Arthritis, RheumatoidPhase 1NCT01484561
A Study To Evaluate The Effect Of CP-690,550 On Measures Of Kidney Function In Patients With Active Rheumatoid Arthritis
A Phase 1 study of Arthritis, Rheumatoid, run by Pfizer at 24 sites in 8 countries.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Arthritis, Rheumatoid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 148 participants
- Where
- 24 sitesin 8 countries
- Study dates
- Apr 2012to Feb 2013
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
24 sites in 8 countries.
24 sites in 8 countries
United States5 sites
Pfizer Investigational Site
Albany, New York, 12206
Pfizer Investigational Site
Dallas, Texas, 75231
Pfizer Investigational Site
Duncansville, Pennsylvania, 16635
Pfizer Investigational Site
South Miami, Florida, 33143
Pfizer Investigational Site
Tacoma, Washington, 98405
Poland5 sites
Pfizer Investigational Site
Bialystok, 15-354
Pfizer Investigational Site
Bydgoszcz, 85-168
Pfizer Investigational Site
Warsaw, 01-192
Pfizer Investigational Site
Warsaw, 02-256
Pfizer Investigational Site
Wroclaw, 50-088
Russia4 sites
Pfizer Investigational Site
Moscow, 115522
Pfizer Investigational Site
Petrozavodsk, 185019
Pfizer Investigational Site
Saint Petersburg, 194291
Pfizer Investigational Site
Saint Petersburg, 197341
Spain4 sites
Pfizer Investigational Site
A Coruña, 15006
Pfizer Investigational Site
Barakaldo, Vizcaya, 48903
Pfizer Investigational Site
Bilbao, Vizcaya, 48013
Pfizer Investigational Site
Seville, Sevilla, 41009
Germany3 sites
Pfizer Investigational Site
Berlin, 13125
Pfizer Investigational Site
Erlangen, 91054
Pfizer Investigational Site
Würzburg, 97080
About this study
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
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).
- Conditions
- Arthritis, Rheumatoid
- Being tested
- CP-690,550 or Placebo, Placebo
- Keywords
- Phase 1
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CP-690,550 or PlaceboDrug
CP-690,550 10 mg twice a day (BID) orally or placebo BID orally, approximately 72 days
PlaceboDrug
Placebo BID orally, approximately 72 days
| Study group | Role | What they receive |
|---|---|---|
| Sequence 1 | Active comparator | Not described Receives: Drug: CP-690,550 or Placebo |
| Sequence 2 | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 1 of Period 1, Day 43 of Period 1
Secondary outcomes (41)
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.
Measured: Day 1 of Period 1, Day 29 of Period 2
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.
Measured: Day 43 of Period 1, Day 29 of Period 2
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.
Measured: Day 1 of Period 1, Day 43 of Period 1
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.
Measured: Day 1 of Period 1, Day 29 of Period 2
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.
Measured: Day 43 of Period 1, Day 29 of Period 2
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.
Measured: Day 1 of Period 1, Day 43 of Period 1
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.
Measured: Day 1 of Period 1, Day 29 of Period 2
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.
Measured: Day 43 of Period 1, Day 29 of Period 2
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.
Measured: Day 1 of Period 1, Day 43 of Period 1
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.
Measured: Day 1 of Period 1, Day 29 of Period 2
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.
Measured: Day 43 of Period 1, Day 29 of Period 2
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).
Measured: Day 1 of Period 1 to Day 43 of Period 1, Day 1 of Period 1 to Day 29 of Period 2
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.
Measured: Day 1 of Period 1 to Day 43 of Period 1, Day 1 of Period 1 to Day 29 of Period 2
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.
Measured: Day 1 of Period 1 to Day 43 of Period 1, Day 1 of Period 1 to Day 29 of Period 2
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.
Measured: Day 1 of Period 1, Day 43 of Period 1
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.
Measured: Day 1 of Period 1, Day 29 of Period 2
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.
Measured: Day 43 of Period 1, Day 29 of Period 2
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.
Measured: Day 1 of Period 1, Day 43 of Period 1
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.
Measured: Day 1 of Period 1, Day 29 of Period 2
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.
Measured: Day 43 of Period 1, Day 29 of Period 2
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]).
Measured: Day 1 of Period 1, Day 43 of Period 1
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]).
