Multi-center open-label tacrolimus inhalation powder trial evaluating safety, tolerability, efficacy, and pharmacokinetics in adult lung transplant recipients with significant renal impairment.

Lung transplantation (LTx) immunosuppression with oral tacrolimus (Tac) is linked to renal impairment. Substituting oral Tac with Tacrolimus Inhalation Powder (TIP) may prevent graft rejection at lower systemic Tac levels. Fourteen bilateral LTx recipients on oral Tac were enrolled with a mean creatinine of 148 ± 19μmol/L (range 124-193) for a 12-week simple inhaler TIP study and possible 2-year extension. TIP Tac blood levels targeted 50%-66% of previous oral levels. A lack of funding saw study termination short of its original larger enrollment target. Thirteen patients completed 12 weeks, and 12 entered the extension study (mean 40 weeks on TIP), demonstrating a 3-4-fold higher systemic bioavailability versus oral Tac, at 15% of the oral dose), achieving a stable 55% of the pre-study oral Tac levels. One patient discontinued TIP at 6 weeks. The study noted stable 12-week and long-term creatinine levels and spirometry. Endobronchial biopsy gene profiling noted a statistically significant decreased expression of rejection-related genes. TIP shows promise as a novel safe LTx immunosuppressant.