Liver Transplant; Complications, Neurotoxicity
Conditions
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.
Interventions
DRUGEnvarsus
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.
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.
Sponsors
Veloxis Pharmaceuticals
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Neurotoxicity Burden | 6 months | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: Control Tacrolimus immediate release twice daily for 6 months
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. | 15 |
| Arm 2: Intervention Envarsus daily for 6 months.
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. | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Arm 2: Intervention | Total | Arm 1: Control |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 28 Participants | 14 Participants |
| Age, Continuous | 52 years STANDARD_DEVIATION 9 | 52 years STANDARD_DEVIATION 11 | 51 years STANDARD_DEVIATION 13 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 27 Participants | 14 Participants |
| Region of Enrollment United States | 15 participants | 30 participants | 15 participants |
| Sex: Female, Male Female | 13 Participants | 22 Participants | 9 Participants |
| Sex: Female, Male Male | 2 Participants | 8 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 0 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 | 1 / 15 |
Outcome results
Primary
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.
Time frame: 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: Control | Change in Neurotoxicity Burden | -5 score on a scale |
| Arm 2: Intervention | Change in Neurotoxicity Burden | -4 score on a scale |