Renal Impairment
Conditions
Keywords
CP-690, 550, pharmacokinetics, renal impairment
Brief summary
A study to evaluate the pharmacokinetics of CP-690,550 in subjects with mild, moderate or severe renal impairment, who do not require hemodialysis, compared to healthy controls.
Interventions
DRUGCP-690,550
10 mg (2 x 5 mg tablets), single dose
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects with normal renal function: Subjects must be healthy with estimated creatinine clearance \>80 mL/min * Subjects with renal impairment: Subjects should be in good general health commensurate with the population with chronic kidney disease
Exclusion criteria
* Kidney transplant patients * Subjects with any condition possibly affecting drug absorption * Subjects with malignancies with the exception of adequately treated basal cell carcinoma of the skin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | 0 (Pre-dose), 0.5, 1, 1.5, 2, 4, 8, 10, 12, 16, 24, 48 hours post-dose | AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). |
| Maximum Observed Plasma Concentration (Cmax) | 0 (Pre-dose), 0.5, 1, 1.5, 2, 4, 8, 10, 12, 16, 24, 48 hours post-dose | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0 (Pre-dose), 0.5, 1, 1.5, 2, 4, 8, 10, 12, 16, 24, 48 hours post-dose | — |
| Plasma Decay Half-Life (t1/2) | 0 (Pre-dose), 0.5, 1, 1.5, 2, 4, 8, 10, 12, 16, 24, 48 hours post-dose | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Renal Clearance (CL R) | 0 (Pre-dose) to 12 hours post-dose, 12 to 24 hours post-dose | Renal clearance is the volume of plasma from which the drug is completely removed by the kidney in a given amount of time. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CP-690,550 (Normal Renal Function) Participants with normal renal function who had creatinine clearance greater than (\>) 80 milliliter/minute (mL/min), received single oral dose of CP-690,550 tablet 10 milligram (mg) orally. | 6 |
| CP-690,550 (Mild Renal Insufficiency) Participants with mild renal insufficiency who had creatinine clearance \>50 mL/min but less than or equal to (=\<) 80 mL/min, received single oral dose of CP-690,550 tablet 10 mg orally. | 6 |
| CP-690,550 (Moderate Renal Insufficiency) Participants with moderate renal insufficiency who had creatinine clearance \>=30 mL/min but =\<50 mL/min, received single oral dose of CP-690,550 tablet 10 mg orally. | 6 |
| CP-690,550 (Severe Renal Insufficiency) Participants with severe renal insufficiency who had creatinine clearance \<30 mL/min, received single oral dose of CP-690,550 tablet 10 mg orally. | 6 |
| Total | 24 |
Baseline characteristics
| Characteristic | CP-690,550 (Normal Renal Function) | CP-690,550 (Mild Renal Insufficiency) | CP-690,550 (Moderate Renal Insufficiency) | CP-690,550 (Severe Renal Insufficiency) | Total |
|---|---|---|---|---|---|
| Age Continuous | 50.8 years STANDARD_DEVIATION 9.7 | 61.2 years STANDARD_DEVIATION 2.8 | 53.5 years STANDARD_DEVIATION 11.1 | 59.0 years STANDARD_DEVIATION 14.6 | 56.1 years STANDARD_DEVIATION 10.7 |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants | 3 Participants | 11 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 2 Participants | 3 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 6 | 0 / 6 | 3 / 6 | 1 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]
AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Time frame: 0 (Pre-dose), 0.5, 1, 1.5, 2, 4, 8, 10, 12, 16, 24, 48 hours post-dose
Population: Analysis set included all participants who received study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 (Normal Renal Function) | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | 268 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 71.5 |
| CP-690,550 (Mild Renal Insufficiency) | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | 370 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 109 |
| CP-690,550 (Moderate Renal Insufficiency) | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | 396 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 154 |
| CP-690,550 (Severe Renal Insufficiency) | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | 615 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 214 |
Comparison: 1 way Analysis of Variance (ANOVA) on natural log-transformed AUC(0-∞) analyzed using linear model with degrees of renal impairment(creatinine clearance\[CLcr, discrete\]) evaluated using blood samples collected at screening as fixed effect. Statistical Analysis System (SAS) mixed procedure (PROC MIXED) was used. Anti-log of adjusted mean difference (CP-690,550\[mild renal insufficiency\] - CP-690,550\[normal renal function\]), 90% confidence interval (CI) were taken to estimate mean ratio and 90% CI.90% CI: [96.77, 194.69]
Comparison: One way ANOVA on natural log-transformed AUC (0 - ∞) were analyzed using linear model containing degrees of renal impairment (CLcr, discrete) calculated using blood samples collected at screening as fixed effects. SAS procedure PROC MIXED was used for analysis. Anti-log of the adjusted mean difference (CP-690,550 \[moderate renal insufficiency\] - CP-690,550 \[normal renal function\]) and its corresponding 90% CI were taken to estimate the mean ratio and corresponding 90% CI.90% CI: [100.53, 202.24]
