22.7%	79 21.1%	42 16.7%	207 20.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	38 10%	47 12.6%	24 9.6%	109 10.9%
Not Hispanic or Latino	193 50.9%	185 49.5%	133 53%	511 50.9%
Unknown or Not Reported	148 39.1%	142 38%	94 37.5%	384 38.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	13 3.4%	21 5.6%	9 3.6%	43 4.3%
Asian	96 25.3%	93 24.9%	59 23.5%	248 24.7%
Native Hawaiian or Other Pacific Islander	1 0.3%	1 0.3%	0 0%	2 0.2%
Black or African American	12 3.2%	13 3.5%	14 5.6%	39 3.9%
White	254 67%	235 62.8%	162 64.5%	651 64.8%
More than one race	2 0.5%	9 2.4%	6 2.4%	17 1.7%
Unknown or Not Reported	1 0.3%	2 0.5%	1 0.4%	4 0.4%
Region of Enrollment (Count of Participants)
United States	126 33.2%	125 33.4%	83 33.1%	334 33.3%
Argentina	7 1.8%	6 1.6%	5 2%	18 1.8%
Colombia	9 2.4%	9 2.4%	5 2%	23 2.3%
Mexico	20 5.3%	25 6.7%	15 6%	60 6%
Bulgaria	13 3.4%	13 3.5%	12 4.8%	38 3.8%
Croatia	2 0.5%	1 0.3%	3 1.2%	6 0.6%
Hungary	3 0.8%	12 3.2%	6 2.4%	21 2.1%
Lithuania	14 3.7%	10 2.7%	11 4.4%	35 3.5%
Poland	27 7.1%	22 5.9%	12 4.8%	61 6.1%
Romania	0 0%	1 0.3%	3 1.2%	4 0.4%
Russia	14 3.7%	13 3.5%	8 3.2%	35 3.5%
Slovakia	8 2.1%	3 0.8%	2 0.8%	13 1.3%
Ukraine	16 4.2%	15 4%	6 2.4%	37 3.7%
Australia	2 0.5%	3 0.8%	2 0.8%	7 0.7%
India	14 3.7%	9 2.4%	9 3.6%	32 3.2%
Japan	44 11.6%	42 11.2%	28 11.2%	114 11.4%
South Korea	7 1.8%	6 1.6%	5 2%	18 1.8%
Malaysia	2 0.5%	4 1.1%	1 0.4%	7 0.7%
New Zealand	6 1.6%	2 0.5%	6 2.4%	14 1.4%
Sri Lanka	4 1.1%	4 1.1%	2 0.8%	10 1%
South Africa	32 8.4%	38 10.2%	24 9.6%	94 9.4%
Taiwan	9 2.4%	11 2.9%	3 1.2%	23 2.3%
Tender Joint Count (68 Count) (joint count) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [joint count]	22.8 (15.5)	23.7 (17.1)	22.8 (15.2)	23.2 (16.0)
Swollen Joint Count (66 Count) (joint count) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [joint count]	14.8 (11.6)	15.3 (11.6)	14.3 (10.6)	14.8 (11.4)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With American College of Rheumatology 20% (ACR20) Response
Description	ACR20 Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis. ACR20 Responder: had >=20% improvement from baseline in both 68 tender and 66 swollen joint counts and >=20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and C-reactive protein (CRP). Percentage of participants achieving ACR20 response=(number of ACR20 responders/number of participants treated)*100. All non-responders at Week 16 as well as all participants who discontinued study treatment at any time, for any reason, were defined as non-responders starting at that timepoint and going forward, including Week 24 endpoint.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants with at least 5/68 tender joints and 5/66 swollen joints at baseline and with evaluable ACR20 data. If participant's CRP was missing, last postbaseline value was used. If ACR was missing after carrying forward CRP, last postbaseline ACR response was used. Data after Week 16 for Week 16 non-responders was not included.

Arm/Group Title	120 mg LY2127399	90 mg LY2127399	Placebo
Arm/Group Description	LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240 mg (2 SC injections of 120 mg each) loading dose when initiating treatment.	LY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180 mg (2 SC injections of 90 mg each) loading dose when initiating treatment.	Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections when initiating treatment.
Measure Participants	320	316	213
Number [percentage of participants]	34.4 9.1%	33.5 9%	31.5 12.5%

2. Secondary Outcome

Title	Percentage of Participants With American College of Rheumatology 50% (ACR50) and 70% (ACR70) Responses
Description	ACR Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis. ACR50 Responder: had >=50% improvement from baseline in both 68 tender joint (TJ) and 66 swollen joint (SJ) counts and >=50% improvement in at least 3/5 criteria: participant's (Pt's) and physician's global assessment of disease activity, HAQ-DI (measured Pts' perceived degree of difficulty performing daily activities), joint pain, and CRP. Percentage of Pt achieving ACR50 response=(number (No) of ACR50 responders/No of Pts treated)*100. ACR70 Responder: had >=70% improvement from baseline in both TJ and SJ counts and >=70% improvement in at least 3 of same 5 criteria for ACR50. Percentage of Pts achieving ACR70 response=(No of ACR70 responders/No of Pts treated)*100. All non-responders at Week 16 as well as all Pts who discontinued study treatment at any time, for any reason, were defined as non-responders starting at that timepoint and going forward, including Week 24 endpoint.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants with at least 5/68 TJ and 5/66 SJ at baseline and with evaluable ACR50 or ACR70 responder data. If participant's CRP was missing, last postbaseline value was used. If ACR was missing after carrying forward CRP, last postbaseline ACR response was used. Data after Week 16 for Week 16 non-responders was not included.

Arm/Group Title	120 mg LY2127399	90 mg LY2127399	Placebo
Arm/Group Description	LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240 mg (2 SC injections of 120 mg each) loading dose when initiating treatment.	LY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180 mg (2 SC injections of 90 mg each) loading dose when initiating treatment.	Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections when initiating treatment.
Measure Participants	320	316	213
ACR50	11.6 3.1%	11.7 3.1%	12.7 5.1%
ACR70	4.7 1.2%	6.3 1.7%	4.7 1.9%

3. Secondary Outcome

Title	Mean Percent Improvement in American College of Rheumatology Percent Improvement (ACR-N)
Description	ACR-N is a continuous measure of clinical, laboratory, and functional outcomes in rheumatoid arthritis that characterizes percentage of improvement in disease activity from baseline based on ACR core set. Percentage of improvement was truncated to range of -100 to 100 to minimize impact of outliers (greater values indicate greater percent improvement). This index was calculated as minimum of a) percentage of improvement in TJ count, b) percentage of improvement in SJ count, or c) third highest percentage of improvement of remaining 5 ACR core criteria: If >=3 components of the 5 ACR core criteria were missing, then c) was set to missing; if any of 3 components a), b), or c) were missing, then ACR-N was set to missing. Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with treatment, region, tumor necrosis factor-inadequate responder treatment history, and disease-modifying anti-rheumatic drug (DMARD) background as fixed factors and baseline as a covariate.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants with at least 5/68 tender joints and at least 5/66 swollen joints at baseline and with evaluable ACR-N data. Modified last observation carried forward (mLOCF) was used to impute missing postbaseline values. Data after Week 16 for Week 16 non-responders was not included.

