Rheumatoid Arthritis
Conditions
Keywords
Arthritis
Brief summary
To evaluate the safety and tolerability of LY2127399 administered as subcutaneous injections for 48 weeks in participants with Rheumatoid Arthritis
Interventions
BIOLOGICALLY2127399
60 milligrams \[(mg) with potential for dose escalation to 120 mg\] subcutaneously every 4 weeks for 48 weeks
Sponsors
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have given written informed consent * Women must not be pregnant, breastfeeding or be at risk to become pregnant during study participation * Have participated in either Study H9B-MC-BCDG (NCT00689728) or Study H9B-MC-BCDH (NCT00785928)
Exclusion criteria
* Have had, during Study H9B-MC-BCDG (NCT00689728) or Study H9B-MC-BCDH (NCT00785928), any safety event, \[including having a recent, ongoing, or serious infection, a serious drug reaction, or any adverse event (AE) that caused discontinuation from treatment\] that in the opinion of the investigator poses an unacceptable risk to participation in the study. * Have received, during Study H9B-MC-BCDG (NCT00689728) or Study H9B-MC-BCDH (NCT00785928), any drug not allowed by the study protocol including unapproved drugs, biologic disease-modifying anti-rheumatic drugs (DMARDs), or live vaccines. * Enrollment in any other clinical trial involving off-label use of an investigational drug or device, or enrollment in any other type of medical research.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Baseline through Week 112 | For each planned laboratory evaluation, the range of values to be reported as AEs, regardless of causality, was pre-specified. A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module. Baseline was defined as Week 0 in this study \[which is equivalent to Week 24 of the participant's prior study: Study H9B-MC-BCDG (NCT00689728) or Study H9B-MC-BCDH (NCT00785928)\]. |
| Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Baseline through Week 52 (up to 48 weeks of treatment or ED and follow-up through Week 52) | A TEAE started on or after the date and time of the first dose of study drug administered in this study, or started prior to the study drug administration but worsened after the study drug started. Clinically significant events were defined as SAEs and other non-serious adverse events (AEs). A summary of SAEs and other non-serious AEs is located in the Reported Adverse Events module. Participants were on treatment up to 48 weeks. If a participant completed 48 weeks of treatment, the post-study treatment follow-up started at the next visit, 4 weeks later (Week 52). If a participant discontinued treatment early \[early discontinuation (ED)\], the post-study treatment follow-up started immediately afterwards. Baseline was defined as Week 0 in this study \[which is equivalent to Week 24 of the participant's prior study: Study H9B-MC-BCDG (NCT00689728) or Study H9B-MC-BCDH (NCT00785928)\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Swollen Joint Count (Individual Component of the ACR Core Set) | Baseline, up to and through Week 52 | The number of swollen joints was determined by examination of 28 joints (14 on each side) which included: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. Joints were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint. Baseline was defined as the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study. A decrease in swollen joint count indicated an improvement in the participant's condition. |
| Change From Baseline in Participant's Assessment of Disease Activity (Individual Component of the ACR Core Set) | Baseline, up to and through Week 52 | Participant's assessment of their current arthritis disease activity using a visual analog scale (VAS), which ranged from 0 millimeters (mm) (no arthritis activity) to 100 mm (extremely active arthritis). Baseline was defined as the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study. A decrease in disease activity score indicated an improvement in the participant's condition. |
| Change From Baseline in Physician's Global Assessment of Disease Activity (Individual Component of the ACR Core Set) | Baseline, up to and through Week 52 | Physician's assessment of disease activity using a VAS that ranged from 0 mm (no arthritis activity) to 100 mm (extremely active arthritis). Baseline was defined as the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study. A decrease in disease activity score indicated an improvement in the participant's condition. |
| Change From Baseline in Health Assessment Questionnaire-Disability Index [(HAQ-DI) Individual Component of the ACR Core Set] | Baseline, up to and through Week 52 | The disability section of the health assessment questionnaire scored 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. Baseline was defined as the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study. A decrease in HAQ-DI score indicated an improvement in the participant's condition. |
| Change From Baseline in Participant's Assessment of Joint Pain (Individual Component of the ACR Core Set) | Baseline, up to and through Week 52 | Participant's assessment of joint pain using a VAS, which ranged from 0 mm (no pain) to 100 mm (worst possible pain). Baseline was defined as the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study. A decrease in joint pain indicated an improvement in the participant's condition. |
| Percent Change From Baseline in C-Reactive Protein [(CRP) Individual Component of the ACR Core Set] | Baseline, up to and through Week 52 | CRP is an indicator of inflammation. The percentage of change in CRP from baseline=\[(post-baseline CRP-baseline CRP)/baseline CRP\]\*100. Baseline was defined as the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study. A negative change indicated an improvement in the participant's condition. |
| Percentage of Participants Achieving ACR20 Response | Baseline, up to and through Week 52 | ACR20 Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis. ACR20 Responder: had ≥20% improvement from baseline in both tender and swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, HAQ-DI (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and CRP. Percentage of participants achieving ACR20 response=(number of ACR20 responders/number of participants treated)\*100. Participants who discontinued from study prior to Week 52 were imputed as non-responders. Participants who reached Week 52 but had ≥1 of 7 components missing had missing components imputed by LOCF. This composite data imputation was denoted as non-responder imputation (NRI)/LOCF. Baseline: the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study. |
| Percentage of Participants ACR50 Response | Baseline, up to and through Week 52 | ACR50 Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis. ACR50 Responder: had ≥50% improvement from baseline in both tender and swollen joint counts and ≥50% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, HAQ-DI (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and CRP. Percentage of participants achieving ACR50 response=(number of ACR50 responders/number of participants treated)\*100. Participants who discontinued from study prior to Week 52 were imputed as non-responders. Participants who reached Week 52 but had ≥1 of 7 components missing had missing components imputed by LOCF. This composite data imputation was denoted as NRI/LOCF. Baseline was defined as the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study. |
| Percentage of Participants Achieving ACR70 Response | Baseline, up to and through Week 52 | ACR70 Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis. ACR70 Responder: had ≥70% improvement from baseline in both tender and swollen joint counts and ≥70% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, HAQ-DI (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and CRP. Percentage of participants achieving ACR70 response=(number of ACR70 responders/number of participants treated)\*100. Participants who discontinued from study prior to Week 52 were imputed as non-responders. Participants who reached Week 52 but had ≥1 of 7 components missing had missing components imputed by LOCF. This composite data imputation was denoted as NRI/LOCF. Baseline was defined as the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study. |
| ACR-N Response | Baseline, up to and through Week 52 | The ACR-N Responder Index was a composite of clinical, laboratory, and functional measures of rheumatoid arthritis. This index was defined as the lowest of either a) percent change in tender joint count, b) percent change in swollen joint count, or c) median percent change in 5 core ACR criteria: participant global assessment of disease activity, physician global assessment of disease activity, HAQ-DI (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and CRP. For example, a participant with an ACR-N of X had an improvement ≥X% in both tender and swollen joint counts and a median improvement ≥X% in the 5 criteria previously mentioned. Baseline was the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study. Results for the 60/120/60 mg LY2127399 treatment arm were not analyzed as the participant did not have an ACR assessment. |
| Change From Baseline in Disease Activity Score Based on 28 Joint Count (DAS28) | Baseline, up to and through Week 52 | The DAS28 consisted of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP (milligrams per liter \[mg/L\]), and participant global assessment of his or her disease activity using a VAS (participant global VAS). The DAS28 was calculated by using the following formula: DAS28-CRP=0.56\*square root(TJC28)+0.28\*square root(SJC28)+0.36\*natural log(CRP+1)+0.014\*participant global VAS+0.96. Scores ranged from 1.0 to 9.4 where lower scores indicated less disease activity and remission is DAS28 \<2.6. Baseline was defined as the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study. A decrease in DAS28 indicated an improvement in the participant's condition. |
