Pharmacokinetics And Dialysability Of CP-690,550 In Subjects With End-Stage Renal Disease

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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End-Stage Renal Disease, Hemodialysis

Intervention / Treatment
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* Drug: CP-690,550


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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<br> | Drug: CP-690,550<br>* CP-690,550 10 mg oral powder for constitution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 - ∞). | 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24 hours (hrs) post-dose in Period 1 | 
| 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) | 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24 hrs post-dose in Period 1 | 
| 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) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24 hrs post-dose in Period 1 | 
| 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. | 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8, 12, 16, 24 hrs post-dose in Period 1 | 
| 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). | 0 to 1 hrs during hemodialysis started 4 hrs post-dose in Period 2 | 
| 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). | 1 to 2 hrs during hemodialysis started 4 hrs post-dose in Period 2 | 
| 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). | 2 to 3 hrs during hemodialysis started 4 hrs post-dose in Period 2 | 
| 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). | 3 to 4 hrs during hemodialysis started 4 hrs post-dose in Period 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fraction of Unbound Drug (fu) | Fraction of unbound drug (fu) is defined as the ratio of unbound drug concentration to the total drug concentration. | 2 hours post-dose in Period 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CP-690, 550, pharmacokinetics, end-stage renal disease