Clinical Radiolabeled Studies

WuXi Biology and Testing works with established clinical centers in the U.S. and China, as well as client-designated clinical trials units, to conduct evaluations of radiolabeled drugs in humans.

Objectives

• Determine the mass balance and routes of elimination of a radiolabeled test compound
• Determine the relative exposure levels of the parent compound and metabolites
• Identify and elucidate structures of key metabolites in circulation and excreta
• Determine the clearance mechanisms

Endpoints

• Quantify the total radioactivity in urine and feces to obtain the drug’s mass balance and determine the major excretion routes
• Identify the major circulating metabolites and determine the clearance mechanism of the major drug-related metabolites
• Determine the total plasma and blood concentration and pharmacokinetic (PK) parameters of total radioactivity (=total drug-related mass)

How Human Mass Balance Data Inform Development

• Guide the design of clinical drug-drug interaction studies in accordance with the major mechanism of drug clearance (metabolic enzymes) in humans
• Determine the major metabolites in the human body and whether any single metabolite in circulation is presented at >10% of total plasma exposure
• Guide dose level selection in Phase II and Phase III clinical trials for a special population

Human mass balance results are integrated with nonclinical metabolism, toxicology, and clinical PK data to determine whether important human metabolites are adequately characterized and whether additional metabolite, DDI, or safety studies are needed. Study timing, design, recovery, metabolite characterization, and reporting should follow current applicable regulatory guidance, including FDA recommendations for human radiolabeled mass balance studies.