| Percentage of Participants With Response Based on European League Against Rheumatism Responder Index, 28 Joint Count (EULAR28) | Baseline, up to and through Week 52 | EULAR28 was defined by the participant's change from baseline in DAS28 score and the absolute DAS28 score achieved. DAS28 consisted of composite score of the following: tender joint count, swollen joint count, CRP, and participant global assessment of his\\her disease activity (participant global VAS). EULAR28 categories included: No Response \[improvement in DAS28 ≤0.6 units (u) or post-baseline DAS28 score \>5.1 with improvement ≤1.2 u\], Moderate Response (post-baseline DAS28 score ≤5.1 with improvement \>0.6 u but \<1.2 u or post-baseline DAS28 score \>3.2 with improvement \>1.2 u), and Good Response (post-baseline DAS28 score ≤3.2 with improvement \>1.2 u). Baseline was the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study. Percentage of participants=(number of participants with specific response/participants assessed)\*100. Displayed percentages may not add up to 100% because of rounding. |
| Change From Baseline in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) Component Scores | Baseline, up to and through Week 52 | SF-36 was a 36-item, health-related survey that assessed participant's quality of life on 8 domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health, mental health, social functioning, vitality and 2 component scores (mental and physical health). Domain scores calculated by summing individual items for each domain and transforming scores into 0 to 100 scale; higher scores indicated better health status. The mental component summary (MCS) score, based on SF-36 domains, consisted of social functioning, vitality, mental health, and role-emotional scales (range: 0 to 100). The physical component summary (PCS) score, based on SF-36 domains, consisted of physical functioning, bodily pain, role-physical, and general health scales (range: 0 to 100). Baseline: last assessment prior to participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study. |
| Pharmacodynamics: Change From Baseline in Total B Cells [Cluster Designation 20+ (CD20+)] Absolute Cell Counts | Baseline, Weeks 52, 60, 72, 80, 88, and 100 | B-lymphocyte antigen CD20+ is an activated-glycosylated phosphoprotein expressed on the surface of all mature B cells. Baseline was defined as the last measurement prior to randomization to any treatment in either Study H9B-MC-BCDG (NCT00689728) or Study H9B-MC-BCDH (NCT00785928). A negative change indicated a decrease in cell count. |
| Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Baseline, Weeks 52, 60, 72, 80, 88, and 100 | Cell surface marker CD19, CD27, and immunoglobulin D (IgD) expression levels were used to define the various B cell subsets. Cell surface markers were defined as being either present (+) or absent (-). Peripheral blood B cell subsets included: mature naive cells (CD19+IgD+CD27-); immature/transitional cells (CD19+IgD-CD27-); switched memory (CD19+IgD-CD27+); and non-switched memory (CD19+IgD+CD27+). Baseline was defined as the last measurement prior to randomization to any treatment in either Study H9B-MC-BCDG (NCT00689728) or Study H9B-MC-BCDH (NCT00785928). A negative change indicated a decrease in cell count. |
| Pharmacodynamics: Change From Baseline in Serum Immunoglobulin | Baseline, up to Week 52 | 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 M (IgM), and immunoglobulin A (IgA) levels are reported. Baseline was defined as the last measurement prior to randomization to any treatment in either Study H9B-MC-BCDG (NCT00689728) or Study H9B-MC-BCDH (NCT00785928). A negative change indicated a decrease in immunoglobulin levels. |
| Pharmacodynamics: Change From Baseline in Rheumatoid Factor (RF) Levels at Week 52 | Baseline, Week 52 | RF is an autoantibody (antibody directed against an organism's own tissues) most relevant in rheumatoid arthritis. Higher RF levels indicate an aggressive rheumatoid arthritis and a higher risk of joint damage. Baseline was defined as Week 0 in this study \[which is equivalent to Week 24 of the participant's prior study: Study H9B-MC-BCDG (NCT00689728) or Study H9B-MC-BCDH (NCT00785928)\]. A decrease in RF levels indicated an improvement in the participant's condition. Results for the 60/120/60 mg LY2127399 treatment arm were not analyzed as the participant did not have a Week 52 RF level assessment. |
| Pharmacodynamics: Change From Baseline in Serum Anti-Cyclic Citrullinated Peptide (Anti-CCP) Antibodies | Baseline, up to Week 52 | Anti-CCP antibodies were measured using an enzyme-linked immunosorbent assay (ELISA) method. In general, high levels of the antibody indicated an aggressive rheumatoid arthritis and a higher risk of joint damage. Baseline was defined as Week 0 in this study \[which is equivalent to Week 24 of the participant's prior study: Study H9B-MC-BCDG (NCT00689728) or Study H9B-MC-BCDH (NCT00785928)\]. A decrease in anti-CCP antibodies indicated an improvement in the participant's condition. |
| Pharmacodynamics: Percent Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Baseline, up to Week 52 | ESR is a laboratory test that provides a non-specific measure of inflammation. The test assessed the rate at which red blood cells fell in a test tube. Normal range was considered to be 0 to 20 or 0 to 30 millimeters per hour (mm/h), depending on the reference range used by the laboratory. Higher scores indicated greater inflammation. Percent change from baseline ESR=\[(post-baseline ESR- baseline ESR)/baseline ESR\]\*100. Baseline was defined as Week 0 in this study \[which is equivalent to Week 24 of the participant's prior study: Study H9B-MC-BCDG (NCT00689728) or Study H9B-MC-BCDH (NCT00785928)\]. A decrease in ESR indicated an improvement in the participant's condition. |
| Number of Participants With LY2127399 Immunogenicity (Anti-LY2127399 Antibodies) | Baseline through Week 52 (up to 48 weeks of treatment or ED and follow-up through Week 52) and post-study treatment follow-up (start of Week 53 or ED up to and through Week 112) | The number of participants who had treatment-emergent or follow-up emergent anti-LY2127399 antibodies \[anti-drug antibodies (ADA)\] is reported. Treatment-emergent was defined as participants who had any sample from baseline through Week 52 that was a 4-fold increase (2 dilution increase) in immunogenicity titer over the baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20). Follow-up emergent was defined as any sample during follow-up that was a 4-fold increase (2 dilution increase) in immunogenicity titer over the baseline titer. The number of participants with baseline positive ADA data is also reported. Baseline was defined as the last measurement prior to randomization to any treatment in either Study H9B-MC-BCDG (NCT00689728) or Study H9B-MC-BCDH (NCT00785928). |
| Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score | Baseline, up to and through Week 52 | The FACIT Fatigue Scale was a brief participant-reported measure of fatigue and consisted of 13 items. Scores ranged from 0 to 52, where higher scores indicated less fatigue. Baseline was defined as the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study. An increase in FACIT fatigue score indicated an improvement of the participant's condition. |
| Change From Baseline in Tender Joint Count [Individual Component of the American College of Rheumatology (ACR) Core Set] | Baseline, up to and through Week 52 | The number of tender and painful joints was determined by examination of 28 joints (14 on each side) which included: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. Joints were assessed by pressure and joint manipulation on physical examination. The participant was asked for pain sensations on these manipulations and the investigator watched for spontaneous pain reactions. Any positive response on pressure, movement, or both was translated into a single tender-versus-nontender dichotomy. Baseline was defined as the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study. A decrease in tender joint count indicated an improvement in the participant's condition. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Died, Any Cause | Baseline through Week 52 (up to 48 weeks of treatment or ED and follow-up through Week 52) and post-study treatment follow-up (start of Week 53 or ED up to and through Week 72 and start of Week 73 up to and through Week 112) | A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module. Baseline was defined as Week 0 in this study \[which is equivalent to Week 24 of the participant's prior study: Study H9B-MC-BCDG (NCT00689728) or Study H9B-MC-BCDH (NCT00785928)\]. Participants were on treatment up to 48 weeks. If a participant completed 48 weeks of treatment, the post-study treatment follow-up started at the next visit, 4 weeks later (Week 52). If a participant discontinued treatment early, the post-study treatment follow-up started immediately afterwards. After treatment discontinuation, participants could be followed beyond Week 72 for B cell recovery (up to Week 112). |
Countries
Australia, Austria, Belgium, Brazil, Canada, Chile, Germany, Hungary, India, Mexico, Poland, Puerto Rico, Romania, United States
Participant flow
Pre-assignment details
After ≥3 months treatment, investigator could choose 1-time dose increase \[120 milligrams (mg) LY2127399 (LY)\] for participants (pts) with ≥4 tender and ≥4 swollen joints. Additionally, 1-time dose decrease back to 60 mg LY permitted. Pts completing Week 72 completed study, but could be followed beyond Week 72 for B cell recovery (up to Week 112).
