Envarsus Neurotoxicity Burden in Liver Transplant Patients

The Effect of Conversion to Once-Daily Envarsus® on the Neurologic Toxicity Burden in Liver Transplant Recipients

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.

Study Overview

• Status: Completed
• Conditions: Neurotoxicity; Liver Transplant; Complications
• Intervention / Treatment: Drug: Tacrolimus Immediate release; Drug: Envarsus

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female adult (≥18 years old) with a history of liver or liver/kidney transplant within the first 6 months of transplant.
2. 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:

1. Patients will be excluded if they are pregnant or nursing females or males with a pregnant female partner
2. HIV positive (HIV ab +)
3. Unable to tolerate oral medications
4. Use of another investigational product within thirty days prior to receiving study medication
5. Moderate acute cellular rejection (RAI ≥ 5) within the past month
6. A condition that is known to cause tremor such as essential tremor, Parkinson disease, or enhanced physiologic tremor.
7. Patients taking medications known to induce tremors or dopamine blocking agents
8. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1: Control; Tacrolimus immediate release twice daily for 6 months	Drug: Tacrolimus Immediate release; 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.
Experimental: Arm 2: Intervention; Envarsus daily for 6 months.	Drug: Envarsus; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mean Fahn-Tolosa-Marin (FTM) score	Estimate the change in the mean FTM score among patients with self-reported tremors from baseline to six months.	6 months

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: Veloxis Pharmaceuticals
• Investigators: Principal Investigator: Derek Dubay, MD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2020
• Primary Completion (Actual): April 30, 2023
• Study Completion (Actual): January 30, 2024

Study Registration Dates

• First Submitted: January 29, 2019
• First Submitted That Met QC Criteria: January 29, 2019
• First Posted (Actual): January 30, 2019

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Nervous System Diseases; Poisoning; Neurotoxicity Syndromes; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: 00083855

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.: Yes