Arthritis, Rheumatoid
Conditions
Brief summary
This is a Phase 2b, outpatient, randomized, double-blinded (with a single-blind extension), placebo-controlled, dose-ranging, parallel-group study of baricitinib (LY3009104) in Japanese participants with active rheumatoid arthritis (RA) on background methotrexate (MTX) therapy. Baricitinib will be orally administered once a day with background methotrexate \[6 to 16 milligrams (mg)/week\] therapy for 12 weeks in the double-blind treatment period (1, 2, 4 or 8 mg/day, or placebo), and for 52 weeks in the single-blind extension period (4 or 8 mg/day).
Interventions
DRUGPlacebo
DRUGBaricitinib
DRUGMethotrexate
Administered orally as background therapy
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Ambulatory males or females between the ages of 20 and 75 years, inclusive, at time of study entry * Diagnosis of adult-onset RA (of at least 6 months duration but not longer than 15 years prior to screening) according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Responder Index classification criteria for RA * Have active RA defined as at least 6 swollen and at least 6 tender joints based on the 66/68 joint count * Regular use of MTX for at least 12 weeks, and treatment at a stable dose of 6 to 16 mg/week (2 or 3 times a week) for at least 8 weeks prior to the treatment period. The dose of MTX should remain stable throughout the study, but may be adjusted for safety reasons. * For participants receiving corticosteroids, they must be on a dose not to exceed 10 mg of prednisone daily (or equivalent) and have been on the same dosing regimen for at least 6 weeks prior to the treatment period * Have C-Reactive Protein (CRP) measurement \> 0.5 milligrams/deciliter (mg/dL) or Erythrocyte Sedimentation Rate (ESR) \> 28 millimeters/hour (mm/hr). The CRP and ESR may be repeated once during the screening period at the discretion of the investigator, and the repeat results may be accepted for study eligibility purposes
Exclusion criteria
* Use of nonsteroidal anti-inflammatories (NSAIDs) for less than 4 weeks prior to the treatment period. If on NSAIDs, must be on a stable dose of the drug for at least 4 weeks prior to the treatment period and must remain on a stable dose throughout the study * Received prior treatment with an oral Janus Kinase (JAK) inhibitor regardless of when they received it * Have a diagnosis of Felty's syndrome * Evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies * Have hepatitis C virus (HCV; positive for anti-hepatitis C antibody with confirmed presence of HCV) * Positive for hepatitis B surface antigen (HBsAg+), OR negative for hepatitis B surface antigen (HBsAg-), but positive for hepatitis B core antibody (HBcAb+) and/or positive for hepatitis B surface antibody (HBsAb+) with positive Hepatitis B virus (HBV)-deoxyribonucleic acid (DNA) \[≥2.1 Log copy/mL by Polymerase Chain Reaction (PCR) method\] detected in the serum * Have a positive result of the QuantiFERON®-tuberculosis (TB) Gold test (QFT-G) or a purified protein derivative (PPD) test * Have estimated Glomerular Filtration Rate (GFR) from serum creatinine using the Modification of Diet in Renal Disease (MDRD) method of \<50 milliliter/minute (mL/min)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in the 4 mg and 8 mg Dose Groups Who Achieved an American College of Rheumatology 20 (ACR20) Responder Index Response Baseline Through Week 12 . | 12 weeks | ACR20 responders are participants with at least 20% improvement from baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: Health Assessment Questionnaire-Disability Index (HAQ-DI) which measured participants perceived degree of difficulty performing daily activities, C-reactive Protein (CRP) and erythrocyte sedimentation rate (ESR), Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS) , Patient's Global Assessment of Disease Activity-VAS (PtGADA-VAS), and Physician's Global Assessment of Disease Activity-VAS (PhGA-VAS). Missing values were imputed using Non-Responder Imputation (NRI), where non-responders were participants who discontinued the study prior to the completion of Part A. Percentage of participants achieving ACR20 response = (number of ACR20 responders) /(number of participants treated) \* 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved an ACR70 Response at 12 Weeks (Part A) | Baseline up to 12 weeks | ACR70 responders were participants with at least 70% improvement from baseline for TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, or PhGA-VAS. Missing values were imputed using NRI, where non-responders were participants who discontinued the study prior to the completion of Part A. Percentage of participants achieving ACR70 response=(number of ACR70 responders / number of participants treated) \* 100. |
| Percentage of Participants Who Achieved an ACR70 Response at 64 Weeks (Part B) | Baseline up to 64 weeks | ACR70 responders were participants with at least 70% improvement from baseline for TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, or PhGA-VAS. Missing values were imputed using NRI, where non-responders were participants who discontinued the study prior to the completion of Part B. Percentage of participants achieving ACR70 response=(number of ACR70 responders) / (number of participants treated) \* 100. |
