Arthritis, Rheumatoid
Conditions
Keywords
Phase 1
Brief summary
The purpose of study is to explore the effect of CP-690,550 (Tofacitinib) on measures of kidney function in patients with active rheumatoid arthritis (RA).
Interventions
DRUGCP-690,550 or Placebo
CP-690,550 10 mg twice a day (BID) orally or placebo BID orally, approximately 72 days
DRUGPlacebo
Placebo BID orally, approximately 72 days
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The patient must meet the American College of Rheumatology (ACR) classification criteria for the diagnosis of rheumatoid arthritis by satisfying at least four of the seven criteria. * The patient must have active disease at both Screening and predose on Day 1 of Period 1. * Patient must have had an inadequate response to at least one disease-modifying antirheumatic drug (DMARD), non-biologic or biologic, due to ineffectiveness or intolerance.
Exclusion criteria
* Pregnant or lactating women * Serious medical conditions that would make treatment with CP-690,550 potentially unsafe. * A patient who has a history of asthma, multiple allergies or severe allergy (eg, anaphylaxis) to any substance. In particular, a history of allergy to iodine, povidone-iodine, iohexol or other iodinated contrast media.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Geometric (Geo) Mean-Fold Change at End of Period 1 From Baseline in Measured Glomerular Filtration Rate (mGFR) | Day 1 of Period 1, Day 43 of Period 1 | Glomerular filtration rate (GFR) is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. GFR can be measured directly or estimated using established formulas. mGFR was determined using iohexol serum clearance using compartmental modeling of the iohexol serum concentration-time data. mGFR values were normalized to 1.73 meters squared (m\^2) body surface area. A normal GFR is greater than (\>)90 milliliters per minute (mL/min), although children and older people usually have a lower GFR. Lower values indicate poor kidney function. A GFR \<15 mL/min is consistent with kidney failure. Baseline was defined as the mean of the values obtained at Run-in and on predose in Period 1/Day 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Geometric Mean-Fold Change at End of Period 2 From End of Period 1 in mGFR | Day 43 of Period 1, Day 29 of Period 2 | mGFR was determined using iohexol serum clearance using compartmental modeling of the iohexol serum concentration-time data. mGFR values were normalized to 1.73 m\^2 body surface area. |
| Adjusted Geometric Mean-Fold Change at End of Period 1 From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using Modified Diet in Renal Disease (MDRD) | Day 1 of Period 1, Day 43 of Period 1 | eGFR was calculated using the MDRD equation and normalized to 1.73 m\^2 body surface area. Baseline was defined as the mean of the values obtained at Screening and on predose in Period 1/Day 1. |
| Adjusted Geometric Mean-Fold Change at End of Period 2 From Baseline in eGFR Using MDRD | Day 1 of Period 1, Day 29 of Period 2 | eGFR was calculated using the MDRD equation with eGFR values normalized to 1.73 m\^2 body surface area. Baseline was defined as the mean of the values obtained at Screening and on predose in Period 1/Day 1. |
| Adjusted Geometric Mean-Fold Change at End of Period 2 From End of Period 1 in eGFR Using MDRD | Day 43 of Period 1, Day 29 of Period 2 | eGFR was calculated using the MDRD equation with eGFR values normalized to 1.73 m\^2 body surface area. |
| Adjusted Geometric Mean-Fold Change at End of Period 1 From Baseline in eGFR Using the Cockcroft-Gault Equation | Day 1 of Period 1, Day 43 of Period 1 | eGFR was calculated using the Cockcroft-Gault equation normalized to 1.73 m\^2 body surface area. Baseline was defined as the mean of the values obtained at Screening and on predose in Period 1/Day 1. |
| Adjusted Geometric Mean-Fold Change at End of Period 2 From Baseline in eGFR Using the Cockcroft-Gault Equation | Day 1 of Period 1, Day 29 of Period 2 | eGFR was calculated using the Cockcroft-Gault equation normalized to 1.73 m\^2 body surface area. Baseline was defined as the mean of the values obtained at Screening and on predose in Period 1/Day 1. |
| Adjusted Geometric Mean-Fold Change at End of Period 2 From End of Period 1 in eGFR Using the Cockcroft-Gault Equation | Day 43 of Period 1, Day 29 of Period 2 | eGFR was calculated using the Cockcroft-Gault equation normalized to 1.73 m\^2 body surface area. |
| Adjusted Geometric Mean-Fold Change at End of Period 1 From Baseline in Serum Creatinine | Day 1 of Period 1, Day 43 of Period 1 | Blood samples were collected from participants at screening, predose on Day 1 of Period 1, on the last day of Period 1 and on the last day of Period 2 for assessment of serum creatinine levels. Serum creatinine values in milligrams per deciliter (mg/dL) reported by the central laboratory were used. Baseline for serum creatinine was defined as the mean of values obtained at screening and predose on Day 1 of Period 1. |
| Adjusted Geometric Mean-Fold Change From End of Period 2 From Baseline in Serum Creatinine | Day 1 of Period 1, Day 29 of Period 2 | Blood samples were collected from participants at screening, predose on Day 1 of Period 1, on the last day of Period 1 and on the last day of Period 2 for assessment of serum creatinine levels. Serum creatinine values in mg/dL reported by the central laboratory were used. Baseline for serum creatinine was defined as the mean of values obtained at screening and predose on Day 1 of Period 1. |
| Adjusted Geometric Mean-Fold Change at End of Period 2 From End of Period 1 in Serum Creatinine | Day 43 of Period 1, Day 29 of Period 2 | Blood samples were collected from participants at screening, predose on Day 1 of Period 1, on the last day of Period 1 and on the last day of Period 2 for assessment of serum creatinine levels. Serum creatinine values in mg/dL reported by the central laboratory were used. |
| Percentage of Participants Achieving an American College of Rheumatology 20% (ACR20) Response | Day 1 of Period 1 to Day 43 of Period 1, Day 1 of Period 1 to Day 29 of Period 2 | ACR20 response: greater than or equal to (≥)20 percent (%) improvement in tender joint count; ≥20% improvement in swollen joint count; and ≥20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP). |
| Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | Day 1 of Period 1 to Day 43 of Period 1, Day 1 of Period 1 to Day 29 of Period 2 | ACR50 response: ≥50% improvement in tender or swollen joint counts and 50% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) participant's assessment of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a HAQ, and 5) CRP at each visit. |
| Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | Day 1 of Period 1 to Day 43 of Period 1, Day 1 of Period 1 to Day 29 of Period 2 | ACR70 response: ≥70% improvement in tender or swollen joint counts and 70% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) participant's assessment of disease activity, 3) participant's assessment of pain, 4) participant' assessment of functional disability via a HAQ, and 5) CRP at each visit. |
