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

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

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.

Study Overview

• Status: Completed
• Conditions: Hemodialysis; End-Stage Renal Disease
• Intervention / Treatment: Drug: CP-690,550

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32806
      • Pfizer Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CP-690,550	Drug: CP-690,550; CP-690,550 10 mg oral powder for constitution

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	0 to 4 hrs during hemodialysis started 4 hrs post-dose in Period 2
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).	3 to 3.5 hrs during hemodialysis started 4 hrs post-dose in Period 2

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Krishnaswami S, Chow V, Boy M, Wang C, Chan G. Pharmacokinetics of tofacitinib, a janus kinase inhibitor, in patients with impaired renal function and end-stage renal disease. J Clin Pharmacol. 2014 Jan;54(1):46-52. doi: 10.1002/jcph.178. Epub 2013 Sep 30.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: February 1, 2003
• Primary Completion (Actual): June 1, 2003
• Study Completion (Actual): June 1, 2003

Study Registration Dates

• First Submitted: October 16, 2012
• First Submitted That Met QC Criteria: October 16, 2012
• First Posted (Estimate): October 18, 2012

Study Record Updates

• Last Update Posted (Estimate): December 18, 2012
• Last Update Submitted That Met QC Criteria: November 19, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: pharmacokinetics; end-stage renal disease; CP-690; 550
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tofacitinib
• Other Study ID Numbers: A3921004