| Mean Change From Baseline to Week 12 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP) | Baseline, 12 weeks | DAS modified included the DAS28 that consisted of a composite score of the following variables: tender joint count out of 28 (TJC28), swollen joint count out of 28 (SJC28), CRP \[milligrams per liter (mg/L)\], and PtGADA on a 0 to 100 millimeter (mm) VAS (0mm=no arthritis activity to 100 mm= extremely active arthritis). DAS28 calculated as: DAS28-CRP = 0.56(square root of TJC28)+0.28(square root of SJC28)+0.36\[ln(CRP +1)\]+0.014(VAS)+0.96. A decrease in DAS28-CRP indicated an improvement in participant's condition. |
| Mean Change From Baseline to Week 64 in DAS Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP) | Baseline, 64 weeks | DAS modified included the 28 diarthroidal joint count (DAS28) that consisted of a composite score of the following variables: TJC28, SJC28, CRP (mg/L), and PtGADA on a 0 to 100 mm VAS (0mm=no arthritis activity to 100 mm= extremely active arthritis). DAS28 calculated as: DAS28-CRP = 0.56(square root of TJC28)+0.28(square root of SJC28)+0.36\[ln(CRP +1)\]+0.014(VAS)+0.96. A decrease in DAS28-CRP indicated an improvement in participant's condition. |
| Percentage of Participants Who Achieved an European League Against Rheumatism Rating of 28-Joint Arthritic Condition (EULAR28) Response at 12 Weeks (Part A) | Baseline up to 12 weeks | EULAR Responder Index based on 28 joint counts categorizes clinical response based on improvement from baseline in DAS28-CRP. DAS28-CRP scores range from 1.0-9.4, where lower scores indicated less disease activity. High disease activity: DAS28-CRP \>5.1, low disease activity: DAS28-CRP ≤3.2, and remission: DAS28-CRP \<2.6. Participants are categorized as EULAR responders or non-responders based on improvement of DAS28-CRP scores from baseline. EULAR DAS28-CRP responder index defines a good (absolute: ≤3.2 and \>1.2 improvement from baseline), moderate (absolute: \>3.2 and ≤5.1 and \>0.6 and ≤1.2 improvement from baseline), or no response (absolute: \>5.1 and ≤0.6 improvement from baseline). Percentage of participants calculated as = (number of good +moderate responders) / (number of participants treated) \* 100. |
| Percentage of Participants Who Achieved an EULAR28 Response at 64 Weeks (Part B) | Baseline up to 64 weeks | EULAR Responder Index based on 28 joint counts categorizes clinical response based on improvement from baseline in DAS28-CRP. DAS28-CRP scores range from 1.0-9.4, where lower scores indicated less disease activity. High disease activity: DAS28-CRP \>5.1, low disease activity: DAS28-CRP \<3.2, and remission: DAS28-CRP \<2.6. Participants are categorized as EULAR responders or non-responders based on improvement of DAS28-CRP scores from baseline. EULAR DAS28-CRP Responder Index defines a good (absolute: ≤3.2 and \>1.2 improvement from baseline), moderate (absolute: \>3.2 and ≤5.1 and \>0.6 and ≤1.2 improvement from baseline), or no response (absolute: \>5.1 and ≤0.6 improvement from baseline). Percentage of participants calculated as = (number of good +moderate responders) / (number of participants treated) \* 100. |
| Mean Change in Simplified Disease Activity Index (SDAI) Responses up to 12 Weeks (Part A) | Baseline up to 12 weeks | The SDAI is the numerical sum of 5 outcome parameters: TJC28, SJC28, patient and physician global assessment of disease activity and CRP. The equation used to calculate the SDAI:SDAI=SJC28+TJC28+PtGADA-VAS+PhGA-VAS+CRP where PtGADA-VAS=PtGADA-VAS / 10 and PhGA-VAS=PhGA-VAS / 10, with lower values indicating fewer symptoms. |
| Mean Change in SDAI Responses up to 64 Weeks (Part B) | Baseline, 64 weeks | The SDAI is the numerical sum of 5 outcome parameters: TJC28, SJC28, PtGADA, PhGA, and CRP. The equation used to calculate the SDAI: SDAI=SJC28+TJC28+PtGADA-VAS+PhGA-VAS+CRP where PtGADA-VAS=PtGADA -VAS/ 10 and PhGA-VAS=PhGA-VAS/ 10, with lower values indicating fewer symptoms. |
| Mean Change in Health Assessment Questionnaire - Disability Index (HAQ-DI) Responses up to 12 Weeks (Part A) | Baseline, 12 weeks | HAQ-DI was a participant-reported questionnaire that consisted of 24 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the week using response categories: without any difficulty (0), with some difficulty (1), with much difficulty (2), and unable to do (3). The highest score for any question in a category was the score of that category unless special aids or devices or help from another person was required. Answers for at least 6 of the 8 domains were required. Otherwise, HAQ-DI score was considered missing. The HAQ-DI score was the sum of the category scores divided by the number of categories scored, with a possible scores range from 0 to 3, 0 being without any difficulty and 3 being unable to do. |
| Percentage of Participants Who Achieved an ACR20 Response at 64 Weeks | Baseline up to 64 weeks | ACR20 responders are participants with at least 20% improvement from baseline for TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI which measured participants perceived degree of difficulty performing daily activities, CRP and ESR, PAAP-VAS, PtGADA-VAS, or PhGA-VAS. Missing values were imputed using NRI, where non-responders were participants who discontinued the study prior to the completion of Part B. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants treated) \* 100. |
