A Randomized Trial of Modified-Release Versus Immediate-Release Tolvaptan in Autosomal Dominant Polycystic Kidney Disease

Abstract Introduction Tolvaptan, for treatment of autosomal dominant polycystic kidney disease (ADPKD), is provided as immediate release (IR) tablets administered twice daily in split-dose regimens to suppress urine osmolality to Methods Multicenter, parallel-arm, randomized, crossover, double-blind, placebo-controlled trial. Each of 2 study arms had 12 subjects and 3 crossover periods. Dose regimens were administered for 7 days; placebo-masked QD versus split-dose treatments. Endpoints included pharmacokinetic parameters, percentage of subjects with urine osmolality Results Tolvaptan MR 20 to 120 mg exhibited dose-proportional pharmacokinetics. Percentage of subjects with spot urine osmolality Conclusion Tolvaptan MR exhibited predictable and dose-proportional pharmacokinetics and no improvement in tolerability versus tolvaptan IR. Tolerability of the urinary effects of treatment within the high-dose MR and IR groups exhibited substantial inter-individual variability.