Drug Interaction With Envarsus XR and Grapefruit Juice

April 4, 2025 updated by: Shirley M. Tsunoda

Assessment of the Intestinal CYP3A Contribution to Drug Interactions With Envarsus XR Using Grapefruit Juice

Transplant patients must take lifelong immunosuppression in order to prevent rejection of their organ. Tacrolimus is the most widely used immnosuppressive agent. Part of the routine education given to patients regarding tacrolimus is that they must avoid many drugs and substances that can interact with tacrolimus so that they don't experience side effects or lack of effect. Patients are told they must avoid readily available substances such as grapefruit juice and St. John's wort. A new once daily formulation of tacrolimus, Envarsus XR, may bypass the place in the gut in which many of these drug interactions occur. We will give kidney transplant patients Envarsus with and without grapefruit juice and measure the effect on blood levels throughout the day. Results from this study will also give us information about the likelihood of other drugs interacting with Envarsus XR.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Actual)

11

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • La Jolla, California, United States, 92093
        • UC San Diego Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Adult (18 years and older) recipients of a primary kidney transplant who are at least 3 months post-transplantation. Patients will be enrolled as outpatients in the abdominal transplant clinic. For the pharmacokinetic study days at Visit A and Visit B, patients will be outpatients at the UCSD Clinical and Translational Research Institute (CTRI).

It is anticipated that we will need to screen approximately 60 patients in order to enroll 20. Since we perform approximately 80-100 kidney transplants per year at UCSD Health, we anticipate enrollment will take 6-10 months. Reasons for patients not participating in the study include: not meeting the inclusion/exclusion criteria; not able or willing to participate in the study because of the time commitment; dropping out. If patients drop out of the study, we will replace them with consecutive patients as they become eligible.

Description

Inclusion Criteria:

  • Primary Kidney Transplant Age > 18 years At least 3 months post-transplantation Taking a stable dose of tacrolimus extended release with a target trough of 8-10 ng/mL BMI between 18-32

Exclusion Criteria:

  • Multi-organ transplant Concomitant use of mTOR inhibitor Concomitant use of belatacept Concomitant use of medication affecting CYP3A or P-gp History of rejection Hypersensitivity to midazolam Hypersensitivity to Envarsus Active diarrhea or constipation BMI < 18 or > 32

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Group A
Tacrolimus Extended Release + Midazolam
Dietary supplement: Grapefruit Juice
Single 8 ounce administration of oral grapefruit juice
Group B
Tacrolimus Extended Release + Midazolam + Grapefruit Juice
Dietary supplement: Grapefruit Juice
Single 8 ounce administration of oral grapefruit juice

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Tacrolimus AUC before and after Grapefruit Juice
Time Frame: 2-4 weeks
2-4 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Tacrolimus AUC compared to Midazolam AUC
Time Frame: 2-4 weeks
2-4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shirley M. Tsunoda

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 25, 2019

Primary Completion (Actual)

December 31, 2022

Study Completion (Actual)

December 31, 2023

Study Registration Dates

First Submitted

April 10, 2019

First Submitted That Met QC Criteria

April 11, 2019

First Posted (Actual)

April 16, 2019

Study Record Updates

Last Update Posted (Actual)

April 9, 2025

Last Update Submitted That Met QC Criteria

April 4, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 190617

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe