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A study to assess the pharmacokinetics, safety and effectiveness of tacrolimus in stable kidney transplant patients converted from a Prograf® based immunosuppression regimen to a modified release tacrolimus based immunosuppression regimen.
This is a Phase II open-label, multi-center conversion study in stable, adult kidney transplant recipients to assess the pharmacokinetics, safety and effectiveness of tacrolimus in stable kidney transplant patients converted from a Prograf® based immunosuppression regimen to a modified release tacrolimus based immunosuppression regimen.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tacrolimus Modified Release | Experimental | Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tacrolimus Modified Release (MR) | Drug | Oral |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) for Tacrolimus | The area under the concentration-time curve was calculated from whole blood tacrolimus concentrations for both tacrolimus and tacrolimus MR at steady state using the trapezoidal rule. | For tacrolimus, Days 1 and 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Days 14 and 21 pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose. |
| Maximum Observed Concentration (Cmax) of Tacrolimus | The maximum concentration was calculated from whole blood tacrolimus concentrations for both tacrolimus and tacrolimus MR at steady state, without interpolation. | For tacrolimus, Days 1 and 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Days 14 and 21 pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose. |
| Minimum Concentration of Tacrolimus (Cmin) | The trough (minimum) concentration of tacrolimus determined from the tacrolimus whole blood concentration value at the 24-hour time point post- dose, prior to receiving the next dose. | Days 1 and 7 (tacrolimus) and Days 14 and 21 (tacrolimus MR), 24 hours post-dose. |
| Time to Maximum Observed Concentration of Tacrolimus (Tmax) | The time to reach the maximum concentration of tacrolimus was calculated from whole blood tacrolimus concentrations for both tacrolimus and tacrolimus MR at steady state, without interpolation. | For tacrolimus, Days 1 and 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Days 14 and 21 pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose. |
| Patient Survival |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Biopsy-confirmed Acute Rejection | Biopsy-confirmed acute rejection (BCAR) is defined as an episode of acute allograft rejection that was confirmed by biopsy results and was Banff grade ≥ IA. Biopsies were graded by the pathologist at the clinical site according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis; Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Central Contact | Astellas Pharma US, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| San Diego | California | United States | ||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17589351 | Background | Alloway R, Steinberg S, Khalil K, Gourishankar S, Miller J, Norman D, Hariharan S, Pirsch J, Matas A, Zaltzman J, Wisemandle K, Fitzsimmons W, First MR. Two years postconversion from a prograf-based regimen to a once-daily tacrolimus extended-release formulation in stable kidney transplant recipients. Transplantation. 2007 Jun 27;83(12):1648-51. doi: 10.1097/01.tp.0000264056.20105.b4. | |
| 15848559 |
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Pharmacokinetic (PK) treatment period was from Day 1 - 35. Participants who completed the PK period were eligible to continue receiving tacrolimus MR in the extended treatment period, from Day 36 up to 60 months.
Stable, adult kidney transplant recipients being treated with tacrolimus (Prograf)-based immunosuppressive regimen.
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| ID | Title | Description |
|---|---|---|
| FG000 | Tacrolimus Modified Release | Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Pharmacokinetic Treatment Period |
|
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| tacrolimus | Drug | Oral |
|
|
Patient Survival defined as any participant who did not die by the time of analysis.
