Trial Outcomes & Findings for Envarsus on the Effect of Total Tacrolimus Dose/Trough Level Ratio on Renal Function (eGFR) in Kidney Transplantation (NCT NCT03511560)
NCT ID: NCT03511560
Last Updated: 2024-07-17
Results Overview
Tacrolimus metabolism was determined for all dates of tacrolimus blood trough concentration collection after renal transplantation by dividing the tacrolimus blood trough concentration (C) by the corresponding total daily tacrolimus dose (D). C/D ratio (ng/mL\*1/mg) = blood tacrolimus trough level (ng/mL)/total daily tacrolimus dose (mg).
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
50 participants
Primary outcome timeframe
Every Month for up to 1 year
Results posted on
2024-07-17
Participant Flow
Participant milestones
| Measure |
Tacrolimus, Immediate Release
Tacrolimus (immediate-release) will be administered twice daily per clinical judgment of supervising physician (dosing and monitoring in accordance with center protocol) to a minimum whole blood tacrolimus concentration of at least 8 ng/mL.
Tacrolimus: Tacrolimus immediate-release, oral; 0.5 mg, 1 mg, 5 mg capsules will be administered twice daily per clinical judgment of supervising physician
|
Envarsus XR
Envarsus XR (Tacrolimus Extended Release Oral Tablet) will be administered once daily at initial weight-based dose of 0.12 mg/kg. Dosing and monitoring thereafter predicated on clinical judgment to a minimum whole blood tacrolimus concentration of at least 8 ng/mL. When possible, patients will receive their daily dose of Envarsus using the fewest number of pills possible.
Tacrolimus Extended Release Oral Tablet: Tacrolimus, extended-release, oral (Envarsus); 0.75 mg, 1 mg, 4 mg tablets will be administered once daily at initial weight-based dose of 0.12 mg/kg.
|
|---|---|---|
|
Overall Study
STARTED
|
25
|
25
|
|
Overall Study
COMPLETED
|
24
|
21
|
|
Overall Study
NOT COMPLETED
|
1
|
4
|
Reasons for withdrawal
| Measure |
Tacrolimus, Immediate Release
Tacrolimus (immediate-release) will be administered twice daily per clinical judgment of supervising physician (dosing and monitoring in accordance with center protocol) to a minimum whole blood tacrolimus concentration of at least 8 ng/mL.
Tacrolimus: Tacrolimus immediate-release, oral; 0.5 mg, 1 mg, 5 mg capsules will be administered twice daily per clinical judgment of supervising physician
|
Envarsus XR
Envarsus XR (Tacrolimus Extended Release Oral Tablet) will be administered once daily at initial weight-based dose of 0.12 mg/kg. Dosing and monitoring thereafter predicated on clinical judgment to a minimum whole blood tacrolimus concentration of at least 8 ng/mL. When possible, patients will receive their daily dose of Envarsus using the fewest number of pills possible.
Tacrolimus Extended Release Oral Tablet: Tacrolimus, extended-release, oral (Envarsus); 0.75 mg, 1 mg, 4 mg tablets will be administered once daily at initial weight-based dose of 0.12 mg/kg.
|
|---|---|---|
|
Overall Study
Death
|
0
|
1
|
|
Overall Study
Adverse Event
|
0
|
2
|
|
Overall Study
Transplant cancelled
|
0
|
1
|
|
Overall Study
Patient switched to another drug
|
1
|
0
|
Baseline Characteristics
Envarsus on the Effect of Total Tacrolimus Dose/Trough Level Ratio on Renal Function (eGFR) in Kidney Transplantation
Baseline characteristics by cohort
| Measure |
Tacrolimus, Immediate Release
n=24 Participants
Tacrolimus (immediate-release) will be administered twice daily per clinical judgment of supervising physician (dosing and monitoring in accordance with center protocol) to a minimum whole blood tacrolimus concentration of at least 8 ng/mL.
Tacrolimus: Tacrolimus immediate-release, oral; 0.5 mg, 1 mg, 5 mg capsules will be administered twice daily per clinical judgment of supervising physician
|
Envarsus XR
n=21 Participants
Envarsus XR (Tacrolimus Extended Release Oral Tablet) will be administered once daily at initial weight-based dose of 0.12 mg/kg. Dosing and monitoring thereafter predicated on clinical judgment to a minimum whole blood tacrolimus concentration of at least 8 ng/mL. When possible, patients will receive their daily dose of Envarsus using the fewest number of pills possible.
Tacrolimus Extended Release Oral Tablet: Tacrolimus, extended-release, oral (Envarsus); 0.75 mg, 1 mg, 4 mg tablets will be administered once daily at initial weight-based dose of 0.12 mg/kg.
|
Total
n=45 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
53 years
n=5 Participants
|
50 years
n=7 Participants
|
52 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
15 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Total # with Diabetes
|
9 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Total # with History of Prior Transplantation(s)
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Every Month for up to 1 yearTacrolimus metabolism was determined for all dates of tacrolimus blood trough concentration collection after renal transplantation by dividing the tacrolimus blood trough concentration (C) by the corresponding total daily tacrolimus dose (D). C/D ratio (ng/mL\*1/mg) = blood tacrolimus trough level (ng/mL)/total daily tacrolimus dose (mg).