Arm/Group Title	120 mg LY2127399	90 mg LY2127399	Placebo
Arm/Group Description	LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240 mg (2 SC injections of 120 mg each) loading dose when initiating treatment.	LY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180 mg (2 SC injections of 90 mg each) loading dose when initiating treatment.	Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections when initiating treatment.
Measure Participants	318	314	211
Least Squares Mean (Standard Error) [units on a scale]	-11.5 (4.6)	-9.5 (4.6)	-11.5 (5.0)

4. Secondary Outcome

Title	Change From Baseline to 24 Weeks in Tender Joint Count (68 Joint Count)
Description	Tender joint count is the number of tender and painful joints determined for each participant by examination of 68 joints. Joints were assessed by pressure and joint manipulation on physical examination. Participants were asked for pain sensations on these manipulations and watched for spontaneous pain reactions. Any positive response on pressure, movement, or both is translated into a single tender-versus-nontender dichotomy. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.
Time Frame	Baseline, up to 24 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants with at least 5/68 tender joints and at least 5/66 swollen joints at baseline and with evaluable tender joint count data. Modified last observation carried forward (mLOCF) was used to impute missing postbaseline values. Data after Week 16 for Week 16 non-responders was not included.

Arm/Group Title	120 mg LY2127399	90 mg LY2127399	Placebo
Arm/Group Description	LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240 mg (2 SC injections of 120 mg each) loading dose when initiating treatment.	LY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180 mg (2 SC injections of 90 mg each) loading dose when initiating treatment.	Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections when initiating treatment.
Measure Participants	318	315	211
Least Squares Mean (Standard Error) [joint count]	-1.61 (1.30)	-1.63 (1.31)	-2.11 (1.40)

5. Secondary Outcome

Title	Change From Baseline to 24 Weeks in Swollen Joint Count (66 Joint Count)
Description	Swollen joint count is the number of swollen joints determined for each participant by examination of 66 joints. Joints were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.
Time Frame	Baseline, up to 24 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants with at least 5/68 tender joints and at least 5/66 swollen joints at baseline and with evaluable swollen joint count data. Modified last observation carried forward (mLOCF) was used to impute missing postbaseline values. Data after Week 16 for Week 16 non-responders was not included.

Arm/Group Title	120 mg LY2127399	90 mg LY2127399	Placebo
Arm/Group Description	LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240 mg (2 SC injections of 120 mg each) loading dose when initiating treatment.	LY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180 mg (2 SC injections of 90 mg each) loading dose when initiating treatment.	Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections when initiating treatment.
Measure Participants	318	315	211
Least Squares Mean (Standard Error) [joint count]	-2.59 (0.97)	-3.18 (0.99)	-3.59 (1.05)

6. Secondary Outcome

Title	Change From Baseline to 24 Weeks in Participant's Assessment of Pain (Visual Analog Scale)
Description	Participant's assessment of their current arthritis pain using a visual analog scale (VAS) ranged from 0 millimeters (mm) (no pain) to 100 mm (worst possible pain). A decrease in pain score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.
Time Frame	Baseline, up to 24 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants with at least 5/68 tender joints and at least 5/66 swollen joints at baseline and with evaluable participant's assessment of pain data. Modified last observation carried forward (mLOCF) was used to impute missing postbaseline values. Data after Week 16 for Week 16 non-responders was not included.

Arm/Group Title	120 mg LY2127399	90 mg LY2127399	Placebo
Arm/Group Description	LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240 mg (2 SC injections of 120 mg each) loading dose when initiating treatment.	LY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180 mg (2 SC injections of 90 mg each) loading dose when initiating treatment.	Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections when initiating treatment.
Measure Participants	313	312	208
Least Squares Mean (Standard Error) [millimeters]	-9.0 (2.3)	-9.6 (2.4)	-6.9 (2.5)

7. Secondary Outcome

Title	Change From Baseline to 24 Weeks in Participant's Global Assessment of Disease Activity (Visual Analog Scale)
Description	Participant's assessment of their current arthritis disease activity using a visual analog scale (VAS) ranged from 0 millimeters (mm) (no arthritis activity) to 100 mm (extremely active arthritis). A decrease in disease activity score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.
Time Frame	Baseline, up to 24 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants with at least 5/68 tender joints and at least 5/66 swollen joints at baseline and with evaluable participant's global assessment of disease activity data. Modified last observation carried forward (mLOCF) was used to impute missing postbaseline values. Data after Week 16 for Week 16 non-responders was not included.

Arm/Group Title	120 mg LY2127399	90 mg LY2127399	Placebo
Arm/Group Description	LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240 mg (2 SC injections of 120 mg each) loading dose when initiating treatment.	LY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180 mg (2 SC injections of 90 mg each) loading dose when initiating treatment.	Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections when initiating treatment.
Measure Participants	317	313	211
Least Squares Mean (Standard Error) [millimeters]	-10.2 (2.3)	-10.2 (2.4)	-6.9 (2.5)

8. Secondary Outcome

Title	Change From Baseline to 24 Weeks in Physician's Global Assessment of Disease Activity (Visual Analog Scale)
Description	Physician's assessment of the participant's current arthritis disease activity using a visual analog scale (VAS) ranged from 0 millimeters (mm) (no arthritis activity) to 100 mm (extremely active arthritis). A decrease in disease activity score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.
Time Frame	Baseline, up to 24 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants with at least 5/68 tender joints and at least 5/66 swollen joints at baseline and with evaluable physician's global assessment of disease activity data. Modified last observation carried forward (mLOCF) was used to impute missing postbaseline values. Data after Week 16 for Week 16 non-responders was not included.

Arm/Group Title	120 mg LY2127399	90 mg LY2127399	Placebo
Arm/Group Description	LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240 mg (2 SC injections of 120 mg each) loading dose when initiating treatment.	LY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180 mg (2 SC injections of 90 mg each) loading dose when initiating treatment.	Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections when initiating treatment.
Measure Participants	308	306	201
Least Squares Mean (Standard Error) [millimeters]	-10.0 (2.3)	-12.4 (2.4)	-9.7 (2.5)

9. Secondary Outcome

Title	Change From Baseline to 24 Weeks in Disease Activity Score (Based on 28 Joint Count)-C-Reactive Protein (DAS28-CRP)
Description	Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP) (milligrams per liter), and participant global assessment of disease activity using visual analog scale (VAS) (participant global VAS). DAS28-CRP was calculated using following formula: DAS28-CRP=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.36*natural log(CRP+1)+0.014*participant global VAS+0.96. Scores ranged 1.0-9.4, where lower scores indicated less disease activity and remission is DAS28-CRP <2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.
Time Frame	Baseline, up to 24 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants, even if participant did not take assigned treatment, did not receive correct treatment, or otherwise did not follow protocol, with evaluable DAS28-CRP data. Modified last observation carried forward (mLOCF) was used to impute missing postbaseline values. Data after Week 16 for Week 16 non-responders was not included.

