CLINICAL TRIALS PROFILE FOR ENVARSUS XR
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505(b)(2) Clinical Trials for Envarsus Xr
| Trial Type | Trial ID | Title | Status | Sponsor | Phase | Start Date | Summary |
|---|---|---|---|---|---|---|---|
| New Formulation | NCT04489134 ↗ | P-glypoprotein Inhibition Effect on the Pharmacokinetics of Two Tacrolimus Formulations: Prolonged and Extended-release | Not yet recruiting | Rennes University Hospital | Phase 2 | 2021-11-01 | Tacrolimus is a drug administered orally available with different formulations: immediate release (Prograf®), prolonged-release (Advagraf®) and an extended-release one named LCP-Tacro (Envarsus®), formulated using the Melt-Dose process. Tacrolimus is a lipophilic macrolide drug able to passive transmembrane diffusion. Its bioavailability displays a large interindividual variability, from 9 to 43%. Indeed, tacrolimus is a substrate of P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4). P-gp is an efflux protein mainly located at the apex of the epithelia of the intestine, lymphocyte, kidney and blood-brain barrier. P-gp therefore limits the intestinal resorption of tacrolimus and also its diffusion into its target compartment (i.e the lymphocyte. The expression of this protein is different throughout the digestive tract with maximum expression at the ileal level. CYP3A4 is a coenzyme that is responsible of more than 90% of the metabolism of tacrolimus, at the digestive and hepatic level. Both P-gp and CYP3A4 play a role in tacrolimus absorption/diffusion process. A new formulation of tacrolimus, LCP-Tacro, (Envarsus®) was approved in 2014. Its efficacy was compared to Prograf® in two phase III de novo or switch Prograf® trials in kidney transplantation. With tacrolimus, there is a strong inter-individual pharmacokinetic variability which, to date, has not been fully characterized. Variations in bioavailability may partly explain this high variability. The different formulations are resorbed at distinct gastrointestinal sites which could explain different absorptions between Prograf/Advagraf and LCP-Tacro forms. These findings raise the question of the role of P-gp in explaining the difference in bioavailability between formulations. The use of a P-gp inhibitor could therefore have a different impact on exposure to different galenic formulations. Verapamil is an inhibitor of P-gp and CYP 3A4, which is frequently prescribed and recommended by FDA for drug-drug interaction studies aiming at evaluating P-gp substrates, used in healthy volunteers at dosages up to 240 mg/D13-14. Otherwise, verapamil-tacrolimus interaction has been characterized in vitro. It has also been shown that inhibitory effect of verapamil at a single dose of 120 mg administered one hour prior to the administration of a P-gp substrate exhibited an optimum power of inhibition. The safety of Advagraf® and Envarsus® administrations have already been subjected to several phase I trials in healthy volunteers reinforcing the knowledge of their safety profile. The aim of the study is to compare the interaction profile of Advagraf® and Envarsus® when co-administered with verapamil in healthy subjects and to provide guidelines on tacrolimus dosage adjustment in such cases. |
| >Trial Type | >Trial ID | >Title | >Status | >Sponsor | >Phase | >Start Date | >Summary |
All Clinical Trials for Envarsus Xr
| Trial ID | Title | Status | Sponsor | Phase | Start Date | Summary |
|---|---|---|---|---|---|---|
| NCT02339246 ↗ | Pharmacokinetic Comparison Of All FK-506 Formulations | Completed | Veloxis Pharmaceuticals | Phase 3 | 2015-01-01 | The purpose of the study is to compare the pharmacokinetic parameters of three different formulations of tacrolimus. Eligible patients will be treated with all three formulations in a pre-defined sequence. |
| NCT02411604 ↗ | Expanded Access Study for Renal Transplant Patients With Envarsus XR ™ | Approved for marketing | Veloxis Pharmaceuticals | 1969-12-31 | Open label, multi-center, expanded access study for renal transplant patients with once daily Envarsus XR (Tacrolimus). | |
| NCT02432833 ↗ | Multicentre, Open Label, Randomized, Two-arm, Parallel-group Study to Assess Efficacy and Safety of ENVARSUS® Compared With Tacrolimus Used as Per Current Clinical Practice in the Initial Maintenance Setting in de Novo Kidney Transplant Patients | Completed | Chiesi Farmaceutici S.p.A. | Phase 4 | 2015-05-01 | The purpose of the study is to compare tacrolimus dosing of the new Envarsus®-based immunosuppressive regimen with current clinical practice (Prograf or Advagraf) over 6 months following de novo renal transplantation in a real-life setting in different European Countries. |
| NCT02500212 ↗ | Pharmacokinetic Study of ENVARSUS in Adult De-novo Kidney Transplant Patients | Completed | Chiesi Farmaceutici S.p.A. | Phase 4 | 2015-07-01 | Open-label, multicentre, randomized clinical trial to compare the pharmacokinetics of ENVARSUS® tablets and ADVAGRAF® capsules administered once daily in adult de-novo kidney transplant patients. |
| NCT02882828 ↗ | PK Assessment of Tacrolimus Exposure Before and After a Switch From Twice Daily Immediate-release (Prograf®) to Once-daily Prolonged Release Tacrolimus (Envarsus®) | Unknown status | University Hospital, Limoges | Phase 4 | 2016-10-01 | Tools have been developed in our unit to calculate the inter-dose AUC (Area Under Curve) of immunosuppressive drugs (ISD) based on a limited number of blood concentrations (i.e., blood samples) using Bayesian methods. Since 2005, we have implemented these tools in an expert system and made them available to the transplant community through our very successful ISBA (Immunosuppressive drugs Bayesian dose Adjustment) website. Briefly, we first need to develop a population pharmacokinetic model using rich pharmacokinetic (PK) profiles (about 10 samples per patient over the dosing interval). The model developed can then be used for inference of ISD PK parameters in new patients using Bayesian estimation. Bayes' theorem is based on conditional probability: individual PK parameters are estimated based on the known PK parameters in the population (mean and distribution), given the dose and concentrations observed in a patient. Our previous studies have shown that a limited sampling strategy (LSS) based on 3 samples collected within the first 3 hours after drug intake can estimate adequately the interdose AUC of ISD. In the present study, the AUC0-24h and the recommended dose will be calculated using Bayesian estimators previously developed using PK data from the clinical trials run by Veloxis, and proposed to the clinicians via a dedicated website comparable with ISBA. |
| NCT02954198 ↗ | Once-daily Regimen With Envarsus® to Optimize Immunosuppression Management and Outcomes in Kidney Transplant Recipients | Completed | Medical University of South Carolina | N/A | 2016-12-01 | With the availability of well-studied once-daily formulations of tacrolimus, the ability to achieve a true once-daily immunosuppressant regimen along with everolimus and steroids may finally be achievable and have the potential to optimize immunosuppression safety and efficacy in kidney transplantation. |
| >Trial ID | >Title | >Status | >Sponsor | >Phase | >Start Date | >Summary |
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