Participants by arm
| Arm | Count |
|---|---|
| 60 mg LY2127399 LY2127399: 60 mg subcutaneous injections every 4 weeks for 48 weeks. | 59 |
| 60/120 mg LY2127399 LY2127399: 60 mg subcutaneous injections every 4 weeks. After at least 3 months of treatment, participants had a dose increase to 120 mg LY2127399, administered once every 4 weeks. Participants remained at this dose level for the remainder of study treatment (48 weeks in total). | 121 |
| 60/120/60 mg LY2127399 LY2127399: 60 mg subcutaneous injections every 4 weeks. After at least 3 months of treatment, the participant had a dose increase to 120 mg LY2127399, administered once every 4 weeks. Subsequently, the participant had a dose decrease back to 60 mg LY2127399, administered once every 4 weeks for the remainder of study treatment (48 weeks in total). | 1 |
| Total | 181 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 6 | 0 |
| Overall Study | Death | 1 | 1 | 0 |
| Overall Study | Lack of Efficacy | 0 | 11 | 0 |
| Overall Study | Lost to Follow-up | 1 | 3 | 0 |
| Overall Study | Physician Decision | 0 | 2 | 1 |
| Overall Study | Sponsor Decision | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 9 | 0 |
Baseline characteristics
| Characteristic | 60 mg LY2127399 | Total | 60/120/60 mg LY2127399 | 60/120 mg LY2127399 |
|---|---|---|---|---|
| Age, Continuous | 53.4 years STANDARD_DEVIATION 11.86 | 52.2 years STANDARD_DEVIATION 12.08 | 61.5 years | 51.5 years STANDARD_DEVIATION 12.2 |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 13 Participants | 0 Participants | 12 Participants |
| Race/Ethnicity, Customized East Asian | 5 Participants | 9 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Hispanic | 19 Participants | 43 Participants | 0 Participants | 24 Participants |
| Race/Ethnicity, Customized West Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 34 Participants | 115 Participants | 1 Participants | 80 Participants |
| Region of Enrollment Australia | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Austria | 3 Participants | 6 Participants | 0 Participants | 3 Participants |
| Region of Enrollment Belgium | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Brazil | 4 Participants | 13 Participants | 0 Participants | 9 Participants |
| Region of Enrollment Canada | 0 Participants | 4 Participants | 0 Participants | 4 Participants |
| Region of Enrollment Chile | 5 Participants | 13 Participants | 0 Participants | 8 Participants |
| Region of Enrollment Germany | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Hungary | 6 Participants | 12 Participants | 0 Participants | 6 Participants |
| Region of Enrollment India | 5 Participants | 9 Participants | 0 Participants | 4 Participants |
| Region of Enrollment Mexico | 12 Participants | 24 Participants | 0 Participants | 12 Participants |
| Region of Enrollment Poland | 12 Participants | 42 Participants | 0 Participants | 30 Participants |
| Region of Enrollment Puerto Rico | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Romania | 3 Participants | 6 Participants | 0 Participants | 3 Participants |
| Region of Enrollment United States | 7 Participants | 47 Participants | 1 Participants | 39 Participants |
| Sex: Female, Male Female | 50 Participants | 150 Participants | 1 Participants | 99 Participants |
| Sex: Female, Male Male | 9 Participants | 31 Participants | 0 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 36 / 60 | 93 / 121 | 1 / 1 | 23 / 60 | 47 / 121 | 0 / 1 |
| serious Total, serious adverse events | 4 / 60 | 16 / 121 | 1 / 1 | 5 / 60 | 4 / 121 | 0 / 1 |
Outcome results
Primary
Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
A TEAE started on or after the date and time of the first dose of study drug administered in this study, or started prior to the study drug administration but worsened after the study drug started. Clinically significant events were defined as SAEs and other non-serious adverse events (AEs). A summary of SAEs and other non-serious AEs is located in the Reported Adverse Events module. Participants were on treatment up to 48 weeks. If a participant completed 48 weeks of treatment, the post-study treatment follow-up started at the next visit, 4 weeks later (Week 52). If a participant discontinued treatment early \[early discontinuation (ED)\], the post-study treatment follow-up started immediately afterwards. Baseline was defined as Week 0 in this study \[which is equivalent to Week 24 of the participant's prior study: Study H9B-MC-BCDG (NCT00689728) or Study H9B-MC-BCDH (NCT00785928)\].
Time frame: Baseline through Week 52 (up to 48 weeks of treatment or ED and follow-up through Week 52)
Population: Participants who received any amount of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 60 mg LY2127399 | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE | 38 Participants |
| 60 mg LY2127399 | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE | 4 Participants |
| 60/120 mg LY2127399 | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE | 95 Participants |
| 60/120 mg LY2127399 | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE | 16 Participants |
| 60/120/60 mg LY2127399 | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE | 1 Participants |
| 60/120/60 mg LY2127399 | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE | 1 Participants |
Primary
Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs
For each planned laboratory evaluation, the range of values to be reported as AEs, regardless of causality, was pre-specified. A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module. Baseline was defined as Week 0 in this study \[which is equivalent to Week 24 of the participant's prior study: Study H9B-MC-BCDG (NCT00689728) or Study H9B-MC-BCDH (NCT00785928)\].
Time frame: Baseline through Week 112
Population: Participants who received any amount of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Vitamin D Decreased | 1 Participants |
| 60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Aspartate Aminotransferase (AST) Increased | 0 Participants |
| 60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Neutrophil Count Increased | 0 Participants |
| 60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hepatic Enzyme Increased | 0 Participants |
| 60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Alanine Aminotransferase (ALT) Increased | 0 Participants |
| 60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Vitamin B12 Deficiency | 0 Participants |
| 60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | B-Lymphocyte Count Decreased | 0 Participants |
| 60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hypokalaemia | 0 Participants |
| 60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hyperlipidaemia | 0 Participants |
| 60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Blood Alkaline Phosphatase Increased | 0 Participants |
| 60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hyperglycaemia | 0 Participants |
| 60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Blood Cholesterol Increased | 1 Participants |
| 60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hypercholesterolaemia | 0 Participants |
| 60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Dyslipidaemia | 0 Participants |
| 60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Blood Immunoglobulin M (IgM) Increased | 0 Participants |
| 60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Vitamin D Deficiency | 0 Participants |
| 60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | White Blood Cell Count Increased | 0 Participants |
| 60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Gamma-Glutamyltransferase (GGT) Increased | 0 Participants |
| 60/120 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Dyslipidaemia | 1 Participants |
| 60/120 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Gamma-Glutamyltransferase (GGT) Increased | 2 Participants |
| 60/120 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Blood Alkaline Phosphatase Increased | 1 Participants |
| 60/120 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Neutrophil Count Increased | 0 Participants |
| 60/120 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Vitamin D Deficiency | 0 Participants |
| 60/120 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hepatic Enzyme Increased | 1 Participants |
| 60/120 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hyperglycaemia | 1 Participants |
| 60/120 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Aspartate Aminotransferase (AST) Increased | 1 Participants |
| 60/120 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Blood Immunoglobulin M (IgM) Increased | 0 Participants |
| 60/120 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Vitamin B12 Deficiency | 1 Participants |
| 60/120 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hypercholesterolaemia | 2 Participants |
| 60/120 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hypokalaemia | 0 Participants |
| 60/120 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | White Blood Cell Count Increased | 0 Participants |
| 60/120 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | B-Lymphocyte Count Decreased | 0 Participants |
| 60/120 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Alanine Aminotransferase (ALT) Increased | 1 Participants |
| 60/120 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Blood Cholesterol Increased | 0 Participants |
| 60/120 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hyperlipidaemia | 0 Participants |
| 60/120 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Vitamin D Decreased | 0 Participants |
| 60/120/60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Blood Cholesterol Increased | 0 Participants |
| 60/120/60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Alanine Aminotransferase (ALT) Increased | 0 Participants |
| 60/120/60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Aspartate Aminotransferase (AST) Increased | 0 Participants |
| 60/120/60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | B-Lymphocyte Count Decreased | 0 Participants |
| 60/120/60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Blood Alkaline Phosphatase Increased | 0 Participants |
| 60/120/60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Blood Immunoglobulin M (IgM) Increased | 0 Participants |
| 60/120/60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Gamma-Glutamyltransferase (GGT) Increased | 0 Participants |
| 60/120/60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hepatic Enzyme Increased | 0 Participants |
| 60/120/60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Neutrophil Count Increased | 0 Participants |
| 60/120/60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Vitamin D Decreased | 0 Participants |
| 60/120/60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | White Blood Cell Count Increased | 0 Participants |
| 60/120/60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Dyslipidaemia | 0 Participants |
| 60/120/60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hypercholesterolaemia | 1 Participants |
| 60/120/60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hyperglycaemia | 0 Participants |
| 60/120/60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hyperlipidaemia | 0 Participants |
| 60/120/60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hypokalaemia | 1 Participants |
| 60/120/60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Vitamin B12 Deficiency | 0 Participants |
| 60/120/60 mg LY2127399 | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Vitamin D Deficiency | 0 Participants |
| 60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Blood Immunoglobulin M (IgM) Increased | 0 Participants |