| Least Squares (LS) Mean Change at End of Period 1 From Baseline in Disease Activity Score Based on 28-Joint Count CRP (DAS28-3 [CRP]) | Day 1 of Period 1, Day 43 of Period 1 | DAS28 calculated from the tender/painful joint count, swollen joint count (SJC) using the 28 joints count, and CRP value. DAS28 less than or equal to (≤)3.2 equals (=) low disease activity, DAS28 greater than (\>)3.2 to 5.1 = moderate to high disease activity. |
| LS Mean Change at End of Period 2 From Baseline in DAS28-3 (CRP) | Day 1 of Period 1, Day 29 of Period 2 | DAS28 calculated from the tender/painful joint count, SJC using the 28 joints count, and CRP value. DAS28 ≤3.2 = low disease activity, DAS28 \>3.2 to 5.1 = moderate to high disease activity. |
| LS Mean Change at End of Period 2 From End of Period 1 in DAS28-3 (CRP) | Day 43 of Period 1, Day 29 of Period 2 | DAS28 calculated from the tender/painful joint count, SJC using the 28 joints count, and CRP value. DAS28 ≤3.2 = low disease activity, DAS28 \>3.2 to 5.1 = moderate to high disease activity. |
| LS Mean Change at End of Period 1 From Baseline DAS28-4 (CRP) | Day 1 of Period 1, Day 43 of Period 1 | DAS28 calculated from the number of SJC and painful joints (PJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment (PGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 ≤3.2 = low disease activity, DAS28 \>3.2 to 5.1 = moderate to high disease activity. |
| LS Mean Change at End of Period 2 From Baseline DAS28-4 (CRP) | Day 1 of Period 1, Day 29 of Period 2 | DAS28 calculated from the number of SJC and PJC using the 28 joints count, the ESR (mm/hour) and PGA of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 ≤3.2 = low disease activity, DAS28 \>3.2 to 5.1 = moderate to high disease activity. |
| LS Mean Change at End of Period 2 From End of Period 1 DAS28-4 (CRP) | Day 43 of Period 1, Day 29 of Period 2 | DAS28 calculated from the number of SJC and PJC using the 28 joints count, the ESR (mm/hour) and PGA of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 ≤3.2 = low disease activity, DAS28 \>3.2 to 5.1 = moderate to high disease activity. |
| LS Mean Change at End of Period 1 From Baseline in Tender/Painful Joint Count | Day 1 of Period 1, Day 43 of Period 1 | 68 joints were assessed by a joint assessor to determine the number of joints that were considered tender or painful Assessed joints included: upper body (temporomandibular, sternoclavicular, acromioclavicular), upper extremity (shoulder, elbow, wrist, MCP, thumb interphalangeal \[IP\], PIP, and distal interphalangeals \[DIP\]), and lower extremity (hip, knee, ankle, tarsus, metatarsophalangeals \[MTP\], great toe IP, proximal and distal interphalangeals combined \[PIP\]). |
| LS Mean Change at End of Period 2 From Baseline in Tender/Painful Joint Count | Day 1 of Period 1, Day 29 of Period 2 | 68 joints were assessed by a joint assessor to determine the number of joints that were considered tender or painful Assessed joints included: upper body (temporomandibular, sternoclavicular, acromioclavicular), upper extremity (shoulder, elbow, wrist, MCP, thumb IP, PIP, and DIP), and lower extremity (hip, knee, ankle, tarsus, MTP, great toe IP, proximal and distal interphalangeals combined \[PIP\]). |
| LS Mean Change at End of Period 2 From End of Period 1 in Tender/Painful Joint Count | Day 43 of Period 1, Day 29 of Period 2 | 68 joints were assessed by a joint assessor to determine the number of joints that were considered tender or painful Assessed joints included: upper body (temporomandibular, sternoclavicular, acromioclavicular), upper extremity (shoulder, elbow, wrist, MCP, thumb IP, PIP, and DIP), and lower extremity (hip, knee, ankle, tarsus, MTP, great toe IP, proximal and distal interphalangeals combined \[PIP\]). |
| LS Mean Change at End of Period 1 From Baseline in Swollen Joint Count | Day 1 of Period 1, Day 43 of Period 1 | Swollen joint count included 66 joints. Assessor assessed joints for swelling using the following scale: present/absent/not done/not applicable (to be used for artificial joints). Joints assessed included: upper body (temporomandibular, sternoclavicular, acromioclavicular), upper extremity (shoulder, elbow, wrist, MCP, thumb IP, PIP, and DIP), and lower extremity (knee, ankle, tarsus, MTP, great toe IP, proximal and distal interphalangeals combined \[PIP\]). |
| LS Mean Change at End of Period 2 From Baseline in Swollen Joint Count | Day 1 of Period 1, Day 29 of Period 2 | Swollen joint count included 66 joints. Assessor assessed joints for swelling using the following scale: present/absent/not done/not applicable (to be used for artificial joints). Joints assessed included: upper body (temporomandibular, sternoclavicular, acromioclavicular), upper extremity (shoulder, elbow, wrist, MCP, thumb IP, PIP, and DIP), and lower extremity (knee, ankle, tarsus, MTP, great toe IP, proximal and distal interphalangeals combined \[PIP\]). |
| LS Mean Change at End of Period 2 From End of Period 1 in Swollen Joint Count | Day 43 of Period 1, Day 29 of Period 2 | Swollen joint count included 66 joints. Assessor assessed joints for swelling using the following scale: present/absent/not done/not applicable (to be used for artificial joints). Joints assessed included: upper body (temporomandibular, sternoclavicular, acromioclavicular), upper extremity (shoulder, elbow, wrist, MCP, thumb IP, PIP, and DIP), and lower extremity (knee, ankle, tarsus, MTP, great toe IP, proximal and distal interphalangeals combined \[PIP\]). |
| LS Mean Change at End of Period 1 From Baseline in CRP | Day 1 of Period 1, Day 43 of Period 1 | — |
| LS Mean Change at End of Period 2 From Baseline in CRP | Day 1 of Period 1, Day 29 of Period 2 | — |
| LS Mean Change at End of Period 2 From End of Period 1 in CRP | Day 43 of Period 1, Day 29 of Period 2 | — |
| LS Mean Change at End of Period 1 From Baseline in Patient Global Assessment of Arthritis (PGAA) | Day 1 of Period 1, Day 43 of Period 1 | Participants answered the following question, Considering all the ways your arthritis affects you, how are you feeling today? Participants responded by using a 0 - 100 millimeter (mm) visual analog scale (VAS), where 0 mm = very well and 100 mm = very poorly. |
| LS Mean Change at End of Period 2 From Baseline in PGAA | Day 1 of Period 1, Day 29 of Period 2 | Participants answered the following question, Considering all the ways your arthritis affects you, how are you feeling today? The participants responses were recorded using a 100 mm VAS, where 0 mm = very well and 100 mm = very poorly. |
| LS Mean Change at End of Period 2 From End of Period 1 in PGAA | Day 43 of Period 1, Day 29 of Period 2 | Participants answered the following question, Considering all the ways your arthritis affects you, how are you feeling today? The participants responses were recorded using a 100 mm VAS, where 0 mm = very well and 100 mm = very poorly. |
| LS Mean Change at End of Period 1 From Baseline in Physician Global Assessment of Arthritis | Day 1 of Period 1, Day 43 of Period 1 | A physician assessed how the participant's overall arthritis appeared at the time of the visit. This was an evaluation based on the participant's disease signs, functional capacity and physical examination. The physician's response was recorded using a 100 mm VAS, where 0 mm = very good and 100 mm = very poor. |
