Clinical trial NCT01484561: A Study To Evaluate The Effect Of CP-690,550 On Measures Of Kidney Function In Patients With Active Rheumatoid Arthritis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Arthritis, Rheumatoid
Keywords: Phase 1
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2011-12-02
Enrollment: 148
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Adjusted Geometric (Geo) Mean-Fold Change at End of Period 1 From Baseline in Measured Glomerular Filtration Rate (mGFR)
timeFrame: Day 1 of Period 1, Day 43 of Period 1
Secondary outcomes:
measure: Adjusted Geometric Mean-Fold Change at the End of Period 2 From Baseline in mGFR
timeFrame: Day 1 of Period 1, Day 29 of Period 2
measure: Adjusted Geometric Mean-Fold Change at End of Period 2 From End of Period 1 in mGFR
timeFrame: Day 43 of Period 1, Day 29 of Period 2
measure: 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)
timeFrame: Day 1 of Period 1, Day 43 of Period 1
measure: Adjusted Geometric Mean-Fold Change at End of Period 2 From Baseline in eGFR Using MDRD
timeFrame: Day 1 of Period 1, Day 29 of Period 2
measure: Adjusted Geometric Mean-Fold Change at End of Period 2 From End of Period 1 in eGFR Using MDRD
timeFrame: Day 43 of Period 1, Day 29 of Period 2
measure: Adjusted Geometric Mean-Fold Change at End of Period 1 From Baseline in eGFR Using the Cockcroft-Gault Equation
timeFrame: Day 1 of Period 1, Day 43 of Period 1
measure: Adjusted Geometric Mean-Fold Change at End of Period 2 From Baseline in eGFR Using the Cockcroft-Gault Equation
timeFrame: Day 1 of Period 1, Day 29 of Period 2
measure: Adjusted Geometric Mean-Fold Change at End of Period 2 From End of Period 1 in eGFR Using the Cockcroft-Gault Equation
timeFrame: Day 43 of Period 1, Day 29 of Period 2
measure: Adjusted Geometric Mean-Fold Change at End of Period 1 From Baseline in Serum Creatinine
timeFrame: Day 1 of Period 1, Day 43 of Period 1
measure: Adjusted Geometric Mean-Fold Change From End of Period 2 From Baseline in Serum Creatinine
timeFrame: Day 1 of Period 1, Day 29 of Period 2
measure: Adjusted Geometric Mean-Fold Change at End of Period 2 From End of Period 1 in Serum Creatinine
timeFrame: Day 43 of Period 1, Day 29 of Period 2
measure: Percentage of Participants Achieving an American College of Rheumatology 20% (ACR20) Response
timeFrame: Day 1 of Period 1 to Day 43 of Period 1, Day 1 of Period 1 to Day 29 of Period 2
measure: Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response
timeFrame: Day 1 of Period 1 to Day 43 of Period 1, Day 1 of Period 1 to Day 29 of Period 2
measure: Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
timeFrame: Day 1 of Period 1 to Day 43 of Period 1, Day 1 of Period 1 to Day 29 of Period 2
measure: 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])
timeFrame: Day 1 of Period 1, Day 43 of Period 1
measure: LS Mean Change at End of Period 2 From Baseline in DAS28-3 (CRP)
timeFrame: Day 1 of Period 1, Day 29 of Period 2
measure: LS Mean Change at End of Period 2 From End of Period 1 in DAS28-3 (CRP)
timeFrame: Day 43 of Period 1, Day 29 of Period 2
measure: LS Mean Change at End of Period 1 From Baseline DAS28-4 (CRP)
timeFrame: Day 1 of Period 1, Day 43 of Period 1
measure: LS Mean Change at End of Period 2 From Baseline DAS28-4 (CRP)
timeFrame: Day 1 of Period 1, Day 29 of Period 2
measure: LS Mean Change at End of Period 2 From End of Period 1 DAS28-4 (CRP)
timeFrame: Day 43 of Period 1, Day 29 of Period 2
measure: LS Mean Change at End of Period 1 From Baseline in Tender/Painful Joint Count
timeFrame: Day 1 of Period 1, Day 43 of Period 1
measure: LS Mean Change at End of Period 2 From Baseline in Tender/Painful Joint Count
timeFrame: Day 1 of Period 1, Day 29 of Period 2
measure: LS Mean Change at End of Period 2 From End of Period 1 in Tender/Painful Joint Count
timeFrame: Day 43 of Period 1, Day 29 of Period 2
measure: LS Mean Change at End of Period 1 From Baseline in Swollen Joint Count
timeFrame: Day 1 of Period 1, Day 43 of Period 1
measure: LS Mean Change at End of Period 2 From Baseline in Swollen Joint Count
timeFrame: Day 1 of Period 1, Day 29 of Period 2
measure: LS Mean Change at End of Period 2 From End of Period 1 in Swollen Joint Count
timeFrame: Day 43 of Period 1, Day 29 of Period 2