| Mean Value of ACR-N Response (Part A) | Baseline up to 12 weeks | The ACR-N Response Index is a continuous measure of clinical, laboratory, and functional measures in RA to characterize the percentage of improvement from baseline in RA disease activity. This index is defined as the lowest of either: a) percent change in TJC, b) percent change in SJC, or c) median percent change of the remaining 5 ACR core criteria (HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, or PhGA-VAS). A participant with an ACR-N of X has improvement of at least X% in tender and swollen joints and a median improvement of at least X% in the 5 remaining ACR core criteria. Since ACR-N is a continuous measure, the mean values are reported instead of the originally registered percentage of participants. |
| Mean Value of ACR-N Response (Part B) | Baseline up to 64 weeks | The ACR-N Response Index is a continuous measure of clinical, laboratory, and functional measures in RA to characterize the percentage of improvement from baseline in RA disease activity. This index is defined as the lowest of either: a) percent change in TJC, b) percent change in SJC, or c) median percent change of the remaining 5 ACR core criteria (HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, or PhGA-VAS). A participant with an ACR-N of X has improvement of at least X% in tender and swollen joints and a median improvement of at least X% in the 5 remaining ACR core criteria. Since ACR-N is a continuous measure, the mean values are reported instead of the originally registered percentage of participants. |
| Percentage of Participants Who Achieved a DAS28 Remission at 12 Weeks (Part A) | Baseline up to 12 weeks | DAS modified included the DAS28 that consisted of a composite score of the following variables: TJC28, SJC28, CRP (mg/L), and PtGADA on a 0 to 100 mm VAS: 0 mm (no arthritis activity) to 100 mm (extremely active arthritis). DAS28 calculated as: DAS28-CRP = 0.56(square root of TJC28)+0.28(square root of SJC28)+0.36\[ln(CRP +1)\]+0.014(VAS)+0.96. For remission, DAS28 is \<2.6. Percentage of participants = (number of participants with DAS28 remission) / (number of participants treated) \* 100. |
| Percentage of Participants Who Achieved a DAS28 Remission at 64 Weeks (Part B) | Baseline up to 64 weeks | DAS modified included the DAS28 that consisted of a composite score of the following variables: TJC28, SJC28, CRP (mg/L), and PtGADA-VAS on a 0 to 100 mm VAS: 0 mm (no arthritis activity) to 100 mm (extremely active arthritis). DAS28 calculated as: DAS28-CRP = 0.56(sqrt of TJC28)+0.28(sqrt of SJC28)+0.36\[ln(CRP +1)\]+0.014(VAS)+0.96. For remission, DAS28 is \<2.6. Percentage of participants = (number of participants with DAS 28 remission) / (number of participants treated) \* 100. |
| Percentage of Participants Who Achieved an SDAI Remission at 12 Weeks (Part A) | Baseline up to 12 weeks | The SDAI is the numerical sum of 5 outcome parameters: TJC28, SJC28, PtGADA, PhGA and CRP. The equation used to calculate the SDAI: SDAI=SJC28+TJC28+PtGADA-VAS+PhGA-VAS+CRP where PtGADA-VAS=PtGADA -VAS/ 10 and PhGA-VAS=PhGA-VAS / 10. Definition of remission is SDAI ≤ 3.3. Percentage of participants = (number of responders) / (number of participants treated) \* 100 |
| Percentage of Participants Who Achieved an SDAI Remission at 64 Weeks (Part B) | Baseline up to 64 weeks | The SDAI is the numerical sum of 5 outcome parameters: TJC28, SJC28, PtGADA, PhGA, and CRP. The equation used to calculate the SDAI: SDAI=SJC28+TJC28+PtGADA-VAS+PhGA-VAS+CRP where PtGADA-VAS=PtGADA-VAS / 10 and PhGA-VAS=PhGA-VAS / 10. Definition of remission is SDAI ≤ 3.3. Percentage of participants = (number of responders) / (number of participants treated) \* 100 |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve at a Dosing Interval at Steady State (AUCtau,ss) of LY3009104 | Weeks (Wks) 0, 8, 12, or 20: Predose, 15 to 30 minutes and 1 to 3 hours postdose; Wks 2 or 4 and 15 or 16: Predose; Wks 28, 40, 52, or 64: random single sample. | Steady state is achieved when the rate of drug input is equal to the rate of drug elimination. The AUC(tau,ss) at 1 dosing interval is the average concentration of the drug at steady state multiplied by the time of the dosing interval. |
| PK: Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104 | Wks 0, 8, 12, or 20: Predose, 15 to 30 minutes and 1 to 3 hours postdose; Wks 2 or 4 and 15 or 16: Predose; Wks 28, 40, 52, or 64: random single sample. | — |
| Mean Change in HAQ-DI Responses up to 64 Weeks (Part B) | Baseline, 64 weeks | HAQ-DI was a participant-reported questionnaire that consisted of 24 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the week using response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). The highest score for any question in a category was the score of that category unless special aids or devices or help from another person was required. Answers for at least 6 of the 8 domains were required. Otherwise, HAQ-DI score was considered missing. The HAQ-DI score was the sum of the category scores divided by the number of categories scored, with a possible scores range from 0 to 3, 0 being without any difficulty and 3 being unable to do. |
Countries
Japan
Participant flow
Pre-assignment details
Participants on background methotrexate therapy were assigned to a dose of 1, 2, 4, 8 mg baricitinib (LY3009104) or placebo capsule once daily in a double blind manner for 12 weeks followed by single blind treatment of 4 mg or 8 mg baricitinib (LY3009104) tablet once daily for 52 weeks extension period.