Arm/Group Title	120 mg LY2127399	90 mg LY2127399	Placebo
Arm/Group Description	LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240 mg (2 SC injections of 120 mg each) loading dose when initiating treatment.	LY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180 mg (2 SC injections of 90 mg each) loading dose when initiating treatment.	Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections when initiating treatment.
Measure Participants	376	369	249
Least Squares Mean (Standard Error) [units on a scale]	-0.42 (0.12)	-0.49 (0.12)	-0.41 (0.13)

10. Secondary Outcome

Title	Change From Baseline to 24 Weeks in Health Assessment Questionnaire-Disability Index (HAQ-DI)
Description	The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty [0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area, which ranged from 0 (no disability) to 3 (severe disability), were averaged to calculate HAQ-DI. A decrease in HAQ-DI score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.
Time Frame	Baseline, up to 24 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants with at least 5/68 tender joints and at least 5/66 swollen joints at baseline and with evaluable HAQ-DI data. Modified last observation carried forward (mLOCF) was used to impute missing postbaseline values. Data after Week 16 for Week 16 non-responders was not included.

Arm/Group Title	120 mg LY2127399	90 mg LY2127399	Placebo
Arm/Group Description	LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240 mg (2 SC injections of 120 mg each) loading dose when initiating treatment.	LY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180 mg (2 SC injections of 90 mg each) loading dose when initiating treatment.	Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections when initiating treatment.
Measure Participants	317	314	211
Least Squares Mean (Standard Error) [units on a scale]	-0.21 (0.05)	-0.18 (0.05)	-0.15 (0.05)

11. Secondary Outcome

Title	Time to American College of Rheumatology 20% (ACR20) Response
Description	ACR20 Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis. ACR20 Responder: had >= 20% improvement from baseline in both 68 tender and 66 swollen joint counts and >=20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and C-reactive protein (CRP). The Kaplan-Meier estimator was used to summarize time to ACR20 response over the Treatment Period (24 weeks). The time to American College of Rheumatology 20% (ACR20) response (in weeks) is calculated as: (Date of the first postbaseline visit during the Treatment Period meeting ACR20 response criteria - Date of first injection of study treatment + 1) / 7.
Time Frame	Baseline through 24 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants with at least 5/68 tender joints and at least 5/66 swollen joints at baseline and with evaluable ACR20 response data. Week 16 non-responders were counted as responders if they responded prior to Week 16. Otherwise, they were censored at the date of the Week 16 injection.

Arm/Group Title	120 mg LY2127399	90 mg LY2127399	Placebo
Arm/Group Description	LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240 mg (2 SC injections of 120 mg each) loading dose when initiating treatment. After 16 weeks, non-responders received 90 mg every 2 weeks for the rest of the 24-week Treatment Period.	LY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180 mg (2 SC injections of 90 mg each) loading dose when initiating treatment. After 16 weeks, non-responders continued to receive 90 mg every 2 weeks for the rest of the 24-week Treatment Period.	Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections when initiating treatment. After 16 weeks, non-responders received 90 milligrams (mg) of LY2127399 every 2 weeks for the rest of the 24-week Treatment Period.
Measure Participants	318	315	210
Median (95% Confidence Interval) [weeks]	16.7	16.1	16.4

12. Secondary Outcome

Title	Probability of an ACR20 Response by 24 Weeks
Description	ACR20 Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis. ACR20 Responder: had >= 20% improvement from baseline in both 68 tender and 66 swollen joint counts and >=20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and C-reactive protein (CRP). The Kaplan-Meier estimator was used to summarize time to ACR20 response over the Treatment Period (24 weeks). The time to American College of Rheumatology 20% (ACR20) response (in weeks) is calculated as: (Date of the first postbaseline visit during the Treatment Period meeting ACR20 response criteria - Date of first injection of study treatment + 1) / 7.
Time Frame	Baseline through 24 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants with at least 5/68 tender joints and at least 5/66 swollen joints at baseline and with evaluable ACR20 response data. Week 16 non-responders were counted as responders if they responded prior to Week 16. Otherwise, they were censored at the date of the Week 16 injection.

Arm/Group Title	120 mg LY2127399	90 mg LY2127399	Placebo
Arm/Group Description	LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240 mg (2 SC injections of 120 mg each) loading dose when initiating treatment. After 16 weeks, non-responders received 90 mg every 2 weeks for the rest of the 24-week Treatment Period.	LY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180 mg (2 SC injections of 90 mg each) loading dose when initiating treatment. After 16 weeks, non-responders continued to receive 90 mg every 2 weeks for the rest of the 24-week Treatment Period.	Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections when initiating treatment. After 16 weeks, non-responders received 90 milligrams (mg) of LY2127399 every 2 weeks for the rest of the 24-week Treatment Period.
Measure Participants	318	315	210
Number [probability of response]	0.612	0.611	0.608

13. Secondary Outcome

Title	Percentage of Participants With DAS28-Based European League Against Rheumatism (EULAR) Response
Description	EULAR Responder index based on 28 joint count categorizes clinical response based on improvement since baseline in DAS28-CRP. Participants are categorized as EULAR responders or non-responders based on improvement of DAS28-CRP scores from baseline. EULAR28 responder is defined as either DAS28-CRP <=5.1 and DAS28-CRP change <-0.6; or DAS28-CRP >5.1 and DAS28-CRP change <-1.2. EULAR28 responder index is defined as good response: DAS28-CRP <=3.2 and DAS28-CRP change <-1.2; moderate response: DAS28-CRP change <-1.2 except cases defined in good response; or DAS28-CRP <=5.1 and DAS28-CRP change <-0.6 and >-1.2. EULAR Remission is defined as a DAS28-CRP score of <2.6.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants with at least 5/68 tender joints and at least 5/66 swollen joints at baseline and with evaluable EULAR response data. Modified last observation carried forward (mLOCF) was used to impute missing postbaseline values. Data after Week 16 for Week 16 non-responders was not included.

