Renal Failure
Conditions
Brief summary
The purpose of the study is to compare the pharmacokinetic parameters of three different formulations of tacrolimus. Eligible patients will be treated with all three formulations in a pre-defined sequence.
Detailed description
The pharmacokinetic parameters T(max), C(max) and AUC(0-24) will be compared between the three formulations Envarsus XR once daily, Astagraf XL once daily and Prograf Twice daily.
Interventions
DRUGPrograf vs Envarsus XR vs Astagraf XL
prograf vs Envarsus XR vs Astagraf XL
DRUGPrograf vs Astagraf XL vs Envarsus XR
Prograf vs Astagraf XL vs Envarsus XR
Sponsors
Veloxis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Renal transplant recipients, males or females, of 18 years of age or above. 2. Able to participate and willing to give written informed consent and to comply with study visits and restrictions. 3. Able to understand English. 4. Patients having received a primary or secondary renal transplant
Exclusion criteria
1. Evidence of acute rejection episode within the past three months prior to screening. 2. Recipients of organ transplants other than kidney. 3. Patients who are known to be HIV positive.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of T(Max) for Envarsus XR, Astagraf XL and Prograf. | 8 days | Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling times was used to calculate T(max). Nominal time points used were: Prograf sampling strategy (21 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20, and 24. Envarsus XR sampling strategy (18 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, 24, and 27. Astagraf XL sampling strategy (17 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, and 24. |
| Evaluation of C(Max) for Envarsus XR, Astagraf XL and Prograf. | 8 days | Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling times was used to calculate C(max). Nominal time points used were: Prograf sampling strategy (21 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20, and 24. Envarsus XR sampling strategy (18 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, 24, and 27. Astagraf XL sampling strategy (17 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, and 24. |
| Evaluation of AUC(0-24) for Envarsus XR, Astagraf XL and Prograf. | 8 days | Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling times was used to calculate AUC(0-24). Nominal time points used were: Prograf sampling strategy (21 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20, and 24. Envarsus XR sampling strategy (18 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, 24, and 27. Astagraf XL sampling strategy (17 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, and 24. |
Countries
United States
Participant flow
Recruitment details
32 patients were screened (enrolled) and 31 were randomized to treatment.
Participants by arm
| Arm | Count |
|---|---|
| Prograf vs Envarsus XR vs Astagraf XL Prograft capsules Twice daily Envarsus XR tablets once daily Astagraf XL capsules once daily
Prograf vs Envarsus XR vs Astagraf XL: prograf vs Envarsus XR vs Astagraf XL | 16 |
| Prograf vs Astagraf XL vs Envarsus XR Prograf capsules twice daily Astagraf XL capsules once daily Envarsus XR tablets once daily
Prograf vs Astagraf XL vs Envarsus XR: Prograf vs Astagraf XL vs Envarsus XR | 15 |
| Total | 31 |
Baseline characteristics
| Characteristic | Prograf vs Astagraf XL vs Envarsus XR | Prograf vs Envarsus XR vs Astagraf XL | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 15 Participants | 29 Participants |
| Age, Continuous | 46.3 years STANDARD_DEVIATION 13.3 | 50.1 years STANDARD_DEVIATION 11 | 48.3 years STANDARD_DEVIATION 12.11 |
| Region of Enrollment United States | 15 participants | 16 participants | 31 participants |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 13 Participants |
| Sex: Female, Male Male | 9 Participants | 9 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 31 | 10 / 31 | 3 / 31 |
| serious Total, serious adverse events | 0 / 31 | 0 / 31 | 0 / 31 |
Outcome results
Primary
Evaluation of AUC(0-24) for Envarsus XR, Astagraf XL and Prograf.
Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling times was used to calculate AUC(0-24). Nominal time points used were: Prograf sampling strategy (21 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20, and 24. Envarsus XR sampling strategy (18 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, 24, and 27. Astagraf XL sampling strategy (17 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, and 24.
Time frame: 8 days
Population: One patient in the Envarsus XR arm was excluded from the analysis due to non compliance.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Envarsus XR | Evaluation of AUC(0-24) for Envarsus XR, Astagraf XL and Prograf. | 213.41 hr*ng/mL | Standard Deviation 83.095 |
| Astagraf XL | Evaluation of AUC(0-24) for Envarsus XR, Astagraf XL and Prograf. | 165.02 hr*ng/mL | Standard Deviation 48.91 |
| Prograf | Evaluation of AUC(0-24) for Envarsus XR, Astagraf XL and Prograf. | 176.52 hr*ng/mL | Standard Deviation 50.799 |
Primary
Evaluation of C(Max) for Envarsus XR, Astagraf XL and Prograf.
Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling times was used to calculate C(max). Nominal time points used were: Prograf sampling strategy (21 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20, and 24. Envarsus XR sampling strategy (18 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, 24, and 27. Astagraf XL sampling strategy (17 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, and 24.
Time frame: 8 days
Population: One patient in the Envarsus XR arm was excluded from the analysis due to non compliance.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Envarsus XR | Evaluation of C(Max) for Envarsus XR, Astagraf XL and Prograf. | 13.88 ng/mL | Standard Deviation 5.331 |
| Astagraf XL | Evaluation of C(Max) for Envarsus XR, Astagraf XL and Prograf. | 13.17 ng/mL | Standard Deviation 12.49 |
| Prograf | Evaluation of C(Max) for Envarsus XR, Astagraf XL and Prograf. | 14.54 ng/mL | Standard Deviation 13.6 |
Primary
Evaluation of T(Max) for Envarsus XR, Astagraf XL and Prograf.
Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling times was used to calculate T(max). Nominal time points used were: Prograf sampling strategy (21 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20, and 24. Envarsus XR sampling strategy (18 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, 24, and 27. Astagraf XL sampling strategy (17 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, and 24.
Time frame: 8 days
Population: One patient in the Envarsus XR arm was excluded from the analysis due to non compliance.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Envarsus XR | Evaluation of T(Max) for Envarsus XR, Astagraf XL and Prograf. | 5.91 hour |
| Astagraf XL | Evaluation of T(Max) for Envarsus XR, Astagraf XL and Prograf. | 1.93 hour |
| Prograf | Evaluation of T(Max) for Envarsus XR, Astagraf XL and Prograf. | 1.48 hour |