Randomized Phase I Trials — One Size Fits All?

In this issue of NEJM Evidence, Gaudet et al. present the safety profile and pharmacodynamics of ARO-APOC3, a small interfering RNA therapeutic that inhibits apolipoprotein C-III (APOC3) mRNA expression in a phase I trial.1 Assignment to treatment was based on fasting levels of triglycerides. The trial included two double-blinded cohorts with 52 randomly assigned healthy participants and 40 patients with hypertriglyceridemia assigned to escalating doses of ARO-APOC3 at 10, 25, 50, or 100 mg or placebo in a single- and/or repeat-dose (days 1 and 29) regimen. An open-label cohort of patients with chylomicronemia was treated with ARO-APOC3 at 50 mg.