Arm/Group Title	120 mg LY2127399	90 mg LY2127399	Placebo
Arm/Group Description	LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240 mg (2 SC injections of 120 mg each) loading dose when initiating treatment.	LY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180 mg (2 SC injections of 90 mg each) loading dose when initiating treatment.	Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections when initiating treatment.
Measure Participants	318	314	211
Number [percentage of participants]	50.3 13.3%	49.7 13.3%	46.4 18.5%

14. Secondary Outcome

Title	Change From Baseline to 24 Weeks in Medical Outcomes Study 36-Item Short Form (SF-36) Health Status Survey Domain and Summary Scores
Description	The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, and 2 component scores (mental [MCS] and physical health [PCS]). Domain scores calculated by summing each item for each domain and transforming scores into 0-100 scale; higher scores indicated better health status. MCS score consisted of social functioning, vitality, mental health, and role-emotional scales. PCS score consisted of physical functioning, bodily pain, role-physical, and general health scales. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.
Time Frame	Baseline, up to 24 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants with at least 5/68 tender joints and at least 5/66 swollen joints at baseline and with evaluable SF-36 domain and summary scores. Modified last observation carried forward (mLOCF) was used to impute missing postbaseline values. Data after Week 16 for Week 16 non-responders was not included.

Arm/Group Title	120 mg LY2127399	90 mg LY2127399	Placebo
Arm/Group Description	LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240 mg (2 SC injections of 120 mg each) loading dose when initiating treatment.	LY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180 mg (2 SC injections of 90 mg each) loading dose when initiating treatment.	Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections when initiating treatment.
Measure Participants	311	304	206
Physical functioning domain	2.07 (0.84)	3.14 (0.85)	1.48 (0.91)
Bodily pain domain	1.62 (0.82)	2.08 (0.83)	1.34 (0.89)
Role limitations due to physical problems domain	1.60 (0.83)	2.40 (0.84)	1.65 (0.91)
Role limitations due to emotional problems domain	3.30 (1.01)	3.23 (1.02)	3.11 (1.09)
General health perception domain	1.93 (0.76)	1.99 (0.77)	1.81 (0.82)
Mental health domain	3.09 (0.89)	3.00 (0.90)	2.31 (0.97)
Social function domain	1.17 (1.00)	1.24 (1.01)	0.33 (1.08)
Vitality domain	2.85 (0.87)	2.58 (0.88)	2.22 (0.94)
Physical component summary score	1.19 (0.79)	2.10 (0.79)	1.14 (0.85)
Mental component summary score	3.18 (0.95)	2.68 (0.96)	2.54 (1.03)

15. Secondary Outcome

Title	Change From Baseline in C-reactive Protein (CRP) up to Week 24 Endpoint
Description	CRP is an indicator of inflammation. A negative change indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.
Time Frame	Baseline, up to 24 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants with at least 5/68 tender joints and 5/66 swollen joints at baseline and with evaluable CRP data. Modified last observation carried forward (mLOCF) was used to impute missing postbaseline values. Data after Week 16 for Week 16 non-responders was not included.

Arm/Group Title	120 mg LY2127399	90 mg LY2127399	Placebo
Arm/Group Description	LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240 mg (2 SC injections of 120 mg each) loading dose when initiating treatment.	LY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180 mg (2 SC injections of 90 mg each) loading dose when initiating treatment.	Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections when initiating treatment.
Measure Participants	318	315	211
Least Squares Mean (Standard Error) [milligrams per liter (mg/L)]	2.69 (1.42)	1.92 (1.44)	1.76 (1.54)

16. Secondary Outcome

Title	Change From Baseline to 24 Weeks in Absolute CD3-CD20+ B-cell Counts
Description	Cell-surface marker cluster designation (CD) 3 negative, CD20 positive (CD3-CD20+) defines total mature B cells. B-lymphocyte antigen CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all mature B cells. Baseline B-cell count is determined by calculating the average of the 2 pretreatment B-cell counts obtained once during Days -28 through -7 and on Day 0. A positive or negative change indicated an increase or decrease, respectively in B-cell count. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.
Time Frame	Baseline, up to 24 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study treatment with evaluable absolute B-cell data. Modified last observation carried forward (mLOCF) was used to impute missing postbaseline values. Data after Week 16 for Week 16 non-responders was not included.

Arm/Group Title	120 mg LY2127399	90 mg LY2127399	Placebo
Arm/Group Description	LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240 mg (2 SC injections of 120 mg each) loading dose when initiating treatment.	LY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180 mg (2 SC injections of 90 mg each) loading dose when initiating treatment.	Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections when initiating treatment.
Measure Participants	376	370	248
Least Squares Mean (Standard Error) [cells per microliter]	-50.5 (19.4)	-74.4 (19.3)	-0.7 (20.9)

17. Secondary Outcome

Title	Change From Baseline to 24 Weeks in Serum Immunoglobulin (Ig) Levels
Description	Immunoglobulins, or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Change from baseline serum immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) levels are reported. A negative change indicated a decrease in immunoglobulin levels. LS means were calculated using ANCOVA with treatment, region, tumor necrosis factor-inadequate responder treatment history, and DMARD background as fixed factors and baseline as a covariate.
Time Frame	Baseline, up to 24 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study treatment with evaluable serum immunoglobulin (Ig) data. Modified last observation carried forward (mLOCF) was used to impute missing postbaseline values.

Arm/Group Title	120 mg LY2127399	90 mg LY2127399	Placebo
Arm/Group Description	LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240 mg (2 SC injections of 120 mg each) loading dose when initiating treatment. After 16 weeks, non-responders received 90 mg every 2 weeks for the rest of the 24-week Treatment Period.	LY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180 mg (2 SC injections of 90 mg each) loading dose when initiating treatment. After 16 weeks, non-responders continued to receive 90 mg every 2 weeks for the rest of the 24-week Treatment Period.	Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections when initiating treatment. After 16 weeks, non-responders received 90 milligrams (mg) of LY2127399 every 2 weeks for the rest of the 24-week Treatment Period.
Measure Participants	374	369	248
Immunoglobulin G	-0.813 (0.165)	-0.758 (0.165)	0.117 (0.178)
Immunoglobulin A	-0.209 (0.044)	-0.224 (0.044)	0.139 (0.047)
Immunoglobulin M	-0.267 (0.026)	-0.275 (0.025)	-0.049 (0.028)

18. Secondary Outcome

Title	Population Pharmacokinetics (PK)
Description	Population estimate of constant clearance as determined by population pharmacokinetics (PK) analysis. A 2-compartment model was used in PK modeling.
Time Frame	Baseline through 24 weeks

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of LY2127399 with evaluable LY2127399 PK data.

