Pharmacokinetic/ Pharmacodynamic Study of Epoetin Alfa (PROCRIT) in Critically Ill Patients.

Anemia Clinical Trial

Official title:

Comparative Pharmacokinetic and Pharmacodynamic Study of Epoetin Alfa (PROCRIT) in Anemic Critically Ill Patients Randomized to One of Six Dose Regimens for 15 Days

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00210756
• Other study ID #: CR004603
• Status: Completed
• Phase: Phase 2
• First received: September 13, 2005
• Last updated: June 8, 2011
• Start date: February 2004
• Est. completion date: February 2006

Study information

• Verified date: April 2010
• Source: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to describe the pharmacokinetics (PK) of six different dosing regimens of epoetin alfa (PROCRIT®) in anemic critically ill subjects

Description:

Currently, the optimal dosing regimen for achieving and maintaining target Hb concentrations in various clinical settings remains incompletely defined. Both IV and SC routes of administration are used in the clinical setting and have been shown to be effective despite different bioavailability and pharmacokinetic profiles. This study is designed to describe the pharmacokinetic and pharmacodynamic profiles of several different epoetin alfa dosing regimens administered by both IV and SC routes in anemic critically ill patients admitted to a critical care area. The dosing regimens selected will be compared among themselves and against the 40,000 IU SC weekly dosing regimen (A) being used in a large registration trial. Specifically, the six dosing regimens were selected to gather PK and PD data about the following questions: 1) Will an early large Cmax, achieved by IV dosing, stimulate more reticulocytosis? (IV vs. SC dosing regimens A vs. B, C vs. D, E vs. F); 2) Do smaller more frequent doses of the same total dose result in the same PD profile? (A vs. C, B vs. D); 3) Does an IV load improve PD response? (E and F vs. C and D); 4) Do large frequent loading doses accumulate? (A vs. E and B vs. F). Results of this study will provide a pharmacokinetic foundation for understanding and potentially maximizing the pharmacodynamic effects of different dosing options in the critically ill patient. In order to maximize subject safety, all dosing will cease when subject's hemoglobin is > 13g/dL. Group A:40 K SC Qw: Days 1,8,15; Group B:40 K IV Qw: Days 1,8,15; Group C:15 K SC QOD: Days 1,3,5,7,9,11,13,15; Group D:15 K IV QOD: Days 1,3,5,7,9,11,13,15; Group E:40 K SC Days 1 and 3, then 15 K SC QOD: Days 5,7,9,11,13,15; Group F: 40 K IV Days 1 and 3, then 15 K SC QOD: Days 5,7,9,11,13,15

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: February 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Critically ill subject admitted to a critical care area with a medical diagnosis, (non-surgical, non-trauma) and without evidence of acute blood loss

• or Critically ill subject who develops a medical diagnosis after surgery or trauma and who has no evidence of active bleeding within the prior week and no current transfusion needs

• Expected hospital stay of >= 7 days beyond study entry, age >=18 years

• Hb:<=12 g/dL.

Exclusion Criteria:

• Primary admitting diagnosis to the critical care area of acute ischemic cardiac disease or ischemic neurological disease (including but not limited to myocardial infarction or unstable angina, transient ischemic attack, cerebrovascular event)

• History of deep vein thrombosis (DVT) or pulmonary embolism (PE)

• Iron deficiency (defined as serum ferritin <50 micrograms/L)

• History of untreated chronic B12 or Folate deficiency (e.g. pernicious anemia). Patients with B12 and folate deficiencies being treated currently may enter the study

• Renal failure on dialysis, including continuous renal replacement therapy (CRRT), at the time of enrollment

• Evidence of acute blood loss within 1 week of enrollment or an active diagnosis of acute or chronic blood loss or hemolysis.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia
• Critical Illness

Intervention

Drug:
• epoetin alfa

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.	Ortho Biotech Products, L.P.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary objective of this study is to describe the PK profiles of six different dosing regimens of epoetin alfa in anemic critically ill subjects, including regimen A, that is being used in a large registration trial
Secondary	To determine reticulocyte response (absolute and %) to the six dosing regimens, as well as the Hb, Hct, and RBC count response. Compare the PD profiles of each dosing regimen to dosing regimen A. describe the safety profile of the six dosing regimens.

External Links

•   Comparative Pharmacokinetic and Pharmacodynamic Study of Epoetin Alfa (PROCRIT) in Anemic Critically Ill Patients Randomized to One of Six Dose Regimens for 15 Days.