measure: LS Mean Change at End of Period 1 From Baseline in CRP
timeFrame: Day 1 of Period 1, Day 43 of Period 1
measure: LS Mean Change at End of Period 2 From Baseline in CRP
timeFrame: Day 1 of Period 1, Day 29 of Period 2
measure: LS Mean Change at End of Period 2 From End of Period 1 in CRP
timeFrame: Day 43 of Period 1, Day 29 of Period 2
measure: LS Mean Change at End of Period 1 From Baseline in Patient Global Assessment of Arthritis (PGAA)
timeFrame: Day 1 of Period 1, Day 43 of Period 1
measure: LS Mean Change at End of Period 2 From Baseline in PGAA
timeFrame: Day 1 of Period 1, Day 29 of Period 2
measure: LS Mean Change at End of Period 2 From End of Period 1 in PGAA
timeFrame: Day 43 of Period 1, Day 29 of Period 2
measure: LS Mean Change at End of Period 1 From Baseline in Physician Global Assessment of Arthritis
timeFrame: Day 1 of Period 1, Day 43 of Period 1
measure: LS Mean Change at End of Period 2 From Baseline in Physician Global Assessment of Arthritis
timeFrame: Day 1 of Period 1, Day 29 of Period 2
measure: LS Mean Change at End of Period 2 From End of Period 1 in Physician Global Assessment of Arthritis
timeFrame: Day 43 of Period 1, Day 29 of Period 1
measure: LS Mean Change at End of Period 1 From Baseline in Patient Assessment of Arthritis Pain
timeFrame: Day 1 of Period 1, Day 43 of Period 1
measure: LS Mean Change at End of Period 2 From Baseline in Patient Assessment of Arthritis Pain
timeFrame: Day 1 of Period 1, Day 29 of Period 2
measure: LS Mean Change at End of Period 2 From End of Period 1 in Patient Assessment of Arthritis Pain
timeFrame: Day 43 of Period 2, Day 29 of Period 2
measure: LS Mean Change at End of Period 1 From Baseline Health Assessment Questionnaire Disability Index (HAQ-DI) Score
timeFrame: Day 1 of Period 1, Day 43 of Period 1
measure: LS Mean Change at End of Period 2 From Baseline HAQ-DI Score
timeFrame: Day 1 of Period 1, Day 29 of Period 2
measure: LS Mean Change at End of Period 2 From End of Period 1 HAQ-DI Score
timeFrame: Day 43 of Period 1, Day 29 of Period 2
Other outcomes:
Locations:
city: South Miami
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Albany
country: United States
facility: Pfizer Investigational Site
state: New York
city: Duncansville
country: United States
facility: Pfizer Investigational Site
state: Pennsylvania
city: Dallas
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Tacoma
country: United States
facility: Pfizer Investigational Site
state: Washington
city: Praha 4
country: Czech Republic
facility: Pfizer Investigational Site
city: Berlin
country: Germany
facility: Pfizer Investigational Site
city: Erlangen
country: Germany
facility: Pfizer Investigational Site
city: Wuerzburg
country: Germany
facility: Pfizer Investigational Site
city: Seoul
country: Korea, Republic of
facility: Pfizer Investigational Site
city: Merida
country: Mexico
facility: Pfizer Investigational Site
state: Yucatan
city: Bialystok
country: Poland
facility: Pfizer Investigational Site
city: Bydgoszcz
country: Poland
facility: Pfizer Investigational Site
city: Warszawa
country: Poland
facility: Pfizer Investigational Site
city: Warszawa
country: Poland
facility: Pfizer Investigational Site
city: Wroclaw
country: Poland
facility: Pfizer Investigational Site
city: Moscow
country: Russian Federation
facility: Pfizer Investigational Site
city: Petrozavodsk
country: Russian Federation
facility: Pfizer Investigational Site
city: Saint Petersburg
country: Russian Federation
facility: Pfizer Investigational Site
city: St. Petersburg
country: Russian Federation
facility: Pfizer Investigational Site
city: Barakaldo
country: Spain
facility: Pfizer Investigational Site
state: Vizcaya
city: Bilbao
country: Spain
facility: Pfizer Investigational Site
state: Vizcaya
city: La Coruna
country: Spain
facility: Pfizer Investigational Site
city: Sevilla
country: Spain
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Winthrop 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.
citation: Cohen 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.
citation: Panaccione 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.
citation: Cohen 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.
citation: Kremer 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.