| 60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | B-Lymphocyte Count Decreased | 0 Participants |
| 60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Alanine Aminotransferase (ALT) Increased | 0 Participants |
| 60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hypercholesterolaemia | 0 Participants |
| 60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Gamma-Glutamyltransferase (GGT) Increased | 1 Participants |
| 60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hyperlipidaemia | 0 Participants |
| 60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Vitamin D Decreased | 0 Participants |
| 60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Blood Alkaline Phosphatase Increased | 0 Participants |
| 60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hyperglycaemia | 0 Participants |
| 60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | White Blood Cell Count Increased | 0 Participants |
| 60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Vitamin B12 Deficiency | 0 Participants |
| 60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hepatic Enzyme Increased | 1 Participants |
| 60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Aspartate Aminotransferase (AST) Increased | 0 Participants |
| 60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Blood Cholesterol Increased | 0 Participants |
| 60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hypokalaemia | 0 Participants |
| 60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Dyslipidaemia | 0 Participants |
| 60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Neutrophil Count Increased | 0 Participants |
| 60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Vitamin D Deficiency | 0 Participants |
| 60/120 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Blood Cholesterol Increased | 0 Participants |
| 60/120 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Blood Immunoglobulin M (IgM) Increased | 1 Participants |
| 60/120 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Vitamin D Decreased | 0 Participants |
| 60/120 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Vitamin B12 Deficiency | 0 Participants |
| 60/120 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | White Blood Cell Count Increased | 1 Participants |
| 60/120 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Dyslipidaemia | 0 Participants |
| 60/120 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Alanine Aminotransferase (ALT) Increased | 1 Participants |
| 60/120 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hypercholesterolaemia | 0 Participants |
| 60/120 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Blood Alkaline Phosphatase Increased | 0 Participants |
| 60/120 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hyperglycaemia | 0 Participants |
| 60/120 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | B-Lymphocyte Count Decreased | 1 Participants |
| 60/120 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hyperlipidaemia | 1 Participants |
| 60/120 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hypokalaemia | 1 Participants |
| 60/120 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Aspartate Aminotransferase (AST) Increased | 1 Participants |
| 60/120 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hepatic Enzyme Increased | 0 Participants |
| 60/120 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Gamma-Glutamyltransferase (GGT) Increased | 0 Participants |
| 60/120 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Vitamin D Deficiency | 1 Participants |
| 60/120 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Neutrophil Count Increased | 1 Participants |
| 60/120/60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Blood Alkaline Phosphatase Increased | 0 Participants |
| 60/120/60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Aspartate Aminotransferase (AST) Increased | 0 Participants |
| 60/120/60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Dyslipidaemia | 0 Participants |
| 60/120/60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Vitamin B12 Deficiency | 0 Participants |
| 60/120/60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Vitamin D Decreased | 0 Participants |
| 60/120/60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hypokalaemia | 0 Participants |
| 60/120/60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Blood Cholesterol Increased | 0 Participants |
| 60/120/60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Gamma-Glutamyltransferase (GGT) Increased | 0 Participants |
| 60/120/60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Blood Immunoglobulin M (IgM) Increased | 0 Participants |
| 60/120/60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Alanine Aminotransferase (ALT) Increased | 0 Participants |
| 60/120/60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | White Blood Cell Count Increased | 0 Participants |
| 60/120/60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hyperglycaemia | 0 Participants |
| 60/120/60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | B-Lymphocyte Count Decreased | 0 Participants |
| 60/120/60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Neutrophil Count Increased | 0 Participants |
| 60/120/60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Vitamin D Deficiency | 0 Participants |
| 60/120/60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hypercholesterolaemia | 0 Participants |
| 60/120/60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hepatic Enzyme Increased | 0 Participants |
| 60/120/60 mg LY2127399 Post-Study Treatment Follow-Up | Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs | Hyperlipidaemia | 0 Participants |
Secondary
ACR-N Response
The ACR-N Responder Index was a composite of clinical, laboratory, and functional measures of rheumatoid arthritis. This index was defined as the lowest of either a) percent change in tender joint count, b) percent change in swollen joint count, or c) median percent change in 5 core ACR criteria: participant global assessment of disease activity, physician global assessment of disease activity, HAQ-DI (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and CRP. For example, a participant with an ACR-N of X had an improvement ≥X% in both tender and swollen joint counts and a median improvement ≥X% in the 5 criteria previously mentioned. Baseline was the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study. Results for the 60/120/60 mg LY2127399 treatment arm were not analyzed as the participant did not have an ACR assessment.
Time frame: Baseline, up to and through Week 52
Population: Participants who received any amount of study drug and had at least 1 post-baseline ACR-N assessment; excludes site with GCP issues; LOCF. No participant was analyzed in the 60/120/60 mg LY2127399 treatment arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 60 mg LY2127399 | ACR-N Response | 31.9 units on a scale | Standard Deviation 47.6 |
| 60/120 mg LY2127399 | ACR-N Response | 11.3 units on a scale | Standard Deviation 46.4 |
Secondary
Change From Baseline in Disease Activity Score Based on 28 Joint Count (DAS28)
The DAS28 consisted of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP (milligrams per liter \[mg/L\]), and participant global assessment of his or her disease activity using a VAS (participant global VAS). The DAS28 was calculated by using the following formula: DAS28-CRP=0.56\*square root(TJC28)+0.28\*square root(SJC28)+0.36\*natural log(CRP+1)+0.014\*participant global VAS+0.96. Scores ranged from 1.0 to 9.4 where lower scores indicated less disease activity and remission is DAS28 \<2.6. Baseline was defined as the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study. A decrease in DAS28 indicated an improvement in the participant's condition.
Time frame: Baseline, up to and through Week 52
Population: Participants who received any amount of study drug and had at least 1 post-baseline DAS28 assessment; excludes site with GCP issues; LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 60 mg LY2127399 | Change From Baseline in Disease Activity Score Based on 28 Joint Count (DAS28) | -2.0 units on a scale | Standard Deviation 1.5 |
| 60/120 mg LY2127399 | Change From Baseline in Disease Activity Score Based on 28 Joint Count (DAS28) | -1.3 units on a scale | Standard Deviation 1.5 |
| 60/120/60 mg LY2127399 | Change From Baseline in Disease Activity Score Based on 28 Joint Count (DAS28) | -1.3 units on a scale | — |
Secondary
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score
The FACIT Fatigue Scale was a brief participant-reported measure of fatigue and consisted of 13 items. Scores ranged from 0 to 52, where higher scores indicated less fatigue. Baseline was defined as the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study. An increase in FACIT fatigue score indicated an improvement of the participant's condition.
Time frame: Baseline, up to and through Week 52
Population: Participants who received any amount of study drug and had at least 1 post-baseline FACIT assessment; excludes site with GCP issues; LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 60 mg LY2127399 | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score | 5.2 units on a scale | Standard Deviation 10.4 |
| 60/120 mg LY2127399 | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score | 5.1 units on a scale | Standard Deviation 10.5 |
| 60/120/60 mg LY2127399 | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score | -6.0 units on a scale | — |
Secondary
Change From Baseline in Health Assessment Questionnaire-Disability Index [(HAQ-DI) Individual Component of the ACR Core Set]
The disability section of the health assessment questionnaire scored 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. Baseline was defined as the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study. A decrease in HAQ-DI score indicated an improvement in the participant's condition.
Time frame: Baseline, up to and through Week 52
Population: Participants who received any amount of study drug and had at least 1 post-baseline HAQ-DI assessment; excludes site with GCP issues; LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 60 mg LY2127399 | Change From Baseline in Health Assessment Questionnaire-Disability Index [(HAQ-DI) Individual Component of the ACR Core Set] | -0.3 units on a scale | Standard Deviation 0.5 |
| 60/120 mg LY2127399 | Change From Baseline in Health Assessment Questionnaire-Disability Index [(HAQ-DI) Individual Component of the ACR Core Set] | -0.3 units on a scale | Standard Deviation 0.6 |
| 60/120/60 mg LY2127399 | Change From Baseline in Health Assessment Questionnaire-Disability Index [(HAQ-DI) Individual Component of the ACR Core Set] | -0.5 units on a scale | — |
Secondary
Change From Baseline in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) Component Scores
SF-36 was a 36-item, health-related survey that assessed participant's quality of life on 8 domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health, mental health, social functioning, vitality and 2 component scores (mental and physical health). Domain scores calculated by summing individual items for each domain and transforming scores into 0 to 100 scale; higher scores indicated better health status. The mental component summary (MCS) score, based on SF-36 domains, consisted of social functioning, vitality, mental health, and role-emotional scales (range: 0 to 100). The physical component summary (PCS) score, based on SF-36 domains, consisted of physical functioning, bodily pain, role-physical, and general health scales (range: 0 to 100). Baseline: last assessment prior to participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study.
