Ignite Creation Date:
2024-05-05 @ 7:33 PM
Last Modification Date:
2024-10-26 @ 9:50 AM
Study NCT ID:
NCT00690014
Status:
COMPLETED
Last Update Posted:
2021-05-11
First Post:
2008-06-02
Brief Title:
Evaluation of Renal Drug Transport in Healthy Volunteers
Sponsor:
University of Maryland Baltimore
Organization:
University of Maryland Baltimore
Study Overview
Official Title:
Evaluation of Renal Drug Transport in Healthy Volunteers
Status:
COMPLETED
Status Verified Date:
2021-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The process of drug elimination that occurs within the kidneys is complex and involves filtration secretion and absorptive mechanisms Many drugs metabolites and toxins including organic anions and cations rely on renal mechanisms for elimination from the body Failure to recognize the contribution of renal mechanisms involved in drug elimination during the drug development process can result in drug interactions or toxicity in clinical trials This is increasingly important due to the use of OAT1 inhibitors such as probenecid that are being used in adjuvant treatment regimens Thus in order to more fully understand the effects renal disease drugs and nephrotoxins on the renal transport pathways of tubular secretion in humans novel approaches that incorporate both in vitro experimental as well as clinical observations clinical trial also called in-vitroin-vivo correlations IVIVC need to be developed These methods can then be used to identify and evaluate specific kidney probe drugs that undergo extensive tubular secretion Such approaches are needed to characterize drug clearance by tubular mechanisms and to identify potentially significant drug-drug interactions prior to exposure to patients in Phase 2 and 3 clinical trials This investigator-initiated pilot project aims to determine the pharmacokinetics of selected FDA-approved compounds PAH iothalamate for use in IVIVC model development The proposed research is innovative because it involves a translational approach to development of an IVIVC model applied to renal drug clearance It is our expectation that the resultant approach will further our understanding of pharmacogenomics inter-subject variability and renal drug clearance This approach will generate important new information regarding in vitro drug-drug interactions in light of many new and potent OAT1 blocking agents being introduced for the treatment of human diseases In future studies we hope to fully characterize the effects of diseases such as diabetes hypertension and nephropathy on renal drug transport mechanisms using IVIVC models We expect that results from this NIH-funded study will provide needed preliminary data to design future pharmacogenomic and drug interaction studies in humans
Detailed Description:
The purpose of this study is to measure GFR using iothalamate clearance and renal tubular function using PAH clearance in healthy subjects The protocol will be approved by the University of Maryland IRB and the General Clinical Research Center GCRC advisory committee GAC Following the informed consent process each subject will be evaluated for past medical history undergo a physical examination and routine laboratory tests including urinary proteincreatinine ratio conducted within 1 month prior to the study visit
Day 1 Vital signs heart rate blood pressure respiratory rate will be recorded hourly throughout each study visit Subjects will have intravenous catheters inserted into forearm veins of each arm for blood collection and intravenous infusion iothalamate and PAH From 30 minutes before marker administration until the end of each evaluation period subjects will remain in a semireclined position except during urine collections A constant-rate infusion will then be initiated at 1 mLmin for a total of 3 hours with the concentration in the infusate determined based on the patients estimated renal clearance and target plasma concentration of 10 mgL and 15 mgL for iothalamate and PAH respectively Day 2 Washout Day 3 Subject will begin taking probenecid Day 4 Study visit 2 Subject will be admitted to the GCRC at 8AM The final dose of probenecid will be administered The renal function test will then be conducted as described for study visit 1 above Day 11 Subject will be contacted for monitoring of adverse events according to GCRC procedures
Day 1 Vital signs heart rate blood pressure respiratory rate will be recorded hourly throughout each study visit Subjects will have intravenous catheters inserted into forearm veins of each arm for blood collection and intravenous infusion iothalamate and PAH From 30 minutes before marker administration until the end of each evaluation period subjects will remain in a semireclined position except during urine collections A constant-rate infusion will then be initiated at 1 mLmin for a total of 3 hours with the concentration in the infusate determined based on the patients estimated renal clearance and target plasma concentration of 10 mgL and 15 mgL for iothalamate and PAH respectively Day 2 Washout Day 3 Subject will begin taking probenecid Day 4 Study visit 2 Subject will be admitted to the GCRC at 8AM The final dose of probenecid will be administered The renal function test will then be conducted as described for study visit 1 above Day 11 Subject will be contacted for monitoring of adverse events according to GCRC procedures
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 1R15GM072526-01 | NIH | None | httpsreporternihgovquickSearch1R15GM072526-01 |