| LS Mean Change at End of Period 2 From Baseline in Physician Global Assessment of Arthritis | Day 1 of Period 1, Day 29 of Period 2 | A physician assessed how the participant's overall arthritis appeared at the time of the visit. This was an evaluation based on the participant's disease signs, functional capacity and physical examination. The physician's response was recorded using a 100 mm VAS, where 0 mm = very good and 100 mm = very poor. |
| LS Mean Change at End of Period 2 From End of Period 1 in Physician Global Assessment of Arthritis | Day 43 of Period 1, Day 29 of Period 1 | A physician assessed how the participant's overall arthritis appeared at the time of the visit. This was an evaluation based on the participant's disease signs, functional capacity and physical examination. The physician's response was recorded using a 100 mm VAS, where 0 mm = very good and 100 mm = very poor. |
| LS Mean Change at End of Period 1 From Baseline in Patient Assessment of Arthritis Pain | Day 1 of Period 1, Day 43 of Period 1 | Participant's assessed the severity of their arthritis pain using a 100 mm VAS placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain. |
| Adjusted Geometric Mean-Fold Change at the End of Period 2 From Baseline in mGFR | Day 1 of Period 1, Day 29 of Period 2 | mGFR was determined using iohexol serum clearance using compartmental modeling of the iohexol serum concentration-time data. mGFR values were normalized to 1.73 m\^2 body surface area. Baseline was defined as the mean of the values obtained at Run-in and on predose in Period 1/Day 1. |
| LS Mean Change at End of Period 2 From End of Period 1 in Patient Assessment of Arthritis Pain | Day 43 of Period 2, Day 29 of Period 2 | Participant's assessed the severity of their arthritis pain using a 100 mm VAS placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain. |
| LS Mean Change at End of Period 1 From Baseline Health Assessment Questionnaire Disability Index (HAQ-DI) Score | Day 1 of Period 1, Day 43 of Period 1 | HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. |
| LS Mean Change at End of Period 2 From Baseline HAQ-DI Score | Day 1 of Period 1, Day 29 of Period 2 | HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. |
| LS Mean Change at End of Period 2 From End of Period 1 HAQ-DI Score | Day 43 of Period 1, Day 29 of Period 2 | HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. |
| LS Mean Change at End of Period 2 From Baseline in Patient Assessment of Arthritis Pain | Day 1 of Period 1, Day 29 of Period 2 | Participant's assessed the severity of their arthritis pain using a 100 mm VAS placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain. |
Countries
Czechia, Germany, Mexico, Poland, Russia, South Korea, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CP-690,550/Placebo Participants received CP-690,550 10 milligram (mg) tablets twice daily (BID) orally for 43 days (up to a maximum of 50 days) in Period 1 (43 days) followed immediately by placebo BID orally for 29 days (up to a maximum of 36 days) in Period 2 | 97 |
| Placebo/Placebo Participants received matching placebo tablets orally for 43 days (up to a maximum of 50 days) in Period 1 immediately followed by matching placebo tablets orally for 29 days (up to a maximum of 36 days) | 51 |
| Total | 148 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 4 |
| Overall Study | Lack of Efficacy | 3 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Other | 1 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 0 |
Baseline characteristics
| Characteristic | CP-690,550/Placebo | Placebo/Placebo | Total |
|---|---|---|---|
| Age, Continuous | 51.9 years STANDARD_DEVIATION 12.7 | 47.3 years STANDARD_DEVIATION 11.8 | 50.3 years STANDARD_DEVIATION 12.6 |
| Sex: Female, Male Female | 75 Participants | 36 Participants | 111 Participants |
| Sex: Female, Male Male | 22 Participants | 15 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 32 / 97 | 26 / 51 |
| serious Total, serious adverse events | 2 / 97 | 0 / 51 |
Outcome results
Primary
Adjusted Geometric (Geo) Mean-Fold Change at End of Period 1 From Baseline in Measured Glomerular Filtration Rate (mGFR)
Glomerular filtration rate (GFR) is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. GFR can be measured directly or estimated using established formulas. mGFR was determined using iohexol serum clearance using compartmental modeling of the iohexol serum concentration-time data. mGFR values were normalized to 1.73 meters squared (m\^2) body surface area. A normal GFR is greater than (\>)90 milliliters per minute (mL/min), although children and older people usually have a lower GFR. Lower values indicate poor kidney function. A GFR \<15 mL/min is consistent with kidney failure. Baseline was defined as the mean of the values obtained at Run-in and on predose in Period 1/Day 1.
Time frame: Day 1 of Period 1, Day 43 of Period 1
Population: Full Analysis Set (FAS): all randomized participants who received at least 1 dose of the test article (CP-690,550 or placebo). Observed Case (OC): missing data were not imputed. One participant was excluded (took wrong treatment) from FAS analysis of change at end of Period 1 from baseline in mGFR.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| CP-690,550/Placebo | Adjusted Geometric (Geo) Mean-Fold Change at End of Period 1 From Baseline in Measured Glomerular Filtration Rate (mGFR) | 0.91 fold change |
| Placebo/Placebo | Adjusted Geometric (Geo) Mean-Fold Change at End of Period 1 From Baseline in Measured Glomerular Filtration Rate (mGFR) | 0.99 fold change |
Comparison: Ratio of adjusted geometric mean-fold Change (CP-690,550-placebo vs. placebo-placebo)90% CI: [0.86, 0.98]ANCOVA
Secondary
Adjusted Geometric Mean-Fold Change at End of Period 1 From Baseline in eGFR Using the Cockcroft-Gault Equation
eGFR was calculated using the Cockcroft-Gault equation normalized to 1.73 m\^2 body surface area. Baseline was defined as the mean of the values obtained at Screening and on predose in Period 1/Day 1.
Time frame: Day 1 of Period 1, Day 43 of Period 1
Population: FAS OC; one participant was excluded (took wrong treatment) from the FAS analysis of change at end of Period 1 from baseline in eGFR (Cockcroft-Gault).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| CP-690,550/Placebo | Adjusted Geometric Mean-Fold Change at End of Period 1 From Baseline in eGFR Using the Cockcroft-Gault Equation | 0.96 fold change |
| Placebo/Placebo | Adjusted Geometric Mean-Fold Change at End of Period 1 From Baseline in eGFR Using the Cockcroft-Gault Equation | 1.01 fold change |
Comparison: Ratio of adjusted geometric mean-fold change (CP-690,550-placebo vs. placebo-placebo)90% CI: [0.92, 0.98]ANCOVA
Secondary
Adjusted Geometric Mean-Fold Change at End of Period 1 From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using Modified Diet in Renal Disease (MDRD)
eGFR was calculated using the MDRD equation and normalized to 1.73 m\^2 body surface area. Baseline was defined as the mean of the values obtained at Screening and on predose in Period 1/Day 1.
