Rheumatoid Arthritis
Conditions
Keywords
Cholesterol metabolism, Cholesterol flux, Rheumatoid Arthritis, Tasocitinib, CP-690, 550
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).
Interventions
DRUGCP-690,550 (tasocitinib)
CP-690,550 (tasocitinib) dosed at 10 mg BID for 6 weeks in patients with active rheumatoid arthritis
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| High-density Lipoprotein Cholesterol (HDL-C) Concentration at Baseline | Baseline | Blood level of HDL-C was measured following a 12-hours fasting. |
| High-density Lipoprotein Cholesterol (HDL-C) Concentration at Week 6 | Week 6 | Blood level of HDL-C was measured following a 12-hours fasting. |
| Cholesterol Ester Production Rate at Baseline | 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 | Week 6 | Cholesterol ester production rate was calculated using a 3-pool model with a simulation, analysis and modeling (SAAM II) program. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| High-density Lipoprotein Associated With Apolipoprotein A1 (HDL-apoA1) Production Rate | Baseline, Week 6 | HDL-apoA1 production rate were calculated using a 3-pool model with a simulation, analysis and modeling (SAAM II) program. |
| Low-density Lipoprotein Cholesterol (LDL-C) and Total Cholesterol Concentration | Baseline, Week 6 | Blood level of LDL-C and total cholesterol (TC) was measured following a 12-hours fasting. |
| Cholesterol Efflux Rate | Baseline, Week 6 | 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. |
| High-density Lipoprotein Associated With Apolipoprotein A1 (HDL-apoA1) Fractional Catabolic Rate | Baseline, Week 6 | 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 Ester Fractional Catabolic Rate | Baseline, Week 6 | 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 | Baseline, Week 6 | 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 | Baseline, Week 6 | 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). |
Countries
Hungary, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rheumatoid Arthritis Cohort Active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days and then received CP-690,550 10 mg tablet orally twice daily for 6 weeks. | 36 |
| Healthy Volunteers Cohort Healthy volunteers with similar baseline demographic characteristics as the active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days. | 33 |
| Total | 69 |
Baseline characteristics
| Characteristic | Total | Healthy Volunteers Cohort | Rheumatoid Arthritis Cohort |
|---|---|---|---|
| Age, Customized 18 to 44 years | 16 participants | 7 participants | 9 participants |
| Age, Customized 45 to 64 years | 50 participants | 25 participants | 25 participants |
| Age, Customized Greater than or equal to (>=) 65 years | 3 participants | 1 participants | 2 participants |
| Sex: Female, Male Female | 58 Participants | 28 Participants | 30 Participants |
| Sex: Female, Male Male | 11 Participants | 5 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / 36 | 6 / 33 |
| serious Total, serious adverse events | 0 / 36 | 0 / 33 |
Outcome results
Primary
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.
Time frame: Baseline
Population: FAS included all enrolled participants who had any measurement of cholesterol ester production rate available. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rheumatoid Arthritis Cohort | Cholesterol Ester Production Rate at Baseline | 1.09 (mg per kilogram) per hour ([mg/kg]/hr) | Standard Deviation 0.24 |
| Healthy Volunteer Cohort | Cholesterol Ester Production Rate at Baseline | 1.11 (mg per kilogram) per hour ([mg/kg]/hr) | Standard Deviation 0.26 |
Primary
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.
Time frame: Week 6
Population: FAS included all enrolled participants who had any measurement of cholesterol ester production rate available. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rheumatoid Arthritis Cohort | Cholesterol Ester Production Rate at Week 6 | 1.12 (mg/kg)/hr | Standard Deviation 0.24 |
Primary
High-density Lipoprotein Cholesterol (HDL-C) Concentration at Baseline
Blood level of HDL-C was measured following a 12-hours fasting.
Time frame: Baseline
Population: Full analysis set (FAS) included all enrolled participants who had any measurement of cholesterol ester production rate available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rheumatoid Arthritis Cohort | High-density Lipoprotein Cholesterol (HDL-C) Concentration at Baseline | 54.30 milligram per deciliter (mg/dL) | Standard Deviation 12.52 |
| Healthy Volunteer Cohort | High-density Lipoprotein Cholesterol (HDL-C) Concentration at Baseline | 63.43 milligram per deciliter (mg/dL) | Standard Deviation 16.89 |
Primary
High-density Lipoprotein Cholesterol (HDL-C) Concentration at Week 6
Blood level of HDL-C was measured following a 12-hours fasting.
