Tacrolimus vs Envarsus for Neurotoxicity in Liver Transplant Patients

Overseen By David Taber, PharmD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Medical University of South Carolina

Must be taking: Immunosuppressants

Must not be taking: Tremor-inducing, Dopamine blockers

Disqualifiers: Pregnancy, HIV, Tremor conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is comparing two drugs used to prevent liver transplant rejection. It aims to see if a medication called Envarsus causes fewer nerve-related side effects than the standard Tacrolimus.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking medications known to cause tremors or block dopamine.

What data supports the effectiveness of the drug Envarsus for liver transplant patients?

Research shows that Envarsus, a once-daily extended-release form of tacrolimus, is effective for liver transplant patients. It has similar effectiveness and tolerability to the immediate-release version, with the added benefit of improved drug absorption and more stable blood levels. ^{1 2 3 4 5}

Is Envarsus (extended-release tacrolimus) safe for liver transplant patients?

Studies show that extended-release tacrolimus (Envarsus) is generally safe for liver transplant patients, with a similar safety profile to immediate-release tacrolimus. It is designed to improve drug absorption and reduce fluctuations in drug levels, which may help decrease side effects. ^{1 2 3 4 5}

How is the drug Envarsus different from other treatments for neurotoxicity in liver transplant patients?

Envarsus is a once-daily, extended-release form of tacrolimus that offers improved bioavailability (how well the drug is absorbed in the body) and more stable blood levels compared to the immediate-release version, which is taken twice daily. This can lead to better adherence to the medication schedule and potentially fewer side effects. ^{1 2 3 4 5}

Research Team

Derek Dubay, MD

Principal Investigator

Medical University of South Carolina

Eligibility Criteria

This trial is for adults over 18 who've had a liver or liver/kidney transplant in the last 6 months. They must understand and agree to the study's terms. It's not for pregnant or nursing individuals, HIV positive patients, those unable to take oral meds, recently used other investigational drugs, have certain rejection issues post-transplant, tremor-causing conditions, or are on tremor-inducing meds.

Inclusion Criteria

You had a liver or liver/kidney transplant within the last 6 months.

Patients must be capable of understanding the purposes and risks of the study and have the ability to give written informed consent and be willing to participate and comply with the study

Exclusion Criteria

Pregnant or nursing females or males with a pregnant female partner

You have tested positive for HIV.

You cannot handle taking pills or tablets.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Envarsus once daily or Tacrolimus immediate release twice daily for 6 months

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Envarsus
• Tacrolimus Immediate release

Trial Overview The study compares two immunosuppressant medications: standard Tacrolimus (taken twice daily) versus Envarsus (once daily), focusing on their neurological side effects in liver transplant patients. The hypothesis suggests that Envarsus may lead to fewer neurologic side effects than Tacrolimus.

Participant Groups

Group I: Arm 2: Intervention Experimental Treatment 1 Intervention

Envarsus daily for 6 months.

Group II: Arm 1: Control Active Control 1 Intervention

Tacrolimus immediate release twice daily for 6 months

Envarsus is already approved in United States for the following indications:

Approved in United States as Envarsus XR for:

• Prophylaxis of organ rejection in kidney transplant patients in combination with other immunosuppressants

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

Veloxis Pharmaceuticals

Industry Sponsor

Trials

43

Recruited

3,200+

Findings from Research

Converting stable liver transplant patients from once-daily prolonged-release tacrolimus to once-daily extended-release tacrolimus is safe, with only two patients experiencing adverse effects that resolved after returning to the original medication.

This conversion not only reduced the mean daily cost of tacrolimus therapy from 5.54 to 4.11 Euros per patient but also required careful monitoring and dose adjustments to maintain effective serum levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conversion From Once-Daily Prolonged-Release Tacrolimus to Once-Daily Extended-Release Tacrolimus in Stable Liver Transplant Recipients. Altieri, M., Delaval, G., Kimmoun, E., et al.[2018]

Tacrolimus prolonged release (PR) is as effective as the immediate release (IR) formulation in kidney transplant recipients, showing noninferiority in phase III trials, while maintaining a similar tolerability profile.

Tacrolimus PR offers improved pharmacokinetic properties, including higher bioavailability and reduced concentration fluctuations, making it a promising option for both kidney and liver transplant recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tacrolimus prolonged release (Envarsus®): a review of its use in kidney and liver transplant recipients. Garnock-Jones, KP.[2022]

In a study of 30 kidney transplant patients transitioning from immediate-release to extended-release tacrolimus, the median weight-based dose that achieved therapeutic levels was approximately 0.158 mg/kg/day, which aligns with the manufacturer's recommendation of 80% of the original dose.

However, the study found significant variability in dosing effectiveness among patients, indicating that a weight-based dosing strategy alone may not reliably predict therapeutic levels for all individuals, particularly across different racial backgrounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Weight-Based Dose During Transition From Immediate-Release to Extended-Release Tacrolimus in Kidney Transplant Recipients. Magid, M., Sanoff, S., Lee, HJ., et al.[2023]

References

1. Turkey pubmed.ncbi.nlm.nih.gov

Conversion From Once-Daily Prolonged-Release Tacrolimus to Once-Daily Extended-Release Tacrolimus in Stable Liver Transplant Recipients. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Evaluating the conversion to extended-release tacrolimus from immediate-release tacrolimus in liver transplant recipients. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Tacrolimus prolonged release (Envarsus®): a review of its use in kidney and liver transplant recipients. [2022]

4. Denmark pubmed.ncbi.nlm.nih.gov

A report of a prospective randomized trial of extended-release tacrolimus versus immediate release tacrolimus after liver transplantation with anti-thymocyte induction in a steroid free protocol. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Evaluation of Weight-Based Dose During Transition From Immediate-Release to Extended-Release Tacrolimus in Kidney Transplant Recipients. [2023]