Time frame: Baseline, up to and through Week 52
Population: Participants who received any amount of study drug and had at least 1 post-baseline SF-36 assessment; excludes site with GCP issues; LOCF.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 60 mg LY2127399 | Change From Baseline in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) Component Scores | Physical Health Component Summary Score | 5.7 units on a scale | Standard Deviation 8 |
| 60 mg LY2127399 | Change From Baseline in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) Component Scores | Mental Health Component Summary Score | 4.7 units on a scale | Standard Deviation 12.2 |
| 60/120 mg LY2127399 | Change From Baseline in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) Component Scores | Physical Health Component Summary Score | 4.1 units on a scale | Standard Deviation 9.6 |
| 60/120 mg LY2127399 | Change From Baseline in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) Component Scores | Mental Health Component Summary Score | 2.9 units on a scale | Standard Deviation 10.1 |
| 60/120/60 mg LY2127399 | Change From Baseline in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) Component Scores | Physical Health Component Summary Score | 1.4 units on a scale | — |
| 60/120/60 mg LY2127399 | Change From Baseline in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) Component Scores | Mental Health Component Summary Score | -2.9 units on a scale | — |
Secondary
Change From Baseline in Participant's Assessment of Disease Activity (Individual Component of the ACR Core Set)
Participant's assessment of their current arthritis disease activity using a visual analog scale (VAS), which ranged from 0 millimeters (mm) (no arthritis activity) to 100 mm (extremely active arthritis). Baseline was defined as the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study. A decrease in disease activity score indicated an improvement in the participant's condition.
Time frame: Baseline, up to and through Week 52
Population: Participants who received any amount of study drug and had at least 1 post-baseline self-rated assessment of disease activity; excludes site with GCP issues; LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 60 mg LY2127399 | Change From Baseline in Participant's Assessment of Disease Activity (Individual Component of the ACR Core Set) | -26.1 mm | Standard Deviation 27.1 |
| 60/120 mg LY2127399 | Change From Baseline in Participant's Assessment of Disease Activity (Individual Component of the ACR Core Set) | -16.7 mm | Standard Deviation 30.7 |
| 60/120/60 mg LY2127399 | Change From Baseline in Participant's Assessment of Disease Activity (Individual Component of the ACR Core Set) | -68.0 mm | — |
Secondary
Change From Baseline in Participant's Assessment of Joint Pain (Individual Component of the ACR Core Set)
Participant's assessment of joint pain using a VAS, which ranged from 0 mm (no pain) to 100 mm (worst possible pain). Baseline was defined as the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study. A decrease in joint pain indicated an improvement in the participant's condition.
Time frame: Baseline, up to and through Week 52
Population: Participants who received any amount of study drug and had at least 1 post-baseline self-rated assessment of joint pain; excludes site with GCP issues; LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 60 mg LY2127399 | Change From Baseline in Participant's Assessment of Joint Pain (Individual Component of the ACR Core Set) | -26.9 mm | Standard Deviation 26.4 |
| 60/120 mg LY2127399 | Change From Baseline in Participant's Assessment of Joint Pain (Individual Component of the ACR Core Set) | -13.4 mm | Standard Deviation 30.2 |
| 60/120/60 mg LY2127399 | Change From Baseline in Participant's Assessment of Joint Pain (Individual Component of the ACR Core Set) | -68.0 mm | — |
Secondary
Change From Baseline in Physician's Global Assessment of Disease Activity (Individual Component of the ACR Core Set)
Physician's assessment of disease activity using a VAS that ranged from 0 mm (no arthritis activity) to 100 mm (extremely active arthritis). Baseline was defined as the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study. A decrease in disease activity score indicated an improvement in the participant's condition.
Time frame: Baseline, up to and through Week 52
Population: Participants who received any amount of study drug and had at least 1 post-baseline physician's global assessment of disease activity; excludes site with GCP issues; LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 60 mg LY2127399 | Change From Baseline in Physician's Global Assessment of Disease Activity (Individual Component of the ACR Core Set) | -29.1 mm | Standard Deviation 23.6 |
| 60/120 mg LY2127399 | Change From Baseline in Physician's Global Assessment of Disease Activity (Individual Component of the ACR Core Set) | -18.4 mm | Standard Deviation 26.9 |
| 60/120/60 mg LY2127399 | Change From Baseline in Physician's Global Assessment of Disease Activity (Individual Component of the ACR Core Set) | -38.0 mm | — |
Secondary
Change From Baseline in Swollen Joint Count (Individual Component of the ACR Core Set)
The number of swollen joints was determined by examination of 28 joints (14 on each side) which included: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. Joints were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint. Baseline was defined as the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study. A decrease in swollen joint count indicated an improvement in the participant's condition.
Time frame: Baseline, up to and through Week 52
Population: Participants who received any amount of study drug and had at least 1 post-baseline swollen joint assessment; excludes site with GCP issues; LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 60 mg LY2127399 | Change From Baseline in Swollen Joint Count (Individual Component of the ACR Core Set) | -7.6 swollen joints | Standard Deviation 6.8 |
| 60/120 mg LY2127399 | Change From Baseline in Swollen Joint Count (Individual Component of the ACR Core Set) | -5.3 swollen joints | Standard Deviation 6.6 |
| 60/120/60 mg LY2127399 | Change From Baseline in Swollen Joint Count (Individual Component of the ACR Core Set) | 2.0 swollen joints | — |
Secondary
Change From Baseline in Tender Joint Count [Individual Component of the American College of Rheumatology (ACR) Core Set]
The number of tender and painful joints was determined by examination of 28 joints (14 on each side) which included: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. Joints were assessed by pressure and joint manipulation on physical examination. The participant was asked for pain sensations on these manipulations and the investigator watched for spontaneous pain reactions. Any positive response on pressure, movement, or both was translated into a single tender-versus-nontender dichotomy. Baseline was defined as the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study. A decrease in tender joint count indicated an improvement in the participant's condition.
Time frame: Baseline, up to and through Week 52
Population: Participants who received any amount of study drug and had at least 1 post-baseline tender joint assessment; excludes site with GCP issues; Last observation carried forward (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 60 mg LY2127399 | Change From Baseline in Tender Joint Count [Individual Component of the American College of Rheumatology (ACR) Core Set] | -9.2 tender joints | Standard Deviation 8 |
| 60/120 mg LY2127399 | Change From Baseline in Tender Joint Count [Individual Component of the American College of Rheumatology (ACR) Core Set] | -6.5 tender joints | Standard Deviation 8.2 |
| 60/120/60 mg LY2127399 | Change From Baseline in Tender Joint Count [Individual Component of the American College of Rheumatology (ACR) Core Set] | -12.0 tender joints | — |
Secondary
Number of Participants With LY2127399 Immunogenicity (Anti-LY2127399 Antibodies)
The number of participants who had treatment-emergent or follow-up emergent anti-LY2127399 antibodies \[anti-drug antibodies (ADA)\] is reported. Treatment-emergent was defined as participants who had any sample from baseline through Week 52 that was a 4-fold increase (2 dilution increase) in immunogenicity titer over the baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20). Follow-up emergent was defined as any sample during follow-up that was a 4-fold increase (2 dilution increase) in immunogenicity titer over the baseline titer. The number of participants with baseline positive ADA data is also reported. Baseline was defined as the last measurement prior to randomization to any treatment in either Study H9B-MC-BCDG (NCT00689728) or Study H9B-MC-BCDH (NCT00785928).
