End-Stage Renal Disease, Hemodialysis
Conditions
Keywords
CP-690, 550, pharmacokinetics, end-stage renal disease
Brief summary
There were 2 study periods in this study. In the Period 1, CP-690,550 was to be administered approximately 1 to 2 hours following hemodialysis. If significant non-renal clearance of the drug occurred such that dialyzability of CP-690,550 could not be assessed in Period 1, a second period (Period 2) will be conducted. In Period 2, a single dose of drug will be administered approximately 4 hours prior to hemodialysis.
Interventions
DRUGCP-690,550
CP-690,550 10 mg oral powder for constitution
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 65 Years
Healthy volunteers
No
Inclusion criteria
* Subjects with end-stage renal disease * Subjects need hemodialysis 3 times weekly
Exclusion criteria
* Subjects with evidence or history of clinically significant disease, excluding those common for subjects with End-Stage Renal Disease (ESRD). * 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 |
|---|---|---|
| Dialyser Clearance (CL HD) From 3 to 4 Hour | 3 to 4 hrs during hemodialysis started 4 hrs post-dose in Period 2 | Dialyser clearance was calculated as amount of drug in dialysate collected over a period of time (AHD) divided by the product of fraction unbound of drug in plasma (fu), corresponding mid-time plasma concentration of drug (Cmid), and duration of dialysate collection period (tm). CL HD = AHD/(fu\*Cmid\*tm). |
| Dialyser Clearance (CL HD) From 0 to 1 Hour | 0 to 1 hrs during hemodialysis started 4 hrs post-dose in Period 2 | Dialyser clearance was calculated as amount of drug in dialysate collected over a period of time (AHD) divided (/) by the product of fraction unbound of drug in plasma (fu), corresponding mid-time plasma concentration of drug (Cmid), and duration of dialysate collection period (tm). CL HD = AHD/(fu\*Cmid\*tm). |
| Dialyser Clearance (CL HD) From 1 to 2 Hour | 1 to 2 hrs during hemodialysis started 4 hrs post-dose in Period 2 | Dialyser clearance was calculated as amount of drug in dialysate collected over a period of time (AHD) divided by the product of fraction unbound of drug in plasma (fu), corresponding mid-time plasma concentration of drug (Cmid), and duration of dialysate collection period (tm). CL HD = AHD/(fu\*Cmid\*tm). |
| Dialyser Clearance (CL HD) From 2 to 3 Hour | 2 to 3 hrs during hemodialysis started 4 hrs post-dose in Period 2 | Dialyser clearance was calculated as amount of drug in dialysate collected over a period of time (AHD) divided by the product of fraction unbound of drug in plasma (fu), corresponding mid-time plasma concentration of drug (Cmid), and duration of dialysate collection period (tm). CL HD = AHD/(fu\*Cmid\*tm). |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24 hours (hrs) post-dose in Period 1 | 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 - ∞). |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24 hrs post-dose in Period 1 | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) |
| Maximum Observed Plasma Concentration (Cmax) | 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24 hrs post-dose in Period 1 | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24 hrs post-dose in Period 1 | — |
| Plasma Decay Half-Life (t1/2) | 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24 hrs post-dose in Period 1 | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Oral Clearance (CLpo) | 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24 hrs post-dose in Period 1 | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. It was calculated by dividing given dose of drug with AUC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fraction of Unbound Drug (fu) | 2 hours post-dose in Period 1 | Fraction of unbound drug (fu) is defined as the ratio of unbound drug concentration to the total drug concentration. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Dialyser Clearance (CL HD) From 3 to 3.5 Hour | 3 to 3.5 hrs during hemodialysis started 4 hrs post-dose in Period 2 | Dialyser clearance was calculated as amount of drug in dialysate collected over a period of time (AHD) divided by the product of fraction unbound of drug in plasma (fu), corresponding mid-time plasma concentration of drug (Cmid), and duration of dialysate collection period (tm). CL HD = AHD/(fu\*Cmid\*tm). |
| Overall Dialyser Clearance (CL HD) | 0 to 4 hrs during hemodialysis started 4 hrs post-dose in Period 2 | Dialyser clearance was calculated as amount of drug in dialysate collected over a period of time (AHD) divided by the product of fraction unbound of drug in plasma (fu), corresponding mid-time plasma concentration of drug (Cmid), and duration of dialysate collection period (tm). CL HD = AHD/(fu\*Cmid\*tm). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes all participants enrolled in the study. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Period 1 | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age Continuous | 45.9 years STANDARD_DEVIATION 7.9 |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 12 | 4 / 11 |
| serious Total, serious adverse events | 0 / 12 | 0 / 11 |
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), 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24 hours (hrs) post-dose in Period 1
Population: Analysis set included all participants who received study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 (Period 1) | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | 396 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 158 |
Primary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Time frame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24 hrs post-dose in Period 1
Population: Analysis set included all participants who received study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 (Period 1) | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 385 ng*hr/mL | Standard Deviation 151 |
Primary
Dialyser Clearance (CL HD) From 0 to 1 Hour
Dialyser clearance was calculated as amount of drug in dialysate collected over a period of time (AHD) divided (/) by the product of fraction unbound of drug in plasma (fu), corresponding mid-time plasma concentration of drug (Cmid), and duration of dialysate collection period (tm). CL HD = AHD/(fu\*Cmid\*tm).