Arm/Group Title	LY2127399
Arm/Group Description	120 milligrams (mg) LY2127399: subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240 mg (2 SC injections of 120 mg each) loading dose when initiating treatment. 90 milligrams (mg) LY2127399: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180 mg (2 SC injections of 90 mg each) loading dose when initiating treatment. After 16 weeks, non-responders received 90 mg every 2 weeks for the rest of the 24-week Treatment Period.
Measure Participants	777
Mean (95% Confidence Interval) [milliliter per hour (mL/h)]	3.60 (2.54)

19. Secondary Outcome

Title	Percentage of Participants Developing Anti-LY2127399 Antibodies
Description	LY2127399 anti-drug antibodies (ADA) were assessed at baseline, 1, 4, 16, and 24 weeks. Percentage of participants (Pts) with ADA=(number of Pts with treatment-emergent ADA/number of Pts assessed)*100. Pts with treatment-emergent ADA were Pts who had any sample from baseline up to and through Week 24 that was a 4-fold increase (2-dilution increase) in immunogenicity titer over baseline titer, or Pts who tested negative at baseline and positive post-baseline (at titer of ≥1:20).
Time Frame	Baseline through 24 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study treatment.

Arm/Group Title	120 mg LY2127399	90 mg LY2127399	Placebo
Arm/Group Description	LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240 mg (2 SC injections of 120 mg each) loading dose when initiating treatment. After 16 weeks, non-responders received 90 mg every 2 weeks for the rest of the 24-week Treatment Period.	LY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180 mg (2 SC injections of 90 mg each) loading dose when initiating treatment. After 16 weeks, non-responders continued to receive 90 mg every 2 weeks for the rest of the 24-week Treatment Period.	Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections when initiating treatment. After 16 weeks, non-responders received 90 milligrams (mg) of LY2127399 every 2 weeks for the rest of the 24-week Treatment Period.
Measure Participants	376	370	248
Number [percentage of participants]	2.4 0.6%	1.9 0.5%	2.8 1.1%

