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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Prograf vs Envarsus XR vs Astagraf XL | Active Comparator | Prograft capsules Twice daily for 7 days, followed by Envarsus XR tablets once daily for 7 days followed by Astagraf XL capsules once daily for 7 days. |
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| Prograf vs Astagraf XL vs Envarsus XR | Active Comparator | Prograf capsules twice daily for 7 days followed by Astagraf XL capsules once daily for 7 days followed by Envarsus XR tablets once daily. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Prograf vs Envarsus XR vs Astagraf XL | Drug | prograf vs Envarsus XR vs Astagraf XL |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 8 days |
| 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. | 8 days |
| 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. | 8 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rita Alloway, PharmD | University of Cincinnati | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Cincinnati | Cincinnati | Ohio | 45267-2827 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29462506 | Derived | Philosophe B, Leca N, West-Thielke PM, Horwedel T, Culkin-Gemmell C, Kistler K, Stevens DR. Evaluation of Flexible Tacrolimus Drug Concentration Monitoring Approach in Patients Receiving Extended-Release Once-Daily Tacrolimus Tablets. J Clin Pharmacol. 2018 Jul;58(7):891-896. doi: 10.1002/jcph.1082. Epub 2018 Feb 20. | |
| 27340950 | Derived |
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32 patients were screened (enrolled) and 31 were randomized to treatment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Envarsus XR | Envarsus XR tablets once daily. |
| FG001 | Astagraf XL | Astagraf XL capsules once daily. |
| FG002 | Prograf | Prograf capsules twice daily. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (7 Days) |
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| Second Intervention (7 Days) |
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| Third Period (7 Days) |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | Prograf vs Astagraf XL vs Envarsus XR |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | One patient in the Envarsus XR arm was excluded from the analysis due to non compliance. | Posted | Median | 95% Confidence Interval | hour | 8 days |
|
Adverse events were collected from time of first dose of study drug and until last visit which was approximately 1 month.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Envarsus XR | Envarsus XR tablets once daily. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Christina Sylvest | Veloxis Pharmaceuticals | +4520553877 | csy@veloxis.com |
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| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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| ID | Term |
|---|---|
| D016559 | Tacrolimus |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
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| Prograf vs Astagraf XL vs Envarsus XR | Drug | Prograf vs Astagraf XL vs Envarsus XR |
|
|
| Tremblay S, Nigro V, Weinberg J, Woodle ES, Alloway RR. A Steady-State Head-to-Head Pharmacokinetic Comparison of All FK-506 (Tacrolimus) Formulations (ASTCOFF): An Open-Label, Prospective, Randomized, Two-Arm, Three-Period Crossover Study. Am J Transplant. 2017 Feb;17(2):432-442. doi: 10.1111/ajt.13935. Epub 2016 Aug 2. |
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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 |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| OG001 | Astagraf XL | Astagraf XL capsules once daily. |
| OG002 | Prograf | Prograf capsules twice daily. |
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| 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. | One patient in the Envarsus XR arm was excluded from the analysis due to non compliance. | Posted | Mean | Standard Deviation | ng/mL | 8 days |
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| 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. | One patient in the Envarsus XR arm was excluded from the analysis due to non compliance. | Posted | Mean | Standard Deviation | hr*ng/mL | 8 days |
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|
| 0 |
| 31 |
| 2 |
| 31 |
| EG001 | Astagraf XR | Astagraf XR capsules once daily. | 0 | 31 | 10 | 31 |
| EG002 | Prograf | Prograf capsules twice daily. | 0 | 31 | 3 | 31 |
| Vomiting | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 17.1 | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA 17.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
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| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |