Characterization of Urinary Kidney Injury Biomarker Profiles in Healthy Japanese Subjects With Reference to a Counterpart US Study.

Drug-induced kidney injury should be monitored throughout the drug development process to ensure patient safety. Standard kidney injury biomarkers may not always correlate with subtle microscopic histopathological kidney injury. Standard biomarkers are insufficiently sensitive for detection of early-phase kidney injury. The need for more sensitive novel kidney injury biomarkers drove quantitative assessment of a panel of urine biomarkers, leading to US FDA qualification of a panel of six novel urine biomarkers for use in phase 1 clinical drug trials in healthy subjects. To qualify these biomarkers for use in the Japanese population, a multistep bridging strategy was developed to extrapolate US-based evidence to Japan. We report the results of the Japanese healthy volunteer study, which was the first step of the clinical phase of the program in Japan. This was a nonintervention study designed to collect blood and urine samples from healthy Japanese subjects. The study design emulated the counterpart US study to facilitate comparisons. Forty subjects completed the Japan study. Geometric means of baseline values were within a twofold difference between the Japan and US studies for nearly all biomarkers. Intra-subject variation was generally similar between the two studies. Application of the US-based abnormality criteria to the Japan study gave satisfactory results with specificity above 0.85 for all biomarkers. This study generated well-annotated biomarker samples in Japanese subjects, offering sufficient evidence to advance the project to the next stage of PMDA biomarker qualification.