Dosing Strategies for de Novo Once-daily Extended Release Tacrolimus (LCPT) in Kidney Transplant Recipients

NCT03713645 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 25286
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Outcomes after kidney transplantation have been significantly enhanced with the advances made in immunosuppressive therapies. Tacrolimus is currently marketed as an extended-release once-daily formulation dosing option for patients, decreasing pill burden and possibly decreasing adverse effects. Some transplant recipients have been shown to have higher dosage requirements. According to the literature, this can be linked to genetic disparities in the metabolism of tacrolimus.. This potential complication, where differences on specific genes alters metabolism of tacrolimus, can increase difficulty in getting to a therapeutic drug level for immunosuppresants and is one large factor that contributes to the fact that kidney transplant survival rates differ between patients. Due to the enhanced bioavailability of Meltdose formulation once-daily extended-release tacrolimus, its de novo use in recent research and practice has been shown to expedite achievement of target tacrolimus trough concentrations. De novo use of once-daily tacrolimus formulations is understudied. Through a prospective investigational study, we aim to determine the optimal strategy for de novo dosing of once-daily extended release tacrolimus (MeltDose formulation) for kidney transplant recipients at Temple University Hospital.

Conditions

Kidney Transplant

Outcome Measures

Primary Outcomes (1)

• Time to First Therapeutic Tacrolimus Trough Concentration From Initiation of Tacrolimus Extended Release Measured in Days

  Therapeutic tacrolimus trough= 8-10ng/mL

  Within the first 30 days of kidney transplant

Secondary Outcomes (7)

• Average Estimated Glomerular Filtration Rate Within 30 Days

  30 days

• Number of Participants With no Impact of Tremor on Quality of Life

  At 30 days after kidney transplant

• Weight-based Tacrolimus Dose During Study Period

  30 days

• Tacrolimus Dose During Study Period

  30 days

• Tacrolimus Trough Level During Study Period

  30 days

Study Arms (1)

Tacrolimus extended-release 0.13mg/kg/day

EXPERIMENTAL

Tacrolimus extended-release is initiated within post-operative day 3 of kidney transplant

Drug: Tacrolimus Extended Release Oral Tablet [Envarsus] 0.13mg/kg/day initiated within post-operative day 3 after kidney transplant

Interventions

Tacrolimus Extended Release Oral Tablet [Envarsus] 0.13mg/kg/day initiated within post-operative day 3 after kidney transplant DRUG

Study drug (tacrolimus extended-release) initiated at 0.13/mg/kg/day for all patients

Tacrolimus extended-release 0.13mg/kg/day

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patient who is 18 years of age or older receiving a kidney transplant at the Temple University Hospital's Kidney Transplant Program who are capable of understanding consent and volunteer to take part in the study

You may not qualify if:

• Scheduled for multiple organ transplant at enrollment Non-English speaking Pregnant women Moderate-severe hepatic impairment (Child Pugh \> 10 or bilirubin \> 2) Existing contraindications to tacrolimus-based products including known hypersensitivity to tacrolimus or any other component of the formulation Receiving concomitant medications known to have strong drug-drug interaction potential with tacrolimus including fluconazole, voriconazole, posaconazole, isavuconazole, itraconazole, ketoconazole, diltiazem, verapamil, metronidazole, erythromycin, clarithromycin, rifampin, rifabutin, rifapentine, phenytoin, fosphenytoin, phenobarbital, primidone, carbamazepine, St. John's Wort, efavirenz, neivrapine, etravirine, atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, ritonavir, nelfinavir, saquinavir, tipranavir, cobicistat

Sponsors & Collaborators

• Temple University: lead
• Veloxis Pharmaceuticals: collaborator

Study Sites (1)

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

MeSH Terms

Interventions

Tacrolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

Single-center design Adjustment of LCPT doses in accordance with institution specific guidelines and physician preference Other genotype impact on tacrolimus metabolism not captured in this study (non-CYP3A5 genetic determinants of metabolic activity) Short follow-up period of 30 days Small sample size Open-label design Single-arm design

Results Point of Contact

• Title: Adam Diamond, PharmD, BCPS, FAST
• Organization: Temple University Hospital, Inc.

adam.diamond@tuhs.temple.edu

215-280-8041

Study Officials

• Adam Diamond, PharmD

  Temple University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2018
• First Posted: October 22, 2018
• Study Start: November 12, 2018
• Primary Completion: May 23, 2021
• Study Completion: January 31, 2022
• Last Updated: May 11, 2023
• Results First Posted: May 11, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)