Participants by arm
| Arm | Count |
|---|---|
| Part A: 1 mg Baricitinib (LY3009104) Participants on background methotrexate therapy were administered 1 mg baricitinib (LY3009104) orally once daily for 12 weeks in Part A and received 4 mg or 8 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B. | 24 |
| Part A: 2 mg Baricitinib (LY3009104) Participants on background methotrexate therapy were administered 2 mg baricitinib (LY3009104) orally once daily for 12 weeks in Part A and received 4 mg or 8 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B. | 24 |
| Part A: 4 mg Baricitinib (LY3009104) Participants on background methotrexate therapy were administered 4 mg baricitinib (LY3009104) orally once daily for 12 weeks in Part A and received 4 mg or 8 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B. | 24 |
| Part A: 8 mg Baricitinib (LY3009104) Participants on background methotrexate therapy were administered 8 mg baricitinib (LY3009104) orally once daily for 12 weeks in Part A and received 4 mg or 8 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B. | 24 |
| Part A: Placebo Participants on background methotrexate therapy were administered placebo orally once daily for 12 weeks in Part A and received 4 mg or 8 mg baricitinib (LY3009104) tablets orally once daily for 52 weeks in Part B. | 49 |
| Total | 145 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part A (Treatment Period) | Adverse Event | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A (Treatment Period) | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part B (Extension Period) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 2 | 5 | 5 | 3 | 3 | 1 | 6 | 3 |
| Part B (Extension Period) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 3 |
Baseline characteristics
| Characteristic | Part A: 1 mg Baricitinib (LY3009104) | Total | Part A: Placebo | Part A: 8 mg Baricitinib (LY3009104) | Part A: 4 mg Baricitinib (LY3009104) | Part A: 2 mg Baricitinib (LY3009104) |
|---|---|---|---|---|---|---|
| Age, Continuous | 52.7 years STANDARD_DEVIATION 12.8 | 53.6 years STANDARD_DEVIATION 11.8 | 51.1 years STANDARD_DEVIATION 12 | 53.6 years STANDARD_DEVIATION 11.3 | 57.5 years STANDARD_DEVIATION 10.4 | 56.1 years STANDARD_DEVIATION 11.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 145 Participants | 49 Participants | 24 Participants | 24 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 24 Participants | 145 Participants | 49 Participants | 24 Participants | 24 Participants | 24 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 24 Participants | 145 Participants | 49 Participants | 24 Participants | 24 Participants | 24 Participants |
| Sex: Female, Male Female | 22 Participants | 118 Participants | 39 Participants | 17 Participants | 19 Participants | 21 Participants |
| Sex: Female, Male Male | 2 Participants | 27 Participants | 10 Participants | 7 Participants | 5 Participants | 3 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 | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 26 / 49 | 11 / 24 | 12 / 24 | 13 / 24 | 17 / 24 | 21 / 24 | 11 / 12 | 11 / 12 | 22 / 23 | 23 / 23 | 11 / 11 | 12 / 12 | 23 / 24 |
| serious Total, serious adverse events | 1 / 49 | 0 / 24 | 1 / 24 | 0 / 24 | 1 / 24 | 1 / 24 | 1 / 12 | 3 / 12 | 3 / 23 | 2 / 23 | 2 / 11 | 2 / 12 | 6 / 24 |
Outcome results
Primary
Percentage of Participants in the 4 mg and 8 mg Dose Groups Who Achieved an American College of Rheumatology 20 (ACR20) Responder Index Response Baseline Through Week 12 .
ACR20 responders are participants with at least 20% improvement from baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: Health Assessment Questionnaire-Disability Index (HAQ-DI) which measured participants perceived degree of difficulty performing daily activities, C-reactive Protein (CRP) and erythrocyte sedimentation rate (ESR), Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS) , Patient's Global Assessment of Disease Activity-VAS (PtGADA-VAS), and Physician's Global Assessment of Disease Activity-VAS (PhGA-VAS). Missing values were imputed using Non-Responder Imputation (NRI), where non-responders were participants who discontinued the study prior to the completion of Part A. Percentage of participants achieving ACR20 response = (number of ACR20 responders) /(number of participants treated) \* 100.
Time frame: 12 weeks
Population: All participants who received at least 1 dose of 4 mg, 8 mg baricitinib (LY3009104) or placebo in Part A as per protocol for combined analysis .
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Combined 4 mg and 8 mg Baricitinib (LY3009104) | Percentage of Participants in the 4 mg and 8 mg Dose Groups Who Achieved an American College of Rheumatology 20 (ACR20) Responder Index Response Baseline Through Week 12 . | 77 percentage of participants |
| Part A: Placebo | Percentage of Participants in the 4 mg and 8 mg Dose Groups Who Achieved an American College of Rheumatology 20 (ACR20) Responder Index Response Baseline Through Week 12 . | 31 percentage of participants |
p-value: <0.001Regression, Logistic
Secondary
Mean Change From Baseline to Week 12 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP)
DAS modified included the DAS28 that consisted of a composite score of the following variables: tender joint count out of 28 (TJC28), swollen joint count out of 28 (SJC28), CRP \[milligrams per liter (mg/L)\], and PtGADA on a 0 to 100 millimeter (mm) VAS (0mm=no arthritis activity to 100 mm= extremely active arthritis). DAS28 calculated as: DAS28-CRP = 0.56(square root of TJC28)+0.28(square root of SJC28)+0.36\[ln(CRP +1)\]+0.014(VAS)+0.96. A decrease in DAS28-CRP indicated an improvement in participant's condition.
Time frame: Baseline, 12 weeks
Population: All randomized participants who received any study drug in Part A and had DAS28-CRP evaluated at analysis time points. The last non-missing post-baseline value in Part A was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Combined 4 mg and 8 mg Baricitinib (LY3009104) | Mean Change From Baseline to Week 12 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP) | -1.52 units on a scale | Standard Deviation 0.97 |
| Part A: Placebo | Mean Change From Baseline to Week 12 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP) | -2.02 units on a scale | Standard Deviation 1.072 |
| 4 mg Baricitinib (LY3009104) | Mean Change From Baseline to Week 12 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP) | -2.09 units on a scale | Standard Deviation 1.105 |
| 8 mg Baricitinib (LY3009104) | Mean Change From Baseline to Week 12 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP) | -1.96 units on a scale | Standard Deviation 0.947 |
| Placebo | Mean Change From Baseline to Week 12 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP) | -0.60 units on a scale | Standard Deviation 1.204 |
Secondary
Mean Change From Baseline to Week 64 in DAS Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP)
DAS modified included the 28 diarthroidal joint count (DAS28) that consisted of a composite score of the following variables: TJC28, SJC28, CRP (mg/L), and PtGADA on a 0 to 100 mm VAS (0mm=no arthritis activity to 100 mm= extremely active arthritis). DAS28 calculated as: DAS28-CRP = 0.56(square root of TJC28)+0.28(square root of SJC28)+0.36\[ln(CRP +1)\]+0.014(VAS)+0.96. A decrease in DAS28-CRP indicated an improvement in participant's condition.