Measured: Day 1 of Period 1, Day 29 of Period 2
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]).
Measured: Day 43 of Period 1, Day 29 of Period 2
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]).
Measured: Day 1 of Period 1, Day 43 of Period 1
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]).
Measured: Day 1 of Period 1, Day 29 of Period 2
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]).
Measured: Day 43 of Period 1, Day 29 of Period 2
LS Mean Change at End of Period 1 From Baseline in CRP
Measured: Day 1 of Period 1, Day 43 of Period 1
LS Mean Change at End of Period 2 From Baseline in CRP
Measured: 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
Measured: 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)
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.
Measured: Day 1 of Period 1, Day 43 of Period 1
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.
Measured: Day 1 of Period 1, Day 29 of Period 2
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.
Measured: Day 43 of Period 1, Day 29 of Period 2
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.
Measured: Day 1 of Period 1, Day 43 of Period 1
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.
Measured: Day 1 of Period 1, Day 29 of Period 2
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.
Measured: Day 43 of Period 1, Day 29 of Period 1
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.
Measured: Day 1 of Period 1, Day 43 of Period 1
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.
Measured: Day 1 of Period 1, Day 29 of Period 2
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.
Measured: Day 43 of Period 2, Day 29 of Period 2
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.
Measured: Day 1 of Period 1, Day 43 of Period 1
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.
Measured: Day 1 of Period 1, Day 29 of Period 2
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.
Measured: Day 43 of Period 1, Day 29 of Period 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2011 (estimated)
- Study startApr 2012
- Primary completionJan 2013
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Arthritis, RheumatoidStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 148 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01484561
- Sponsor's protocol ID
- A3921152
- Status last verified
- Mar 2014
- First submitted
- 30 Nov 2011
- Last updated
- 2 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Kristensen LE, Danese S, Yndestad A, Wang C, Nagy E, Modesto I, Rivas J, Benda B. Identification of two tofacitinib subpopulations with different relative risk versus TNF inhibitors: an analysis of the open label, randomised controlled study ORAL Surveillance. Ann Rheum Dis. 2023 Jul;82(7):901-910. doi: 10.1136/ard-2022-223715. Epub 2023 Mar 17.
PubMed 36931693Hansen KE, Mortezavi M, Nagy E, Wang C, Connell CA, Radi Z, Litman HJ, Adami G, Rossini M. Fracture in clinical studies of tofacitinib in rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2022 Dec 27;14:1759720X221142346. doi: 10.1177/1759720X221142346. eCollection 2022.
PubMed 36601090Curtis JR, Yamaoka K, Chen YH, Bhatt DL, Gunay LM, Sugiyama N, Connell CA, Wang C, Wu J, Menon S, Vranic I, Gomez-Reino JJ. Malignancy risk with tofacitinib versus TNF inhibitors in rheumatoid arthritis: results from the open-label, randomised controlled ORAL Surveillance trial. Ann Rheum Dis. 2023 Mar;82(3):331-343. doi: 10.1136/ard-2022-222543. Epub 2022 Dec 5.
PubMed 36600185Winthrop KL, Yndestad A, Henrohn D, Danese S, Marsal S, Galindo M, Woolcott JC, Jo H, Kwok K, Shapiro AB, Jones TV, Diehl A, Su C, Panes J, Cohen SB. Influenza Adverse Events in Patients with Rheumatoid Arthritis, Ulcerative Colitis, or Psoriatic Arthritis in the Tofacitinib Clinical Development Programs. Rheumatol Ther. 2023 Apr;10(2):357-373. doi: 10.1007/s40744-022-00507-z. Epub 2022 Dec 17.
PubMed 36526796Winthrop KL, Curtis JR, Yamaoka K, Lee EB, Hirose T, Rivas JL, Kwok K, Burmester GR. Clinical Management of Herpes Zoster in Patients With Rheumatoid Arthritis or Psoriatic Arthritis Receiving Tofacitinib Treatment. Rheumatol Ther. 2022 Feb;9(1):243-263. doi: 10.1007/s40744-021-00390-0. Epub 2021 Dec 6.
PubMed 34870800Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, Winthrop KL, Charles-Schoeman C, Wang L, Chen C, Kwok K, Biswas P, Shapiro A, Madsen A, Wollenhaupt J. Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme. RMD Open. 2020 Oct;6(3):e001395. doi: 10.1136/rmdopen-2020-001395.
