Pharmacokinetic Study of Tacrolimus and Mycophenolate Mofetil in Kidney Transplant Recipients With Hyperkalemia Receiving Patiromer

Hyperkalemia (high potassium in blood) is a common condition found in kidney transplant patients. Risk factors include poor kidney function and exposure to various drugs. Regardless of the causes, current treatment options are limited. Previously, the only available potassium binder for lowering potassium in the blood is sodium polystyrene sulfonate, which has unknown drug interaction profile with transplant medications. Patiromer is a newly approved potassium binder indicated for the treatment of hyperkalemia. Kidney transplant patients with hyperkalemia may benefit from patiromer. However, the interaction of patiromer and transplant medications has not been studied. The goal of this study is to look into the drug interactions between patiromer and transplant medications.

Study Overview

• Status: Completed
• Conditions: Hyperkalemia; Kidney Transplant
• Intervention / Treatment: Drug: Patiromer

Detailed Description

This is an open-label single center pharmacokinetic study of kidney transplant recipients with hyperkalemia receiving tacrolimus and MMF-based immunosuppression.

Subjects will be screened for inclusion and exclusion criteria during the screening visit. There will be 2 study visits (visit 0 and visit 1) for each subject after successful screening. Visit 0 occurs within 14 days (± 3 days) after screening. Visit 1 occurs at 7 days (± 3 days) after visit 0. There will be 3 clinical visits (standard of care) after visit 1. A total of 6 visits are anticipated for this study.

Standard diet for lunch and dinner will be provided to subjects during visit 0 and visit 1. Meals provided will be monitored in relationship to C0 and C12.

During screening visit, blood tests for baseline BMP, aldosterone, magnesium, tacrolimus, DSA, and MMF will be obtained. If applicable, concomitant fludrocortiosone will be stopped prior to screening.

During visit 0, tacrolimus levels will be drawn immediately before (0 hr) and at 8 intervals after dosing (1,2,3,4,5,6,9,12 hrs). MMF levels will be drawn immediately before (0 hr) and at 9 intervals after dosing (1,2,3,4,5,6,7,9,12 hrs). Basic metabolic profile and serum magnesium levels will be drawn immediately before tacrolimus dosing. Oral MMF and tacrolimus will be dosed at 8am ± 1hr.

Enrollment is defined as the first day when subject receives patiromer treatment. Patiromer (8.4 grams) will be taken daily at 3 hours after oral tacrolimus and MMF dosing by subjects commencing 3 days (± 1 day) prior to visit 1. No tacrolimus or MMF dosing changes are allowed between visit 0 and 1. The addition of new concomitant drugs causing interactions with tacrolimus and MMF are prohibited between visit 0 and 1.

During visit 1, subjects will follow the same protocol of blood draws as visit 0. Tacrolimus levels will be drawn immediately before (0 hr) and at 8 intervals after tacrolimus dosing (1,2,3,4,5,6,9,12 hrs). MMF levels will be drawn immediately before (0 hr) and at 9 intervals after MMF dosing (1,2,3,4,5,6,7,9,12 hrs). Basic metabolic profile and serum magnesium levels will be drawn immediately before tacrolimus dosing. Patiromer at 8.4 grams will be given 3 hrs after tacrolimus and MMF dosing. Oral MMF and tacrolimus will be dosed at 8am ± 1hr.

All subjects will followup for clinical visits (2-4) with the PI or their transplant nephrologists after visit 1 according to schedule (see appendix for study visit events). Subjects will complete study by 30 days (± 7 days) after visit 0. Adjustment of patiromer dosing is at the discretion of PIs after visit 2. After completion of study visits, subjects will continue to follow with transplant clinic monthly for 2 months or sooner if clinically indicated per the discretion of the treating transplant nephrologist. After 2 months, clinic visits will be conducted per routine clinic schedule.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • The Rogosin Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female, 18 years of age or older.
2. Patient is capable of understanding the purposes and risks of the study, who can give written informed consent and who are willing to participate in and comply with the study.
3. Kidney transplant recipient.
4. Must be receiving MMF for maintenance immunosuppression
5. Must be receiving tacrolimus for maintenance immunosuppression
6. Subjects must have hyperkalemia (serum potassium ≥ 5.0 mEq/L and ≤ 6.0 mEq/L).
7. Prior to enrollment, subjects must be taking a steady dose of tacrolimus for 3 days.

Exclusion Criteria:

1. Use of Kayexalate 1 day prior to screening visit.
2. Serum potassium level of greater than 6.0 mEq/L at screening.
3. Serum magnesium level of less than 1.0mg/dL at screening.
4. Acute rejection episode within 30 days prior to enrollment.
5. Anemia with hemoglobin level of ≤ 9.0 g/dL prior to screening.
6. Patient has hypersensitivity to patiromer.
7. Receiving maintenance corticosteroid for immunosuppression
8. Serious medical (including history of cardiac arrhythmias) or psychiatric illness likely to interfere with participation in this clinical study.
9. Patients with known donor-specific antibodies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patiromer	Drug: Patiromer; Patiromer (8.4 grams) will be taken daily at 3 hours after oral tacrolimus and MMF dosing by subjects commencing 3 days (± 1 day) prior to visit 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC	Investigate the pharmacokinetics of tacrolimus and mycophenolate mofetil in kidney transplant recipients receiving patiromer. Investigators will obtain serum levels of tacrolimus and mycophenolate mofetil before and after the administration of the study drug patiromer. Investigators will measure the areas under the curve of tacrolimus and mycophenolate mofetil before and after exposure to patiromer.	Within 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum potassium levels	To assess the effect of patiromer in reducing hyperkalemia. Investigators will measure the serum potassium levels after the administration of the study drug patiromer.	Within 30 days

Collaborators and Investigators

• Sponsor: The Rogosin Institute
• Collaborators: Weill Medical College of Cornell University
• Investigators: Principal Investigator: Jun Lee, MD, The Rogosin Institute

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2017
• Primary Completion (Actual): August 7, 2019
• Study Completion (Actual): August 7, 2019

Study Registration Dates

• First Submitted: June 12, 2017
• First Submitted That Met QC Criteria: July 24, 2017
• First Posted (Actual): July 25, 2017

Study Record Updates

• Last Update Posted (Actual): April 13, 2020
• Last Update Submitted That Met QC Criteria: April 9, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Water-Electrolyte Imbalance; Hyperkalemia
• Other Study ID Numbers: 1606017355

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

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