| From enrollment until the end of study (up to 60 months). |
| Graft Survival | Graft survival was defined as any participant who did not meet the definition of graft loss, where graft loss was defined as graft failure (re-transplant or permanent return to dialysis (for more than 30 days)) or participants death. | From enrollment until the end of study (up to 60 months). |
| From enrollment until the end of study (up to 60 months). |
| Change From Baseline in Serum Creatinine | Renal function was assessed using serum creatinine levels over the course of the study. | Baseline (the last day of tacrolimus on Day 7), Day 35 (end of the pharmacokinetic phase) and end of treatment (EOT; the last observed value during treatment, maximum time on study was 60 months). |
| Change From Baseline in Creatinine Clearance | Renal function was assessed using creatinine clearance levels calculated using the Cockcroft-Gault formula, over the course of the study. | Baseline (the last day of tacrolimus on Day 7), Day 35 (end of the pharmacokinetic phase) and end of treatment (EOT; the last observed value during treatment, maximum time on study was 60 months). |
| Time to Event for Patient Non Survival | For participants who died on study, the median number of days from enrollment to death due to any cause. | From enrollment until the end of study (up to 60 months). |
| Time to Event for Graft Non Survival | For participants with graft loss, the median number of days from enrollment to graft loss. Graft loss was defined as graft failure (re-transplant or permanent return to dialysis (for more than 30 days)) or participant death. | From enrollment until the end of study (up to 60 months). |
| Time to First Biopsy-confirmed Acute Rejection | For participants with a biopsy-confirmed acute rejection, the median number of days from enrollment to the date of biopsy confirmation. Biopsy-confirmed acute rejection (BCAR) is defined as an episode of acute allograft rejection that was confirmed by biopsy results and was Banff grade ≥ IA. Biopsies were graded by the pathologist at the clinical site according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis; Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel. | From enrollment until the end of study (up to 60 months). |
| Grade of Biopsy-confirmed Acute Rejection Episodes | Biopsy-confirmed acute rejection (BCAR) is defined as an episode of acute allograft rejection that was confirmed by biopsy results and was Banff grade ≥ IA. Biopsies were graded by the pathologist at the clinical site according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis; Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel. For participants with more than one biopsy-confirmed acute rejection episode, the worst case grade is reported. | From enrollment until the end of study (up to 60 months). |
| Number of Participants Receiving Anti-lymphocyte Antibody Therapy for Acute Rejection | Steroid-resistant rejection episodes were treated with anti-lymphocyte antibodies. If a participant had a histologically proven Banff Grade II or III rejection, they could be initiated on anti-lymphocyte antibody treatment per institutional practice. Biopsies were graded by the pathologist at the clinical site according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis; Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel. | From enrollment until the end of study (up to 60 months). |
| Number of Participants With Multiple Rejection Episodes | This analysis includes rejection episodes that were either confirmed by biopsy by the clinical site pathologist or were clinically treated. | From enrollment until the end of study (up to 60 months). |
| Number of Participants With Clinically Treated Acute Rejection Episodes | A clinically treated acute rejection episode was any biopsy-confirmed or suspected rejection episode that was treated with immunosuppressive therapy. | From enrollment until the end of study (up to 60 months). |
| Number of Participants With Chronic Rejection | Due to the low number of participants with biopsy-confirmed acute rejection episodes, chronic rejection was not analyzed. | From enrollment until the end of study (up to 60 months). |
| Number of Participants With Treatment Failure | Treatment failure was defined as discontinuation of study drug for any reason. Due to discontinuation of the study by the sponsor, treatment failure was not analyzed. | From enrollment until the end of study (up to 60 months). |
| Primary Reason for Graft Loss | The primary reason for graft loss was recorded by the Investigator. Graft loss was defined as graft failure (re-transplant or permanent return to dialysis) or death. GBM = glomerular basement membrane. | From enrollment until the end of study (up to 60 months). |
| Number of Participants Returning to Permanent Dialysis | Permanent dialysis defined as dialysis for longer than 30 days. | From enrollment until the end of study (up to 60 months). |
| Safety as Assessed by Adverse Events, Laboratory Parameters and Vital Signs | An adverse event was defined as any reaction, side effect or other untoward medical occurrence, regardless of the relationship to study drug which occurred during the conduct of a clinical study. Clinically significant adverse changes in clinical status, routine laboratory studies or physical examinations were considered adverse events. A serious adverse event was any adverse event occurring at any dose that resulted in any of the following outcomes:
| From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). |
| Miami |
| Florida |
| 33136 |
| United States |
| Minneapolis | Minnesota | 55455 | United States |
| Cincinnati | Ohio | 45267 | United States |
| Portland | Oregon | 97239 | United States |
| Madison | Wisconsin | 53792 | United States |
| Milwaukee | Wisconsin | 53226 | United States |
| Edmonton | Alberta | T6G 2B7 | Canada |
| Toronto | Ontario | M5C 2T2 | Canada |
| Background |
| Alloway R, Steinberg S, Khalil K, Gourishankar S, Miller J, Norman D, Hariharan S, Pirsch J, Matas A, Zaltzman J, Wisemandle K, Fitzsimmons W, First MR. Conversion of stable kidney transplant recipients from a twice daily Prograf-based regimen to a once daily modified release tacrolimus-based regimen. Transplant Proc. 2005 Mar;37(2):867-70. doi: 10.1016/j.transproceed.2004.12.222. |
| Received Tacrolimus |
|
| Received Tacrolimus MR |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Extended Treatment Period |
|
|
Pharmacokinetic evaluable set defined as all patients with all five complete pharmacokinetic profiles (two tacrolimus and three tacrolimus MR).
