Kolesar JM, Andrews S, Green H, et al. - Researchers assessed the safety and pharmacokinetics of 9cUAB30 (a synthetic analogue of 9-cis retinoic acid with chemoprevention activity in cell lines and animal models) in this phase I placebo-controlled, double-blinded, dose escalation study. They also determined a dose for future phase II investigations. The regimen used was as follows: a single dose of study drug (placebo or 9cUAB30) administered on day 1 followed by a 6-day drug-free period and then 28 days of continuous daily dosing beginning on day 8. In five dose cohorts (20, 40, 80, 160, and 240 mg), they enrolled 53 healthy volunteers. They found good tolerability of 9cUAB30. No dose limiting toxicities were documented, and no persistent rises in serum triglycerides or cholesterol were evident. As anticipated, a rise in the AUC was noted between day 1 (single dose) and day 36 (steady state). Findings revealed a favorable safety and pharmacokinetic profile of 9cUAB30 delivered by daily oral dosing. The suggested phase II dose with the current formulation is 160 mg once daily, based on the perceived safety profile and absence of linearity in pharmacokinetics at doses greater than 160 mg.