Trial Outcomes & Findings for Extended Release Tacrolimus vs. Twice-Daily Tacrolimus (NCT NCT03289650)
NCT ID: NCT03289650
Last Updated: 2023-04-10
Results Overview
change in the mean eGFR from the baseline (2 weeks post transplant), 3 months (post transplant) , and 12 months (post transplant).
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
29 participants
Primary outcome timeframe
2 weeks post transplant through 12 months post transplant
Results posted on
2023-04-10
Participant Flow
Participant milestones
| Measure |
Group 1: Control Arm: Standard of Care (SOC) Tacrolimus
1-2 mg 2x daily (BID), per SOC. The dose will be modified to achieve 12 hours trough concentrations of 8-12 ng/ml
|
Group 2: Interventional Arm: Study Related Drug: LCP-Tacrolimus/Envarsus XR (LCP-Tacro/Envarsus XR)
One 5mg extended-release tablet taken once daily (QD) to achieve a 24-hour trough concentrations of 8-12 ng/ml
|
|---|---|---|
|
Overall Study
STARTED
|
14
|
15
|
|
Overall Study
COMPLETED
|
14
|
15
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Extended Release Tacrolimus vs. Twice-Daily Tacrolimus
Baseline characteristics by cohort
| Measure |
Standard of Care Tacrolimus Twice-daily
n=14 Participants
Tacrolimus: immunosuppressive agent tacrolimus, given twice-daily
|
Extended-release Tacrolimus Once-daily
n=15 Participants
Tacrolimus Extended Release Oral Tablet \[Envarsus\]: immunosuppressive agent extended-release tacrolimus, given once daily
|
Total
n=29 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
43.14 years
STANDARD_DEVIATION 12.7 • n=99 Participants
|
47.53 years
STANDARD_DEVIATION 16.04 • n=107 Participants
|
45.4 years
STANDARD_DEVIATION 14.4 • n=206 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=99 Participants
|
12 Participants
n=107 Participants
|
23 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=99 Participants
|
13 Participants
n=107 Participants
|
23 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Cause of Kidney Disease
Diabetes
|
3 participants
n=99 Participants
|
4 participants
n=107 Participants
|
7 participants
n=206 Participants
|
|
Cause of Kidney Disease
Glomerulonephritis
|
3 participants
n=99 Participants
|
4 participants
n=107 Participants
|
7 participants
n=206 Participants
|
|
Cause of Kidney Disease
Obstructive Nephropathy
|
2 participants
n=99 Participants
|
0 participants
n=107 Participants
|
2 participants
n=206 Participants
|
|
Cause of Kidney Disease
Congenital
|
1 participants
n=99 Participants
|
2 participants
n=107 Participants
|
3 participants
n=206 Participants
|
|
Cause of Kidney Disease
Others
|
5 participants
n=99 Participants
|
5 participants
n=107 Participants
|
10 participants
n=206 Participants
|
|
Type of Donor
Cadaveric
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Type of Donor
Living
|
14 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
28 Participants
n=206 Participants
|
|
Panel reactive antibodies (PRA)
Major histocompatibility complex class I (MHC-I) antibodies
|
1.93 percentage
STANDARD_DEVIATION 2.79 • n=99 Participants
|
4.20 percentage
STANDARD_DEVIATION 8.44 • n=107 Participants
|
3.1 percentage
STANDARD_DEVIATION 6.4 • n=206 Participants
|
|
Panel reactive antibodies (PRA)
Major histocompatibility complex class II (MHC-II) antibodies
|
3.07 percentage
STANDARD_DEVIATION 5.18 • n=99 Participants
|
4.07 percentage
STANDARD_DEVIATION 9.01 • n=107 Participants
|
3.6 percentage
STANDARD_DEVIATION 7.3 • n=206 Participants
|
|
Estimated glomerular filtration rate (eGFR)
|
52.43 ml/min/1.73m2
STANDARD_DEVIATION 9.26 • n=99 Participants
|
51.77 ml/min/1.73m2
STANDARD_DEVIATION 9.69 • n=107 Participants
|
52.1 ml/min/1.73m2
STANDARD_DEVIATION 10.6 • n=206 Participants
|
PRIMARY outcome
Timeframe: 2 weeks post transplant through 12 months post transplantchange in the mean eGFR from the baseline (2 weeks post transplant), 3 months (post transplant) , and 12 months (post transplant).