PubMed 33127856Panaccione R, Isaacs JD, Chen LA, Wang W, Marren A, Kwok K, Wang L, Chan G, Su C. Characterization of Creatine Kinase Levels in Tofacitinib-Treated Patients with Ulcerative Colitis: Results from Clinical Trials. Dig Dis Sci. 2021 Aug;66(8):2732-2743. doi: 10.1007/s10620-020-06560-4. Epub 2020 Aug 20.
PubMed 32816215Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, Winthrop KL, Charles-Schoeman C, Thirunavukkarasu K, DeMasi R, Geier J, Kwok K, Wang L, Riese R, Wollenhaupt J. Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials. Ann Rheum Dis. 2017 Jul;76(7):1253-1262. doi: 10.1136/annrheumdis-2016-210457. Epub 2017 Jan 31.
PubMed 28143815Kremer JM, Kivitz AJ, Simon-Campos JA, Nasonov EL, Tony HP, Lee SK, Vlahos B, Hammond C, Bukowski J, Li H, Schulman SL, Raber S, Zuckerman A, Isaacs JD. Evaluation of the effect of tofacitinib on measured glomerular filtration rate in patients with active rheumatoid arthritis: results from a randomised controlled trial. Arthritis Res Ther. 2015 Apr 6;17(1):95. doi: 10.1186/s13075-015-0612-7.
PubMed 25889308
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01484561
- Acronym / sponsor ID
- A3921152
- Conditions
- Arthritis, Rheumatoid
- Keywords
- Phase 1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 148 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- Apr 2012
- Primary completion
- Jan 2013 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 2 Dec 2011 (estimated)
- Results
- Posted 2 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sequence 1 | Active comparator | Drug: CP-690,550 or Placebo |
| Sequence 2 | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CP-690,550 or PlaceboCP-690,550 10 mg twice a day (BID) orally or placebo BID orally, approximately 72 days | Drug | Sequence 1 |
| PlaceboPlacebo BID orally, approximately 72 days | Drug | Sequence 2 |
Primary outcome
Adjusted Geometric (Geo) Mean-Fold Change at End of Period 1 From Baseline in Measured Glomerular Filtration Rate (mGFR)
Time frame: 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.
41 secondary outcomes
Adjusted Geometric Mean-Fold Change at the End of Period 2 From Baseline in mGFR
Time frame: Day 1 of Period 1, Day 29 of Period 2
Adjusted Geometric Mean-Fold Change at End of Period 2 From End of Period 1 in mGFR
Time frame: Day 43 of Period 1, Day 29 of Period 2
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)
Time frame: Day 1 of Period 1, Day 43 of Period 1
Adjusted Geometric Mean-Fold Change at End of Period 2 From Baseline in eGFR Using MDRD
Time frame: Day 1 of Period 1, Day 29 of Period 2
Adjusted Geometric Mean-Fold Change at End of Period 2 From End of Period 1 in eGFR Using MDRD
Time frame: Day 43 of Period 1, Day 29 of Period 2
Adjusted Geometric Mean-Fold Change at End of Period 1 From Baseline in eGFR Using the Cockcroft-Gault Equation
Time frame: Day 1 of Period 1, Day 43 of Period 1
Adjusted Geometric Mean-Fold Change at End of Period 2 From Baseline in eGFR Using the Cockcroft-Gault Equation
Time frame: Day 1 of Period 1, Day 29 of Period 2
Adjusted Geometric Mean-Fold Change at End of Period 2 From End of Period 1 in eGFR Using the Cockcroft-Gault Equation
Time frame: Day 43 of Period 1, Day 29 of Period 2
Adjusted Geometric Mean-Fold Change at End of Period 1 From Baseline in Serum Creatinine
Time frame: Day 1 of Period 1, Day 43 of Period 1
Adjusted Geometric Mean-Fold Change From End of Period 2 From Baseline in Serum Creatinine
Time frame: Day 1 of Period 1, Day 29 of Period 2
Adjusted Geometric Mean-Fold Change at End of Period 2 From End of Period 1 in Serum Creatinine
Time frame: Day 43 of Period 1, Day 29 of Period 2
Percentage of Participants Achieving an American College of Rheumatology 20% (ACR20) Response
Time frame: Day 1 of Period 1 to Day 43 of Period 1, Day 1 of Period 1 to Day 29 of Period 2
