Statistical design and data analysis for the effect of multiple doses of a treatment on renal functions using a pharmacodynamic biomarker

Normally, the safety evaluation starts at a phase 1 study using healthy subjects, since the main purpose of phase 1 studies is to find out maximum tolerated doses and side effects. Sometimes, a multiple-dose study may be necessary to further understand the side effects of a treatment, since a specific side effect has been identified during the post-market safety evaluation after drugs are repeatedly administered to patients for treating a disease for a long time. Particularly, Phase 1 trial of interest here evaluates the effect of multiple doses of a drug on a renal function via measurement of a metabolite clearance in healthy subjects. In general, we know that the renal function will be adversely impaired by the drug intake. We propose a non-inferiority analysis allowing a small decrease in the renal function after the drug is taken. In this study, we discuss the design, power and sample size, and statistical data analysis.