Clinical Trials Logo

Clinical Trial Summary

The objective of this study is to confirm the feasibility of using a panel of endogenous substrates/metabolites as a robust biomarker of OCTs and OATs by conducting a controlled, comprehensive clinical drug-drug interaction study in healthy adult volunteers. Metformin and furosemide will be used as probe drugs for OCTs and OATs, respectively; cimetidine and probenecid will be used as corresponding inhibitors. Results from this study will validate this novel approach, which will be extended to children by collaborators at Children's Mercy Hospital in Kansas City, MO.


Clinical Trial Description

The kidneys are major organs responsible for the excretion of both endogenous and exogenous compounds, the latter including drugs and other xenobiotics. Excretion occurs via passive or active processes, the latter involving transporters such as organic cation transporters (OCTs) and organic anion transporters (OATs). Inhibition of these transporters, coupled with the large interindividual variability in transporter expression, can lead to toxic accumulation of compounds/xenobiotics cleared primarily by this route. During drug discovery and development, if in vitro evidence suggests renal transporters mediate excretion of a new chemical entity, the Food and Drug Administration recommends conducting a controlled clinical study to evaluate potential risks. These time-consuming and expensive clinical studies routinely involve adult participants and known substrates of renal transporters. However, such studies are not always feasible in children due to the enhanced potential for toxicities. This limitation led to the hypothesis that endogenous substrates could be used as surrogates, or biomarkers, of individual renal transporter function. Endogenous OCT substrates, such as 1-methyladenosine (m1A) and 1-methylnicotinamide (MNA), as well as OATs, such as homovanillic acid (HVA) and pyridoxic acid (PDA), are promising biomarkers of renal transporters in adults. However, using one or few such endogenous substrates can be misleading due to factors other than variability in specific renal transporter function. We propose to address this knowledge gap by using a panel of endogenous substrates/metabolites that recently has been identified as a robust biomarker of rodent Octs and Oats. Validation of these substrates/metabolites as biomarkers of OCTs and OATs in humans, both adults and children, will aid in the development of physiologically-based pharmacokinetic models that can be used to predict renal transporter-mediated xenobiotic excretion, drug-drug interactions, and toxicity in children. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT05365451
Study type Interventional
Source Washington State University
Contact
Status Completed
Phase Early Phase 1
Start date April 11, 2022
Completion date July 22, 2023

See also
  Status Clinical Trial Phase
Completed NCT02926326 - The Effect of Azithromycin on BCT197 Exposure in Healthy Male Volunteers Phase 1
Completed NCT04257955 - COMMUNIcation and Patient Engagement at Diagnosis of PAncreatic CAncer
Recruiting NCT04249674 - Impact of CYP2D6 Genetic Polymorphisms on the Vulnerability to Drug-drug Interactions With Tramadol
Completed NCT01482117 - The Effect of Genetic Polymorphism on Interactions of Clopidogrel and Cilostazol in Healthy Volunteers N/A
Terminated NCT04842981 - Interleukin-6 Inhibitors and Drug-drug Interactions in Patients With Rheumatoid Arthritis Phase 1/Phase 2
Completed NCT01447472 - -Methylenedioxymethamphetamine (MDMA, Ecstasy) Induced Changes in Drug Metabolism: Gender and Genetic Polymorphisms Phase 1
Completed NCT03498170 - The Effect of Itraconazole on BCT197 Exposure in Healthy Male Participants Phase 1
Recruiting NCT06053411 - Contribution of UGT2B17 to the Pharmacokinetics of Diclofenac Early Phase 1
Completed NCT06411509 - Integration of Tai Chi and Repetitive Transcranial Magnetic Stimulation for Sleep Disturbance in Older Adults N/A
Active, not recruiting NCT05425303 - System Dynamics Model for Acute Non-contact Lower Extremity Injuries Prediction
Completed NCT02067936 - Walking the Isobole of Drug Interaction N/A