Time frame: 0 to 1 hrs during hemodialysis started 4 hrs post-dose in Period 2
Population: Analysis set included all participants who received study medication. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 (Period 1) | Dialyser Clearance (CL HD) From 0 to 1 Hour | 311 mL/min | Standard Deviation 124 |
Primary
Dialyser Clearance (CL HD) From 1 to 2 Hour
Dialyser clearance was calculated as amount of drug in dialysate collected over a period of time (AHD) divided by the product of fraction unbound of drug in plasma (fu), corresponding mid-time plasma concentration of drug (Cmid), and duration of dialysate collection period (tm). CL HD = AHD/(fu\*Cmid\*tm).
Time frame: 1 to 2 hrs during hemodialysis started 4 hrs post-dose in Period 2
Population: Analysis set included all participants who received study medication. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 (Period 1) | Dialyser Clearance (CL HD) From 1 to 2 Hour | 325 mL/min | Standard Deviation 138 |
Primary
Dialyser Clearance (CL HD) From 2 to 3 Hour
Dialyser clearance was calculated as amount of drug in dialysate collected over a period of time (AHD) divided by the product of fraction unbound of drug in plasma (fu), corresponding mid-time plasma concentration of drug (Cmid), and duration of dialysate collection period (tm). CL HD = AHD/(fu\*Cmid\*tm).
Time frame: 2 to 3 hrs during hemodialysis started 4 hrs post-dose in Period 2
Population: Analysis set included all participants who received study medication. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 (Period 1) | Dialyser Clearance (CL HD) From 2 to 3 Hour | 332 mL/min | Standard Deviation 135 |
Primary
Dialyser Clearance (CL HD) From 3 to 4 Hour
Dialyser clearance was calculated as amount of drug in dialysate collected over a period of time (AHD) divided by the product of fraction unbound of drug in plasma (fu), corresponding mid-time plasma concentration of drug (Cmid), and duration of dialysate collection period (tm). CL HD = AHD/(fu\*Cmid\*tm).
Time frame: 3 to 4 hrs during hemodialysis started 4 hrs post-dose in Period 2
Population: Analysis set included all participants who received study medication. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 (Period 1) | Dialyser Clearance (CL HD) From 3 to 4 Hour | 292 mL/min | Standard Deviation 111 |
Primary
Maximum Observed Plasma Concentration (Cmax)
Time frame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24 hrs post-dose in Period 1
Population: Analysis set included all participants who received study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 (Period 1) | Maximum Observed Plasma Concentration (Cmax) | 106 nanogram/milliliter (ng/mL) | Standard Deviation 23.9 |
Primary
Oral Clearance (CLpo)
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. It was calculated by dividing given dose of drug with AUC.
Time frame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24 hrs post-dose in Period 1
Population: Analysis set included all participants who received study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 (Period 1) | Oral Clearance (CLpo) | 501 milliliter/minute (mL/min) | Standard Deviation 243 |
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), 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24 hrs post-dose in Period 1
Population: Analysis set included all participants who received study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 (Period 1) | Plasma Decay Half-Life (t1/2) | 3.46 hr | Standard Deviation 1.18 |
Primary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24 hrs post-dose in Period 1
Population: Analysis set included all participants who received study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CP-690,550 (Period 1) | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0.5 hr |
Secondary
Fraction of Unbound Drug (fu)
Fraction of unbound drug (fu) is defined as the ratio of unbound drug concentration to the total drug concentration.
Time frame: 2 hours post-dose in Period 1
Population: Analysis set included all participants who received study medication. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 (Period 1) | Fraction of Unbound Drug (fu) | 0.390 ratio | Standard Deviation 0.042 |
Other Pre-specified
Dialyser Clearance (CL HD) From 3 to 3.5 Hour
Dialyser clearance was calculated as amount of drug in dialysate collected over a period of time (AHD) divided by the product of fraction unbound of drug in plasma (fu), corresponding mid-time plasma concentration of drug (Cmid), and duration of dialysate collection period (tm). CL HD = AHD/(fu\*Cmid\*tm).
Time frame: 3 to 3.5 hrs during hemodialysis started 4 hrs post-dose in Period 2
Population: Analysis set included all participants who received study medication. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 (Period 1) | Dialyser Clearance (CL HD) From 3 to 3.5 Hour | 377 mL/min | Standard Deviation 200 |
Other Pre-specified
Overall Dialyser Clearance (CL HD)
Dialyser clearance was calculated as amount of drug in dialysate collected over a period of time (AHD) divided by the product of fraction unbound of drug in plasma (fu), corresponding mid-time plasma concentration of drug (Cmid), and duration of dialysate collection period (tm). CL HD = AHD/(fu\*Cmid\*tm).
Time frame: 0 to 4 hrs during hemodialysis started 4 hrs post-dose in Period 2
Population: Analysis set included all participants who received study medication. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 (Period 1) | Overall Dialyser Clearance (CL HD) | 318 mL/min | Standard Deviation 132 |