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response
Time frame: Day 1 of Period 1 to Day 43 of Period 1, Day 1 of Period 1 to Day 29 of Period 2
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
Time frame: Day 1 of Period 1 to Day 43 of Period 1, Day 1 of Period 1 to Day 29 of Period 2
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])
Time frame: Day 1 of Period 1, Day 43 of Period 1
LS Mean Change at End of Period 2 From Baseline in DAS28-3 (CRP)
Time frame: Day 1 of Period 1, Day 29 of Period 2
LS Mean Change at End of Period 2 From End of Period 1 in DAS28-3 (CRP)
Time frame: Day 43 of Period 1, Day 29 of Period 2
LS Mean Change at End of Period 1 From Baseline DAS28-4 (CRP)
Time frame: Day 1 of Period 1, Day 43 of Period 1
LS Mean Change at End of Period 2 From Baseline DAS28-4 (CRP)
Time frame: Day 1 of Period 1, Day 29 of Period 2
LS Mean Change at End of Period 2 From End of Period 1 DAS28-4 (CRP)
Time frame: Day 43 of Period 1, Day 29 of Period 2
LS Mean Change at End of Period 1 From Baseline in Tender/Painful Joint Count
Time frame: Day 1 of Period 1, Day 43 of Period 1
LS Mean Change at End of Period 2 From Baseline in Tender/Painful Joint Count
Time frame: Day 1 of Period 1, Day 29 of Period 2
LS Mean Change at End of Period 2 From End of Period 1 in Tender/Painful Joint Count
Time frame: Day 43 of Period 1, Day 29 of Period 2
LS Mean Change at End of Period 1 From Baseline in Swollen Joint Count
Time frame: Day 1 of Period 1, Day 43 of Period 1
LS Mean Change at End of Period 2 From Baseline in Swollen Joint Count
Time frame: Day 1 of Period 1, Day 29 of Period 2
LS Mean Change at End of Period 2 From End of Period 1 in Swollen Joint Count
Time frame: Day 43 of Period 1, Day 29 of Period 2
LS Mean Change at End of Period 1 From Baseline in CRP
Time frame: Day 1 of Period 1, Day 43 of Period 1
LS Mean Change at End of Period 2 From Baseline in CRP
Time frame: 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
Time frame: 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)
Time frame: Day 1 of Period 1, Day 43 of Period 1
LS Mean Change at End of Period 2 From Baseline in PGAA
Time frame: Day 1 of Period 1, Day 29 of Period 2
LS Mean Change at End of Period 2 From End of Period 1 in PGAA
Time frame: Day 43 of Period 1, Day 29 of Period 2
LS Mean Change at End of Period 1 From Baseline in Physician Global Assessment of Arthritis
Time frame: Day 1 of Period 1, Day 43 of Period 1
LS Mean Change at End of Period 2 From Baseline in Physician Global Assessment of Arthritis
Time frame: Day 1 of Period 1, Day 29 of Period 2
LS Mean Change at End of Period 2 From End of Period 1 in Physician Global Assessment of Arthritis
Time frame: Day 43 of Period 1, Day 29 of Period 1
LS Mean Change at End of Period 1 From Baseline in Patient Assessment of Arthritis Pain
Time frame: Day 1 of Period 1, Day 43 of Period 1
LS Mean Change at End of Period 2 From Baseline in Patient Assessment of Arthritis Pain
Time frame: Day 1 of Period 1, Day 29 of Period 2
LS Mean Change at End of Period 2 From End of Period 1 in Patient Assessment of Arthritis Pain
Time frame: Day 43 of Period 2, Day 29 of Period 2
LS Mean Change at End of Period 1 From Baseline Health Assessment Questionnaire Disability Index (HAQ-DI) Score
Time frame: Day 1 of Period 1, Day 43 of Period 1
LS Mean Change at End of Period 2 From Baseline HAQ-DI Score
Time frame: Day 1 of Period 1, Day 29 of Period 2
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36931693Kristensen LE, Danese S, Yndestad A, Wang C, Nagy E, Modesto I, Rivas J, Benda B. Identification of two tofacitinib subpopulations with different relative risk versus TNF inhibitors: an analysis of the open label, randomised controlled study ORAL Surveillance. Ann Rheum Dis. 2023 Jul;82(7):901-910. doi: 10.1136/ard-2022-223715. Epub 2023 Mar 17.
