A Study To Evaluate The Effect Of CP-690,550 On Measures Of Kidney Function In Patients With Active Rheumatoid Arthritis

Phase 1

Completed

Conditions: Arthritis, Rheumatoid

Interventions: Drug: CP-690,550 or Placebo
Drug: Placebo

Registration Number: NCT01484561

Lead Sponsor: Pfizer

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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 148

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sequence 1	CP-690,550 or Placebo	-
Sequence 2	Placebo	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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.
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.
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.
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 \[PIP\]).