Time frame: Day 1 of Period 1, Day 43 of Period 1
Population: FAS (OC); one participant was excluded (took wrong treatment) from the FAS analysis of change at end of Period 1 from baseline in eGFR (MDRD).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| CP-690,550/Placebo | Adjusted Geometric Mean-Fold Change at End of Period 1 From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using Modified Diet in Renal Disease (MDRD) | 0.96 fold change |
| Placebo/Placebo | Adjusted Geometric Mean-Fold Change at End of Period 1 From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using Modified Diet in Renal Disease (MDRD) | 1.01 fold change |
Comparison: Ratio of adjusted geometric mean-fold change (CP-690,550-placebo vs. placebo-placebo)90% CI: [0.91, 0.97]ANCOVA
Secondary
Adjusted Geometric Mean-Fold Change at End of Period 1 From Baseline in Serum Creatinine
Blood samples were collected from participants at screening, predose on Day 1 of Period 1, on the last day of Period 1 and on the last day of Period 2 for assessment of serum creatinine levels. Serum creatinine values in milligrams per deciliter (mg/dL) reported by the central laboratory were used. Baseline for serum creatinine was defined as the mean of values obtained at screening and predose on Day 1 of Period 1.
Time frame: Day 1 of Period 1, Day 43 of Period 1
Population: FAS OC; one participant was excluded (took wrong treatment) from the FAS analysis of change at end of Period 1 from baseline in serum creatinine.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| CP-690,550/Placebo | Adjusted Geometric Mean-Fold Change at End of Period 1 From Baseline in Serum Creatinine | 1.04 fold change |
| Placebo/Placebo | Adjusted Geometric Mean-Fold Change at End of Period 1 From Baseline in Serum Creatinine | 0.99 fold change |
Comparison: Ratio of adjusted geometric mean-fold change (CP-690,550-placebo vs. placebo-placebo)90% CI: [1.02, 1.08]ANCOVA
Secondary
Adjusted Geometric Mean-Fold Change at End of Period 2 From Baseline in eGFR Using MDRD
eGFR was calculated using the MDRD equation with eGFR values normalized to 1.73 m\^2 body surface area. Baseline was defined as the mean of the values obtained at Screening and on predose in Period 1/Day 1.
Time frame: Day 1 of Period 1, Day 29 of Period 2
Population: FAS OC; three participants were excluded (took wrong treatment) from the FAS analysis of change at end of Period 2 from baseline in eGFR (MDRD).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| CP-690,550/Placebo | Adjusted Geometric Mean-Fold Change at End of Period 2 From Baseline in eGFR Using MDRD | 0.99 fold change |
| Placebo/Placebo | Adjusted Geometric Mean-Fold Change at End of Period 2 From Baseline in eGFR Using MDRD | 1.01 fold change |
Comparison: Ratio of adjusted geometric mean-fold change (CP-690,550-placebo vs. placebo-placebo)90% CI: [0.96, 1.02]ANCOVA
Secondary
Adjusted Geometric Mean-Fold Change at End of Period 2 From Baseline in eGFR Using the Cockcroft-Gault Equation
eGFR was calculated using the Cockcroft-Gault equation normalized to 1.73 m\^2 body surface area. Baseline was defined as the mean of the values obtained at Screening and on predose in Period 1/Day 1.
Time frame: Day 1 of Period 1, Day 29 of Period 2
Population: FAS OC; three participants were excluded (took wrong treatment) from the FAS analysis of change at end of Period 2 from baseline in eGFR (Cockcroft-Gault).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| CP-690,550/Placebo | Adjusted Geometric Mean-Fold Change at End of Period 2 From Baseline in eGFR Using the Cockcroft-Gault Equation | 1.00 fold change |
| Placebo/Placebo | Adjusted Geometric Mean-Fold Change at End of Period 2 From Baseline in eGFR Using the Cockcroft-Gault Equation | 1.01 fold change |
Comparison: Ratio of adjusted geometric mean-fold change (CP-690,550-placebo vs. placebo-placebo)90% CI: [0.97, 1.02]ANCOVA
Secondary
Adjusted Geometric Mean-Fold Change at End of Period 2 From End of Period 1 in eGFR Using MDRD
eGFR was calculated using the MDRD equation with eGFR values normalized to 1.73 m\^2 body surface area.
Time frame: Day 43 of Period 1, Day 29 of Period 2
Population: FAS (OC); three participants were excluded (took wrong treatment) from the FAS analysis of change at end of Period 2 from end of Period 1 in eGFR (MDRD).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| CP-690,550/Placebo | Adjusted Geometric Mean-Fold Change at End of Period 2 From End of Period 1 in eGFR Using MDRD | 1.04 fold change |
| Placebo/Placebo | Adjusted Geometric Mean-Fold Change at End of Period 2 From End of Period 1 in eGFR Using MDRD | 1.00 fold change |
Comparison: Ratio of adjusted geometric mean-fold change (CP-690,550-placebo vs. placebo-placebo)90% CI: [1, 1.08]ANCOVA
Secondary
Adjusted Geometric Mean-Fold Change at End of Period 2 From End of Period 1 in eGFR Using the Cockcroft-Gault Equation
eGFR was calculated using the Cockcroft-Gault equation normalized to 1.73 m\^2 body surface area.
Time frame: Day 43 of Period 1, Day 29 of Period 2
Population: FAS OC; three participants were excluded (took wrong treatment) from the FAS analysis of change at end of Period 2 from end of Period 1 in eGFR (Cockcroft-Gault).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| CP-690,550/Placebo | Adjusted Geometric Mean-Fold Change at End of Period 2 From End of Period 1 in eGFR Using the Cockcroft-Gault Equation | 1.03 fold change |
| Placebo/Placebo | Adjusted Geometric Mean-Fold Change at End of Period 2 From End of Period 1 in eGFR Using the Cockcroft-Gault Equation | 1.00 fold change |
Comparison: Ratio of adjusted geometric mean-fold change (CP-690,550-placebo vs. placebo-placebo)90% CI: [1.01, 1.07]ANCOVA
Secondary
Adjusted Geometric Mean-Fold Change at End of Period 2 From End of Period 1 in mGFR
mGFR was determined using iohexol serum clearance using compartmental modeling of the iohexol serum concentration-time data. mGFR values were normalized to 1.73 m\^2 body surface area.
Time frame: Day 43 of Period 1, Day 29 of Period 2
Population: FAS OC; three participants were excluded (took wrong treatment) from the FAS analysis of change at end of Period 2 from end of Period 1 in mGFR.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| CP-690,550/Placebo | Adjusted Geometric Mean-Fold Change at End of Period 2 From End of Period 1 in mGFR | 1.03 fold change |
| Placebo/Placebo | Adjusted Geometric Mean-Fold Change at End of Period 2 From End of Period 1 in mGFR | 0.95 fold change |
Comparison: Ratio of adjusted geometric mean-fold change (CP-690,550-placebo vs. placebo-placebo)90% CI: [1.02, 1.16]ANCOVA
Secondary
Adjusted Geometric Mean-Fold Change at End of Period 2 From End of Period 1 in Serum Creatinine
Blood samples were collected from participants at screening, predose on Day 1 of Period 1, on the last day of Period 1 and on the last day of Period 2 for assessment of serum creatinine levels. Serum creatinine values in mg/dL reported by the central laboratory were used.
