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

Arthritis, Rheumatoid Clinical Trial

Official title:

A Phase 1, Randomized, Placebo-Controlled, Two-Period, Fixed Sequence Study To Evaluate The Effect Of CP-690,550 On Measured Glomerular Filtration Rate In Patients With Active Rheumatoid Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01484561
• Other study ID #: A3921152
• Status: Completed
• Phase: Phase 1
• First received: November 30, 2011
• Last updated: March 4, 2014
• Start date: April 2012
• Est. completion date: February 2013

Study information

• Verified date: March 2014
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 148
• Est. completion date: February 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Drug:
• CP-690,550 or Placebo
CP-690,550 10 mg twice a day (BID) orally or placebo BID orally, approximately 72 days
• Placebo
Placebo BID orally, approximately 72 days

Locations

Country	Name	City	State
Czech Republic	Pfizer Investigational Site	Praha 4
Germany	Pfizer Investigational Site	Berlin
Germany	Pfizer Investigational Site	Erlangen
Germany	Pfizer Investigational Site	Wuerzburg
Korea, Republic of	Pfizer Investigational Site	Seoul
Mexico	Pfizer Investigational Site	Merida	Yucatan
Poland	Pfizer Investigational Site	Bialystok
Poland	Pfizer Investigational Site	Bydgoszcz
Poland	Pfizer Investigational Site	Warszawa
Poland	Pfizer Investigational Site	Warszawa
Poland	Pfizer Investigational Site	Wroclaw
Russian Federation	Pfizer Investigational Site	Moscow
Russian Federation	Pfizer Investigational Site	Petrozavodsk
Russian Federation	Pfizer Investigational Site	Saint Petersburg
Russian Federation	Pfizer Investigational Site	St. Petersburg
Spain	Pfizer Investigational Site	Barakaldo	Vizcaya
Spain	Pfizer Investigational Site	Bilbao	Vizcaya
Spain	Pfizer Investigational Site	La Coruna
Spain	Pfizer Investigational Site	Sevilla
United States	Pfizer Investigational Site	Albany	New York
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Duncansville	Pennsylvania
United States	Pfizer Investigational Site	South Miami	Florida
United States	Pfizer Investigational Site	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Czech Republic,  Germany,  Korea, Republic of,  Mexico,  Poland,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Day 1 of Period 1, Day 43 of Period 1	Yes
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.	Day 1 of Period 1, Day 29 of Period 2	Yes
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.	Day 43 of Period 1, Day 29 of Period 2	Yes
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.	Day 1 of Period 1, Day 43 of Period 1	Yes
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.	Day 1 of Period 1, Day 29 of Period 2	Yes
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.	Day 43 of Period 1, Day 29 of Period 2	Yes
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.	Day 1 of Period 1, Day 43 of Period 1	Yes
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.	Day 1 of Period 1, Day 29 of Period 2	Yes
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.	Day 43 of Period 1, Day 29 of Period 2	Yes
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.	Day 1 of Period 1, Day 43 of Period 1	Yes
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.	Day 1 of Period 1, Day 29 of Period 2	Yes
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.	Day 43 of Period 1, Day 29 of Period 2	Yes
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).	Day 1 of Period 1 to Day 43 of Period 1, Day 1 of Period 1 to Day 29 of Period 2	No
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.	Day 1 of Period 1 to Day 43 of Period 1, Day 1 of Period 1 to Day 29 of Period 2	No
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.	Day 1 of Period 1 to Day 43 of Period 1, Day 1 of Period 1 to Day 29 of Period 2	No
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.	Day 1 of Period 1, Day 43 of Period 1	No
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.	Day 1 of Period 1, Day 29 of Period 2	No
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.	Day 43 of Period 1, Day 29 of Period 2	No
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.	Day 1 of Period 1, Day 43 of Period 1	No
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.	Day 1 of Period 1, Day 29 of Period 2	No
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.	Day 43 of Period 1, Day 29 of Period 2	No
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]).	Day 1 of Period 1, Day 43 of Period 1	No
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]).	Day 1 of Period 1, Day 29 of Period 2	No
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]).	Day 43 of Period 1, Day 29 of Period 2	No
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]).	Day 1 of Period 1, Day 43 of Period 1	No
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]).	Day 1 of Period 1, Day 29 of Period 2	No
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]).	Day 43 of Period 1, Day 29 of Period 2	No
Secondary	LS Mean Change at End of Period 1 From Baseline in CRP		Day 1 of Period 1, Day 43 of Period 1	No
Secondary	LS Mean Change at End of Period 2 From Baseline in CRP		Day 1 of Period 1, Day 29 of Period 2	No
Secondary	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	No
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.	Day 1 of Period 1, Day 43 of Period 1	No
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.	Day 1 of Period 1, Day 29 of Period 2	No
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.	Day 43 of Period 1, Day 29 of Period 2	No
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.	Day 1 of Period 1, Day 43 of Period 1	No
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.	Day 1 of Period 1, Day 29 of Period 2	No
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.	Day 43 of Period 1, Day 29 of Period 1	No
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.	Day 1 of Period 1, Day 43 of Period 1	No
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.	Day 1 of Period 1, Day 29 of Period 2	No
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.	Day 43 of Period 2, Day 29 of Period 2	No
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.	Day 1 of Period 1, Day 43 of Period 1	No
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.	Day 1 of Period 1, Day 29 of Period 2	No
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.	Day 43 of Period 1, Day 29 of Period 2	No

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