Time frame: Week 6
Population: FAS included all enrolled participants who had any measurement of cholesterol ester production rate available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rheumatoid Arthritis Cohort | High-density Lipoprotein Cholesterol (HDL-C) Concentration at Week 6 | 62.34 mg/dL | Standard Deviation 15.24 |
Secondary
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.
Time frame: Baseline, Week 6
Population: FAS included all enrolled participants who had any measurement of cholesterol ester production rate available. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rheumatoid Arthritis Cohort | Cholesterol Efflux Rate | Baseline | 4.02 (mg/kg)/hr | Standard Deviation 0.96 |
| Rheumatoid Arthritis Cohort | Cholesterol Efflux Rate | Week 6 | 4.04 (mg/kg)/hr | Standard Deviation 1.08 |
| Healthy Volunteer Cohort | Cholesterol Efflux Rate | Baseline | 4.35 (mg/kg)/hr | Standard Deviation 1.53 |
| Healthy Volunteer Cohort | Cholesterol Efflux Rate | Week 6 | NA (mg/kg)/hr | — |
Secondary
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.
Time frame: Baseline, Week 6
Population: FAS included all enrolled participants who had any measurement of cholesterol ester production rate available. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rheumatoid Arthritis Cohort | Cholesterol Ester Fractional Catabolic Rate | Week 6 | 2.23 percentage ester per hour (%/hr) | Standard Deviation 0.31 |
| Rheumatoid Arthritis Cohort | Cholesterol Ester Fractional Catabolic Rate | Baseline | 2.43 percentage ester per hour (%/hr) | Standard Deviation 0.39 |
| Healthy Volunteer Cohort | Cholesterol Ester Fractional Catabolic Rate | Baseline | 2.17 percentage ester per hour (%/hr) | Standard Deviation 0.36 |
| Healthy Volunteer Cohort | Cholesterol Ester Fractional Catabolic Rate | Week 6 | NA percentage ester per hour (%/hr) | — |
Secondary
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.
Time frame: Baseline, Week 6
Population: FAS included all enrolled participants who had any measurement of cholesterol ester production rate available. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rheumatoid Arthritis Cohort | High-density Lipoprotein Associated With Apolipoprotein A1 (HDL-apoA1) Fractional Catabolic Rate | Baseline | 1.08 %/hr | Standard Deviation 0.22 |
| Rheumatoid Arthritis Cohort | High-density Lipoprotein Associated With Apolipoprotein A1 (HDL-apoA1) Fractional Catabolic Rate | Week 6 | 1.11 %/hr | Standard Deviation 0.28 |
| Healthy Volunteer Cohort | High-density Lipoprotein Associated With Apolipoprotein A1 (HDL-apoA1) Fractional Catabolic Rate | Baseline | 1.02 %/hr | Standard Deviation 0.22 |
| Healthy Volunteer Cohort | High-density Lipoprotein Associated With Apolipoprotein A1 (HDL-apoA1) Fractional Catabolic Rate | Week 6 | NA %/hr | — |
Secondary
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.
Time frame: Baseline, Week 6
Population: FAS included all enrolled participants who had any measurement of cholesterol ester production rate available. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rheumatoid Arthritis Cohort | High-density Lipoprotein Associated With Apolipoprotein A1 (HDL-apoA1) Production Rate | Week 6 | 0.65 mg/kg/hr | Standard Deviation 0.15 |
| Rheumatoid Arthritis Cohort | High-density Lipoprotein Associated With Apolipoprotein A1 (HDL-apoA1) Production Rate | Baseline | 0.57 mg/kg/hr | Standard Deviation 0.11 |
| Healthy Volunteer Cohort | High-density Lipoprotein Associated With Apolipoprotein A1 (HDL-apoA1) Production Rate | Baseline | 0.59 mg/kg/hr | Standard Deviation 0.16 |
| Healthy Volunteer Cohort | High-density Lipoprotein Associated With Apolipoprotein A1 (HDL-apoA1) Production Rate | Week 6 | NA mg/kg/hr | — |
Secondary
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).