Time frame: Day 43 of Period 1, Day 29 of Period 2
Population: FAS OC; three participants were excluded (took wrong treatment) from the FAS analysis of change at end of Period 2 from end of Period 1 in serum creatinine.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| CP-690,550/Placebo | Adjusted Geometric Mean-Fold Change at End of Period 2 From End of Period 1 in Serum Creatinine | 0.97 fold change |
| Placebo/Placebo | Adjusted Geometric Mean-Fold Change at End of Period 2 From End of Period 1 in Serum Creatinine | 1.00 fold change |
Comparison: Ratio of adjusted geometric mean-fold change (CP-690,550-placebo vs. placebo-placebo)90% CI: [0.94, 1]ANCOVA
Secondary
Adjusted Geometric Mean-Fold Change at the End of Period 2 From Baseline in mGFR
mGFR was determined using iohexol serum clearance using compartmental modeling of the iohexol serum concentration-time data. mGFR values were normalized to 1.73 m\^2 body surface area. Baseline was defined as the mean of the values obtained at Run-in and on predose in Period 1/Day 1.
Time frame: Day 1 of Period 1, Day 29 of Period 2
Population: FAS OC; three participants were excluded (took wrong treatment) from the FAS analysis of change at end of Period 2 from baseline in mGFR.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| CP-690,550/Placebo | Adjusted Geometric Mean-Fold Change at the End of Period 2 From Baseline in mGFR | 0.96 fold change |
| Placebo/Placebo | Adjusted Geometric Mean-Fold Change at the End of Period 2 From Baseline in mGFR | 0.92 fold change |
Comparison: Ratio of adjusted geometric mean-fold change (CP-690,550-placebo vs. placebo-placebo)90% CI: [0.97, 1.11]ANCOVA
Secondary
Adjusted Geometric Mean-Fold Change From End of Period 2 From Baseline in Serum Creatinine
Blood samples were collected from participants at screening, predose on Day 1 of Period 1, on the last day of Period 1 and on the last day of Period 2 for assessment of serum creatinine levels. Serum creatinine values in mg/dL reported by the central laboratory were used. Baseline for serum creatinine was defined as the mean of values obtained at screening and predose on Day 1 of Period 1.
Time frame: Day 1 of Period 1, Day 29 of Period 2
Population: FAS OC; three participants were excluded (took wrong treatment) from the FAS analysis of change at end of Period 2 from baseline in serum creatinine.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| CP-690,550/Placebo | Adjusted Geometric Mean-Fold Change From End of Period 2 From Baseline in Serum Creatinine | 1.00 fold change |
| Placebo/Placebo | Adjusted Geometric Mean-Fold Change From End of Period 2 From Baseline in Serum Creatinine | 1.00 fold change |
Comparison: Ratio of adjusted geometric mean-fold change (CP-690,550-placebo vs. placebo-placebo)90% CI: [0.98, 1.04]ANCOVA
Secondary
Least Squares (LS) Mean Change at End of Period 1 From Baseline in Disease Activity Score Based on 28-Joint Count CRP (DAS28-3 [CRP])
DAS28 calculated from the tender/painful joint count, swollen joint count (SJC) using the 28 joints count, and CRP value. DAS28 less than or equal to (≤)3.2 equals (=) low disease activity, DAS28 greater than (\>)3.2 to 5.1 = moderate to high disease activity.
Time frame: Day 1 of Period 1, Day 43 of Period 1
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | Least Squares (LS) Mean Change at End of Period 1 From Baseline in Disease Activity Score Based on 28-Joint Count CRP (DAS28-3 [CRP]) | -1.71 score on a scale | Standard Error 0.13 |
| Placebo/Placebo | Least Squares (LS) Mean Change at End of Period 1 From Baseline in Disease Activity Score Based on 28-Joint Count CRP (DAS28-3 [CRP]) | -0.55 score on a scale | Standard Error 0.19 |
p-value: <0.00190% CI: [-1.53, -0.78]Mixed Models Analysis
Secondary
LS Mean Change at End of Period 1 From Baseline DAS28-4 (CRP)
DAS28 calculated from the number of SJC and painful joints (PJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment (PGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 ≤3.2 = low disease activity, DAS28 \>3.2 to 5.1 = moderate to high disease activity.
Time frame: Day 1 of Period 1, Day 43 of Period 1
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | LS Mean Change at End of Period 1 From Baseline DAS28-4 (CRP) | -1.88 score on a scale | Standard Error 0.14 |
| Placebo/Placebo | LS Mean Change at End of Period 1 From Baseline DAS28-4 (CRP) | -0.62 score on a scale | Standard Error 0.21 |
p-value: <0.00190% CI: [-1.67, -0.84]Mixed Models Analysis
Secondary
LS Mean Change at End of Period 1 From Baseline Health Assessment Questionnaire Disability Index (HAQ-DI) Score
HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Time frame: Day 1 of Period 1, Day 43 of Period 1
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | LS Mean Change at End of Period 1 From Baseline Health Assessment Questionnaire Disability Index (HAQ-DI) Score | -0.44 score on a scale | Standard Error 0.06 |
| Placebo/Placebo | LS Mean Change at End of Period 1 From Baseline Health Assessment Questionnaire Disability Index (HAQ-DI) Score | -0.04 score on a scale | Standard Error 0.08 |
p-value: <0.00190% CI: [-0.56, -0.23]Mixed Models Analysis
Secondary
LS Mean Change at End of Period 1 From Baseline in CRP
Time frame: Day 1 of Period 1, Day 43 of Period 1
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | LS Mean Change at End of Period 1 From Baseline in CRP | -13.81 mg/L | Standard Error 2.17 |
| Placebo/Placebo | LS Mean Change at End of Period 1 From Baseline in CRP | -0.08 mg/L | Standard Error 3.01 |
p-value: <0.00190% CI: [-19.87, -7.59]Mixed Models Analysis
Secondary
LS Mean Change at End of Period 1 From Baseline in Patient Assessment of Arthritis Pain
Participant's assessed the severity of their arthritis pain using a 100 mm VAS placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain.
Time frame: Day 1 of Period 1, Day 43 of Period 1
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | LS Mean Change at End of Period 1 From Baseline in Patient Assessment of Arthritis Pain | -23.53 mm | Standard Error 2.61 |
| Placebo/Placebo | LS Mean Change at End of Period 1 From Baseline in Patient Assessment of Arthritis Pain | -8.23 mm | Standard Error 3.69 |
p-value: <0.00190% CI: [-22.78, -7.82]Mixed Models Analysis
Secondary
LS Mean Change at End of Period 1 From Baseline in Patient Global Assessment of Arthritis (PGAA)
Participants answered the following question, Considering all the ways your arthritis affects you, how are you feeling today? Participants responded by using a 0 - 100 millimeter (mm) visual analog scale (VAS), where 0 mm = very well and 100 mm = very poorly.
