Pharmacokinetics in Patients with Impaired Renal Function — Study Design, Data Analysis, and Impact on Dosing and Labeling | FDA

Pharmacokinetics in Patients with Impaired Renal Function — Study Design, Data Analysis, and Impact on Dosing and Labeling | FDA





FDA Issues Revised Draft Guidance, “Pharmacokinetics in Patients with Impaired Renal Function -- Study Design, Data Analysis, and Impact on Dosing”

Today, the U.S. Food and Drug Administration (FDA) issued a draft guidance for industry entitled, “Pharmacokinetics in Patients with Impaired Renal Function -- Study Design, Data Analysis, and Impact on Dosing.” This revised draft guidance assists sponsors in the design and analysis of studies that assess the influence of impaired renal function on the pharmacokinetics and/or pharmacodynamics of an investigational drug and addresses how such information can inform product labeling.

Drugs are eliminated from the body through a variety of mechanisms, including renal excretion. If a drug is eliminated primarily through renal excretion, then impaired renal function usually alters the drug’s pharmacokinetics where a change in the dosing regimen used in patients with normal renal function should be considered. Individuals with advanced renal disease are frequently excluded from participation in late-phase clinical trials, hindering a safe and effective dosing regimen determination for the patient population. A well-planned drug development program can enable prospective dosage adjustment based on the observed or expected changes in the pharmacokinetics of a drug due to impaired renal function before initiating phase 2 or phase 3 trials. 

This draft guidance revises and replaces the FDA draft guidance entitled, “Pharmacokinetics in Patients with Impaired Renal Function — Study Design, Data Analysis and Impact on Dosing and Labeling (March 2010)” and provides updated recommendations on the following topics:

• When a standalone study of a drug’s PK in subjects with impaired renal function is recommended and when it may not be needed
• The design and conduct of PK studies in subjects with impaired renal function
• considerations for characterizing a drug’s PK in patients undergoing intermittent or continuous dialytic therapies
• The use of PK information from phase 2 and 3 studies to inform dosing recommendations for patients with impaired renal function
• The analysis and reporting of the results of studies that characterize the impact of impaired renal function and how these data inform dosing recommendations in labeling

The FDA encourages stakeholders to provide comments to the public docket (docket number FDA-2010-D-0133) available at https://www.regulations.gov up to 90 days following publication in the Federal Register.