Trial Outcomes & Findings for Dosing Strategies for de Novo Once-daily Extended Release Tacrolimus (LCPT) in Kidney Transplant Recipients (NCT NCT03713645)
NCT ID: NCT03713645
Last Updated: 2023-05-11
Results Overview
Therapeutic tacrolimus trough= 8-10ng/mL
COMPLETED
PHASE4
36 participants
Within the first 30 days of kidney transplant
2023-05-11
Participant Flow
Participant milestones
| Measure |
Tacrolimus Extended-release 0.13mg/kg/Day
Tacrolimus extended-release is initiated within post-operative day 3 of kidney transplant
Tacrolimus Extended Release Oral Tablet \[Envarsus\] 0.13mg/kg/day initiated within post-operative day 3 after kidney transplant: Study drug (tacrolimus extended-release) initiated at 0.13/mg/kg/day for all patients
|
|---|---|
|
Overall Study
STARTED
|
36
|
|
Overall Study
COMPLETED
|
36
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Dosing Strategies for de Novo Once-daily Extended Release Tacrolimus (LCPT) in Kidney Transplant Recipients
Baseline characteristics by cohort
| Measure |
Tacrolimus Extended-release 0.13mg/kg/Day
n=36 Participants
Tacrolimus extended-release is initiated within post-operative day 3 of kidney transplant
Tacrolimus Extended Release Oral Tablet \[Envarsus\] 0.13mg/kg/day initiated within post-operative day 3 after kidney transplant: Study drug (tacrolimus extended-release) initiated at 0.13/mg/kg/day for all patients
|
|---|---|
|
Age, Continuous
|
55 years
STANDARD_DEVIATION 13.7 • n=99 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
24 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=99 Participants
|
|
History of hypertension
|
28 participants
n=99 Participants
|
|
History of diabetes mellitus
|
9 participants
n=99 Participants
|
|
History of focal segmental glomerulosclerosis
|
1 participants
n=99 Participants
|
|
Calculated panel reactive antibody (%)
|
0 percentage
n=99 Participants
|
|
Actual body weight (kg)
|
87.4 kg
STANDARD_DEVIATION 18.4 • n=99 Participants
|
|
Body mass index
|
30 kg/m^2
STANDARD_DEVIATION 5.5 • n=99 Participants
|
|
Deceased donor
|
25 participants
n=99 Participants
|
|
Living Donor
|
11 participants
n=99 Participants
|
|
History of prior transplant
|
1 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Within the first 30 days of kidney transplantPopulation: Two participants were not included in the genotype analysis comparison since their genotype samples were unable to be analyzed.
Therapeutic tacrolimus trough= 8-10ng/mL
Outcome measures
| Measure |
Non-Expresser
n=15 Participants
Participant who did not express activity of the CYP3A5 enzyme
|
Intermediate Metabolizer
n=13 Participants
Participant who expressed at least one CYP3A5\*1 allele
|
Extensive Metabolizer
n=6 Participants
Participant who expressed two CYP3A5\*1 alleles
|
|---|---|---|---|
|
Time to First Therapeutic Tacrolimus Trough Concentration From Initiation of Tacrolimus Extended Release Measured in Days
|
4.5 days
Interval 1.0 to 7.0
|
6 days
Interval 4.0 to 11.5
|
13.5 days
Interval 7.5 to 20.25
|
SECONDARY outcome
Timeframe: 30 daysPopulation: Kidney transplant recipients
eGFR
Outcome measures
| Measure |
Non-Expresser
n=15 Participants
Participant who did not express activity of the CYP3A5 enzyme
|
Intermediate Metabolizer
n=13 Participants
Participant who expressed at least one CYP3A5\*1 allele
|
Extensive Metabolizer
n=6 Participants
Participant who expressed two CYP3A5\*1 alleles
|
|---|---|---|---|
|
Average Estimated Glomerular Filtration Rate Within 30 Days
|
40 ml/min/173m^2
Interval 27.0 to 58.0
|
46 ml/min/173m^2
Interval 30.0 to 58.5
|
31.5 ml/min/173m^2
Interval 25.0 to 56.3
|
SECONDARY outcome
Timeframe: At 30 days after kidney transplantPopulation: Kidney transplant recipients
Assessed via QUEST questionnaire which includes a self-assessment of tremor impact on quality of life. The following areas related to impact on tremor are assessed by this scale: 1. Patients will select the severity of tremor in each of the following body parts on a scale of (none: no tremor at any time, mild: mild tremor not causing difficulty in performing any activities, moderate: tremor causes difficulty in performing some activities, marked: tremor causes difficulty in performing most or all activities, severe: tremor prevents performing some activities). * Head * Voice * Right arm/hand * Left arm/hand * Right leg/foot * Left leg/foot 2. Several questions will be answered relating to specific situations and the impact of tremor on those situations (scale: never/no, rarely, sometimes, frequently, always/yes, not applicable)