Time frame: Baseline, 64 weeks
Population: All randomized participants who received any study drug in Part B and had DAS28-CRP evaluated at analysis time points. The last non-missing post-baseline value in Part B was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Combined 4 mg and 8 mg Baricitinib (LY3009104) | Mean Change From Baseline to Week 64 in DAS Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP) | -2.44 units on a scale | Standard Deviation 1.152 |
| Part A: Placebo | Mean Change From Baseline to Week 64 in DAS Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP) | -2.48 units on a scale | Standard Deviation 1.109 |
Secondary
Mean Change in HAQ-DI Responses up to 64 Weeks (Part B)
HAQ-DI was a participant-reported questionnaire that consisted of 24 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the week using response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). The highest score for any question in a category was the score of that category unless special aids or devices or help from another person was required. Answers for at least 6 of the 8 domains were required. Otherwise, HAQ-DI score was considered missing. The HAQ-DI score was the sum of the category scores divided by the number of categories scored, with a possible scores range from 0 to 3, 0 being without any difficulty and 3 being unable to do.
Time frame: Baseline, 64 weeks
Population: All participants who received any amount of study drug in Part B and had HAQ-DI evaluated at analysis time points. The last non-missing post-baseline value in Part B was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Combined 4 mg and 8 mg Baricitinib (LY3009104) | Mean Change in HAQ-DI Responses up to 64 Weeks (Part B) | -0.498 units on a scale | Standard Deviation 0.4779 |
| Part A: Placebo | Mean Change in HAQ-DI Responses up to 64 Weeks (Part B) | -0.568 units on a scale | Standard Deviation 0.6203 |
Secondary
Mean Change in Health Assessment Questionnaire - Disability Index (HAQ-DI) Responses up to 12 Weeks (Part A)
HAQ-DI was a participant-reported questionnaire that consisted of 24 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the week using response categories: without any difficulty (0), with some difficulty (1), with much difficulty (2), and unable to do (3). The highest score for any question in a category was the score of that category unless special aids or devices or help from another person was required. Answers for at least 6 of the 8 domains were required. Otherwise, HAQ-DI score was considered missing. The HAQ-DI score was the sum of the category scores divided by the number of categories scored, with a possible scores range from 0 to 3, 0 being without any difficulty and 3 being unable to do.
Time frame: Baseline, 12 weeks
Population: All participants who received any amount of study drug in Part A and had HAQ-DI evaluated at analysis time points. The last non-missing post-baseline value in Part A was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Combined 4 mg and 8 mg Baricitinib (LY3009104) | Mean Change in Health Assessment Questionnaire - Disability Index (HAQ-DI) Responses up to 12 Weeks (Part A) | -0.302 units on a scale | Standard Deviation 0.3336 |
| Part A: Placebo | Mean Change in Health Assessment Questionnaire - Disability Index (HAQ-DI) Responses up to 12 Weeks (Part A) | -0.396 units on a scale | Standard Deviation 0.4759 |
| 4 mg Baricitinib (LY3009104) | Mean Change in Health Assessment Questionnaire - Disability Index (HAQ-DI) Responses up to 12 Weeks (Part A) | -0.469 units on a scale | Standard Deviation 0.3463 |
| 8 mg Baricitinib (LY3009104) | Mean Change in Health Assessment Questionnaire - Disability Index (HAQ-DI) Responses up to 12 Weeks (Part A) | -0.422 units on a scale | Standard Deviation 0.3646 |
| Placebo | Mean Change in Health Assessment Questionnaire - Disability Index (HAQ-DI) Responses up to 12 Weeks (Part A) | -0.077 units on a scale | Standard Deviation 0.3552 |
Secondary
Mean Change in SDAI Responses up to 64 Weeks (Part B)
The SDAI is the numerical sum of 5 outcome parameters: TJC28, SJC28, PtGADA, PhGA, and CRP. The equation used to calculate the SDAI: SDAI=SJC28+TJC28+PtGADA-VAS+PhGA-VAS+CRP where PtGADA-VAS=PtGADA -VAS/ 10 and PhGA-VAS=PhGA-VAS/ 10, with lower values indicating fewer symptoms.
Time frame: Baseline, 64 weeks
Population: All participants who received any amount of study drug in Part B and had data for SDAI at analysis time points. The last non-missing post-baseline value in Part B was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Combined 4 mg and 8 mg Baricitinib (LY3009104) | Mean Change in SDAI Responses up to 64 Weeks (Part B) | -20.42 units on a scale | Standard Deviation 9.671 |
| Part A: Placebo | Mean Change in SDAI Responses up to 64 Weeks (Part B) | -21.33 units on a scale | Standard Deviation 10.318 |
Secondary
Mean Change in Simplified Disease Activity Index (SDAI) Responses up to 12 Weeks (Part A)
The SDAI is the numerical sum of 5 outcome parameters: TJC28, SJC28, patient and physician global assessment of disease activity and CRP. The equation used to calculate the SDAI:SDAI=SJC28+TJC28+PtGADA-VAS+PhGA-VAS+CRP where PtGADA-VAS=PtGADA-VAS / 10 and PhGA-VAS=PhGA-VAS / 10, with lower values indicating fewer symptoms.