Time frame: Day 1 of Period 1, Day 43 of Period 1
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | LS Mean Change at End of Period 1 From Baseline in Patient Global Assessment of Arthritis (PGAA) | -23.28 mm | Standard Error 2.81 |
| Placebo/Placebo | LS Mean Change at End of Period 1 From Baseline in Patient Global Assessment of Arthritis (PGAA) | -7.38 mm | Standard Error 3.98 |
p-value: 0.00190% CI: [-23.96, -7.84]Mixed Models Analysis
Secondary
LS Mean Change at End of Period 1 From Baseline in Physician Global Assessment of Arthritis
A physician assessed how the participant's overall arthritis appeared at the time of the visit. This was an evaluation based on the participant's disease signs, functional capacity and physical examination. The physician's response was recorded using a 100 mm VAS, where 0 mm = very good and 100 mm = very poor.
Time frame: Day 1 of Period 1, Day 43 of Period 1
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | LS Mean Change at End of Period 1 From Baseline in Physician Global Assessment of Arthritis | -29.83 mm | Standard Error 2.24 |
| Placebo/Placebo | LS Mean Change at End of Period 1 From Baseline in Physician Global Assessment of Arthritis | -14.71 mm | Standard Error 3.19 |
p-value: <0.00190% CI: [-21.58, -8.67]Mixed Models Analysis
Secondary
LS Mean Change at End of Period 1 From Baseline in Swollen Joint Count
Swollen joint count included 66 joints. Assessor assessed joints for swelling using the following scale: present/absent/not done/not applicable (to be used for artificial joints). Joints assessed included: upper body (temporomandibular, sternoclavicular, acromioclavicular), upper extremity (shoulder, elbow, wrist, MCP, thumb IP, PIP, and DIP), and lower extremity (knee, ankle, tarsus, MTP, great toe IP, proximal and distal interphalangeals combined \[PIP\]).
Time frame: Day 1 of Period 1, Day 43 of Period 1
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | LS Mean Change at End of Period 1 From Baseline in Swollen Joint Count | -7.07 swollen joints | Standard Error 0.59 |
| Placebo/Placebo | LS Mean Change at End of Period 1 From Baseline in Swollen Joint Count | -4.81 swollen joints | Standard Error 0.84 |
p-value: 0.0390% CI: [-3.96, -0.55]Mixed Models Analysis
Secondary
LS Mean Change at End of Period 1 From Baseline in Tender/Painful Joint Count
68 joints were assessed by a joint assessor to determine the number of joints that were considered tender or painful Assessed joints included: upper body (temporomandibular, sternoclavicular, acromioclavicular), upper extremity (shoulder, elbow, wrist, MCP, thumb interphalangeal \[IP\], PIP, and distal interphalangeals \[DIP\]), and lower extremity (hip, knee, ankle, tarsus, metatarsophalangeals \[MTP\], great toe IP, proximal and distal interphalangeals combined \[PIP\]).
Time frame: Day 1 of Period 1, Day 43 of Period 1
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | LS Mean Change at End of Period 1 From Baseline in Tender/Painful Joint Count | -9.88 tender/painful joints | Standard Error 1.16 |
| Placebo/Placebo | LS Mean Change at End of Period 1 From Baseline in Tender/Painful Joint Count | -5.79 tender/painful joints | Standard Error 1.66 |
p-value: 0.04590% CI: [-7.44, -0.74]Mixed Models Analysis
Secondary
LS Mean Change at End of Period 2 From Baseline DAS28-4 (CRP)
DAS28 calculated from the number of SJC and PJC using the 28 joints count, the ESR (mm/hour) and PGA of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 ≤3.2 = low disease activity, DAS28 \>3.2 to 5.1 = moderate to high disease activity.
Time frame: Day 1 of Period 1, Day 29 of Period 2
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | LS Mean Change at End of Period 2 From Baseline DAS28-4 (CRP) | -1.46 score on a scale | Standard Error 0.13 |
| Placebo/Placebo | LS Mean Change at End of Period 2 From Baseline DAS28-4 (CRP) | -0.96 score on a scale | Standard Error 0.19 |
p-value: 0.03190% CI: [-0.88, -0.12]Mixed Models Analysis
Secondary
LS Mean Change at End of Period 2 From Baseline HAQ-DI Score
HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Time frame: Day 1 of Period 1, Day 29 of Period 2
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | LS Mean Change at End of Period 2 From Baseline HAQ-DI Score | -0.34 score on a scale | Standard Error 0.05 |
| Placebo/Placebo | LS Mean Change at End of Period 2 From Baseline HAQ-DI Score | -0.17 score on a scale | Standard Error 0.07 |
p-value: 0.05390% CI: [-0.31, -0.03]Mixed Models Analysis
Secondary
LS Mean Change at End of Period 2 From Baseline in CRP
Time frame: Day 1 of Period 1, Day 29 of Period 2
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | LS Mean Change at End of Period 2 From Baseline in CRP | -8.37 mg/L | Standard Error 2.34 |
| Placebo/Placebo | LS Mean Change at End of Period 2 From Baseline in CRP | 0.53 mg/L | Standard Error 3.29 |
p-value: 0.02990% CI: [-15.58, -2.21]Mixed Models Analysis
Secondary
LS Mean Change at End of Period 2 From Baseline in DAS28-3 (CRP)
DAS28 calculated from the tender/painful joint count, SJC using the 28 joints count, and CRP value. DAS28 ≤3.2 = low disease activity, DAS28 \>3.2 to 5.1 = moderate to high disease activity.
Time frame: Day 1 of Period 1, Day 29 of Period 2
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | LS Mean Change at End of Period 2 From Baseline in DAS28-3 (CRP) | -1.36 score on a scale | Standard Error 0.12 |
| Placebo/Placebo | LS Mean Change at End of Period 2 From Baseline in DAS28-3 (CRP) | -0.89 score on a scale | Standard Error 0.17 |
p-value: 0.02890% CI: [-0.83, -0.12]Mixed Models Analysis
Secondary
LS Mean Change at End of Period 2 From Baseline in Patient Assessment of Arthritis Pain
Participant's assessed the severity of their arthritis pain using a 100 mm VAS placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain.
Time frame: Day 1 of Period 1, Day 29 of Period 2
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | LS Mean Change at End of Period 2 From Baseline in Patient Assessment of Arthritis Pain | -14.70 mm | Standard Error 2.8 |
| Placebo/Placebo | LS Mean Change at End of Period 2 From Baseline in Patient Assessment of Arthritis Pain | -9.08 mm | Standard Error 3.94 |
p-value: 0.24790% CI: [-13.62, 2.38]Mixed Models Analysis
Secondary
LS Mean Change at End of Period 2 From Baseline in PGAA
Participants answered the following question, Considering all the ways your arthritis affects you, how are you feeling today? The participants responses were recorded using a 100 mm VAS, where 0 mm = very well and 100 mm = very poorly.