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Tacrolimus Modified Release | Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean | Standard Deviation | years |
| ||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||||||||||||||
| Race/Ethnicity, Customized | Number | participants |
| |||||||||||||||||||||||
| Reason for End Stage Renal Disease | Number | participants |
| |||||||||||||||||||||||
| Type of Current Transplant | Number | participants |
| |||||||||||||||||||||||
| Re-transplant | Number | participants |
| |||||||||||||||||||||||
| History of Pre-Study Dialysis | Number | 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 | Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) for Tacrolimus | The area under the concentration-time curve was calculated from whole blood tacrolimus concentrations for both tacrolimus and tacrolimus MR at steady state using the trapezoidal rule. | The number of participants analyzed represents the Pharmacokinetic evaluable set, defined as patients with all five complete pharmacokinetic profiles (two tacrolimus and three tacrolimus MR). | Posted | Mean | Standard Deviation | ng*hr/mL | For tacrolimus, Days 1 and 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Days 14 and 21 pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose. |
|
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| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Biopsy-confirmed Acute Rejection | Biopsy-confirmed acute rejection (BCAR) is defined as an episode of acute allograft rejection that was confirmed by biopsy results and was Banff grade ≥ IA. Biopsies were graded by the pathologist at the clinical site according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis; Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel. | Modified full analysis set | Posted | Number | 95% Confidence Interval | percentage of participants | From enrollment until the end of study (up to 60 months). |
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| Primary | Maximum Observed Concentration (Cmax) of Tacrolimus | The maximum concentration was calculated from whole blood tacrolimus concentrations for both tacrolimus and tacrolimus MR at steady state, without interpolation. | The number of participants analyzed represents the Pharmacokinetic evaluable set. | Posted | Mean | Standard Deviation | ng/mL | For tacrolimus, Days 1 and 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Days 14 and 21 pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose. |
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| Primary | Minimum Concentration of Tacrolimus (Cmin) | The trough (minimum) concentration of tacrolimus determined from the tacrolimus whole blood concentration value at the 24-hour time point post- dose, prior to receiving the next dose. | The number of participants analyzed represents the trough evaluable set defined as all patients with replicate trough measurements for both tacrolimus and tacrolimus MR. | Posted | Mean | Standard Deviation | ng/mL | Days 1 and 7 (tacrolimus) and Days 14 and 21 (tacrolimus MR), 24 hours post-dose. |
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| Primary | Time to Maximum Observed Concentration of Tacrolimus (Tmax) | The time to reach the maximum concentration of tacrolimus was calculated from whole blood tacrolimus concentrations for both tacrolimus and tacrolimus MR at steady state, without interpolation. | The number of participants analyzed represents the trough evaluable set defined as all patients with replicate trough measurements for both tacrolimus and tacrolimus MR. | Posted | Mean | Standard Deviation | hours | For tacrolimus, Days 1 and 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Days 14 and 21 pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose. |
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| Primary | Patient Survival | Patient Survival defined as any participant who did not die by the time of analysis. | Modified full analysis set, defined as all patients who took at least one dose of tacrolimus MR during the extension portion of the study. | Posted | Number | 95% Confidence Interval | percentage of participants | From enrollment until the end of study (up to 60 months). |
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| Primary | Graft Survival | Graft survival was defined as any participant who did not meet the definition of graft loss, where graft loss was defined as graft failure (re-transplant or permanent return to dialysis (for more than 30 days)) or participants death. | Modified full analysis set, defined as all patients who took at least one dose of tacrolimus MR during the extension portion of the study. | Posted | Number | 95% Confidence Interval | percentage of participants | From enrollment until the end of study (up to 60 months). |
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| Secondary | Change From Baseline in Serum Creatinine | Renal function was assessed using serum creatinine levels over the course of the study. | Modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus and at least one dose of tacrolimus MR during the pharmacokinetic portion of the study. "N" indicates the number of participants with available data at each time point." | Posted | Mean | Standard Deviation | mg/dL | Baseline (the last day of tacrolimus on Day 7), Day 35 (end of the pharmacokinetic phase) and end of treatment (EOT; the last observed value during treatment, maximum time on study was 60 months). |
