LCPT once-daily extended-release tacrolimus tablets versus twice-daily capsules: a pooled analysis of two phase 3 trials in important de novo and stable kidney transplant recipient subgroups

Transpl Int. 2016 May;29(5):603-11. doi: 10.1111/tri.12770. Epub 2016 Apr 3.

Abstract

African-American and elderly kidney transplant recipients (KTR) have increased risk for poor clinical outcomes post-transplant. Management of immunosuppression may be challenging in these patients and contribute to worse outcomes. A novel once-daily formulation of tacrolimus (LCPT) has demonstrated noninferiority, similar safety, improved bioavailability, a consistent concentration time profile, and less peak and peak-trough fluctuations vs. tacrolimus twice-daily (Tac BID). This pooled analysis of two phase 3 randomized, controlled trials, including 861 (LCPT N = 428; Tac BID N = 433; 38% of patients were stable KTR, and 62% were de novo KTR) patients, examined the efficacy of LCPT in KTR subgroups (blacks, females, and age ≥65). Overall, treatment failure [death, graft failure, centrally read biopsy-proven acute rejection (BPAR), or lost to follow-up] at 12 months was as follows: LCPT: 11.9%, BID Tac: 13.4% [-1.48% (-5.95%, 2.99%)]. BPAR rates were as follows: LCPT: 8.2%, Tac BID: 9.5% [-1.29% (-5.14%, 2.55%)]. Numerically, fewer treatment failure events with LCPT were found in the majority of subgroups, with significantly less treatment failure associated with LCPT among black KTR [-13.82% (-27.22%, -0.31%)] and KTR ≥65 [-13.46% (-25.27%, -0.78%)]. This pooled analysis suggests numerically lower efficacy failure rates associated with LCPT among high-risk subgroups, in particular black KTR and KTR ≥65 years old.

Keywords: efficacy; extended-release; immunosuppression; kidney transplantation; tacrolimus.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Biopsy
  • Data Interpretation, Statistical
  • Delayed-Action Preparations
  • Drug Administration Schedule
  • Female
  • Graft Rejection / etiology
  • Graft Survival
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Kidney / surgery
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Prospective Studies
  • Tablets
  • Tacrolimus / administration & dosage*
  • Treatment Outcome

Substances

  • Delayed-Action Preparations
  • Immunosuppressive Agents
  • Tablets
  • Tacrolimus