Phase 1, Open-Label Study Of The Pharmacokinetics, Non-Renal Clearance And Dialyzability Of CP-690,550 In Subjects With End-Stage Renal Disease Undergoing Hemodialysis
Overview
- Phase
- Phase 1
- Intervention
- CP-690,550
- Conditions
- End-Stage Renal Disease
- Sponsor
- Pfizer
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Maximum Observed Plasma Concentration (Cmax)
- Status
- Completed
- Last Updated
- 13 years ago
Overview
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.
Investigators
Eligibility Criteria
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.
Arms & Interventions
CP-690,550
Intervention: CP-690,550
Outcomes
Primary Outcomes
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
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
Plasma Decay Half-Life (t1/2)
Time Frame: 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.
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]
Time Frame: 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)
Time Frame: 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)
Oral Clearance (CLpo)
Time Frame: 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.
Dialyser Clearance (CL HD) From 0 to 1 Hour
Time Frame: 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
Time Frame: 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
Time Frame: 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).
Dialyser Clearance (CL HD) From 3 to 4 Hour
Time Frame: 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).
Secondary Outcomes
- Fraction of Unbound Drug (fu)(2 hours post-dose in Period 1)