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

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

Official Title
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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

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: CP-690,550 (tasocitinib)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CP-690,550 (tasocitinib) 10 mg twice daily (BID)<br> | Drug: CP-690,550 (tasocitinib)<br>* CP-690,550 (tasocitinib) dosed at 10 mg BID for 6 weeks in patients with active rheumatoid arthritis<br>|
| No Intervention: Healthy Volunteers<br>No intervention | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| High-density Lipoprotein Cholesterol (HDL-C) Concentration at Baseline | Blood level of HDL-C was measured following a 12-hours fasting. | Baseline | 
| High-density Lipoprotein Cholesterol (HDL-C) Concentration at Week 6 | Blood level of HDL-C was measured following a 12-hours fasting. | Week 6 | 
| 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. | Baseline | 
| 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. | Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, Week 6 | 
| 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. | Baseline, Week 6 | 
| 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. | Baseline, Week 6 | 
| 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). | Baseline, Week 6 | 
| 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. | Baseline, Week 6 | 
| 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. | Baseline, Week 6 | 
| 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. | Baseline, Week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cholesterol metabolism, Cholesterol flux, Rheumatoid Arthritis, Tasocitinib, CP-690, 550