Outcome measures
| Measure |
Tacrolimus, Immediate Release
n=24 Participants
Tacrolimus (immediate-release) will be administered twice daily per clinical judgment of supervising physician (dosing and monitoring in accordance with center protocol) to a minimum whole blood tacrolimus concentration of at least 8 ng/mL.
Tacrolimus: Tacrolimus immediate-release, oral; 0.5 mg, 1 mg, 5 mg capsules will be administered twice daily per clinical judgment of supervising physician
|
Envarsus XR
n=21 Participants
Envarsus XR (Tacrolimus Extended Release Oral Tablet) will be administered once daily at initial weight-based dose of 0.12 mg/kg. Dosing and monitoring thereafter predicated on clinical judgment to a minimum whole blood tacrolimus concentration of at least 8 ng/mL. When possible, patients will receive their daily dose of Envarsus using the fewest number of pills possible.
Tacrolimus Extended Release Oral Tablet: Tacrolimus, extended-release, oral (Envarsus); 0.75 mg, 1 mg, 4 mg tablets will be administered once daily at initial weight-based dose of 0.12 mg/kg.
|
|---|---|---|
|
Mean C/D Ratio
Month 1
|
1.68 ng/mL*1/mg
Standard Deviation 1.09
|
1.47 ng/mL*1/mg
Standard Deviation .98
|
|
Mean C/D Ratio
Month 2
|
1.86 ng/mL*1/mg
Standard Deviation .93
|
1.85 ng/mL*1/mg
Standard Deviation 1.07
|
|
Mean C/D Ratio
Month 3
|
2.00 ng/mL*1/mg
Standard Deviation 1.17
|
1.95 ng/mL*1/mg
Standard Deviation 1.17
|
|
Mean C/D Ratio
Month 6
|
1.92 ng/mL*1/mg
Standard Deviation 1.07
|
2.86 ng/mL*1/mg
Standard Deviation 2.13
|
|
Mean C/D Ratio
Month 9
|
2.05 ng/mL*1/mg
Standard Deviation 0.91
|
2.77 ng/mL*1/mg
Standard Deviation 2.33
|
|
Mean C/D Ratio
Month 12
|
1.92 ng/mL*1/mg
Standard Deviation 1.72
|
1.97 ng/mL*1/mg
Standard Deviation 1.6
|
SECONDARY outcome
Timeframe: 12 monthsSerum creatinine levels were measured to assess kidney function following transplantation
Outcome measures
| Measure |
Tacrolimus, Immediate Release
n=24 Participants
Tacrolimus (immediate-release) will be administered twice daily per clinical judgment of supervising physician (dosing and monitoring in accordance with center protocol) to a minimum whole blood tacrolimus concentration of at least 8 ng/mL.
Tacrolimus: Tacrolimus immediate-release, oral; 0.5 mg, 1 mg, 5 mg capsules will be administered twice daily per clinical judgment of supervising physician
|
Envarsus XR
n=21 Participants
Envarsus XR (Tacrolimus Extended Release Oral Tablet) will be administered once daily at initial weight-based dose of 0.12 mg/kg. Dosing and monitoring thereafter predicated on clinical judgment to a minimum whole blood tacrolimus concentration of at least 8 ng/mL. When possible, patients will receive their daily dose of Envarsus using the fewest number of pills possible.
Tacrolimus Extended Release Oral Tablet: Tacrolimus, extended-release, oral (Envarsus); 0.75 mg, 1 mg, 4 mg tablets will be administered once daily at initial weight-based dose of 0.12 mg/kg.
|
|---|---|---|
|
Mean Serum Creatinine Level
|
1.43 mg/dL
Standard Deviation 0.79
|
1.48 mg/dL
Standard Deviation 0.46
|
SECONDARY outcome
Timeframe: 12 monthsPatient survival is any subject that is known to be alive at the study conclusion.
Outcome measures
| Measure |
Tacrolimus, Immediate Release
n=24 Participants
Tacrolimus (immediate-release) will be administered twice daily per clinical judgment of supervising physician (dosing and monitoring in accordance with center protocol) to a minimum whole blood tacrolimus concentration of at least 8 ng/mL.
Tacrolimus: Tacrolimus immediate-release, oral; 0.5 mg, 1 mg, 5 mg capsules will be administered twice daily per clinical judgment of supervising physician
|
Envarsus XR
n=21 Participants
Envarsus XR (Tacrolimus Extended Release Oral Tablet) will be administered once daily at initial weight-based dose of 0.12 mg/kg. Dosing and monitoring thereafter predicated on clinical judgment to a minimum whole blood tacrolimus concentration of at least 8 ng/mL. When possible, patients will receive their daily dose of Envarsus using the fewest number of pills possible.