Comparison: One way ANOVA on natural log-transformed AUC (0 - ∞) were analyzed using linear model containing degrees of renal impairment (CLcr, discrete) calculated using blood samples collected at screening as fixed effects. SAS procedure PROC MIXED was used for analysis. Anti-log of the adjusted mean difference (CP-690,550 \[severe renal insufficiency\] - CP-690,550 \[normal renal function\]) and its corresponding 90% CI were taken to estimate the mean ratio and corresponding 90% CI.90% CI: [157.02, 315.89]
Primary
Maximum Observed Plasma Concentration (Cmax)
Time frame: 0 (Pre-dose), 0.5, 1, 1.5, 2, 4, 8, 10, 12, 16, 24, 48 hours post-dose
Population: Analysis set included all participants who received study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 (Normal Renal Function) | Maximum Observed Plasma Concentration (Cmax) | 94.2 ng/mL | Standard Deviation 25.3 |
| CP-690,550 (Mild Renal Insufficiency) | Maximum Observed Plasma Concentration (Cmax) | 87.3 ng/mL | Standard Deviation 23.2 |
| CP-690,550 (Moderate Renal Insufficiency) | Maximum Observed Plasma Concentration (Cmax) | 104 ng/mL | Standard Deviation 47.5 |
| CP-690,550 (Severe Renal Insufficiency) | Maximum Observed Plasma Concentration (Cmax) | 111 ng/mL | Standard Deviation 28.6 |
Comparison: One way ANOVA on natural log-transformed Cmax were analyzed using linear model containing degrees of renal impairment (CLcr, discrete) calculated using blood samples collected at screening as fixed effects. SAS procedure PROC MIXED was used for analysis. Anti-log of the adjusted mean difference (CP-690,550 \[mild renal insufficiency\] - CP-690,550 \[normal renal function\]) and its corresponding 90% CI were taken to estimate the mean ratio and corresponding 90% CI.90% CI: [67.22, 129.06]
Comparison: One way ANOVA on natural log-transformed Cmax were analyzed using linear model containing degrees of renal impairment (CLcr, discrete) calculated using blood samples collected at screening as fixed effects. SAS procedure PROC MIXED was used for analysis. Anti-log of the adjusted mean difference (CP-690,550 \[moderate renal insufficiency\] - CP-690,550 \[normal renal function\]) and its corresponding 90% CI were taken to estimate the mean ratio and corresponding 90% CI.90% CI: [75.18, 144.34]
Comparison: One way ANOVA on natural log-transformed Cmax were analyzed using linear model containing degrees of renal impairment (CLcr, discrete) calculated using blood samples collected at screening as fixed effects. SAS procedure PROC MIXED was used for analysis. Anti-log of the adjusted mean difference (CP-690,550 \[severe renal insufficiency\] - CP-690,550 \[normal renal function\]) and its corresponding 90% CI were taken to estimate the mean ratio and corresponding 90% CI.95% CI: [84.91, 163.02]
Primary
Plasma Decay Half-Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: 0 (Pre-dose), 0.5, 1, 1.5, 2, 4, 8, 10, 12, 16, 24, 48 hours post-dose
Population: Analysis set included all participants who received study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 (Normal Renal Function) | Plasma Decay Half-Life (t1/2) | 2.37 hours | Standard Deviation 0.363 |
| CP-690,550 (Mild Renal Insufficiency) | Plasma Decay Half-Life (t1/2) | 2.83 hours | Standard Deviation 0.857 |
| CP-690,550 (Moderate Renal Insufficiency) | Plasma Decay Half-Life (t1/2) | 2.88 hours | Standard Deviation 0.653 |
| CP-690,550 (Severe Renal Insufficiency) | Plasma Decay Half-Life (t1/2) | 3.77 hours | Standard Deviation 0.48 |
Primary
Renal Clearance (CL R)
Renal clearance is the volume of plasma from which the drug is completely removed by the kidney in a given amount of time.
Time frame: 0 (Pre-dose) to 12 hours post-dose, 12 to 24 hours post-dose
Population: Analysis set included all participants who received study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 (Normal Renal Function) | Renal Clearance (CL R) | 113 mL/min | Standard Deviation 16.2 |
| CP-690,550 (Mild Renal Insufficiency) | Renal Clearance (CL R) | 84.7 mL/min | Standard Deviation 28.7 |
| CP-690,550 (Moderate Renal Insufficiency) | Renal Clearance (CL R) | 27.4 mL/min | Standard Deviation 15.9 |
| CP-690,550 (Severe Renal Insufficiency) | Renal Clearance (CL R) | 19.9 mL/min | Standard Deviation 7.52 |
Primary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: 0 (Pre-dose), 0.5, 1, 1.5, 2, 4, 8, 10, 12, 16, 24, 48 hours post-dose
Population: Analysis set included all participants who received study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CP-690,550 (Normal Renal Function) | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0.75 hours |
| CP-690,550 (Mild Renal Insufficiency) | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 1.00 hours |
| CP-690,550 (Moderate Renal Insufficiency) | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0.75 hours |
| CP-690,550 (Severe Renal Insufficiency) | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0.75 hours |