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| Secondary | Change From Baseline in Creatinine Clearance | Renal function was assessed using creatinine clearance levels calculated using the Cockcroft-Gault formula, over the course of the study. | Modified safety analysis set | Posted | Mean | Standard Deviation | mL/minute | Baseline (the last day of tacrolimus on Day 7), Day 35 (end of the pharmacokinetic phase) and end of treatment (EOT; the last observed value during treatment, maximum time on study was 60 months). |
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| Secondary | Time to Event for Patient Non Survival | For participants who died on study, the median number of days from enrollment to death due to any cause. | Participants in the modified full analysis set who died on study. | Posted | Median | Full Range | days | From enrollment until the end of study (up to 60 months). |
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| Secondary | Time to Event for Graft Non Survival | For participants with graft loss, the median number of days from enrollment to graft loss. Graft loss was defined as graft failure (re-transplant or permanent return to dialysis (for more than 30 days)) or participant death. | Participants in the modified full analysis set with graft loss. | Posted | Median | Full Range | days | From enrollment until the end of study (up to 60 months). |
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| Secondary | Time to First Biopsy-confirmed Acute Rejection | For participants with a biopsy-confirmed acute rejection, the median number of days from enrollment to the date of biopsy confirmation. Biopsy-confirmed acute rejection (BCAR) is defined as an episode of acute allograft rejection that was confirmed by biopsy results and was Banff grade ≥ IA. Biopsies were graded by the pathologist at the clinical site according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis; Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel. | Participants in the modified full analysis set with a biopsy-confirmed acute rejection. | Posted | Median | Full Range | days | From enrollment until the end of study (up to 60 months). |
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| Secondary | Grade of Biopsy-confirmed Acute Rejection Episodes | Biopsy-confirmed acute rejection (BCAR) is defined as an episode of acute allograft rejection that was confirmed by biopsy results and was Banff grade ≥ IA. Biopsies were graded by the pathologist at the clinical site according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis; Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel. For participants with more than one biopsy-confirmed acute rejection episode, the worst case grade is reported. | Participants in the modified full analysis set with a biopsy-confirmed acute rejection. | Posted | Number | participants | From enrollment until the end of study (up to 60 months). |
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| Secondary | Number of Participants Receiving Anti-lymphocyte Antibody Therapy for Acute Rejection | Steroid-resistant rejection episodes were treated with anti-lymphocyte antibodies. If a participant had a histologically proven Banff Grade II or III rejection, they could be initiated on anti-lymphocyte antibody treatment per institutional practice. Biopsies were graded by the pathologist at the clinical site according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis; Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel. | Modified full analysis set | Posted | Number | participants | From enrollment until the end of study (up to 60 months). |
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| Secondary | Number of Participants With Multiple Rejection Episodes | This analysis includes rejection episodes that were either confirmed by biopsy by the clinical site pathologist or were clinically treated. | Modified full analysis set | Posted | Number | participants | From enrollment until the end of study (up to 60 months). |
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| Secondary | Number of Participants With Clinically Treated Acute Rejection Episodes | A clinically treated acute rejection episode was any biopsy-confirmed or suspected rejection episode that was treated with immunosuppressive therapy. | Modified full analysis set | Posted | Number | participants | From enrollment until the end of study (up to 60 months). |
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| Secondary | Number of Participants With Chronic Rejection | Due to the low number of participants with biopsy-confirmed acute rejection episodes, chronic rejection was not analyzed. | Posted | From enrollment until the end of study (up to 60 months). |
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| Secondary | Number of Participants With Treatment Failure | Treatment failure was defined as discontinuation of study drug for any reason. Due to discontinuation of the study by the sponsor, treatment failure was not analyzed. | Posted | From enrollment until the end of study (up to 60 months). |
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| Secondary | Primary Reason for Graft Loss | The primary reason for graft loss was recorded by the Investigator. Graft loss was defined as graft failure (re-transplant or permanent return to dialysis) or death. GBM = glomerular basement membrane. | Participants in the modified full analysis set with graft loss. | Posted | Number | participants | From enrollment until the end of study (up to 60 months). |
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| Secondary | Number of Participants Returning to Permanent Dialysis | Permanent dialysis defined as dialysis for longer than 30 days. | Modified full analysis set | Posted | Number | participants | From enrollment until the end of study (up to 60 months). |