Time frame: Baseline up to 12 weeks
Population: All participants who received any amount of study drug in Part A and had SDAI data at analysis time points. The last non-missing post-baseline value in Part A was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Combined 4 mg and 8 mg Baricitinib (LY3009104) | Mean Change in Simplified Disease Activity Index (SDAI) Responses up to 12 Weeks (Part A) | -13.11 units on a scale | Standard Deviation 8.918 |
| Part A: Placebo | Mean Change in Simplified Disease Activity Index (SDAI) Responses up to 12 Weeks (Part A) | -16.85 units on a scale | Standard Deviation 9.517 |
| 4 mg Baricitinib (LY3009104) | Mean Change in Simplified Disease Activity Index (SDAI) Responses up to 12 Weeks (Part A) | -18.17 units on a scale | Standard Deviation 9.202 |
| 8 mg Baricitinib (LY3009104) | Mean Change in Simplified Disease Activity Index (SDAI) Responses up to 12 Weeks (Part A) | -18.02 units on a scale | Standard Deviation 8.293 |
| Placebo | Mean Change in Simplified Disease Activity Index (SDAI) Responses up to 12 Weeks (Part A) | -4.54 units on a scale | Standard Deviation 13.113 |
Secondary
Mean Value of ACR-N Response (Part A)
The ACR-N Response Index is a continuous measure of clinical, laboratory, and functional measures in RA to characterize the percentage of improvement from baseline in RA disease activity. This index is defined as the lowest of either: a) percent change in TJC, b) percent change in SJC, or c) median percent change of the remaining 5 ACR core criteria (HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, or PhGA-VAS). A participant with an ACR-N of X has improvement of at least X% in tender and swollen joints and a median improvement of at least X% in the 5 remaining ACR core criteria. Since ACR-N is a continuous measure, the mean values are reported instead of the originally registered percentage of participants.
Time frame: Baseline up to 12 weeks
Population: All participants who received any study drug in Part A and had baseline and at least one post baseline ACR-N response measure. LOCF was used to impute missing post-baseline values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Combined 4 mg and 8 mg Baricitinib (LY3009104) | Mean Value of ACR-N Response (Part A) | 28.76 percentage of responders | Standard Deviation 38.65 |
| Part A: Placebo | Mean Value of ACR-N Response (Part A) | 42.48 percentage of responders | Standard Deviation 39.52 |
| 4 mg Baricitinib (LY3009104) | Mean Value of ACR-N Response (Part A) | 45.17 percentage of responders | Standard Deviation 33.75 |
| 8 mg Baricitinib (LY3009104) | Mean Value of ACR-N Response (Part A) | 25.58 percentage of responders | Standard Deviation 130.02 |
| Placebo | Mean Value of ACR-N Response (Part A) | -9.98 percentage of responders | Standard Deviation 58.1 |
Secondary
Mean Value of ACR-N Response (Part B)
The ACR-N Response Index is a continuous measure of clinical, laboratory, and functional measures in RA to characterize the percentage of improvement from baseline in RA disease activity. This index is defined as the lowest of either: a) percent change in TJC, b) percent change in SJC, or c) median percent change of the remaining 5 ACR core criteria (HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, or PhGA-VAS). A participant with an ACR-N of X has improvement of at least X% in tender and swollen joints and a median improvement of at least X% in the 5 remaining ACR core criteria. Since ACR-N is a continuous measure, the mean values are reported instead of the originally registered percentage of participants.
Time frame: Baseline up to 64 weeks
Population: All participants who received any study drug in Part B and had baseline and at least one post baseline ACR-N response measure. LOCF was used to impute missing post-baseline values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Combined 4 mg and 8 mg Baricitinib (LY3009104) | Mean Value of ACR-N Response (Part B) | 61.14 percentage of responders | Standard Deviation 30.7 |
| Part A: Placebo | Mean Value of ACR-N Response (Part B) | 61.07 percentage of responders | Standard Deviation 33.22 |
Secondary
Percentage of Participants Who Achieved a DAS28 Remission at 12 Weeks (Part A)
DAS modified included the DAS28 that consisted of a composite score of the following variables: TJC28, SJC28, CRP (mg/L), and PtGADA on a 0 to 100 mm VAS: 0 mm (no arthritis activity) to 100 mm (extremely active arthritis). DAS28 calculated as: DAS28-CRP = 0.56(square root of TJC28)+0.28(square root of SJC28)+0.36\[ln(CRP +1)\]+0.014(VAS)+0.96. For remission, DAS28 is \<2.6. Percentage of participants = (number of participants with DAS28 remission) / (number of participants treated) \* 100.
Time frame: Baseline up to 12 weeks
Population: All participants who received any amount of study treatment in Part A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Combined 4 mg and 8 mg Baricitinib (LY3009104) | Percentage of Participants Who Achieved a DAS28 Remission at 12 Weeks (Part A) | 33 percentage of participants |
| Part A: Placebo | Percentage of Participants Who Achieved a DAS28 Remission at 12 Weeks (Part A) | 33 percentage of participants |
| 4 mg Baricitinib (LY3009104) | Percentage of Participants Who Achieved a DAS28 Remission at 12 Weeks (Part A) | 42 percentage of participants |
| 8 mg Baricitinib (LY3009104) | Percentage of Participants Who Achieved a DAS28 Remission at 12 Weeks (Part A) | 50 percentage of participants |
| Placebo | Percentage of Participants Who Achieved a DAS28 Remission at 12 Weeks (Part A) | 22 percentage of participants |
Secondary
Percentage of Participants Who Achieved a DAS28 Remission at 64 Weeks (Part B)
DAS modified included the DAS28 that consisted of a composite score of the following variables: TJC28, SJC28, CRP (mg/L), and PtGADA-VAS on a 0 to 100 mm VAS: 0 mm (no arthritis activity) to 100 mm (extremely active arthritis). DAS28 calculated as: DAS28-CRP = 0.56(sqrt of TJC28)+0.28(sqrt of SJC28)+0.36\[ln(CRP +1)\]+0.014(VAS)+0.96. For remission, DAS28 is \<2.6. Percentage of participants = (number of participants with DAS 28 remission) / (number of participants treated) \* 100.
