RAPS is closely monitoring developments in the Coronavirus (COVID-19) outbreak. See our public safety page for the latest updates.

 
Regulatory Focus™ > News Articles > 2020 > 9 > FDA updates PK guidance for patients with impaired renal function

FDA updates PK guidance for patients with impaired renal function

Posted 08 September 2020 | By Mary Ellen Schneider 

FDA updates PK guidance for patients with impaired renal function

The US Food and Drug Administration (FDA) has updated its draft guidance for the design and analysis of trials to assess how impaired renal function impacts the pharmacokinetics and pharmacodynamics of investigational drugs.

The guidance, issued on 03 September 2020, provides an update to a previous draft issued in March 2010. Specifically, the new document offers updated advice on when a standalone pharmacokinetic study is necessary, the appropriate study design, considerations for patients undergoing dialysis, and how to use pharmacokinetic data from Phase 2 and 3 studies.  

The changes to the draft guidance arose mainly from a May 2019 meeting of the FDA’s Pharmaceutical Science and Clinical Pharmacology Advisory Committee. The committee considered the evaluation of patients with renal impairment during drug development and its impact on dosing and labeling.

There are a variety of ways that drug sponsors can assess the impact of impaired renal function on a drug’s pharmacokinetics, ranging from standalone studies, to modeling and simulation strategies, to alternative enrollment designs.

The FDA says that dedicated renal impairment studies are generally recommended when the drug is likely to be used in patients with impaired renal function and when the drug is substantially eliminated by a renal route, making it likely that the impaired renal function could alter the pharmacokinetics of the drug or its active metabolites.

“A drug is considered to be substantially eliminated by the renal route when the fraction of systematically available drug or active metabolite that is eliminated unchanged in the urine (fe) is 0.3 or greater,” the FDA advises.

The FDA is also recommending pharmacokinetic studies among patients with impaired renal function in the case of certain biologic drugs, specifically therapeutic proteins and peptides with a molecular weight less than 69 kDa.

Pharmacokinetics should also be evaluated if the drug is likely to be used in patients with end-stage renal disease undergoing dialysis, unless the dialysis regimen is unlikely to result in significant elimination of the drug or its active metabolites, according to the agency.

For drugs that are mainly eliminated via non-renal routes but that will be used in patients with impaired renal function, the FDA says a reduced study design is usually sufficient. This type of study design is used to demonstrate a “worst-case scenario,” looking at the greatest impact that impaired renal function could have on the pharmacokinetics of the drug.

Drug sponsors could also assess the impact of impaired renal function by including these patients in late-stage clinical trials. Population pharmacokinetic (popPK) analyses of data from phase 2 or 3 clinical trials “could be sufficient to characterize the impact of renal function on drug exposure for the population that was represented in the trials,” the agency advised in the latest guidance.
 

Regulatory Focus newsletters

All the biggest regulatory news and happenings.

Subscribe