- Derived from this study: PubMed 36601090Hansen KE, Mortezavi M, Nagy E, Wang C, Connell CA, Radi Z, Litman HJ, Adami G, Rossini M. Fracture in clinical studies of tofacitinib in rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2022 Dec 27;14:1759720X221142346. doi: 10.1177/1759720X221142346. eCollection 2022.
- Derived from this study: PubMed 36600185Curtis JR, Yamaoka K, Chen YH, Bhatt DL, Gunay LM, Sugiyama N, Connell CA, Wang C, Wu J, Menon S, Vranic I, Gomez-Reino JJ. Malignancy risk with tofacitinib versus TNF inhibitors in rheumatoid arthritis: results from the open-label, randomised controlled ORAL Surveillance trial. Ann Rheum Dis. 2023 Mar;82(3):331-343. doi: 10.1136/ard-2022-222543. Epub 2022 Dec 5.
- Derived from this study: PubMed 36526796Winthrop KL, Yndestad A, Henrohn D, Danese S, Marsal S, Galindo M, Woolcott JC, Jo H, Kwok K, Shapiro AB, Jones TV, Diehl A, Su C, Panes J, Cohen SB. Influenza Adverse Events in Patients with Rheumatoid Arthritis, Ulcerative Colitis, or Psoriatic Arthritis in the Tofacitinib Clinical Development Programs. Rheumatol Ther. 2023 Apr;10(2):357-373. doi: 10.1007/s40744-022-00507-z. Epub 2022 Dec 17.
- Derived from this study: PubMed 34870800Winthrop KL, Curtis JR, Yamaoka K, Lee EB, Hirose T, Rivas JL, Kwok K, Burmester GR. Clinical Management of Herpes Zoster in Patients With Rheumatoid Arthritis or Psoriatic Arthritis Receiving Tofacitinib Treatment. Rheumatol Ther. 2022 Feb;9(1):243-263. doi: 10.1007/s40744-021-00390-0. Epub 2021 Dec 6.
- Derived from this study: PubMed 33127856Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, Winthrop KL, Charles-Schoeman C, Wang L, Chen C, Kwok K, Biswas P, Shapiro A, Madsen A, Wollenhaupt J. Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme. RMD Open. 2020 Oct;6(3):e001395. doi: 10.1136/rmdopen-2020-001395.
- Derived from this study: PubMed 32816215Panaccione R, Isaacs JD, Chen LA, Wang W, Marren A, Kwok K, Wang L, Chan G, Su C. Characterization of Creatine Kinase Levels in Tofacitinib-Treated Patients with Ulcerative Colitis: Results from Clinical Trials. Dig Dis Sci. 2021 Aug;66(8):2732-2743. doi: 10.1007/s10620-020-06560-4. Epub 2020 Aug 20.
- Derived from this study: PubMed 28143815Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, Winthrop KL, Charles-Schoeman C, Thirunavukkarasu K, DeMasi R, Geier J, Kwok K, Wang L, Riese R, Wollenhaupt J. Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials. Ann Rheum Dis. 2017 Jul;76(7):1253-1262. doi: 10.1136/annrheumdis-2016-210457. Epub 2017 Jan 31.
- Derived from this study: PubMed 25889308Kremer JM, Kivitz AJ, Simon-Campos JA, Nasonov EL, Tony HP, Lee SK, Vlahos B, Hammond C, Bukowski J, Li H, Schulman SL, Raber S, Zuckerman A, Isaacs JD. Evaluation of the effect of tofacitinib on measured glomerular filtration rate in patients with active rheumatoid arthritis: results from a randomised controlled trial. Arthritis Res Ther. 2015 Apr 6;17(1):95. doi: 10.1186/s13075-015-0612-7.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
24 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study of Arthritis, Rheumatoid, run by Pfizer at 24 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States, Poland, Russia, Spain, Germany and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adjusted Geometric (Geo) Mean-Fold Change at End of Period 1 From Baseline in Measured Glomerular Filtration Rate (mGFR) (time frame: Day 1 of Period 1, Day 43 of Period 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01484561, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2014.