Time frame: Baseline, Week 6
Population: FAS included all enrolled participants who had any measurement of cholesterol ester production rate available. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rheumatoid Arthritis Cohort | Low-density Lipoprotein Associated With Apolipoprotein B (LDL-apoB) Fractional Catabolic Rate | Baseline | 1.61 %/hr | Standard Deviation 0.37 |
| Rheumatoid Arthritis Cohort | Low-density Lipoprotein Associated With Apolipoprotein B (LDL-apoB) Fractional Catabolic Rate | Week 6 | 1.57 %/hr | Standard Deviation 0.41 |
| Healthy Volunteer Cohort | Low-density Lipoprotein Associated With Apolipoprotein B (LDL-apoB) Fractional Catabolic Rate | Baseline | 1.50 %/hr | Standard Deviation 0.35 |
| Healthy Volunteer Cohort | Low-density Lipoprotein Associated With Apolipoprotein B (LDL-apoB) Fractional Catabolic Rate | Week 6 | NA %/hr | — |
Secondary
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.
Time frame: Baseline, Week 6
Population: FAS included all enrolled participants who had any measurement of cholesterol ester production rate available. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rheumatoid Arthritis Cohort | Low-density Lipoprotein Associated With Apolipoprotein B (LDL-apoB) Production Rate | Baseline | 0.49 (mg/kg)/hr | Standard Deviation 0.12 |
| Rheumatoid Arthritis Cohort | Low-density Lipoprotein Associated With Apolipoprotein B (LDL-apoB) Production Rate | Week 6 | 0.52 (mg/kg)/hr | Standard Deviation 0.12 |
| Healthy Volunteer Cohort | Low-density Lipoprotein Associated With Apolipoprotein B (LDL-apoB) Production Rate | Baseline | 0.50 (mg/kg)/hr | Standard Deviation 0.13 |
| Healthy Volunteer Cohort | Low-density Lipoprotein Associated With Apolipoprotein B (LDL-apoB) Production Rate | Week 6 | NA (mg/kg)/hr | — |
Secondary
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.
Time frame: Baseline, Week 6
Population: FAS included all enrolled participants who had any measurement of cholesterol ester production rate available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rheumatoid Arthritis Cohort | Low-density Lipoprotein Cholesterol (LDL-C) and Total Cholesterol Concentration | Baseline: LDL-C | 124.61 mg/dL | Standard Deviation 28.55 |
| Rheumatoid Arthritis Cohort | Low-density Lipoprotein Cholesterol (LDL-C) and Total Cholesterol Concentration | Baseline: TC | 193.79 mg/dL | Standard Deviation 32.56 |
| Rheumatoid Arthritis Cohort | Low-density Lipoprotein Cholesterol (LDL-C) and Total Cholesterol Concentration | Week 6: LDL-C | 142.68 mg/dL | Standard Deviation 39.02 |
| Rheumatoid Arthritis Cohort | Low-density Lipoprotein Cholesterol (LDL-C) and Total Cholesterol Concentration | Week 6: TC | 219.83 mg/dL | Standard Deviation 41.33 |
| Healthy Volunteer Cohort | Low-density Lipoprotein Cholesterol (LDL-C) and Total Cholesterol Concentration | Week 6: TC | NA mg/dL | — |
| Healthy Volunteer Cohort | Low-density Lipoprotein Cholesterol (LDL-C) and Total Cholesterol Concentration | Baseline: LDL-C | 144.88 mg/dL | Standard Deviation 36.36 |
| Healthy Volunteer Cohort | Low-density Lipoprotein Cholesterol (LDL-C) and Total Cholesterol Concentration | Week 6: LDL-C | NA mg/dL | — |
| Healthy Volunteer Cohort | Low-density Lipoprotein Cholesterol (LDL-C) and Total Cholesterol Concentration | Baseline: TC | 221.57 mg/dL | Standard Deviation 42.12 |