Time frame: Baseline up to 64 weeks
Population: All participants who received any amount of study drug in Part B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Combined 4 mg and 8 mg Baricitinib (LY3009104) | Percentage of Participants Who Achieved a DAS28 Remission at 64 Weeks (Part B) | 66 percentage of participants |
| Part A: Placebo | Percentage of Participants Who Achieved a DAS28 Remission at 64 Weeks (Part B) | 66 percentage of participants |
Secondary
Percentage of Participants Who Achieved an ACR20 Response at 64 Weeks
ACR20 responders are participants with at least 20% improvement from baseline for TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI which measured participants perceived degree of difficulty performing daily activities, CRP and ESR, PAAP-VAS, PtGADA-VAS, or PhGA-VAS. Missing values were imputed using NRI, where non-responders were participants who discontinued the study prior to the completion of Part B. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants treated) \* 100.
Time frame: Baseline up to 64 weeks
Population: All participants who received any amount of study drug in Part B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Combined 4 mg and 8 mg Baricitinib (LY3009104) | Percentage of Participants Who Achieved an ACR20 Response at 64 Weeks | 66 percentage of participants |
| Part A: Placebo | Percentage of Participants Who Achieved an ACR20 Response at 64 Weeks | 73 percentage of participants |
Secondary
Percentage of Participants Who Achieved an ACR70 Response at 12 Weeks (Part A)
ACR70 responders were participants with at least 70% improvement from baseline for TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, or PhGA-VAS. Missing values were imputed using NRI, where non-responders were participants who discontinued the study prior to the completion of Part A. Percentage of participants achieving ACR70 response=(number of ACR70 responders / number of participants treated) \* 100.
Time frame: Baseline up to 12 weeks
Population: All participants who received any study drug in Part A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Combined 4 mg and 8 mg Baricitinib (LY3009104) | Percentage of Participants Who Achieved an ACR70 Response at 12 Weeks (Part A) | 13 percentage of participants |
| Part A: Placebo | Percentage of Participants Who Achieved an ACR70 Response at 12 Weeks (Part A) | 29 percentage of participants |
| 4 mg Baricitinib (LY3009104) | Percentage of Participants Who Achieved an ACR70 Response at 12 Weeks (Part A) | 29 percentage of participants |
| 8 mg Baricitinib (LY3009104) | Percentage of Participants Who Achieved an ACR70 Response at 12 Weeks (Part A) | 21 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR70 Response at 12 Weeks (Part A) | 0 percentage of participants |
p-value: 0.009Cochran-Armitage trend test
Secondary
Percentage of Participants Who Achieved an ACR70 Response at 64 Weeks (Part B)
ACR70 responders were participants with at least 70% improvement from baseline for TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, or PhGA-VAS. Missing values were imputed using NRI, where non-responders were participants who discontinued the study prior to the completion of Part B. Percentage of participants achieving ACR70 response=(number of ACR70 responders) / (number of participants treated) \* 100.
Time frame: Baseline up to 64 weeks
Population: All participants who received any study drug in Part B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Combined 4 mg and 8 mg Baricitinib (LY3009104) | Percentage of Participants Who Achieved an ACR70 Response at 64 Weeks (Part B) | 37 percentage of participants |
| Part A: Placebo | Percentage of Participants Who Achieved an ACR70 Response at 64 Weeks (Part B) | 34 percentage of participants |
Secondary
Percentage of Participants Who Achieved an EULAR28 Response at 64 Weeks (Part B)
EULAR Responder Index based on 28 joint counts categorizes clinical response based on improvement from baseline in DAS28-CRP. DAS28-CRP scores range from 1.0-9.4, where lower scores indicated less disease activity. High disease activity: DAS28-CRP \>5.1, low disease activity: DAS28-CRP \<3.2, and remission: DAS28-CRP \<2.6. Participants are categorized as EULAR responders or non-responders based on improvement of DAS28-CRP scores from baseline. EULAR DAS28-CRP Responder Index defines a good (absolute: ≤3.2 and \>1.2 improvement from baseline), moderate (absolute: \>3.2 and ≤5.1 and \>0.6 and ≤1.2 improvement from baseline), or no response (absolute: \>5.1 and ≤0.6 improvement from baseline). Percentage of participants calculated as = (number of good +moderate responders) / (number of participants treated) \* 100.
Time frame: Baseline up to 64 weeks
Population: All participants who received any amount of study drug in Part B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Combined 4 mg and 8 mg Baricitinib (LY3009104) | Percentage of Participants Who Achieved an EULAR28 Response at 64 Weeks (Part B) | 94 percentage of participants |
| Part A: Placebo | Percentage of Participants Who Achieved an EULAR28 Response at 64 Weeks (Part B) | 94 percentage of participants |
Secondary
Percentage of Participants Who Achieved an European League Against Rheumatism Rating of 28-Joint Arthritic Condition (EULAR28) Response at 12 Weeks (Part A)
EULAR Responder Index based on 28 joint counts categorizes clinical response based on improvement from baseline in DAS28-CRP. DAS28-CRP scores range from 1.0-9.4, where lower scores indicated less disease activity. High disease activity: DAS28-CRP \>5.1, low disease activity: DAS28-CRP ≤3.2, and remission: DAS28-CRP \<2.6. Participants are categorized as EULAR responders or non-responders based on improvement of DAS28-CRP scores from baseline. EULAR DAS28-CRP responder index defines a good (absolute: ≤3.2 and \>1.2 improvement from baseline), moderate (absolute: \>3.2 and ≤5.1 and \>0.6 and ≤1.2 improvement from baseline), or no response (absolute: \>5.1 and ≤0.6 improvement from baseline). Percentage of participants calculated as = (number of good +moderate responders) / (number of participants treated) \* 100.