Time frame: Baseline through Week 52 (up to 48 weeks of treatment or ED and follow-up through Week 52) and post-study treatment follow-up (start of Week 53 or ED up to and through Week 112)
Population: Participants who received any amount of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 60 mg LY2127399 | Number of Participants With LY2127399 Immunogenicity (Anti-LY2127399 Antibodies) | Treatment-Emergent ADA | 6 Participants |
| 60 mg LY2127399 | Number of Participants With LY2127399 Immunogenicity (Anti-LY2127399 Antibodies) | Baseline Positive ADA | 2 Participants |
| 60 mg LY2127399 | Number of Participants With LY2127399 Immunogenicity (Anti-LY2127399 Antibodies) | Follow-Up Emergent ADA | 2 Participants |
| 60/120 mg LY2127399 | Number of Participants With LY2127399 Immunogenicity (Anti-LY2127399 Antibodies) | Treatment-Emergent ADA | 15 Participants |
| 60/120 mg LY2127399 | Number of Participants With LY2127399 Immunogenicity (Anti-LY2127399 Antibodies) | Baseline Positive ADA | 1 Participants |
| 60/120 mg LY2127399 | Number of Participants With LY2127399 Immunogenicity (Anti-LY2127399 Antibodies) | Follow-Up Emergent ADA | 5 Participants |
| 60/120/60 mg LY2127399 | Number of Participants With LY2127399 Immunogenicity (Anti-LY2127399 Antibodies) | Baseline Positive ADA | 0 Participants |
| 60/120/60 mg LY2127399 | Number of Participants With LY2127399 Immunogenicity (Anti-LY2127399 Antibodies) | Follow-Up Emergent ADA | 0 Participants |
| 60/120/60 mg LY2127399 | Number of Participants With LY2127399 Immunogenicity (Anti-LY2127399 Antibodies) | Treatment-Emergent ADA | 0 Participants |
Secondary
Percentage of Participants Achieving ACR20 Response
ACR20 Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis. ACR20 Responder: had ≥20% improvement from baseline in both tender and swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, HAQ-DI (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and CRP. Percentage of participants achieving ACR20 response=(number of ACR20 responders/number of participants treated)\*100. Participants who discontinued from study prior to Week 52 were imputed as non-responders. Participants who reached Week 52 but had ≥1 of 7 components missing had missing components imputed by LOCF. This composite data imputation was denoted as non-responder imputation (NRI)/LOCF. Baseline: the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study.
Time frame: Baseline, up to and through Week 52
Population: Participants who received any amount of study drug and had at least 1 post-baseline ACR20 assessment; excludes site with GCP issues; missing data imputed by NRI/LOCF. Four (4), 29, and 1 participants were imputed as non-responders for the 60 mg, 60/120 mg, and 60/120/60 mg LY2127399 groups, respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 60 mg LY2127399 | Percentage of Participants Achieving ACR20 Response | 66.1 percentage of participants |
| 60/120 mg LY2127399 | Percentage of Participants Achieving ACR20 Response | 32.5 percentage of participants |
| 60/120/60 mg LY2127399 | Percentage of Participants Achieving ACR20 Response | 0.0 percentage of participants |
Secondary
Percentage of Participants Achieving ACR70 Response
ACR70 Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis. ACR70 Responder: had ≥70% improvement from baseline in both tender and swollen joint counts and ≥70% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, HAQ-DI (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and CRP. Percentage of participants achieving ACR70 response=(number of ACR70 responders/number of participants treated)\*100. Participants who discontinued from study prior to Week 52 were imputed as non-responders. Participants who reached Week 52 but had ≥1 of 7 components missing had missing components imputed by LOCF. This composite data imputation was denoted as NRI/LOCF. Baseline was defined as the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study.
Time frame: Baseline, up to and through Week 52
Population: Participants who received any amount of study drug and had at least 1 post-baseline ACR70 assessment; excludes site with GCP issues; missing data imputed by NRI/LOCF. Four (4), 29, and 1 participants were imputed as non-responders for the 60 mg, 60/120 mg, and 60/120/60 mg LY2127399 groups, respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 60 mg LY2127399 | Percentage of Participants Achieving ACR70 Response | 18.6 percentage of participants |
| 60/120 mg LY2127399 | Percentage of Participants Achieving ACR70 Response | 6.7 percentage of participants |
| 60/120/60 mg LY2127399 | Percentage of Participants Achieving ACR70 Response | 0.0 percentage of participants |
Secondary
Percentage of Participants ACR50 Response
ACR50 Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis. ACR50 Responder: had ≥50% improvement from baseline in both tender and swollen joint counts and ≥50% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, HAQ-DI (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and CRP. Percentage of participants achieving ACR50 response=(number of ACR50 responders/number of participants treated)\*100. Participants who discontinued from study prior to Week 52 were imputed as non-responders. Participants who reached Week 52 but had ≥1 of 7 components missing had missing components imputed by LOCF. This composite data imputation was denoted as NRI/LOCF. Baseline was defined as the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study.
Time frame: Baseline, up to and through Week 52
Population: Participants who received any amount of study drug and had at least 1 post-baseline ACR50 assessment; excludes site with GCP issues; missing data imputed by NRI/LOCF. Four (4), 29, and 1 participants were imputed as non-responders for the 60 mg, 60/120 mg, and 60/120/60 mg LY2127399 groups, respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 60 mg LY2127399 | Percentage of Participants ACR50 Response | 33.9 percentage of participants |
| 60/120 mg LY2127399 | Percentage of Participants ACR50 Response | 13.3 percentage of participants |
| 60/120/60 mg LY2127399 | Percentage of Participants ACR50 Response | 0.0 percentage of participants |
Secondary
Percentage of Participants With Response Based on European League Against Rheumatism Responder Index, 28 Joint Count (EULAR28)
EULAR28 was defined by the participant's change from baseline in DAS28 score and the absolute DAS28 score achieved. DAS28 consisted of composite score of the following: tender joint count, swollen joint count, CRP, and participant global assessment of his\\her disease activity (participant global VAS). EULAR28 categories included: No Response \[improvement in DAS28 ≤0.6 units (u) or post-baseline DAS28 score \>5.1 with improvement ≤1.2 u\], Moderate Response (post-baseline DAS28 score ≤5.1 with improvement \>0.6 u but \<1.2 u or post-baseline DAS28 score \>3.2 with improvement \>1.2 u), and Good Response (post-baseline DAS28 score ≤3.2 with improvement \>1.2 u). Baseline was the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study. Percentage of participants=(number of participants with specific response/participants assessed)\*100. Displayed percentages may not add up to 100% because of rounding.
Time frame: Baseline, up to and through Week 52
Population: Participants who received any amount of study drug and had at least 1 post-baseline EULAR28 assessment; excludes site with GCP issues; LOCF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 60 mg LY2127399 | Percentage of Participants With Response Based on European League Against Rheumatism Responder Index, 28 Joint Count (EULAR28) | Moderate response | 48.2 percentage of participants |
| 60 mg LY2127399 | Percentage of Participants With Response Based on European League Against Rheumatism Responder Index, 28 Joint Count (EULAR28) | No response | 16.1 percentage of participants |
| 60 mg LY2127399 | Percentage of Participants With Response Based on European League Against Rheumatism Responder Index, 28 Joint Count (EULAR28) | Good response | 35.7 percentage of participants |
| 60/120 mg LY2127399 | Percentage of Participants With Response Based on European League Against Rheumatism Responder Index, 28 Joint Count (EULAR28) | Moderate response | 39.3 percentage of participants |
| 60/120 mg LY2127399 | Percentage of Participants With Response Based on European League Against Rheumatism Responder Index, 28 Joint Count (EULAR28) | No response | 44.4 percentage of participants |
| 60/120 mg LY2127399 | Percentage of Participants With Response Based on European League Against Rheumatism Responder Index, 28 Joint Count (EULAR28) | Good response | 16.2 percentage of participants |
| 60/120/60 mg LY2127399 | Percentage of Participants With Response Based on European League Against Rheumatism Responder Index, 28 Joint Count (EULAR28) | No response | 0 percentage of participants |
| 60/120/60 mg LY2127399 | Percentage of Participants With Response Based on European League Against Rheumatism Responder Index, 28 Joint Count (EULAR28) | Good response | 0 percentage of participants |
| 60/120/60 mg LY2127399 | Percentage of Participants With Response Based on European League Against Rheumatism Responder Index, 28 Joint Count (EULAR28) | Moderate response | 100.0 percentage of participants |
Secondary
Percent Change From Baseline in C-Reactive Protein [(CRP) Individual Component of the ACR Core Set]
CRP is an indicator of inflammation. The percentage of change in CRP from baseline=\[(post-baseline CRP-baseline CRP)/baseline CRP\]\*100. Baseline was defined as the last assessment prior to the participant's first dose of LY2127399 in Study H9B-MC-BCDG (NCT00689728), Study H9B-MC-BCDH (NCT00785928), or this study. A negative change indicated an improvement in the participant's condition.
