Envarsus Neurotoxicity Burden in Liver Transplant Patients

NCT03823768 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 00083855
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study will compare neurologic side effects associated with two immunosuppressant medications used in liver transplant patients. The standard therapy of twice daily immediate release Tacrolimus will be compared to Envarsus once daily. We hypothesize that Envarsus will show a lower rate of neurologic side effects than immediate release tacrolimus.

Conditions

Neurotoxicity; Liver Transplant; Complications

Outcome Measures

Primary Outcomes (1)

• Change in Neurotoxicity Burden

  Estimate the change from baseline to six months in neurotoxicity burden measured by a composite Patient Global Impression of Improvement score (PGI-I, with a range of 4-28) The PGI-I is a global index that may be used to rate the response of a condition to a therapy (transition scale). Scale min=4, scale max=28. The scale is made up of four questions, each question has a total of 7 responses, the total score is the sum of each questions choice (1-7). Higher values represent a worsening condition. A score of 16 would indicate no overall change. A score of 15 or lower indicates improvement in the condition and a score of 17 or higher indicates a worsening of the condition. A score of 28 would indicate "very much worse," while a score of 4 would indicate "very much better." A relative change of 2 points would be considered a significant change from baseline.

  6 months

Study Arms (2)

Arm 1: Control

ACTIVE COMPARATOR

Tacrolimus immediate release twice daily for 6 months

Drug: Tacrolimus Immediate release

Arm 2: Intervention

EXPERIMENTAL

Envarsus daily for 6 months.

Drug: Envarsus

Interventions

Envarsus DRUG

Subjects in this group will take Envarsus daily for 6 months of treatment (goal 24 hour trough: 3-10 ng/mL) +/- adjunctive agent and prednisone.

Arm 2: Intervention

Tacrolimus Immediate release DRUG

Subjects in this group will take Tacrolimus immediate release for 6 months of treatment (goal 12 hour trough: 3-10 ng/mL) +/- adjunctive agent and prednisone.

Arm 1: Control

Eligibility Criteria

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

You may qualify if:

• Male or female adult (≥18 years old) with a history of liver or liver/kidney transplant within the first 6 months of transplant.
• 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.

You may not qualify if:

• Patients will be excluded if they are pregnant or nursing females or males with a pregnant female partner
• HIV positive (HIV ab +)
• Unable to tolerate oral medications
• Use of another investigational product within thirty days prior to receiving study medication
• Moderate acute cellular rejection (RAI ≥ 5) within the past month
• A condition that is known to cause tremor such as essential tremor, Parkinson disease, or enhanced physiologic tremor.
• Patients taking medications known to induce tremors or dopamine blocking agents
• A condition or disorder that, in the opinion of the investigator, may adversely affect the outcome of the study or the safety of the subject

Sponsors & Collaborators

• Medical University of South Carolina: lead
• Veloxis Pharmaceuticals: collaborator

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Publications (1)

• Coffman KS, Revuelta GJ, DeTurk N, Palmer C, Culpepper H, Overstreet M, Fleming J, Terry K, Patel N, McGillicuddy J, Nagaraju S, Rice TC, Taber DJ. Results of a Randomized Controlled Trial Evaluating the Impact of Conversion to LCP Tacrolimus on Neurologic Toxicities in Liver Transplant Recipients. Int J Hepatol. 2025 Oct 6;2025:4374144. doi: 10.1155/ijh/4374144. eCollection 2025.

  PMID: 41089174 DERIVED

MeSH Terms

Conditions

Neurotoxicity Syndromes

Interventions

Tacrolimus

Condition Hierarchy (Ancestors)

Nervous System Diseases; Poisoning; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

Study conducted during COVID 19 pandemic.

Results Point of Contact

• Title: Professor
• Organization: Medical University of South Carolina

taberd@musc.edu

8437922724

Study Officials

• Derek Dubay, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor-Faculty

Study Record Dates

• First Submitted: January 29, 2019
• First Posted: January 30, 2019
• Study Start: January 31, 2020
• Primary Completion: April 30, 2023
• Study Completion: January 30, 2024
• Last Updated: March 30, 2025
• Results First Posted: June 27, 2024

Record last verified: 2025-03

Locations

US (1)