Time frame: Baseline up to 12 weeks
Population: All participants who received any amount of study drug in Part A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Combined 4 mg and 8 mg Baricitinib (LY3009104) | Percentage of Participants Who Achieved an European League Against Rheumatism Rating of 28-Joint Arthritic Condition (EULAR28) Response at 12 Weeks (Part A) | 83 percentage of participants |
| Part A: Placebo | Percentage of Participants Who Achieved an European League Against Rheumatism Rating of 28-Joint Arthritic Condition (EULAR28) Response at 12 Weeks (Part A) | 88 percentage of participants |
| 4 mg Baricitinib (LY3009104) | Percentage of Participants Who Achieved an European League Against Rheumatism Rating of 28-Joint Arthritic Condition (EULAR28) Response at 12 Weeks (Part A) | 92 percentage of participants |
| 8 mg Baricitinib (LY3009104) | Percentage of Participants Who Achieved an European League Against Rheumatism Rating of 28-Joint Arthritic Condition (EULAR28) Response at 12 Weeks (Part A) | 92 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an European League Against Rheumatism Rating of 28-Joint Arthritic Condition (EULAR28) Response at 12 Weeks (Part A) | 47 percentage of participants |
Secondary
Percentage of Participants Who Achieved an SDAI Remission at 12 Weeks (Part A)
The SDAI is the numerical sum of 5 outcome parameters: TJC28, SJC28, PtGADA, PhGA and CRP. The equation used to calculate the SDAI: SDAI=SJC28+TJC28+PtGADA-VAS+PhGA-VAS+CRP where PtGADA-VAS=PtGADA -VAS/ 10 and PhGA-VAS=PhGA-VAS / 10. Definition of remission is SDAI ≤ 3.3. Percentage of participants = (number of responders) / (number of participants treated) \* 100
Time frame: Baseline up to 12 weeks
Population: All participants who received any amount of study drug in Part A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Combined 4 mg and 8 mg Baricitinib (LY3009104) | Percentage of Participants Who Achieved an SDAI Remission at 12 Weeks (Part A) | 4 percentage of participants |
| Part A: Placebo | Percentage of Participants Who Achieved an SDAI Remission at 12 Weeks (Part A) | 29 percentage of participants |
| 4 mg Baricitinib (LY3009104) | Percentage of Participants Who Achieved an SDAI Remission at 12 Weeks (Part A) | 17 percentage of participants |
| 8 mg Baricitinib (LY3009104) | Percentage of Participants Who Achieved an SDAI Remission at 12 Weeks (Part A) | 17 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an SDAI Remission at 12 Weeks (Part A) | 8 percentage of participants |
Secondary
Percentage of Participants Who Achieved an SDAI Remission at 64 Weeks (Part B)
The SDAI is the numerical sum of 5 outcome parameters: TJC28, SJC28, PtGADA, PhGA, and CRP. The equation used to calculate the SDAI: SDAI=SJC28+TJC28+PtGADA-VAS+PhGA-VAS+CRP where PtGADA-VAS=PtGADA-VAS / 10 and PhGA-VAS=PhGA-VAS / 10. Definition of remission is SDAI ≤ 3.3. Percentage of participants = (number of responders) / (number of participants treated) \* 100
Time frame: Baseline up to 64 weeks
Population: All participants who received any amount of study drug in Part B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Combined 4 mg and 8 mg Baricitinib (LY3009104) | Percentage of Participants Who Achieved an SDAI Remission at 64 Weeks (Part B) | 39 percentage of participants |
| Part A: Placebo | Percentage of Participants Who Achieved an SDAI Remission at 64 Weeks (Part B) | 39 percentage of participants |
Secondary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve at a Dosing Interval at Steady State (AUCtau,ss) of LY3009104
Steady state is achieved when the rate of drug input is equal to the rate of drug elimination. The AUC(tau,ss) at 1 dosing interval is the average concentration of the drug at steady state multiplied by the time of the dosing interval.
Time frame: Weeks (Wks) 0, 8, 12, or 20: Predose, 15 to 30 minutes and 1 to 3 hours postdose; Wks 2 or 4 and 15 or 16: Predose; Wks 28, 40, 52, or 64: random single sample.
Population: All participants who received any study drug and had evaluable data for AUC(tau,ss).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Combined 4 mg and 8 mg Baricitinib (LY3009104) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve at a Dosing Interval at Steady State (AUCtau,ss) of LY3009104 | 237 nanomoles*hour (nM*h) | Geometric Coefficient of Variation 28.8 |
| Part A: Placebo | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve at a Dosing Interval at Steady State (AUCtau,ss) of LY3009104 | 525 nanomoles*hour (nM*h) | Geometric Coefficient of Variation 21 |
| 4 mg Baricitinib (LY3009104) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve at a Dosing Interval at Steady State (AUCtau,ss) of LY3009104 | 1020 nanomoles*hour (nM*h) | Geometric Coefficient of Variation 32.5 |
| 8 mg Baricitinib (LY3009104) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve at a Dosing Interval at Steady State (AUCtau,ss) of LY3009104 | 1900 nanomoles*hour (nM*h) | Geometric Coefficient of Variation 24.1 |
Secondary
PK: Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104
Time frame: Wks 0, 8, 12, or 20: Predose, 15 to 30 minutes and 1 to 3 hours postdose; Wks 2 or 4 and 15 or 16: Predose; Wks 28, 40, 52, or 64: random single sample.
Population: All participants who received any study drug and had evaluable Cmax data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Combined 4 mg and 8 mg Baricitinib (LY3009104) | PK: Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104 | 35.7 nM | Geometric Coefficient of Variation 20.9 |
| Part A: Placebo | PK: Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104 | 73.5 nM | Geometric Coefficient of Variation 22.5 |
| 4 mg Baricitinib (LY3009104) | PK: Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104 | 147 nM | Geometric Coefficient of Variation 20.6 |
| 8 mg Baricitinib (LY3009104) | PK: Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104 | 278 nM | Geometric Coefficient of Variation 21.7 |