Adverse Events

Arm/Group Title	120 mg LY2127399, Randomized Treatment Period		90 mg LY2127399, Randomized Treatment Period		Placebo, Randomized Treatment Period		120 mg LY2127399, Rescue Period		90 mg LY2127399, Rescue Period		Placebo, Rescue Period		120 mg LY2127399, Follow-up Period		90 mg LY2127399, Follow-up Period		Placebo, Follow-up Period		120 mg LY2127399 to 90 mg LY212739 (Week 16), Follow-up Period		Placebo to 90 mg LY2127399 (Week 16), Follow-up Period
Arm/Group Description	LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240 mg (2 SC injections of 120 mg each) loading dose when initiating treatment. During the Treatment Period, for blinding purposes, participants alternated injections of LY2127399 and injections of placebo every 2 weeks. The Randomized Treatment Period was defined as the time all data was collected during the Treatment Period, excluding the data collected after the date of the Week 16 injection for the Week 16 non-responders.		LY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180 mg (2 SC injections of 90 mg each) loading dose when initiating treatment. The Randomized Treatment Period was defined as the time all data was collected during the Treatment Period, excluding the data collected after the date of the Week 16 injection for the Week 16 non-responders.		Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections when initiating treatment. The Randomized Treatment Period was defined as the time all data was collected during the Treatment Period, excluding the data collected after the date of the Week 16 injection for the Week 16 non-responders.		LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240 mg (2 SC injections of 120 mg each) loading dose when initiating treatment. During the Treatment Period, for blinding purposes, participants alternated injections of LY2127399 and injections of placebo every 2 weeks. After 16 weeks, non-responders received 90 mg every 2 weeks for the rest of the 24-week Treatment Period. The Rescue Treatment Period was defined as all data collected after the date of the Week 16 injection during the Treatment Period for Week 16 non-responders.		LY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180 mg (2 SC injections of 90 mg each) loading dose when initiating treatment. After 16 weeks, non-responders continued to receive 90 mg every 2 weeks for the rest of the 24-week Treatment Period. The Rescue Treatment Period was defined as all data collected after the date of the Week 16 injection during the Treatment Period for Week 16 non-responders.		Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections when initiating treatment. After 16 weeks, non-responders received 90 milligrams (mg) of LY2127399 every 2 weeks for the rest of the 24-week Treatment Period. The Rescue Treatment Period was defined as all data collected after the date of the Week 16 injection during the Treatment Period for Week 16 non-responders.		LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240 mg (2 SC injections of 120 mg each) loading dose when initiating treatment. During the Treatment Period, for blinding purposes, participants alternated injections of LY2127399 and injections of placebo every 2 weeks. The Post-Treatment Follow-Up Period started after Week 24 or the early discontinuation visit and lasted up to 48 weeks following the last injection of study treatment.		LY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180 mg (2 SC injections of 90 mg each) loading dose when initiating treatment. The Post-Treatment Follow-Up Period started after Week 24 or the early discontinuation visit and lasted up to 48 weeks following the last injection of study treatment.		Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections when initiating treatment. The Post-Treatment Follow-Up Period started after Week 24 or the early discontinuation visit and lasted up to 48 weeks following the last injection of study treatment.		LY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240 mg (2 SC injections of 120 mg each) loading dose when initiating treatment. During the Treatment Period, for blinding purposes, participants alternated injections of LY2127399 and injections of placebo every 2 weeks. After 16 weeks, non-responders received 90 mg every 2 weeks for the rest of the 24-week Treatment Period. The Post-Treatment Follow-Up Period started after Week 24 or the early discontinuation visit and lasted up to 48 weeks following the last injection of study treatment.		Placebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections when initiating treatment. After 16 weeks, non-responders received 90 milligrams (mg) of LY2127399 every 2 weeks for the rest of the 24-week Treatment Period. The Post-Treatment Follow-Up Period started after Week 24 or the early discontinuation visit and lasted up to 48 weeks following the last injection of study treatment.
All Cause Mortality
	120 mg LY2127399, Randomized Treatment Period		90 mg LY2127399, Randomized Treatment Period		Placebo, Randomized Treatment Period		120 mg LY2127399, Rescue Period		90 mg LY2127399, Rescue Period		Placebo, Rescue Period		120 mg LY2127399, Follow-up Period		90 mg LY2127399, Follow-up Period		Placebo, Follow-up Period		120 mg LY2127399 to 90 mg LY212739 (Week 16), Follow-up Period		Placebo to 90 mg LY2127399 (Week 16), Follow-up Period
	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)
Serious Adverse Events
	120 mg LY2127399, Randomized Treatment Period		90 mg LY2127399, Randomized Treatment Period		Placebo, Randomized Treatment Period		120 mg LY2127399, Rescue Period		90 mg LY2127399, Rescue Period		Placebo, Rescue Period		120 mg LY2127399, Follow-up Period		90 mg LY2127399, Follow-up Period		Placebo, Follow-up Period		120 mg LY2127399 to 90 mg LY212739 (Week 16), Follow-up Period		Placebo to 90 mg LY2127399 (Week 16), Follow-up Period
	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	14/379 (3.7%)		8/371 (2.2%)		7/250 (2.8%)		5/81 (6.2%)		0/72 (0%)		0/56 (0%)		0/40 (0%)		4/45 (8.9%)		3/37 (8.1%)		1/7 (14.3%)		2/12 (16.7%)
Cardiac disorders
Atrial fibrillation	1/379 (0.3%)	1	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Atrioventricular block complete	1/379 (0.3%)	1	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Myocardial infarction	1/379 (0.3%)	1	1/371 (0.3%)	1	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Pericarditis	0/379 (0%)	0	1/371 (0.3%)	1	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Gastrointestinal disorders
Gastric ulcer	1/379 (0.3%)	1	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Gastric ulcer haemorrhage	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	1/7 (14.3%)	1	0/12 (0%)	0
Gastrooesophageal reflux disease	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Upper gastrointestinal haemorrhage	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Immune system disorders
Anaphylactic reaction	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	1/37 (2.7%)	1	0/7 (0%)	0	0/12 (0%)	0
Infections and infestations
Bronchitis	0/379 (0%)	0	0/371 (0%)	0	1/250 (0.4%)	1	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Cellulitis	0/379 (0%)	0	1/371 (0.3%)	1	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Device related infection	1/379 (0.3%)	1	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Neutropenic sepsis	1/379 (0.3%)	1	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Peritonsillar abscess	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	1/81 (1.2%)	1	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Rectal abscess	1/379 (0.3%)	1	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Viral upper respiratory tract infection	1/379 (0.3%)	1	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Wound sepsis	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Injury, poisoning and procedural complications
Compression fracture	1/379 (0.3%)	1	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Joint dislocation postoperative	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	1/12 (8.3%)	1