Time frame: Day 1 of Period 1, Day 29 of Period 2
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | LS Mean Change at End of Period 2 From Baseline in PGAA | -16.12 mm | Standard Error 2.87 |
| Placebo/Placebo | LS Mean Change at End of Period 2 From Baseline in PGAA | -10.41 mm | Standard Error 4.03 |
p-value: 0.25190% CI: [-13.9, 2.5]Mixed Models Analysis
Secondary
LS Mean Change at End of Period 2 From Baseline in Physician Global Assessment of Arthritis
A physician assessed how the participant's overall arthritis appeared at the time of the visit. This was an evaluation based on the participant's disease signs, functional capacity and physical examination. The physician's response was recorded using a 100 mm VAS, where 0 mm = very good and 100 mm = very poor.
Time frame: Day 1 of Period 1, Day 29 of Period 2
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | LS Mean Change at End of Period 2 From Baseline in Physician Global Assessment of Arthritis | -24.61 mm | Standard Error 2.76 |
| Placebo/Placebo | LS Mean Change at End of Period 2 From Baseline in Physician Global Assessment of Arthritis | -22.21 mm | Standard Error 3.89 |
p-value: 0.61690% CI: [-10.3, 5.5]Mixed Models Analysis
Secondary
LS Mean Change at End of Period 2 From Baseline in Swollen Joint Count
Swollen joint count included 66 joints. Assessor assessed joints for swelling using the following scale: present/absent/not done/not applicable (to be used for artificial joints). Joints assessed included: upper body (temporomandibular, sternoclavicular, acromioclavicular), upper extremity (shoulder, elbow, wrist, MCP, thumb IP, PIP, and DIP), and lower extremity (knee, ankle, tarsus, MTP, great toe IP, proximal and distal interphalangeals combined \[PIP\]).
Time frame: Day 1 of Period 1, Day 29 of Period 2
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | LS Mean Change at End of Period 2 From Baseline in Swollen Joint Count | -6.63 swollen joints | Standard Error 0.64 |
| Placebo/Placebo | LS Mean Change at End of Period 2 From Baseline in Swollen Joint Count | -5.83 swollen joints | Standard Error 0.91 |
p-value: 0.47290% CI: [-2.64, 1.04]Mixed Models Analysis
Secondary
LS Mean Change at End of Period 2 From Baseline in Tender/Painful Joint Count
68 joints were assessed by a joint assessor to determine the number of joints that were considered tender or painful Assessed joints included: upper body (temporomandibular, sternoclavicular, acromioclavicular), upper extremity (shoulder, elbow, wrist, MCP, thumb IP, PIP, and DIP), and lower extremity (hip, knee, ankle, tarsus, MTP, great toe IP, proximal and distal interphalangeals combined \[PIP\]).
Time frame: Day 1 of Period 1, Day 29 of Period 2
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | LS Mean Change at End of Period 2 From Baseline in Tender/Painful Joint Count | -8.13 tender/painful joints | Standard Error 1.02 |
| Placebo/Placebo | LS Mean Change at End of Period 2 From Baseline in Tender/Painful Joint Count | -8.27 tender/painful joints | Standard Error 1.44 |
p-value: 0.93690% CI: [-2.78, 3.06]Mixed Models Analysis
Secondary
LS Mean Change at End of Period 2 From End of Period 1 DAS28-4 (CRP)
DAS28 calculated from the number of SJC and PJC using the 28 joints count, the ESR (mm/hour) and PGA of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 ≤3.2 = low disease activity, DAS28 \>3.2 to 5.1 = moderate to high disease activity.
Time frame: Day 43 of Period 1, Day 29 of Period 2
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | LS Mean Change at End of Period 2 From End of Period 1 DAS28-4 (CRP) | 0.42 score on a scale | Standard Error 0.14 |
| Placebo/Placebo | LS Mean Change at End of Period 2 From End of Period 1 DAS28-4 (CRP) | -0.34 score on a scale | Standard Error 0.2 |
p-value: 0.00290% CI: [0.36, 1.15]Mixed Models Analysis
Secondary
LS Mean Change at End of Period 2 From End of Period 1 HAQ-DI Score
HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Time frame: Day 43 of Period 1, Day 29 of Period 2
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | LS Mean Change at End of Period 2 From End of Period 1 HAQ-DI Score | 0.09 score on a scale | Standard Error 0.04 |
| Placebo/Placebo | LS Mean Change at End of Period 2 From End of Period 1 HAQ-DI Score | -0.13 score on a scale | Standard Error 0.06 |
p-value: 0.00390% CI: [0.1, 0.35]Mixed Models Analysis
Secondary
LS Mean Change at End of Period 2 From End of Period 1 in CRP
Time frame: Day 43 of Period 1, Day 29 of Period 2
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | LS Mean Change at End of Period 2 From End of Period 1 in CRP | 5.44 mg/L | Standard Error 1.71 |
| Placebo/Placebo | LS Mean Change at End of Period 2 From End of Period 1 in CRP | 0.61 mg/L | Standard Error 2.44 |
p-value: 0.10790% CI: [-0.1, 9.77]Mixed Models Analysis
Secondary
LS Mean Change at End of Period 2 From End of Period 1 in DAS28-3 (CRP)
DAS28 calculated from the tender/painful joint count, SJC using the 28 joints count, and CRP value. DAS28 ≤3.2 = low disease activity, DAS28 \>3.2 to 5.1 = moderate to high disease activity.
Time frame: Day 43 of Period 1, Day 29 of Period 2
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | LS Mean Change at End of Period 2 From End of Period 1 in DAS28-3 (CRP) | 0.35 score on a scale | Standard Error 0.12 |
| Placebo/Placebo | LS Mean Change at End of Period 2 From End of Period 1 in DAS28-3 (CRP) | -0.34 score on a scale | Standard Error 0.18 |
p-value: 0.00290% CI: [0.32, 1.04]Mixed Models Analysis
Secondary
LS Mean Change at End of Period 2 From End of Period 1 in Patient Assessment of Arthritis Pain
Participant's assessed the severity of their arthritis pain using a 100 mm VAS placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain.
Time frame: Day 43 of Period 2, Day 29 of Period 2
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | LS Mean Change at End of Period 2 From End of Period 1 in Patient Assessment of Arthritis Pain | 8.83 mm | Standard Error 2.69 |
| Placebo/Placebo | LS Mean Change at End of Period 2 From End of Period 1 in Patient Assessment of Arthritis Pain | -0.85 mm | Standard Error 3.81 |
p-value: 0.0490% CI: [1.95, 17.41]Mixed Models Analysis
Secondary
LS Mean Change at End of Period 2 From End of Period 1 in PGAA
Participants answered the following question, Considering all the ways your arthritis affects you, how are you feeling today? The participants responses were recorded using a 100 mm VAS, where 0 mm = very well and 100 mm = very poorly.
