Drug Interaction With Envarsus XR and Grapefruit Juice

NCT03916380 | Completed FDA Drug

• 1 other identifier: 190617
• Study Type: observational
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Kidney Transplant; Complications; Drug Interaction Food

Keywords

Tacrolimus; Grapefruit Juice; CYP3A4; Midazolam; Kidney Transplant

Outcome Measures

Primary Outcomes (1)

• Tacrolimus AUC before and after Grapefruit Juice

  2-4 weeks

Secondary Outcomes (1)

• Tacrolimus AUC compared to Midazolam AUC

  2-4 weeks

Study Arms (2)

Group A

Tacrolimus Extended Release + Midazolam

Dietary Supplement: Grapefruit Juice

Group B

Tacrolimus Extended Release + Midazolam + Grapefruit Juice

Dietary Supplement: Grapefruit Juice

Interventions

Grapefruit Juice DIETARY_SUPPLEMENT

Single 8 ounce administration of oral grapefruit juice

Group A; Group B

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shirley M. Tsunoda: lead

Study Sites (1)

UC San Diego Health

La Jolla, California, 92093, United States

Location

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prinicipal Investigator

Study Record Dates

• First Submitted: April 10, 2019
• First Posted: April 16, 2019
• Study Start: October 25, 2019
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2023
• Last Updated: April 9, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)