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Effects Of CP-690,550 (Tasocitinib) On Cholesterol Metabolism In Patients With Active Rheumatoid Arthritis

Primary Purpose

Rheumatoid Arthritis

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
CP-690,550 (tasocitinib)
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Rheumatoid Arthritis focused on measuring Cholesterol metabolism, Cholesterol flux, Rheumatoid Arthritis, Tasocitinib, CP-690, 550

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Males or females, 18 years of age or older with active rheumatoid arthritis; Or male and female healthy volunteers 18 years of age and older

Exclusion Criteria:

  • Pregnant or lactating women
  • Clinically significant systemic disease (other than RA for RA arm)
  • Use of lipid-regulating agents

Sites / Locations

  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

CP-690,550 (tasocitinib) 10 mg twice daily (BID)

Healthy Volunteers

Arm Description

No intervention

Outcomes

Primary Outcome Measures

High-density Lipoprotein Cholesterol (HDL-C) Concentration at Baseline
Blood level of HDL-C was measured following a 12-hours fasting.
High-density Lipoprotein Cholesterol (HDL-C) Concentration at Week 6
Blood level of HDL-C was measured following a 12-hours fasting.
Cholesterol Ester Production Rate at Baseline
Cholesterol ester production rate was calculated using a 3-pool model with a simulation, analysis and modeling (SAAM II) program.
Cholesterol Ester Production Rate at Week 6
Cholesterol ester production rate was calculated using a 3-pool model with a simulation, analysis and modeling (SAAM II) program.

Secondary Outcome Measures

Low-density Lipoprotein Cholesterol (LDL-C) and Total Cholesterol Concentration
Blood level of LDL-C and total cholesterol (TC) was measured following a 12-hours fasting.
Cholesterol Ester Fractional Catabolic Rate
Cholesterol ester fractional catabolic rate were calculated using a 3-pool model with a simulation, analysis and modeling (SAAM II) program. Fractional catabolic rate was the percentage of cholesterol ester which was replaced, transferred or lost per unit of time.
Low-density Lipoprotein Associated With Apolipoprotein B (LDL-apoB) Production Rate
LDL-apoB production rate were calculated using a 3-pool model with a simulation, analysis and modeling (SAAM II) program.
Low-density Lipoprotein Associated With Apolipoprotein B (LDL-apoB) Fractional Catabolic Rate
Fractional catabolic rate for LDL ApoB were calculated using the 13 carbon (13C) isotopic enrichment of very low density lipoprotein (VLDL) as the limiting value. Isotope 13C in plasma was measured using Gas Chromatography-Combustion-Isotope Ratio Mass Spectrometry (GC-C-IRMS).
High-density Lipoprotein Associated With Apolipoprotein A1 (HDL-apoA1) Production Rate
HDL-apoA1 production rate were calculated using a 3-pool model with a simulation, analysis and modeling (SAAM II) program.
High-density Lipoprotein Associated With Apolipoprotein A1 (HDL-apoA1) Fractional Catabolic Rate
Fractional catabolic rate for HDL-apoA1 were calculated using the 13C isotopic enrichment of VLDL as the limiting value. Isotope 13C in plasma was measured using GC-C-IRMS.
Cholesterol Efflux Rate
Cholesterol efflux rate was measured using isotope dilution method in which rate of appearance of isotope 13C-free cholesterol in plasma representing whole body efflux from tissues was assessed. Isotope 13C in plasma was measured using GC-C-IRMS.

Full Information

First Posted
November 15, 2010
Last Updated
December 17, 2012
Sponsor
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT01262118
Brief Title
Effects Of CP-690,550 (Tasocitinib) On Cholesterol Metabolism In Patients With Active Rheumatoid Arthritis
Official Title
An Exploratory Phase 1, Fixed Sequence, Open-Label Study To Assess The Effects Of CP-690,550 On The Kinetics Of Cholesterol Flux Through The High Density Lipoprotein/Reverse Cholesterol Transport Pathway In Patients With Active Rheumatoid Arthritis
Study Type
Interventional

2. Study Status

Record Verification Date
December 2012
Overall Recruitment Status
Completed
Study Start Date
May 2011 (undefined)
Primary Completion Date
January 2012 (Actual)
Study Completion Date
February 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of study is to explore the effect of CP-690,550 (tasocitinib) on cholesterol metabolism in patients with active rheumatoid arthritis (RA).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Cholesterol metabolism, Cholesterol flux, Rheumatoid Arthritis, Tasocitinib, CP-690, 550

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
69 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CP-690,550 (tasocitinib) 10 mg twice daily (BID)
Arm Type
Experimental
Arm Title
Healthy Volunteers
Arm Type
No Intervention
Arm Description
No intervention
Intervention Type
Drug
Intervention Name(s)
CP-690,550 (tasocitinib)
Intervention Description
CP-690,550 (tasocitinib) dosed at 10 mg BID for 6 weeks in patients with active rheumatoid arthritis
Primary Outcome Measure Information:
Title
High-density Lipoprotein Cholesterol (HDL-C) Concentration at Baseline
Description
Blood level of HDL-C was measured following a 12-hours fasting.
Time Frame
Baseline
Title
High-density Lipoprotein Cholesterol (HDL-C) Concentration at Week 6
Description
Blood level of HDL-C was measured following a 12-hours fasting.
Time Frame
Week 6
Title
Cholesterol Ester Production Rate at Baseline
Description
Cholesterol ester production rate was calculated using a 3-pool model with a simulation, analysis and modeling (SAAM II) program.
Time Frame
Baseline
Title
Cholesterol Ester Production Rate at Week 6
Description
Cholesterol ester production rate was calculated using a 3-pool model with a simulation, analysis and modeling (SAAM II) program.
Time Frame
Week 6
Secondary Outcome Measure Information:
Title
Low-density Lipoprotein Cholesterol (LDL-C) and Total Cholesterol Concentration
Description
Blood level of LDL-C and total cholesterol (TC) was measured following a 12-hours fasting.
Time Frame
Baseline, Week 6
Title
Cholesterol Ester Fractional Catabolic Rate
Description
Cholesterol ester fractional catabolic rate were calculated using a 3-pool model with a simulation, analysis and modeling (SAAM II) program. Fractional catabolic rate was the percentage of cholesterol ester which was replaced, transferred or lost per unit of time.
Time Frame
Baseline, Week 6
Title
Low-density Lipoprotein Associated With Apolipoprotein B (LDL-apoB) Production Rate
Description
LDL-apoB production rate were calculated using a 3-pool model with a simulation, analysis and modeling (SAAM II) program.
Time Frame
Baseline, Week 6
Title
Low-density Lipoprotein Associated With Apolipoprotein B (LDL-apoB) Fractional Catabolic Rate
Description
Fractional catabolic rate for LDL ApoB were calculated using the 13 carbon (13C) isotopic enrichment of very low density lipoprotein (VLDL) as the limiting value. Isotope 13C in plasma was measured using Gas Chromatography-Combustion-Isotope Ratio Mass Spectrometry (GC-C-IRMS).
Time Frame
Baseline, Week 6
Title
High-density Lipoprotein Associated With Apolipoprotein A1 (HDL-apoA1) Production Rate
Description
HDL-apoA1 production rate were calculated using a 3-pool model with a simulation, analysis and modeling (SAAM II) program.
Time Frame
Baseline, Week 6
Title
High-density Lipoprotein Associated With Apolipoprotein A1 (HDL-apoA1) Fractional Catabolic Rate
Description
Fractional catabolic rate for HDL-apoA1 were calculated using the 13C isotopic enrichment of VLDL as the limiting value. Isotope 13C in plasma was measured using GC-C-IRMS.
Time Frame
Baseline, Week 6
Title
Cholesterol Efflux Rate
Description
Cholesterol efflux rate was measured using isotope dilution method in which rate of appearance of isotope 13C-free cholesterol in plasma representing whole body efflux from tissues was assessed. Isotope 13C in plasma was measured using GC-C-IRMS.
Time Frame
Baseline, Week 6

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Males or females, 18 years of age or older with active rheumatoid arthritis; Or male and female healthy volunteers 18 years of age and older Exclusion Criteria: Pregnant or lactating women Clinically significant systemic disease (other than RA for RA arm) Use of lipid-regulating agents
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Pfizer Investigational Site
City
Anniston
State/Province
Alabama
ZIP/Postal Code
36201
Country
United States
Facility Name
Pfizer Investigational Site
City
Anniston
State/Province
Alabama
ZIP/Postal Code
36207
Country
United States
Facility Name
Pfizer Investigational Site
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72201
Country
United States
Facility Name
Pfizer Investigational Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Pfizer Investigational Site
City
Daytona Beach
State/Province
Florida
ZIP/Postal Code
32114
Country
United States
Facility Name
Pfizer Investigational Site
City
Ormond Beach
State/Province
Florida
ZIP/Postal Code
32174
Country
United States
Facility Name
Pfizer Investigational Site
City
South Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
Pfizer Investigational Site
City
Bingham Farms
State/Province
Michigan
ZIP/Postal Code
48025
Country
United States
Facility Name
Pfizer Investigational Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Pfizer Investigational Site
City
Balatonfured
ZIP/Postal Code
8230
Country
Hungary
Facility Name
Pfizer Investigational Site
City
Budapest
ZIP/Postal Code
1032
Country
Hungary

12. IPD Sharing Statement

Citations:
PubMed Identifier
34870800
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.
Results Reference
derived
PubMed Identifier
33127856
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.
Results Reference
derived
PubMed Identifier
32816215
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. Erratum In: Dig Dis Sci. 2020 Oct 10;:
Results Reference
derived
PubMed Identifier
28143815
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.
Results Reference
derived
PubMed Identifier
25470338
Citation
Charles-Schoeman C, Fleischmann R, Davignon J, Schwartz H, Turner SM, Beysen C, Milad M, Hellerstein MK, Luo Z, Kaplan IV, Riese R, Zuckerman A, McInnes IB. Potential mechanisms leading to the abnormal lipid profile in patients with rheumatoid arthritis versus healthy volunteers and reversal by tofacitinib. Arthritis Rheumatol. 2015 Mar;67(3):616-25. doi: 10.1002/art.38974.
Results Reference
derived
PubMed Identifier
25047021
Citation
Cohen S, Radominski SC, Gomez-Reino JJ, Wang L, Krishnaswami S, Wood SP, Soma K, Nduaka CI, Kwok K, Valdez H, Benda B, Riese R. Analysis of infections and all-cause mortality in phase II, phase III, and long-term extension studies of tofacitinib in patients with rheumatoid arthritis. Arthritis Rheumatol. 2014 Nov;66(11):2924-37. doi: 10.1002/art.38779.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A3921130&StudyName=Effects%20Of%20CP-690%2C550%20%28Tasocitinib%29%20On%20Cholesterol%20Metabolism%20In%20Patients%20With%20Active%20Rheumatoid%20Arthritis%20
Description
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Effects Of CP-690,550 (Tasocitinib) On Cholesterol Metabolism In Patients With Active Rheumatoid Arthritis

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