Bioequivalence Study of Tacrolimus in Healthy Volunteers

Healthy Volunteers Clinical Trial

Official title: A Single Dose, Open-Label, Randomized, Four-Way Crossover, Fully Replicate, Bioequivalence Study of Generic Tacrolimus and Prograf® Capsules in Healthy Volunteers Under Fasting Conditions

Status Completed

Clinical Trial Summary

This is an in-vivo study to investigate the bioequivalence of generic tacrolimus and its reference listed drug (RLD). The objective of this study is to investigate the bioequivalence of generic Tacrolimus and RLD in healthy male and non-pregnant, non-lactating female volunteers under fasting conditions. The outcome of this study will help further understanding about pharmacokinetic (PK) performance of tacrolimus in a healthy volunteer population and improve review standards for bioequivalence of narrow therapeutic index (NTI) drugs.

Clinical Trial Description

This is a single-dose, randomized, open-label, fully replicate crossover, four-period, two- treatment, two-sequence, bioequivalence study to investigate the bioequivalence of generic tacrolimus and its reference listed drug (RLD).

Tacrolimus, a calcineurin inhibitor (CNI), has been widely used in solid organ and bone marrow transplants for more than two decades. Calcineurin, a calcium-dependent phosphatase, is instrumental for signal transduction for activation of T cell and B cell, which in turn cause production of autoinflammatory cytokines such as such as interleukin 2 (IL- 2), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ). CNIs prevents the dephosphorylation and translocation of various factors such as the nuclear factor of activated T-cells (NF-AT), and nuclear factor kappa-light-chain enhancer of activated B-cells (NF-κB), thereby inhibiting the signal transduction responsible for growth and proliferation of activated T cells and expression of autoinflammatory cytokines. This mechanism of action results in immunosuppression and prevents organ rejection.

However, therapeutic drug monitoring is required for tacrolimus since the range between tacrolimus therapeutic and toxic tacrolimus whole blood concentrations is narrow and some toxicities are serious and/or irreversible. The objective of this study is to investigate the bioequivalence of generic Tacrolimus and RLD in healthy male and non-pregnant, non-lactating female volunteers under fasting conditions.

The outcome of this study will help further understanding about pharmacokinetic (PK) performance of tacrolimus in a healthy volunteer population and improve review standards for bioequivalence of narrow therapeutic index (NTI) drugs. ;

Related Conditions & MeSH terms

• Healthy Volunteers

• NCT number: NCT04725682
• Study type: Interventional
• Source: Food and Drug Administration (FDA)
• Status: Completed
• Phase: Phase 1
• Start date: January 5, 2021
• Completion date: June 17, 2021