Tacrolimus Extended Release Oral Tablet: Tacrolimus, extended-release, oral (Envarsus); 0.75 mg, 1 mg, 4 mg tablets will be administered once daily at initial weight-based dose of 0.12 mg/kg.
|
|---|---|---|
|
Patient Survival Rate
|
24 Participants
|
21 Participants
|
SECONDARY outcome
Timeframe: 12 monthsGraft survival is defined as any subject that does not fit the following definition of graft loss: subject death, re-transplantation, transplant nephrectomy, or return to dialysis for a period of ≥6 weeks by study end.
Outcome measures
| Measure |
Tacrolimus, Immediate Release
n=24 Participants
Tacrolimus (immediate-release) will be administered twice daily per clinical judgment of supervising physician (dosing and monitoring in accordance with center protocol) to a minimum whole blood tacrolimus concentration of at least 8 ng/mL.
Tacrolimus: Tacrolimus immediate-release, oral; 0.5 mg, 1 mg, 5 mg capsules will be administered twice daily per clinical judgment of supervising physician
|
Envarsus XR
n=21 Participants
Envarsus XR (Tacrolimus Extended Release Oral Tablet) will be administered once daily at initial weight-based dose of 0.12 mg/kg. Dosing and monitoring thereafter predicated on clinical judgment to a minimum whole blood tacrolimus concentration of at least 8 ng/mL. When possible, patients will receive their daily dose of Envarsus using the fewest number of pills possible.
Tacrolimus Extended Release Oral Tablet: Tacrolimus, extended-release, oral (Envarsus); 0.75 mg, 1 mg, 4 mg tablets will be administered once daily at initial weight-based dose of 0.12 mg/kg.
|
|---|---|---|
|
Graft Survival Rate
|
24 Participants
|
21 Participants
|
SECONDARY outcome
Timeframe: 12 monthsFor study purposes, diagnoses of rejection require biopsy confirmation.
Outcome measures
| Measure |
Tacrolimus, Immediate Release
n=24 Participants
Tacrolimus (immediate-release) will be administered twice daily per clinical judgment of supervising physician (dosing and monitoring in accordance with center protocol) to a minimum whole blood tacrolimus concentration of at least 8 ng/mL.
Tacrolimus: Tacrolimus immediate-release, oral; 0.5 mg, 1 mg, 5 mg capsules will be administered twice daily per clinical judgment of supervising physician
|
Envarsus XR
n=21 Participants
Envarsus XR (Tacrolimus Extended Release Oral Tablet) will be administered once daily at initial weight-based dose of 0.12 mg/kg. Dosing and monitoring thereafter predicated on clinical judgment to a minimum whole blood tacrolimus concentration of at least 8 ng/mL. When possible, patients will receive their daily dose of Envarsus using the fewest number of pills possible.
Tacrolimus Extended Release Oral Tablet: Tacrolimus, extended-release, oral (Envarsus); 0.75 mg, 1 mg, 4 mg tablets will be administered once daily at initial weight-based dose of 0.12 mg/kg.
|
|---|---|---|
|
Number of Rejection Episodes
C4D+ antibody-mediated biopsy proven rejection
|
2 episodes
|
1 episodes
|
|
Number of Rejection Episodes
Borderline acute cellular rejection, possible antibody-mediated rejection
|
1 episodes
|
0 episodes
|
Adverse Events
Tacrolimus, Immediate Release
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Envarsus XR
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Tacrolimus, Immediate Release
n=24 participants at risk
Tacrolimus (immediate-release) will be administered twice daily per clinical judgment of supervising physician (dosing and monitoring in accordance with center protocol) to a minimum whole blood tacrolimus concentration of at least 8 ng/mL.
Tacrolimus: Tacrolimus immediate-release, oral; 0.5 mg, 1 mg, 5 mg capsules will be administered twice daily per clinical judgment of supervising physician
|
Envarsus XR
n=21 participants at risk
Envarsus XR (Tacrolimus Extended Release Oral Tablet) will be administered once daily at initial weight-based dose of 0.12 mg/kg. Dosing and monitoring thereafter predicated on clinical judgment to a minimum whole blood tacrolimus concentration of at least 8 ng/mL. When possible, patients will receive their daily dose of Envarsus using the fewest number of pills possible.
Tacrolimus Extended Release Oral Tablet: Tacrolimus, extended-release, oral (Envarsus); 0.75 mg, 1 mg, 4 mg tablets will be administered once daily at initial weight-based dose of 0.12 mg/kg.
|
|---|---|---|
|
Infections and infestations
BK Viremia
|
25.0%
6/24 • Number of events 6 • 1 year from transplantation
|
19.0%
4/21 • Number of events 4 • 1 year from transplantation
|
|
Infections and infestations
Cytomegalovirus
|
4.2%
1/24 • Number of events 1 • 1 year from transplantation
|
4.8%
1/21 • Number of events 1 • 1 year from transplantation
|
|
Infections and infestations
Epstein-Barr Virus
|
0.00%
0/24 • 1 year from transplantation
|
4.8%
1/21 • Number of events 1 • 1 year from transplantation
|
|
Infections and infestations
COVID-19 infection
|
4.2%
1/24 • Number of events 1 • 1 year from transplantation
|
0.00%
0/21 • 1 year from transplantation
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place