Outcome measures
| Measure |
Group 1: Control Arm: Standard of Care (SOC) Tacrolimus
n=14 Participants
Tacrolimus: immunosuppressive agent tacrolimus, 1-2 mg 2x daily (BID), per SOC. The dose will be modified to achieve 12 hours trough concentrations of 8-12 ng/ml
|
Group 2: Interventional Arm: Study Related Drug: LCP-Tacrolimus/Envarsus XR (LCP-Tacro/Envarsus XR)
n=15 Participants
Tacrolimus Extended Release Oral Tablet \[Envarsus\]: immunosuppressive agent extended-release tacrolimus, One 5mg extended-release tablet taken once daily (QD) to achieve a 24-hour trough concentrations of 8-12 ng/ml
|
|---|---|---|
|
Change in Kidney Transplant Function From 2 Weeks Post Transplant Through 12 Months Post Transplant
|
2.03 mL/min/1.73m^2
Standard Error 1.71
|
-2.19 mL/min/1.73m^2
Standard Error 1.77
|
SECONDARY outcome
Timeframe: Measured at 2 weeks post transplant, 3 months post transplant, 12 months post transplantPopulation: Secondary outcome data will not be reported because support to collect secondary data was not present
Blood, urine and kidney tissue analysis via serial flow cytometric immunophenotyping (includes regulatory T and B cell populations as well as immune functions).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Measured at 3 months post transplant, 12 months post transplantAcute rejection of kidney transplant is determined via biopsy.
Outcome measures
| Measure |
Group 1: Control Arm: Standard of Care (SOC) Tacrolimus
n=14 Participants
Tacrolimus: immunosuppressive agent tacrolimus, 1-2 mg 2x daily (BID), per SOC. The dose will be modified to achieve 12 hours trough concentrations of 8-12 ng/ml
|
Group 2: Interventional Arm: Study Related Drug: LCP-Tacrolimus/Envarsus XR (LCP-Tacro/Envarsus XR)
n=15 Participants
Tacrolimus Extended Release Oral Tablet \[Envarsus\]: immunosuppressive agent extended-release tacrolimus, One 5mg extended-release tablet taken once daily (QD) to achieve a 24-hour trough concentrations of 8-12 ng/ml
|
|---|---|---|
|
Number of Participants With Acute Rejection at 3 Months and 12 Months Post-Transplant
Acute rejection at 3 months
|
0 Participants
|
1 Participants
|
|
Number of Participants With Acute Rejection at 3 Months and 12 Months Post-Transplant
Acute rejection at 12 months
|
0 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Measured at 3 months post transplant, 12 months post transplantGraft loss is determined via biopsy.
Outcome measures
| Measure |
Group 1: Control Arm: Standard of Care (SOC) Tacrolimus
n=14 Participants
Tacrolimus: immunosuppressive agent tacrolimus, 1-2 mg 2x daily (BID), per SOC. The dose will be modified to achieve 12 hours trough concentrations of 8-12 ng/ml
|
Group 2: Interventional Arm: Study Related Drug: LCP-Tacrolimus/Envarsus XR (LCP-Tacro/Envarsus XR)
n=15 Participants
Tacrolimus Extended Release Oral Tablet \[Envarsus\]: immunosuppressive agent extended-release tacrolimus, One 5mg extended-release tablet taken once daily (QD) to achieve a 24-hour trough concentrations of 8-12 ng/ml
|
|---|---|---|
|
Number of Participants With Graft Loss at 3 Months and 12 Months Post-Transplant
Graft Loss at 3 months
|
0 Participants
|
0 Participants
|
|
Number of Participants With Graft Loss at 3 Months and 12 Months Post-Transplant
Graft loss at 12 months
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Through 12 months post transplantSubject survival status is continually monitored via routine follow-up visits.
