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

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ClinicalTrials.gov Identifier: NCT03713645
Recruitment Status : Recruiting
First Posted : October 22, 2018
Last Update Posted : November 14, 2018
Sponsor:
Collaborator:
Veloxis Pharmaceuticals
Information provided by (Responsible Party):
Temple University

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.

Condition or disease Intervention/treatment Phase
Kidney Transplant Drug: Tacrolimus Extended Release Oral Tablet [Envarsus] 0.13mg/kg/day initiated within post-operative day 3 after kidney transplant Phase 4

Detailed Description:

Patients will be identified when an organ from live or deceased donor becomes available for kidney transplant. Prior to receiving their kidney transplant, subjects will be screened for inclusion/exclusion criteria on the day of transplantation. During the pre-operative preparation for transplant, patients will be consented for surgery and consented for the study at the same time if they volunteer to be included. The transplant surgeon performing the transplant operation will be responsible for screening the patients for inclusion and exclusion criteria as well as obtaining informed consent. Patients will need to provide informed consent to be included in the study, and will receive a copy of their consent. Each potential participant will be approached by the transplant surgeon and informed of all information pertinent to the study prior to providing consent. No advertisements for recruitment will be performed and no compensation will be provided for participation.

This study is a single center prospective observational study conducted at Temple University Hospital (TUH). All participants will be consented for all procedures involved in this study. This study will utilize the QUEST questionnaire (attached) to evaluate the severity of tremors at 1 month. Data to be collected includes tacrolimus trough levels, study drug dosing, hemoglobin A1c, incidence and severity of tremors, potassium, glomerular filtration rate, and rejection episodes.

Day 0 Study drug (tacrolimus) initiated at 0.13/mg/kg/day for all patients (the day of initiation decided per transplant surgeon discretion)

Day 0-4 Inpatient laboratory parameters checked every 24 hours (serum creatinine, tacrolimus level, glomerular filtration rate, potassium, blood glucose)

Day 4-30 Outpatient laboratory parameters checked three times weekly on Monday, Wednesday, and Friday (serum creatinine, tacrolimus level, glomerular filtration rate, potassium, blood glucose)

Day 30 visit (within 5 days) Draw tacrolimus trough levels, serum creatinine, estimated glomerular filtration rate, serum potassium, and blood glucose. Complete tremor questionnaire with participant.

During or prior to Day 30 visit Oral swab performed to be analyzed for testing of metabolic enzymatic activity (This will be performed to determine ability of the patient to metabolize tacrolimus)


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Dosing Strategies for de Novo Once-daily Extended Release Tacrolimus (LCPT) in Kidney Transplant Recipients
Actual Study Start Date : November 12, 2018
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Tacrolimus

Arm Intervention/treatment
Experimental: Tacrolimus extended-release 0.13mg/kg/day
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
Study drug (tacrolimus extended-release) initiated at 0.13/mg/kg/day for all patients




Primary Outcome Measures :
  1. Time to first therapeutic tacrolimus trough concentration from initiation of tacrolimus extended release measured in days [ Time Frame: Within the first 30 days of kidney transplant ]
    Therapeutic tacrolimus trough= 8-10ng/mL


Secondary Outcome Measures :
  1. Number of dose adjustments between initiation of tacrolimus extended release and first therapeutic trough level [ Time Frame: Within the first 30 days of kidney transplant ]
    Total number of increases in dosage compared to starting dose

  2. Percent increase in dosage between initiation of tacrolimus extended release and first therapeutic trough level [ Time Frame: Within the first 30 days of kidney transplant ]
    Total percentage of dosage increases

  3. Number of patients with supratherapeutic tacrolimus trough levels within 30 days [ Time Frame: Within the first 30 days of kidney transplant ]
    Supratherapeutic tacrolimus trough= greater than 12 ng/mL

  4. Average estimated glomerular filtration rate within 30 days [ Time Frame: Within the first 30 days of kidney transplant ]
    eGFR calculated utilizing MDRD formula

  5. Incidence of acute rejection episodes within 30 days [ Time Frame: Within the first 30 days of kidney transplant ]
    Biopsy-proven rejection

  6. Impact of tremor on quality of life at 30 days [ Time Frame: At 30 days after kidney transplant ]
    Assessed via QUEST questionnaire which includes a self-assessment of tremor impact on quality of life. Patients will answer questions related to a tremors impact on their activities of daily living. Scores for each question range from never, rarely, sometimes, frequently and always as it relates to impact on quality of life. In addition, ratings on the severity of tremor in the head, voice, hand, and feet is performed via self-answered questions related to the impact on performing daily activities

  7. Incidence of hyperkalemia (Potassium > 5.5) [ Time Frame: Within the first 30 days of kidney transplant ]
    Potassium blood draw

  8. Incidence of new-onset diabetes after transplant (HgbA1C > 7%) [ Time Frame: Within the first 30 days of kidney transplant ]
    HbA1C

  9. Incidence of CYP3A5 genotype expressers and non-expressers [ Time Frame: Sample collected within 30 days after kidney transplant ]
    Oral swab collected for CYP3A5 genotype analysis

  10. Graft survival at 12 months [ Time Frame: Reported at 12 months ]
  11. Patient survival at 12 months [ Time Frame: Reported at 12 months ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03713645


Contacts
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Contact: Adam Diamond, PharmD 215-280-8041 adam.diamond@tuhs.temple.edu
Contact: Antonio Di Carlo, MD 267-314-3431 Antonio.DiCarlo@tuhs.temple.edu

Locations
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United States, Pennsylvania
Temple University Hospital Recruiting
Philadelphia, Pennsylvania, United States, 19140
Contact: Temple U Hospital    215-280-8041      
Sponsors and Collaborators
Temple University
Veloxis Pharmaceuticals
Investigators
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Principal Investigator: Adam Diamond, PharmD Temple University Hospital

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Responsible Party: Temple University
ClinicalTrials.gov Identifier: NCT03713645     History of Changes
Other Study ID Numbers: 25286
First Posted: October 22, 2018    Key Record Dates
Last Update Posted: November 14, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action