Time frame: Baseline, up to and through Week 52
Population: Participants who received any amount of study drug and had at least 1 post-baseline CRP assessment; excludes site with GCP issues; LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 60 mg LY2127399 | Percent Change From Baseline in C-Reactive Protein [(CRP) Individual Component of the ACR Core Set] | -11.1 percent change | Standard Deviation 164.6 |
| 60/120 mg LY2127399 | Percent Change From Baseline in C-Reactive Protein [(CRP) Individual Component of the ACR Core Set] | 50.7 percent change | Standard Deviation 214.4 |
| 60/120/60 mg LY2127399 | Percent Change From Baseline in C-Reactive Protein [(CRP) Individual Component of the ACR Core Set] | 241.4 percent change | — |
Secondary
Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts)
Cell surface marker CD19, CD27, and immunoglobulin D (IgD) expression levels were used to define the various B cell subsets. Cell surface markers were defined as being either present (+) or absent (-). Peripheral blood B cell subsets included: mature naive cells (CD19+IgD+CD27-); immature/transitional cells (CD19+IgD-CD27-); switched memory (CD19+IgD-CD27+); and non-switched memory (CD19+IgD+CD27+). Baseline was defined as the last measurement prior to randomization to any treatment in either Study H9B-MC-BCDG (NCT00689728) or Study H9B-MC-BCDH (NCT00785928). A negative change indicated a decrease in cell count.
Time frame: Baseline, Weeks 52, 60, 72, 80, 88, and 100
Population: Participants who received any amount of study drug and had the specified peripheral blood B cell subset assessment post-baseline at the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Non-Switched Memory Cells, Week 52 | 6.0 cells/µL | Standard Deviation 22 |
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Mature Naive Cells, Week 60 | -138.8 cells/µL | Standard Deviation 67.1 |
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Mature Naive Cells, Week 72 | -95.9 cells/µL | Standard Deviation 75.4 |
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Mature Naive Cells, Week 80 | -189.0 cells/µL | — |
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Mature Naive Cells, Week 88 | -116.5 cells/µL | Standard Deviation 99.7 |
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Immature/Transitional Cells, Week 52 | -5.8 cells/µL | Standard Deviation 7.1 |
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Immature/Transitional Cells, Week 60 | -6.5 cells/µL | Standard Deviation 7.9 |
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Immature/Transitional Cells, Week 72 | -8.6 cells/µL | Standard Deviation 8.9 |
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Immature/Transitional Cells, Week 80 | -5.0 cells/µL | — |
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Immature/Transitional Cells, Week 88 | -3.0 cells/µL | Standard Deviation 4.2 |
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Switched Memory Cells, Week 52 | 12.6 cells/µL | Standard Deviation 27.1 |
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Switched Memory Cells, Week 60 | -6.5 cells/µL | Standard Deviation 16.3 |
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Switched Memory Cells, Week 72 | -14.7 cells/µL | Standard Deviation 18.9 |
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Switched Memory Cells, Week 80 | -10.0 cells/µL | — |
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Switched Memory Cells, Week 88 | -10.0 cells/µL | Standard Deviation 5.7 |
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Mature Naive Cells, Week 52 | -115.0 cells/µL | Standard Deviation 79.9 |
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Non-Switched Memory Cells, Week 60 | -3.8 cells/µL | Standard Deviation 2.2 |
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Non-Switched Memory Cells, Week 72 | -10.5 cells/µL | Standard Deviation 18 |
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Non-Switched Memory Cells, Week 80 | -4.0 cells/µL | — |
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Non-Switched Memory Cells, Week 88 | -18.0 cells/µL | Standard Deviation 17 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Non-Switched Memory Cells, Week 80 | -3.6 cells/µL | Standard Deviation 4.3 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Immature/Transitional Cells, Week 100 | -6.5 cells/µL | Standard Deviation 0.7 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Non-Switched Memory Cells, Week 52 | 8.3 cells/µL | Standard Deviation 22.2 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Switched Memory Cells, Week 52 | 13.1 cells/µL | Standard Deviation 31.4 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Immature/Transitional Cells, Week 72 | -8.5 cells/µL | Standard Deviation 15.5 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Switched Memory Cells, Week 100 | -13.0 cells/µL | Standard Deviation 22.6 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Immature/Transitional Cells, Week 80 | -9.0 cells/µL | Standard Deviation 12.1 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Immature/Transitional Cells, Week 88 | -9.0 cells/µL | Standard Deviation 10.5 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Mature Naive Cells, Week 52 | -109.2 cells/µL | Standard Deviation 92.2 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Non-Switched Memory Cells, Week 100 | -10.5 cells/µL | Standard Deviation 9.2 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Switched Memory Cells, Week 72 | -17.7 cells/µL | Standard Deviation 36.1 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Mature Naive Cells, Week 72 | -102.6 cells/µL | Standard Deviation 90.4 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Non-Switched Memory Cells, Week 72 | -7.3 cells/µL | Standard Deviation 18.7 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Mature Naive Cells, Week 80 | -80.1 cells/µL | Standard Deviation 62.8 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Switched Memory Cells, Week 80 | -7.5 cells/µL | Standard Deviation 17.3 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Mature Naive Cells, Week 88 | -111.7 cells/µL | Standard Deviation 75.5 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Mature Naive Cells, Week 100 | -89.0 cells/µL | Standard Deviation 108.9 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Immature/Transitional Cells, Week 52 | -4.5 cells/µL | Standard Deviation 13.2 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Non-Switched Memory Cells, Week 88 | -8.2 cells/µL | Standard Deviation 9.7 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Switched Memory Cells, Week 88 | -9.0 cells/µL | Standard Deviation 10.2 |
| 60/120/60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Non-Switched Memory Cells, Week 80 | -35.0 cells/µL | — |
| 60/120/60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Mature Naive Cells, Week 80 | -123.0 cells/µL | — |
| 60/120/60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Immature/Transitional Cells, Week 80 | -10.0 cells/µL | — |
| 60/120/60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Peripheral Blood B Cell Subsets (Absolute Cell Counts) | Switched Memory Cells, Week 80 | -23.0 cells/µL | — |
Secondary
Pharmacodynamics: Change From Baseline in Rheumatoid Factor (RF) Levels at Week 52
RF is an autoantibody (antibody directed against an organism's own tissues) most relevant in rheumatoid arthritis. Higher RF levels indicate an aggressive rheumatoid arthritis and a higher risk of joint damage. Baseline was defined as Week 0 in this study \[which is equivalent to Week 24 of the participant's prior study: Study H9B-MC-BCDG (NCT00689728) or Study H9B-MC-BCDH (NCT00785928)\]. A decrease in RF levels indicated an improvement in the participant's condition. Results for the 60/120/60 mg LY2127399 treatment arm were not analyzed as the participant did not have a Week 52 RF level assessment.
Time frame: Baseline, Week 52
Population: Participants who received any amount of study drug and had Week 52 post-baseline RF level assessment, excluding the site with GCP issues. No participant was analyzed in the 60/120/60 mg LY2127399 treatment arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Rheumatoid Factor (RF) Levels at Week 52 | -26.9 international units/milliliter (IU/mL) | Standard Deviation 241.4 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Rheumatoid Factor (RF) Levels at Week 52 | -53.8 international units/milliliter (IU/mL) | Standard Deviation 312.6 |
Secondary
Pharmacodynamics: Change From Baseline in Serum Anti-Cyclic Citrullinated Peptide (Anti-CCP) Antibodies
Anti-CCP antibodies were measured using an enzyme-linked immunosorbent assay (ELISA) method. In general, high levels of the antibody indicated an aggressive rheumatoid arthritis and a higher risk of joint damage. Baseline was defined as Week 0 in this study \[which is equivalent to Week 24 of the participant's prior study: Study H9B-MC-BCDG (NCT00689728) or Study H9B-MC-BCDH (NCT00785928)\]. A decrease in anti-CCP antibodies indicated an improvement in the participant's condition.
Time frame: Baseline, up to Week 52
Population: Participants who received any amount of study drug and had at least 1 post-baseline anti-CCP assessment, excluding site with GCP issues; LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Serum Anti-Cyclic Citrullinated Peptide (Anti-CCP) Antibodies | 6.9 units per milliliter (U/mL) | Standard Deviation 241.9 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Serum Anti-Cyclic Citrullinated Peptide (Anti-CCP) Antibodies | -19.4 units per milliliter (U/mL) | Standard Deviation 358.7 |
| 60/120/60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Serum Anti-Cyclic Citrullinated Peptide (Anti-CCP) Antibodies | 0.0 units per milliliter (U/mL) | — |
Secondary
Pharmacodynamics: Change From Baseline in Serum Immunoglobulin
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 M (IgM), and immunoglobulin A (IgA) levels are reported. Baseline was defined as the last measurement prior to randomization to any treatment in either Study H9B-MC-BCDG (NCT00689728) or Study H9B-MC-BCDH (NCT00785928). A negative change indicated a decrease in immunoglobulin levels.
