Renal Impairment Studies

Many drugs are eliminated from the body through a combination of some or all of the following organs: small intestine, liver and kidneys. For those drugs cleared primarily via renal excretion, it is known that impaired renal function will typically alter the drug’s pharmacokinetics (PK), as well as potentially impact the drug’s absorption, bioavailability, tissue distribution and plasma protein binding (1,2). Therefore, in order to prevent a loss of therapeutic effect and/or increase in safety risks, a different dosing regimen between patients with normal renal function and those with impaired renal function should be given consideration.

To inform the dosing recommendations, a dedicated renal impairment study is generally recommended. A renal impairment study aims to study the effect of mild, moderate and severe renal impairment on the PK of a drug or its active metabolites.

The team at Dr. Vince Clinical Research understands the unique challenges associated with PK renal impairment studies and provides a wide range of services to conduct them efficiently and as expeditiously as possible.

Reach Out Today

Learn how DVCR can support your renal impairment clinical trials.

Renal and Hepatic Impairment Studies Fact Sheet

WEBINAR

Effective Study Design and Execution of Renal and Hepatic Impairment Trials

Many drugs are eliminated from the body through a combination of some or all of the following organs: small intestine, liver and kidneys. For those drugs cleared primarily via renal excretion, it is known that impaired renal function will typically alter the drug’s pharmacokinetics (PK), as well as potentially impact the drug’s absorption, bioavailability, tissue distribution and plasma protein binding (1,2). Therefore, in order to prevent a loss of therapeutic effect and/or increase in safety risks, a different dosing regimen between patients with normal renal function and those with impaired renal function should be given consideration.

To inform the dosing recommendations, a dedicated renal impairment study is generally recommended. A renal impairment study aims to study the effect of mild, moderate and severe renal impairment on the PK of a drug or its active metabolites.

The team at Dr. Vince Clinical Research understands the unique challenges associated with PK renal impairment studies and provides a wide range of services to conduct them efficiently and as expeditiously as possible.

Reach Out Today

Learn how DVCR can support your renal impairment clinical trials.

Renal & Hepatic Impairment Studies Fact Sheet

Renal & Hepatic Impairment Studies Fact Sheet

WEBINAR

Effective Study Design and Execution of Renal and Hepatic Impairment Trials

WEBINAR

Effective Study Design and Execution of Renal and Hepatic Impairment Trials

Our Model for Renal Impairment Studies

In order to offer the best solution possible, DVCR has prioritized its relationship with a network of strategically selected sites that have extensive experience conducting renal impairment studies. Our team has built trusted relationships with these sites, and our site-centric approach ensures sites are highly engaged and collaborative. Not only do these sites have access to the necessary patient populations as referenced in the FDA guidance, but they are also overseen by well-known Subject Matter Experts in this space who understand how to operationalize each study.

Our model for successfully conducting renal impairment studies involves:

Establishing governance charters, clear communication and escalation pathways through a proactive approach to site partnerships

Expediting site payments to de-risk study delays and encourage site engagement and study prioritization

Assigning only tenured project managers who have experience overseeing multisite studies and understand the nuances of complex clinical pharmacology studies

Our approach positively impacts study timelines, patient recruitment and data quality. For these studies, DVCR actively manages the sites, ensuring patient recruitment and other deliverables are met on time. Our CRO services, including data management, biostatistics and programming, monitoring and medical writing provide a seamless solution for our biopharma clients.

Site Network Overview

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If you would like to learn more about how our CRO can support your upcoming renal impairment clinical trial, please contact us.

Robust network of sites across North America

Our site network has conducted over 130 PK renal impairment studies over the past five years

Access to over 350 beds for overnight confinement

Access to patients with mild, moderate and severe renal impairment as well as patients with End Stage Renal Disease (ESRD) on hemodialysis

Site Network Overview

Our site network has conducted over 130 PK renal impairment studies over the past five years

Access to over 350 beds for overnight confinement

Robust network of sites across North America

Access to patients with mild, moderate and severe renal impairment as well as patients with End Stage Renal Disease (ESRD) on hemodialysis

Reach Out Today

If you would like to learn more about how our CRO can support your upcoming renal impairment clinical trial, please contact us.

PK Renal Impairment Study Design

A dedicated renal impairment study is generally recommended when the drug is likely to be used in patients of this population, or when impaired renal function is likely to alter the PK of the drug or its metabolites. This is because they are substantially eliminated by the renal route. Furthermore, data from reviews of biologics applications “indicate that impaired renal function decreased the renal clearance of therapeutic proteins and peptides that have a molecular weight of less than 69kDa (1).” However, “drugs with a narrow therapeutic window may likely require PK evaluation for dose recommendation independent of whether this drug is renally excreted or not (2).”