Outcome measures
| Measure |
Non-Expresser
n=36 Participants
Participant who did not express activity of the CYP3A5 enzyme
|
Intermediate Metabolizer
Participant who expressed at least one CYP3A5\*1 allele
|
Extensive Metabolizer
Participant who expressed two CYP3A5\*1 alleles
|
|---|---|---|---|
|
Number of Participants With no Impact of Tremor on Quality of Life
|
35 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 30 daysPopulation: Kidney transplant recipients
Weight-based tacrolimus dose during study period
Outcome measures
| Measure |
Non-Expresser
n=15 Participants
Participant who did not express activity of the CYP3A5 enzyme
|
Intermediate Metabolizer
n=13 Participants
Participant who expressed at least one CYP3A5\*1 allele
|
Extensive Metabolizer
n=6 Participants
Participant who expressed two CYP3A5\*1 alleles
|
|---|---|---|---|
|
Weight-based Tacrolimus Dose During Study Period
|
0.128 mg/kg/day
Interval 0.102 to 0.142
|
0.136 mg/kg/day
Interval 0.108 to 0.169
|
0.176 mg/kg/day
Interval 0.128 to 0.217
|
SECONDARY outcome
Timeframe: 30 daysPopulation: Kidney transplant recipients
Tacrolimus dose during study period
Outcome measures
| Measure |
Non-Expresser
n=15 Participants
Participant who did not express activity of the CYP3A5 enzyme
|
Intermediate Metabolizer
n=13 Participants
Participant who expressed at least one CYP3A5\*1 allele
|
Extensive Metabolizer
n=6 Participants
Participant who expressed two CYP3A5\*1 alleles
|
|---|---|---|---|
|
Tacrolimus Dose During Study Period
|
9.6 mg/day
Interval 9.2 to 10.1
|
12.5 mg/day
Interval 10.6 to 14.5
|
13.8 mg/day
Interval 10.4 to 14.4
|
SECONDARY outcome
Timeframe: 30 daysPopulation: Kidney transplant recipients
Tacrolimus trough level during study period
Outcome measures
| Measure |
Non-Expresser
n=15 Participants
Participant who did not express activity of the CYP3A5 enzyme
|
Intermediate Metabolizer
n=13 Participants
Participant who expressed at least one CYP3A5\*1 allele
|
Extensive Metabolizer
n=6 Participants
Participant who expressed two CYP3A5\*1 alleles
|
|---|---|---|---|
|
Tacrolimus Trough Level During Study Period
|
10.78 ng/mL
Standard Deviation 2.1
|
9.18 ng/mL
Standard Deviation 1.6
|
7.98 ng/mL
Standard Deviation 1.3
|
SECONDARY outcome
Timeframe: At time of therapeutic tacrolimus concentration up to 30 daysPopulation: Kidney transplant recipients
Weight based tacrolimus dose at therapeutic concentration
Outcome measures
| Measure |
Non-Expresser
n=15 Participants
Participant who did not express activity of the CYP3A5 enzyme
|
Intermediate Metabolizer
n=13 Participants
Participant who expressed at least one CYP3A5\*1 allele
|
Extensive Metabolizer
n=6 Participants
Participant who expressed two CYP3A5\*1 alleles
|
|---|---|---|---|
|
Weight Based Tacrolimus Dose at Therapeutic Concentration
|
0.13 mg/kg/day
Interval 0.12 to 0.165
|
0.20 mg/kg/day
Interval 0.125 to 0.25
|
0.19 mg/kg/day
Interval 0.138 to 0.265
|
SECONDARY outcome
Timeframe: At time of therapeutic tacrolimus concentration up to 30 daysPopulation: Kidney transplant recipients
Tacrolimus dose at therapeutic tacrolimus concentration
Outcome measures
| Measure |
Non-Expresser
n=15 Participants
Participant who did not express activity of the CYP3A5 enzyme
|
Intermediate Metabolizer
n=13 Participants
Participant who expressed at least one CYP3A5\*1 allele
|
Extensive Metabolizer
n=6 Participants
Participant who expressed two CYP3A5\*1 alleles
|
|---|---|---|---|
|
Tacrolimus Dose at Therapeutic Tacrolimus Concentration
|
12 mg/day
Interval 10.0 to 14.0
|
16 mg/day
Interval 13.0 to 20.0
|
16 mg/day
Interval 11.0 to 20.5
|
Adverse Events
Tacrolimus Extended-release 0.13mg/kg/Day
Serious adverse events
| Measure |
Tacrolimus Extended-release 0.13mg/kg/Day
n=36 participants at risk
Tacrolimus extended-release is initiated within post-operative day 3 of kidney transplant
Tacrolimus Extended Release Oral Tablet \[Envarsus\] 0.13mg/kg/day initiated within post-operative day 3 after kidney transplant: Study drug (tacrolimus extended-release) initiated at 0.13/mg/kg/day for all patients
|
|---|---|
|
Nervous system disorders
Neurotoxicity
|
2.8%
1/36 • Number of events 1 • 30 days
|
Other adverse events
Adverse event data not reported
Additional Information
Adam Diamond, PharmD, BCPS, FAST
Temple University Hospital, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place