OSAKA trial: a randomized, controlled trial comparing tacrolimus QD and BD in kidney transplantation.

Tacrolimus has a narrow therapeutic index resulting in a tightly defined range of optimal drug exposure (1, 2). A prolonged-release formulation, providing once-daily (QD) dosing, allows tacrolimus to be absorbed over a greater proportion of the gastrointestinal tract. Tacrolimus QD reduces variability in bioavailability and delivers more consistent blood concentration, which may improve long-term patient outcomes (3–5). QD morning dosing is convenient for patients and improves treatment adherence (6–9). Pharmacokinetic data demonstrated that mean tacrolimus exposure (AUC0–24) on day 1 was approximately 30% lower with tacrolimus QD versus twice-daily dosing (BD) at equivalent starting doses. Mean exposure on day 4 was comparable between regimens (10). Optimising immunoSuppression After Kidney transplantation with ADVAGRAF (OSAKA) assessed the noninferiority of immunosuppressive protocols with tacrolimus QD versus tacrolimus BD in kidney transplantation. Various starting doses of tacrolimus QD were employed in consideration of differences in mean exposure early after transplantation. A tacrolimus QD steroid-avoidance regimen was included. This was one of the largest randomized clinical studies ever conducted in kidney transplantation, and the first European large-scale, open-label study to use the novel composite primary endpoint of efficacy failure (graft loss, biopsy-confirmed acute rejection [BCAR], and graft dysfunction), as recommended by the European Medicines Agency (11).