Time frame: Day 43 of Period 1, Day 29 of Period 2
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | LS Mean Change at End of Period 2 From End of Period 1 in PGAA | 7.16 mm | Standard Error 2.54 |
| Placebo/Placebo | LS Mean Change at End of Period 2 From End of Period 1 in PGAA | -3.03 mm | Standard Error 3.62 |
p-value: 0.02390% CI: [2.87, 17.52]Mixed Models Analysis
Secondary
LS Mean Change at End of Period 2 From End of Period 1 in Physician Global Assessment of Arthritis
A physician assessed how the participant's overall arthritis appeared at the time of the visit. This was an evaluation based on the participant's disease signs, functional capacity and physical examination. The physician's response was recorded using a 100 mm VAS, where 0 mm = very good and 100 mm = very poor.
Time frame: Day 43 of Period 1, Day 29 of Period 1
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | LS Mean Change at End of Period 2 From End of Period 1 in Physician Global Assessment of Arthritis | 5.22 mm | Standard Error 2.39 |
| Placebo/Placebo | LS Mean Change at End of Period 2 From End of Period 1 in Physician Global Assessment of Arthritis | -7.50 mm | Standard Error 3.41 |
p-value: 0.00390% CI: [5.82, 19.62]Mixed Models Analysis
Secondary
LS Mean Change at End of Period 2 From End of Period 1 in Swollen Joint Count
Swollen joint count included 66 joints. Assessor assessed joints for swelling using the following scale: present/absent/not done/not applicable (to be used for artificial joints). Joints assessed included: upper body (temporomandibular, sternoclavicular, acromioclavicular), upper extremity (shoulder, elbow, wrist, MCP, thumb IP, PIP, and DIP), and lower extremity (knee, ankle, tarsus, MTP, great toe IP, proximal and distal interphalangeals combined \[PIP\]).
Time frame: Day 43 of Period 1, Day 29 of Period 2
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | LS Mean Change at End of Period 2 From End of Period 1 in Swollen Joint Count | 0.43 swollen joints | Standard Error 0.59 |
| Placebo/Placebo | LS Mean Change at End of Period 2 From End of Period 1 in Swollen Joint Count | -1.02 swollen joints | Standard Error 0.84 |
p-value: 0.15890% CI: [-0.24, 3.15]Mixed Models Analysis
Secondary
LS Mean Change at End of Period 2 From End of Period 1 in Tender/Painful Joint Count
68 joints were assessed by a joint assessor to determine the number of joints that were considered tender or painful Assessed joints included: upper body (temporomandibular, sternoclavicular, acromioclavicular), upper extremity (shoulder, elbow, wrist, MCP, thumb IP, PIP, and DIP), and lower extremity (hip, knee, ankle, tarsus, MTP, great toe IP, proximal and distal interphalangeals combined \[PIP\]).
Time frame: Day 43 of Period 1, Day 29 of Period 2
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550/Placebo | LS Mean Change at End of Period 2 From End of Period 1 in Tender/Painful Joint Count | 1.75 tender/painful joints | Standard Error 1.11 |
| Placebo/Placebo | LS Mean Change at End of Period 2 From End of Period 1 in Tender/Painful Joint Count | -2.48 tender/painful joints | Standard Error 1.58 |
p-value: 0.0390% CI: [1.04, 7.42]Mixed Models Analysis
Secondary
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response
ACR50 response: ≥50% improvement in tender or swollen joint counts and 50% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) participant's assessment of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a HAQ, and 5) CRP at each visit.
Time frame: Day 1 of Period 1 to Day 43 of Period 1, Day 1 of Period 1 to Day 29 of Period 2
Population: FAS (NRI, LOCF)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CP-690,550/Placebo | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | End of Period 1 (Day 43) | 28.87 percentage of participants |
| CP-690,550/Placebo | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | End of Period 2 (Day 29) | 26.80 percentage of participants |
| Placebo/Placebo | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | End of Period 1 (Day 43) | 7.84 percentage of participants |
| Placebo/Placebo | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | End of Period 2 (Day 29) | 9.80 percentage of participants |
Comparison: Between-group difference in ACR50 Response at End of Period 1p-value: <0.00190% CI: [11.24, 30.8]Normal approximation for proportions
Comparison: Between-group difference in ACR50 Response at End of Period 2p-value: 0.00690% CI: [6.92, 27.08]Normal approximation for proportions
Secondary
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
ACR70 response: ≥70% improvement in tender or swollen joint counts and 70% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) participant's assessment of disease activity, 3) participant's assessment of pain, 4) participant' assessment of functional disability via a HAQ, and 5) CRP at each visit.
Time frame: Day 1 of Period 1 to Day 43 of Period 1, Day 1 of Period 1 to Day 29 of Period 2
Population: FAS (NRI, LOCF)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CP-690,550/Placebo | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | End of Period 1 (Day 43) | 18.56 percentage of participants |
| CP-690,550/Placebo | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | End of Period 2 (Day 29) | 9.28 percentage of participants |
| Placebo/Placebo | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | End of Period 2 (Day 29) | 1.96 percentage of participants |
| Placebo/Placebo | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | End of Period 1 (Day 43) | 0.00 percentage of participants |
Comparison: Between-group difference in ACR70 Response at End of Period 1p-value: <0.00190% CI: [12.06, 25.05]Normal approximation for proportions
Comparison: Between-group difference in ACR70 Response at End of Period 2p-value: 0.03890% CI: [1.51, 13.12]Normal approximation for proportions
Secondary
Percentage of Participants Achieving an American College of Rheumatology 20% (ACR20) Response
ACR20 response: greater than or equal to (≥)20 percent (%) improvement in tender joint count; ≥20% improvement in swollen joint count; and ≥20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP).
Time frame: Day 1 of Period 1 to Day 43 of Period 1, Day 1 of Period 1 to Day 29 of Period 2
Population: FAS, missing values while participant was still enrolled utilized last observation carried forward (LOCF) imputation while participants with missing values after a participant was discontinued from study participation (for any reason) were considered to be nonresponders (nonresponder imputation \[NRI\])
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CP-690,550/Placebo | Percentage of Participants Achieving an American College of Rheumatology 20% (ACR20) Response | End of Period 1 (Day 43) | 57.73 percentage of participants |
| CP-690,550/Placebo | Percentage of Participants Achieving an American College of Rheumatology 20% (ACR20) Response | End of Period 2 (Day 29) | 45.36 percentage of participants |
| Placebo/Placebo | Percentage of Participants Achieving an American College of Rheumatology 20% (ACR20) Response | End of Period 2 (Day 29) | 29.41 percentage of participants |
| Placebo/Placebo | Percentage of Participants Achieving an American College of Rheumatology 20% (ACR20) Response | End of Period 1 (Day 43) | 21.57 percentage of participants |
Comparison: Between-group difference in ACR20 Response at End of Period 1p-value: <0.00190% CI: [23.6, 48.73]Normal approximation for proportions
Comparison: Between-group difference in ACR20 Response at End of Period 2p-value: 0.0590% CI: [2.56, 29.34]Normal approximation for proportions