Typically, a single-dose study is sufficient to accurately describe the PK of the drug and its active metabolites. In most single-dose studies, the same dose can be administered to all patients regardless of renal function because the peak concentration of the drug is not substantially impacted by renal function. A parallel group study design is used, and each group should enroll between 6-8 subjects (2).

Subject Selection
The FDA guidance outlines the classifications of renal function for dedicated renal impairment studies in the chart below (1).
Renal function as determined by measuring Estimated Glomerular Filtration Rate (eGFR) is recommended (1).

For the control group, consideration should be given to matching various demographic factors such as age, weight, sex and ethnicity. A 1:1 matching strategy can be utilized, wherein participants in each impaired group are matched with individuals in the control group (2).

In some cases a Sponsor may opt to perform a reduced pharmacokinetic study design for those drugs which are predominantly eliminated via non-renal routes and likely to be used in patients with impaired renal function. This study is an adaptive two-stage design used to evaluate the initial PK effects in subjects at the extremes of renal function and determine if a full design is necessary (2). This study represents a “worst-case scenario,” which demonstrates the greatest impact that impaired renal function could have on the PK of the drug using patients categorized as having severe levels of impairment according to the chart above (1). If this study demonstrates a clinically relevant effect on the PK of the drug, then the Sponsor should subsequently enroll those subjects in the remaining levels of impaired renal function.
References

1 U.S. Food and Drug Administration, & Center for Drug Evaluation and Research (CDER). (2020). (rep.). Pharmacokinetics in Patients with Impaired Renal Function — Study Design, Data Analysis, and Impact on Dosing. U.S. Food and Drug Administration. Retrieved October 24, 2023, from https://www.fda.gov/media/78573/download.

2 Ravenstijn, P., Chetty, M., & Manchandani, P. (2021). Design and conduct considerations for studies in patients with impaired renal function. Clinical and Translational Science, 14(5), 1689–1704. https://doi.org/10.1111/cts.13061

PK Renal Impairment Study Design

A dedicated renal impairment study is generally recommended when the drug is likely to be used in patients of this population, or when impaired renal function is likely to alter the PK of the drug or its metabolites. This is because they are substantially eliminated by the renal route. Furthermore, data from reviews of biologics applications “indicate that impaired renal function decreased the renal clearance of therapeutic proteins and peptides that have a molecular weight of less than 69kDa (1).” However, “drugs with a narrow therapeutic window may likely require PK evaluation for dose recommendation independent of whether this drug is renally excreted or not (2).”

Typically, a single-dose study is sufficient to accurately describe the PK of the drug and its active metabolites. In most single-dose studies, the same dose can be administered to all patients regardless of renal function because the peak concentration of the drug is not substantially impacted by renal function. A parallel group study design is used, and each group should enroll between 6-8 subjects (2).

Subject Selection
The FDA guidance outlines the classifications of renal function for dedicated renal impairment studies in the chart below (1).
Renal function as determined by measuring Estimated Glomerular Filtration Rate (eGFR) is recommended (1).

For the control group, consideration should be given to matching various demographic factors such as age, weight, sex and ethnicity. A 1:1 matching strategy can be utilized, wherein participants in each impaired group are matched with individuals in the control group (2).

In some cases a Sponsor may opt to perform a reduced pharmacokinetic study design for those drugs which are predominantly eliminated via non-renal routes and likely to be used in patients with impaired renal function. This study is an adaptive two-stage design used to evaluate the initial PK effects in subjects at the extremes of renal function and determine if a full design is necessary (2). This study represents a “worst-case scenario,” which demonstrates the greatest impact that impaired renal function could have on the PK of the drug, using patients categorized as having severe levels of impairment according to the chart above (1). If this study demonstrates a clinically relevant effect on the PK of the drug then the Sponsor should subsequently enroll those subjects in the remaining levels of impaired renal function.
References

1 U.S. Food and Drug Administration, & Center for Drug Evaluation and Research (CDER). (2020). (rep.). Pharmacokinetics in Patients with Impaired Renal Function — Study Design, Data Analysis, and Impact on Dosing. U.S. Food and Drug Administration. Retrieved October 24, 2023, from https://www.fda.gov/media/78573/download.

2 Ravenstijn, P., Chetty, M., & Manchandani, P. (2021). Design and conduct considerations for studies in patients with impaired renal function. Clinical and Translational Science, 14(5), 1689–1704. https://doi.org/10.1111/cts.13061