Radius fracture	0/379 (0%)	0	1/371 (0.3%)	1	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Ulna fracture	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	1/81 (1.2%)	1	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Wrist fracture	1/379 (0.3%)	1	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Musculoskeletal and connective tissue disorders
Juvenile arthritis	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	1/12 (8.3%)	1
Osteoarthritis	1/379 (0.3%)	1	0/371 (0%)	0	1/250 (0.4%)	1	1/81 (1.2%)	1	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Rheumatoid arthritis	2/379 (0.5%)	2	0/371 (0%)	0	3/250 (1.2%)	3	1/81 (1.2%)	1	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	1/37 (2.7%)	1	0/7 (0%)	0	0/12 (0%)	0
Spinal osteoarthritis	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	1/12 (8.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	1/379 (0.3%)	1	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Oesophageal adenocarcinoma	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Spindle cell sarcoma	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	1/12 (8.3%)	1
Uterine cancer	0/293 (0%)	0	0/292 (0%)	0	0/208 (0%)	0	0/61 (0%)	0	0/60 (0%)	0	0/42 (0%)	0	0/31 (0%)	0	0/35 (0%)	0	1/27 (3.7%)	1	0/7 (0%)	0	0/12 (0%)	0
Uterine leiomyoma	1/293 (0.3%)	1	0/292 (0%)	0	0/208 (0%)	0	0/61 (0%)	0	0/60 (0%)	0	0/42 (0%)	0	0/31 (0%)	0	0/35 (0%)	0	0/27 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Nervous system disorders
Altered state of consciousness	0/379 (0%)	0	0/371 (0%)	0	1/250 (0.4%)	1	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Cerebrovascular accident	1/379 (0.3%)	1	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Dystonia	1/379 (0.3%)	1	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Peripheral sensorimotor neuropathy	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	1/81 (1.2%)	1	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Psychiatric disorders
Intentional self-injury	0/379 (0%)	0	1/371 (0.3%)	1	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Suicide attempt	0/379 (0%)	0	1/371 (0.3%)	1	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Renal and urinary disorders
Calculus urinary	0/379 (0%)	0	1/371 (0.3%)	1	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Stress urinary incontinence	0/379 (0%)	0	1/371 (0.3%)	1	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Reproductive system and breast disorders
Cystocele	0/293 (0%)	0	1/292 (0.3%)	1	0/208 (0%)	0	0/61 (0%)	0	0/60 (0%)	0	0/42 (0%)	0	0/31 (0%)	0	0/35 (0%)	0	0/27 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Dysfunctional uterine bleeding	1/293 (0.3%)	1	0/292 (0%)	0	0/208 (0%)	0	0/61 (0%)	0	0/60 (0%)	0	0/42 (0%)	0	0/31 (0%)	0	0/35 (0%)	0	0/27 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Postmenopausal haemorrhage	0/293 (0%)	0	0/292 (0%)	0	1/208 (0.5%)	1	0/61 (0%)	0	0/60 (0%)	0	0/42 (0%)	0	0/31 (0%)	0	0/35 (0%)	0	0/27 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema	0/379 (0%)	0	1/371 (0.3%)	1	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Vascular disorders
Hypertension	0/379 (0%)	0	1/371 (0.3%)	1	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Other (Not Including Serious) Adverse Events
	120 mg LY2127399, Randomized Treatment Period		90 mg LY2127399, Randomized Treatment Period		Placebo, Randomized Treatment Period		120 mg LY2127399, Rescue Period		90 mg LY2127399, Rescue Period		Placebo, Rescue Period		120 mg LY2127399, Follow-up Period		90 mg LY2127399, Follow-up Period		Placebo, Follow-up Period		120 mg LY2127399 to 90 mg LY212739 (Week 16), Follow-up Period		Placebo to 90 mg LY2127399 (Week 16), Follow-up Period
	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	174/379 (45.9%)		154/371 (41.5%)		98/250 (39.2%)		23/81 (28.4%)		16/72 (22.2%)		9/56 (16.1%)		12/40 (30%)		17/45 (37.8%)		13/37 (35.1%)		5/7 (71.4%)		2/12 (16.7%)
Blood and lymphatic system disorders
Anaemia	3/379 (0.8%)	3	4/371 (1.1%)	4	1/250 (0.4%)	1	2/81 (2.5%)	2	2/72 (2.8%)	2	0/56 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Iron deficiency anaemia	0/379 (0%)	0	1/371 (0.3%)	1	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	1/37 (2.7%)	1	0/7 (0%)	0	0/12 (0%)	0
Cardiac disorders
Mitral valve prolapse	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	1/37 (2.7%)	1	0/7 (0%)	0	0/12 (0%)	0
Eye disorders
Conjunctivitis	2/379 (0.5%)	2	0/371 (0%)	0	1/250 (0.4%)	1	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	1/12 (8.3%)	1
Macular pigmentation	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Gastrointestinal disorders
Abdominal pain upper	3/379 (0.8%)	3	6/371 (1.6%)	7	2/250 (0.8%)	3	1/81 (1.2%)	1	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	1/37 (2.7%)	1	0/7 (0%)	0	0/12 (0%)	0
Constipation	0/379 (0%)	0	5/371 (1.3%)	6	1/250 (0.4%)	1	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	1/37 (2.7%)	1	0/7 (0%)	0	0/12 (0%)	0
Dental caries	2/379 (0.5%)	2	0/371 (0%)	0	2/250 (0.8%)	2	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	1/37 (2.7%)	1	0/7 (0%)	0	0/12 (0%)	0
Diarrhoea	8/379 (2.1%)	8	8/371 (2.2%)	10	3/250 (1.2%)	4	0/81 (0%)	0	1/72 (1.4%)	1	1/56 (1.8%)	1	1/40 (2.5%)	1	0/45 (0%)	0	1/37 (2.7%)	1	0/7 (0%)	0	0/12 (0%)	0
Gastrooesophageal reflux disease	2/379 (0.5%)	2	1/371 (0.3%)	1	3/250 (1.2%)	3	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Nausea	9/379 (2.4%)	9	8/371 (2.2%)	10	6/250 (2.4%)	8	1/81 (1.2%)	1	3/72 (4.2%)	3	1/56 (1.8%)	1	0/40 (0%)	0	1/45 (2.2%)	1	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Stomatitis	3/379 (0.8%)	3	1/371 (0.3%)	1	1/250 (0.4%)	1	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	1/37 (2.7%)	2	0/7 (0%)	0	0/12 (0%)	0
Toothache	1/379 (0.3%)	1	3/371 (0.8%)	3	1/250 (0.4%)	1	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	1/40 (2.5%)	1	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Vomiting	4/379 (1.1%)	4	3/371 (0.8%)	3	3/250 (1.2%)	3	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
General disorders
Fatigue	5/379 (1.3%)	5	5/371 (1.3%)	5	7/250 (2.8%)	7	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	1/40 (2.5%)	1	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Injection site erythema	4/379 (1.1%)	9	10/371 (2.7%)	27	2/250 (0.8%)	3	1/81 (1.2%)	1	2/72 (2.8%)	4	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Injection site reaction	8/379 (2.1%)	10	11/371 (3%)	34	2/250 (0.8%)	2	1/81 (1.2%)	5	0/72 (0%)	0	1/56 (1.8%)	1	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Pyrexia	7/379 (1.8%)	7	10/371 (2.7%)	10	5/250 (2%)	6	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Hepatobiliary disorders
Cholecystitis	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	1/12 (8.3%)	1
Infections and infestations
Bronchitis	14/379 (3.7%)	14	9/371 (2.4%)	9	2/250 (0.8%)	2	1/81 (1.2%)	1	2/72 (2.8%)	2	1/56 (1.8%)	1	1/40 (2.5%)	1	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Folliculitis	0/379 (0%)	0	2/371 (0.5%)	3	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	1/37 (2.7%)	1	0/7 (0%)	0	0/12 (0%)	0
Gastroenteritis	1/379 (0.3%)	1	4/371 (1.1%)	4	4/250 (1.6%)	4	0/81 (0%)	0	1/72 (1.4%)	1	0/56 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Gastroenteritis viral	0/379 (0%)	0	1/371 (0.3%)	1	1/250 (0.4%)	1	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	1/37 (2.7%)	1	0/7 (0%)	0	0/12 (0%)	0
Herpes zoster	1/379 (0.3%)	1	2/371 (0.5%)	2	2/250 (0.8%)	3	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	1/7 (14.3%)	1	0/12 (0%)	0
Nasopharyngitis	17/379 (4.5%)	20	14/371 (3.8%)	16	9/250 (3.6%)	10	1/81 (1.2%)	1	0/72 (0%)	0	1/56 (1.8%)	1	0/40 (0%)	0	0/45 (0%)	0	2/37 (5.4%)	2	0/7 (0%)	0	0/12 (0%)	0
Pharyngitis	5/379 (1.3%)	5	2/371 (0.5%)	2	3/250 (1.2%)	4	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	1/40 (2.5%)	1	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Pneumonia mycoplasmal	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	1/37 (2.7%)	1	0/7 (0%)	0	0/12 (0%)	0