Time frame: Baseline, up to Week 52
Population: Participants who received any amount of study drug and had at least 1 post-baseline serum immunoglobulin assessment; LOCF.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Serum Immunoglobulin | IgM | -0.3 grams per liter (g/L) | Standard Deviation 0.4 |
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Serum Immunoglobulin | IgG | -1.8 grams per liter (g/L) | Standard Deviation 2.1 |
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Serum Immunoglobulin | IgA | -0.6 grams per liter (g/L) | Standard Deviation 0.8 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Serum Immunoglobulin | IgM | -0.3 grams per liter (g/L) | Standard Deviation 0.5 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Serum Immunoglobulin | IgG | -2.0 grams per liter (g/L) | Standard Deviation 3.8 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Serum Immunoglobulin | IgA | -0.5 grams per liter (g/L) | Standard Deviation 0.7 |
| 60/120/60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Serum Immunoglobulin | IgG | -1.9 grams per liter (g/L) | — |
| 60/120/60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Serum Immunoglobulin | IgA | -0.8 grams per liter (g/L) | — |
| 60/120/60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Serum Immunoglobulin | IgM | -0.2 grams per liter (g/L) | — |
Secondary
Pharmacodynamics: Change From Baseline in Total B Cells [Cluster Designation 20+ (CD20+)] Absolute Cell Counts
B-lymphocyte antigen CD20+ is an activated-glycosylated phosphoprotein expressed on the surface of all mature B cells. Baseline was defined as the last measurement prior to randomization to any treatment in either Study H9B-MC-BCDG (NCT00689728) or Study H9B-MC-BCDH (NCT00785928). A negative change indicated a decrease in cell count.
Time frame: Baseline, Weeks 52, 60, 72, 80, 88, and 100
Population: Participants who received any amount of study drug and a post-baseline total B cell assessment at the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Total B Cells [Cluster Designation 20+ (CD20+)] Absolute Cell Counts | Week 60 | -135.9 cells per microliter (cells/µL) | Standard Deviation 119 |
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Total B Cells [Cluster Designation 20+ (CD20+)] Absolute Cell Counts | Week 80 | -137.6 cells per microliter (cells/µL) | Standard Deviation 85.7 |
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Total B Cells [Cluster Designation 20+ (CD20+)] Absolute Cell Counts | Week 52 | -113.1 cells per microliter (cells/µL) | Standard Deviation 103.4 |
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Total B Cells [Cluster Designation 20+ (CD20+)] Absolute Cell Counts | Week 100 | -71.7 cells per microliter (cells/µL) | Standard Deviation 68.7 |
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Total B Cells [Cluster Designation 20+ (CD20+)] Absolute Cell Counts | Week 88 | -109.9 cells per microliter (cells/µL) | Standard Deviation 83.8 |
| 60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Total B Cells [Cluster Designation 20+ (CD20+)] Absolute Cell Counts | Week 72 | -141.0 cells per microliter (cells/µL) | Standard Deviation 105.4 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Total B Cells [Cluster Designation 20+ (CD20+)] Absolute Cell Counts | Week 88 | -148.6 cells per microliter (cells/µL) | Standard Deviation 131.3 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Total B Cells [Cluster Designation 20+ (CD20+)] Absolute Cell Counts | Week 52 | -110.3 cells per microliter (cells/µL) | Standard Deviation 121.7 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Total B Cells [Cluster Designation 20+ (CD20+)] Absolute Cell Counts | Week 60 | -143.1 cells per microliter (cells/µL) | Standard Deviation 135.3 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Total B Cells [Cluster Designation 20+ (CD20+)] Absolute Cell Counts | Week 72 | -151.6 cells per microliter (cells/µL) | Standard Deviation 117.8 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Total B Cells [Cluster Designation 20+ (CD20+)] Absolute Cell Counts | Week 80 | -150.9 cells per microliter (cells/µL) | Standard Deviation 127.7 |
| 60/120 mg LY2127399 | Pharmacodynamics: Change From Baseline in Total B Cells [Cluster Designation 20+ (CD20+)] Absolute Cell Counts | Week 100 | -127.3 cells per microliter (cells/µL) | Standard Deviation 121.4 |
| 60/120/60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Total B Cells [Cluster Designation 20+ (CD20+)] Absolute Cell Counts | Week 80 | -262.0 cells per microliter (cells/µL) | — |
| 60/120/60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Total B Cells [Cluster Designation 20+ (CD20+)] Absolute Cell Counts | Week 100 | -95.0 cells per microliter (cells/µL) | — |
| 60/120/60 mg LY2127399 | Pharmacodynamics: Change From Baseline in Total B Cells [Cluster Designation 20+ (CD20+)] Absolute Cell Counts | Week 88 | -143.0 cells per microliter (cells/µL) | — |
Secondary
Pharmacodynamics: Percent Change From Baseline in Erythrocyte Sedimentation Rate (ESR)
ESR is a laboratory test that provides a non-specific measure of inflammation. The test assessed the rate at which red blood cells fell in a test tube. Normal range was considered to be 0 to 20 or 0 to 30 millimeters per hour (mm/h), depending on the reference range used by the laboratory. Higher scores indicated greater inflammation. Percent change from baseline ESR=\[(post-baseline ESR- baseline ESR)/baseline ESR\]\*100. Baseline was defined as Week 0 in this study \[which is equivalent to Week 24 of the participant's prior study: Study H9B-MC-BCDG (NCT00689728) or Study H9B-MC-BCDH (NCT00785928)\]. A decrease in ESR indicated an improvement in the participant's condition.
Time frame: Baseline, up to Week 52
Population: Participants who received any amount of study drug and had at least 1 post-baseline ESR assessment, excluding site with GCP issues; LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 60 mg LY2127399 | Pharmacodynamics: Percent Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | 5.0 percent change | Standard Deviation 63.7 |
| 60/120 mg LY2127399 | Pharmacodynamics: Percent Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | 20.9 percent change | Standard Deviation 103.9 |
| 60/120/60 mg LY2127399 | Pharmacodynamics: Percent Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | -25.0 percent change | — |
Other Pre-specified
Number of Participants Who Died, Any Cause
A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module. Baseline was defined as Week 0 in this study \[which is equivalent to Week 24 of the participant's prior study: Study H9B-MC-BCDG (NCT00689728) or Study H9B-MC-BCDH (NCT00785928)\]. Participants were on treatment up to 48 weeks. If a participant completed 48 weeks of treatment, the post-study treatment follow-up started at the next visit, 4 weeks later (Week 52). If a participant discontinued treatment early, the post-study treatment follow-up started immediately afterwards. After treatment discontinuation, participants could be followed beyond Week 72 for B cell recovery (up to Week 112).
Time frame: Baseline through Week 52 (up to 48 weeks of treatment or ED and follow-up through Week 52) and post-study treatment follow-up (start of Week 53 or ED up to and through Week 72 and start of Week 73 up to and through Week 112)
Population: Participants who received any amount of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 60 mg LY2127399 | Number of Participants Who Died, Any Cause | Died post-study treatment Wk 73 through Wk 100 | 1 Participants |
| 60 mg LY2127399 | Number of Participants Who Died, Any Cause | Died on study treatment [up to Week (Wk) 52] | 0 Participants |
| 60 mg LY2127399 | Number of Participants Who Died, Any Cause | Died post-study treatment Wk 53/ED through Wk 72 | 1 Participants |
| 60/120 mg LY2127399 | Number of Participants Who Died, Any Cause | Died post-study treatment Wk 73 through Wk 100 | 1 Participants |
| 60/120 mg LY2127399 | Number of Participants Who Died, Any Cause | Died post-study treatment Wk 53/ED through Wk 72 | 0 Participants |
| 60/120 mg LY2127399 | Number of Participants Who Died, Any Cause | Died on study treatment [up to Week (Wk) 52] | 1 Participants |
| 60/120/60 mg LY2127399 | Number of Participants Who Died, Any Cause | Died post-study treatment Wk 73 through Wk 100 | 0 Participants |
| 60/120/60 mg LY2127399 | Number of Participants Who Died, Any Cause | Died post-study treatment Wk 53/ED through Wk 72 | 0 Participants |
| 60/120/60 mg LY2127399 | Number of Participants Who Died, Any Cause | Died on study treatment [up to Week (Wk) 52] | 0 Participants |