Outcome measures
| Measure |
Group 1: Control Arm: Standard of Care (SOC) Tacrolimus
n=14 Participants
Tacrolimus: immunosuppressive agent tacrolimus, 1-2 mg 2x daily (BID), per SOC. The dose will be modified to achieve 12 hours trough concentrations of 8-12 ng/ml
|
Group 2: Interventional Arm: Study Related Drug: LCP-Tacrolimus/Envarsus XR (LCP-Tacro/Envarsus XR)
n=15 Participants
Tacrolimus Extended Release Oral Tablet \[Envarsus\]: immunosuppressive agent extended-release tacrolimus, One 5mg extended-release tablet taken once daily (QD) to achieve a 24-hour trough concentrations of 8-12 ng/ml
|
|---|---|---|
|
Number of Subjects Deceased at at 3 Months and 12 Months Post-Transplant
Subject Death at 3 months
|
0 Participants
|
0 Participants
|
|
Number of Subjects Deceased at at 3 Months and 12 Months Post-Transplant
Subject Death at 12 months
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Measured at 3 months post transplant, 12 months post transplantTissue analysis via immunohistopathological staining and microscopic examination Moderate acute tubular necrosis =\> presence of focal coagulative necrosis or infarction on histopathologic examination Arteriolar hyalinosis grade 2 means: Replacement of degenerated smooth muscle cells by hyaline deposits in more than 1 arteriole, without circumferential involvement Global glomerulosclerosis \>grade 2, means glomerulosclerosis affecting more than 50% of glomeruli in the biopsy sample IFTA : Interstitial fibrosis and tubular atrophy: Inflammation in 26% to 50% of scarred cortical parenchyma
Outcome measures
| Measure |
Group 1: Control Arm: Standard of Care (SOC) Tacrolimus
n=14 Participants
Tacrolimus: immunosuppressive agent tacrolimus, 1-2 mg 2x daily (BID), per SOC. The dose will be modified to achieve 12 hours trough concentrations of 8-12 ng/ml
|
Group 2: Interventional Arm: Study Related Drug: LCP-Tacrolimus/Envarsus XR (LCP-Tacro/Envarsus XR)
n=15 Participants
Tacrolimus Extended Release Oral Tablet \[Envarsus\]: immunosuppressive agent extended-release tacrolimus, One 5mg extended-release tablet taken once daily (QD) to achieve a 24-hour trough concentrations of 8-12 ng/ml
|
|---|---|---|
|
Number of Participants With Change in Allograft Immunohistopathology Profile
Acute tubular necrosis > moderate >=2
|
2 Participants
|
2 Participants
|
|
Number of Participants With Change in Allograft Immunohistopathology Profile
Arteriolar Hyalinosis >= grade 2
|
2 Participants
|
2 Participants
|
|
Number of Participants With Change in Allograft Immunohistopathology Profile
isometric vacuolization of tubules
|
0 Participants
|
1 Participants
|
|
Number of Participants With Change in Allograft Immunohistopathology Profile
Arteriolar myocyte vacuolization
|
0 Participants
|
0 Participants
|
|
Number of Participants With Change in Allograft Immunohistopathology Profile
Thrombotic microangiopathy
|
1 Participants
|
1 Participants
|
|
Number of Participants With Change in Allograft Immunohistopathology Profile
Global glomerulosclerosis >grade 2
|
1 Participants
|
2 Participants
|
|
Number of Participants With Change in Allograft Immunohistopathology Profile
IFTA > grade 2
|
1 Participants
|
2 Participants
|
Adverse Events
Standard of Care Tacrolimus Twice-daily
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Extended-release Tacrolimus Once-daily
Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Standard of Care Tacrolimus Twice-daily
n=14 participants at risk
Tacrolimus: immunosuppressive agent tacrolimus, given twice-daily
|
Extended-release Tacrolimus Once-daily
n=15 participants at risk
Tacrolimus Extended Release Oral Tablet \[Envarsus\]: immunosuppressive agent extended-release tacrolimus, given once daily
|
|---|---|---|
|
Renal and urinary disorders
Hospitalizations
|
0.00%
0/14 • Adverse events were reviewed at 1 year after tranplant
|
6.7%
1/15 • Number of events 1 • Adverse events were reviewed at 1 year after tranplant
|
Other adverse events
| Measure |
Standard of Care Tacrolimus Twice-daily
n=14 participants at risk
Tacrolimus: immunosuppressive agent tacrolimus, given twice-daily
|
Extended-release Tacrolimus Once-daily
n=15 participants at risk
Tacrolimus Extended Release Oral Tablet \[Envarsus\]: immunosuppressive agent extended-release tacrolimus, given once daily
|
|---|---|---|
|
Immune system disorders
Infections
|
7.1%
1/14 • Number of events 1 • Adverse events were reviewed at 1 year after tranplant
|
6.7%
1/15 • Number of events 1 • Adverse events were reviewed at 1 year after tranplant
|
|
Immune system disorders
Malignancy
|
0.00%
0/14 • Adverse events were reviewed at 1 year after tranplant
|
0.00%
0/15 • Adverse events were reviewed at 1 year after tranplant
|
|
Immune system disorders
Leukopenia
|
28.6%
4/14 • Number of events 4 • Adverse events were reviewed at 1 year after tranplant
|
26.7%
4/15 • Number of events 4 • Adverse events were reviewed at 1 year after tranplant
|
|
Renal and urinary disorders
BK Viremia
|
14.3%
2/14 • Number of events 2 • Adverse events were reviewed at 1 year after tranplant
|
0.00%
0/15 • Adverse events were reviewed at 1 year after tranplant
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place