Respiratory tract infection viral	0/379 (0%)	0	0/371 (0%)	0	2/250 (0.8%)	2	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Sinusitis	6/379 (1.6%)	6	11/371 (3%)	12	6/250 (2.4%)	6	2/81 (2.5%)	2	1/72 (1.4%)	1	1/56 (1.8%)	1	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	1/7 (14.3%)	1	0/12 (0%)	0
Tuberculosis	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Upper respiratory tract infection	12/379 (3.2%)	15	28/371 (7.5%)	29	10/250 (4%)	12	3/81 (3.7%)	3	2/72 (2.8%)	2	0/56 (0%)	0	1/40 (2.5%)	1	3/45 (6.7%)	4	1/37 (2.7%)	1	0/7 (0%)	0	0/12 (0%)	0
Urinary tract infection	7/379 (1.8%)	8	4/371 (1.1%)	5	6/250 (2.4%)	8	2/81 (2.5%)	2	2/72 (2.8%)	2	2/56 (3.6%)	2	0/40 (0%)	0	1/45 (2.2%)	1	1/37 (2.7%)	1	1/7 (14.3%)	1	0/12 (0%)	0
Viral upper respiratory tract infection	3/379 (0.8%)	3	2/371 (0.5%)	2	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Vulvovaginal mycotic infection	0/293 (0%)	0	1/292 (0.3%)	1	0/208 (0%)	0	0/61 (0%)	0	0/60 (0%)	0	0/42 (0%)	0	0/31 (0%)	0	0/35 (0%)	0	1/27 (3.7%)	1	0/7 (0%)	0	0/12 (0%)	0
Injury, poisoning and procedural complications
Contusion	6/379 (1.6%)	6	4/371 (1.1%)	6	1/250 (0.4%)	1	0/81 (0%)	0	0/72 (0%)	0	1/56 (1.8%)	1	0/40 (0%)	0	0/45 (0%)	0	1/37 (2.7%)	1	0/7 (0%)	0	0/12 (0%)	0
Procedural pain	2/379 (0.5%)	2	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	1/12 (8.3%)	1
Investigations
Alanine aminotransferase increased	4/379 (1.1%)	4	3/371 (0.8%)	4	1/250 (0.4%)	1	0/81 (0%)	0	1/72 (1.4%)	1	0/56 (0%)	0	0/40 (0%)	0	2/45 (4.4%)	2	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Aspartate aminotransferase increased	2/379 (0.5%)	2	2/371 (0.5%)	3	1/250 (0.4%)	1	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Blood potassium decreased	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	1/37 (2.7%)	1	0/7 (0%)	0	0/12 (0%)	0
Computerised tomogram abnormal	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	1/37 (2.7%)	1	0/7 (0%)	0	0/12 (0%)	0
Liver function test abnormal	5/379 (1.3%)	5	1/371 (0.3%)	1	0/250 (0%)	0	0/81 (0%)	0	1/72 (1.4%)	1	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	1/37 (2.7%)	1	0/7 (0%)	0	0/12 (0%)	0
Vitamin d decreased	0/379 (0%)	0	0/371 (0%)	0	1/250 (0.4%)	1	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Weight increased	1/379 (0.3%)	1	1/371 (0.3%)	1	1/250 (0.4%)	1	2/81 (2.5%)	2	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	1/37 (2.7%)	1	0/7 (0%)	0	0/12 (0%)	0
White blood cell count decreased	0/379 (0%)	0	1/371 (0.3%)	1	1/250 (0.4%)	1	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	1/37 (2.7%)	1	0/7 (0%)	0	0/12 (0%)	0
Metabolism and nutrition disorders
Hyperlipidaemia	0/379 (0%)	0	1/371 (0.3%)	1	1/250 (0.4%)	1	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	11/379 (2.9%)	11	6/371 (1.6%)	6	8/250 (3.2%)	9	1/81 (1.2%)	1	0/72 (0%)	0	1/56 (1.8%)	1	0/40 (0%)	0	0/45 (0%)	0	1/37 (2.7%)	1	0/7 (0%)	0	0/12 (0%)	0
Back pain	10/379 (2.6%)	11	9/371 (2.4%)	9	3/250 (1.2%)	3	2/81 (2.5%)	2	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	1/37 (2.7%)	1	0/7 (0%)	0	0/12 (0%)	0
Bursitis	0/379 (0%)	0	3/371 (0.8%)	3	1/250 (0.4%)	1	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Joint swelling	1/379 (0.3%)	1	2/371 (0.5%)	2	2/250 (0.8%)	2	1/81 (1.2%)	1	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	1/37 (2.7%)	1	0/7 (0%)	0	0/12 (0%)	0
Muscle spasms	4/379 (1.1%)	5	1/371 (0.3%)	1	6/250 (2.4%)	6	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	1/7 (14.3%)	2	0/12 (0%)	0
Myalgia	4/379 (1.1%)	4	2/371 (0.5%)	3	2/250 (0.8%)	2	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	1/37 (2.7%)	1	0/7 (0%)	0	0/12 (0%)	0
Osteopenia	2/379 (0.5%)	2	1/371 (0.3%)	1	0/250 (0%)	0	1/81 (1.2%)	1	0/72 (0%)	0	0/56 (0%)	0	1/40 (2.5%)	1	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Rheumatoid arthritis	17/379 (4.5%)	17	10/371 (2.7%)	12	13/250 (5.2%)	13	1/81 (1.2%)	1	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	2/37 (5.4%)	2	1/7 (14.3%)	1	1/12 (8.3%)	1
Synovial cyst	1/379 (0.3%)	1	1/371 (0.3%)	1	2/250 (0.8%)	4	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	1/40 (2.5%)	2	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Synovitis	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	2	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Nervous system disorders
Balance disorder	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	1/40 (2.5%)	1	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Dizziness	12/379 (3.2%)	12	5/371 (1.3%)	7	3/250 (1.2%)	3	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Headache	16/379 (4.2%)	17	13/371 (3.5%)	16	6/250 (2.4%)	9	1/81 (1.2%)	1	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Hypoaesthesia	3/379 (0.8%)	3	2/371 (0.5%)	2	3/250 (1.2%)	4	2/81 (2.5%)	2	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Neuropathy peripheral	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	1/40 (2.5%)	1	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Sciatica	1/379 (0.3%)	1	1/371 (0.3%)	1	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	1/37 (2.7%)	1	0/7 (0%)	0	0/12 (0%)	0
Pregnancy, puerperium and perinatal conditions
Pregnancy	2/293 (0.7%)	2	0/292 (0%)	0	0/208 (0%)	0	0/61 (0%)	0	0/60 (0%)	0	0/42 (0%)	0	1/31 (3.2%)	1	0/35 (0%)	0	0/27 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Psychiatric disorders
Depression	7/379 (1.8%)	7	4/371 (1.1%)	4	2/250 (0.8%)	2	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	1/40 (2.5%)	1	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Insomnia	5/379 (1.3%)	5	10/371 (2.7%)	10	1/250 (0.4%)	1	0/81 (0%)	0	0/72 (0%)	0	1/56 (1.8%)	1	0/40 (0%)	0	1/45 (2.2%)	1	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Renal and urinary disorders
Cystitis noninfective	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	1/37 (2.7%)	1	0/7 (0%)	0	0/12 (0%)	0
Dysuria	0/379 (0%)	0	1/371 (0.3%)	1	1/250 (0.4%)	1	0/81 (0%)	0	0/72 (0%)	0	1/56 (1.8%)	1	1/40 (2.5%)	1	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Haematuria	0/379 (0%)	0	1/371 (0.3%)	1	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Pollakiuria	0/379 (0%)	0	1/371 (0.3%)	1	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	1/40 (2.5%)	1	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Reproductive system and breast disorders
Balanitis	0/86 (0%)	0	0/79 (0%)	0	0/42 (0%)	0	0/20 (0%)	0	0/12 (0%)	0	0/14 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Vaginal haemorrhage	0/293 (0%)	0	0/292 (0%)	0	0/208 (0%)	0	0/61 (0%)	0	0/60 (0%)	0	0/42 (0%)	0	1/31 (3.2%)	1	0/35 (0%)	0	0/27 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Vulvovaginal pruritus	0/293 (0%)	0	0/292 (0%)	0	0/208 (0%)	0	0/61 (0%)	0	0/60 (0%)	0	0/42 (0%)	0	0/31 (0%)	0	1/35 (2.9%)	1	0/27 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	4/379 (1.1%)	4	5/371 (1.3%)	6	2/250 (0.8%)	2	1/81 (1.2%)	1	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Sinus congestion	1/379 (0.3%)	1	1/371 (0.3%)	1	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Skin and subcutaneous tissue disorders
Haemorrhage subcutaneous	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	1/40 (2.5%)	1	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Papule	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Rash	2/379 (0.5%)	2	4/371 (1.1%)	4	6/250 (2.4%)	6	2/81 (2.5%)	2	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	0/45 (0%)	0	0/37 (0%)	0	1/7 (14.3%)	1	0/12 (0%)	0
Skin exfoliation	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	1/40 (2.5%)	1	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Skin ulcer	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	1/40 (2.5%)	1	0/45 (0%)	0	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0
Vascular disorders
Hypertension	7/379 (1.8%)	7	8/371 (2.2%)	8	6/250 (2.4%)	7	0/81 (0%)	0	1/72 (1.4%)	1	0/56 (0%)	0	1/40 (2.5%)	1	0/45 (0%)	0	2/37 (5.4%)	2	0/7 (0%)	0	0/12 (0%)	0
Hypertensive crisis	0/379 (0%)	0	0/371 (0%)	0	0/250 (0%)	0	0/81 (0%)	0	0/72 (0%)	0	0/56 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1	0/37 (0%)	0	0/7 (0%)	0	0/12 (0%)	0

Limitations/Caveats

[Not Specified]

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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.