|
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| Secondary | Safety as Assessed by Adverse Events, Laboratory Parameters and Vital Signs | An adverse event was defined as any reaction, side effect or other untoward medical occurrence, regardless of the relationship to study drug which occurred during the conduct of a clinical study. Clinically significant adverse changes in clinical status, routine laboratory studies or physical examinations were considered adverse events. A serious adverse event was any adverse event occurring at any dose that resulted in any of the following outcomes:
| Modified safety analysis set | Posted | Number | participants | From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). |
|
From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months).
Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tacrolimus Modified Release | Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons. | 39 | 67 | 48 | 67 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cellulitis | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Escherichia urinary tract infection | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Abscess limb | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Cellulitis staphylococcal | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Clostridium colitis | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Hepatitis c | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Human polyomavirus infection | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Orchitis | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Pneumonitis cryptococcal | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Pyelonephritis acute | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Sepsis syndrome | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Tracheobronchitis | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Urinary tract infection bacterial | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Abdominal pain lower | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Abdominal strangulated hernia | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Anal ulcer | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Coeliac disease | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Diarrhoea haemorrhagic | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Intestinal perforation | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Palatal dysplasia | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (6.1) | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (6.1) | Systematic Assessment |
| |
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (6.1) | Systematic Assessment |
| |
| Bladder cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (6.1) | Systematic Assessment |
| |
| Bowen's disease | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (6.1) | Systematic Assessment |
| |
| Lung neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (6.1) | Systematic Assessment |
| |
| Lung Nodule | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (6.1) | Systematic Assessment |
| |
| Lymphoproliferative disorder | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (6.1) | Systematic Assessment |
| |
| Papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (6.1) | Systematic Assessment |
| |
| Renal cell carcinoma stage unspecified | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (6.1) | Systematic Assessment |
| |
| Tonsil cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (6.1) | Systematic Assessment |
| |
| Tumour lysis syndrome | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (6.1) | Systematic Assessment |
| |
| Renal failure acute | Renal and urinary disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Renal insufficiency | Renal and urinary disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Glomerulonephritis focal | Renal and urinary disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Renal failure chronic | Renal and urinary disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Tubulointestitial nephritis | Renal and urinary disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Diabetic ketoacidosis | Metabolism and nutrition disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Fluid overload | Metabolism and nutrition disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Hypervolaemia | Metabolism and nutrition disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Hypovolaemia | Metabolism and nutrition disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Arteriovenous graft site complications | Injury, poisoning and procedural complications | MedDRA (6.1) | Systematic Assessment |
| |
| Complications of transplant surgery | Injury, poisoning and procedural complications | MedDRA (6.1) | Systematic Assessment |
| |
| Drug toxicity | Injury, poisoning and procedural complications | MedDRA (6.1) | Systematic Assessment |
| |
| Incisional hernia | Injury, poisoning and procedural complications | MedDRA (6.1) | Systematic Assessment |
| |
| Injury | Injury, poisoning and procedural complications | MedDRA (6.1) | Systematic Assessment |
| |
| Intentional misuse | Injury, poisoning and procedural complications | MedDRA (6.1) | Systematic Assessment |
| |
| Medication error | Injury, poisoning and procedural complications | MedDRA (6.1) | Systematic Assessment |
| |
| Post procedural diarrhoea | Injury, poisoning and procedural complications | MedDRA (6.1) | Systematic Assessment |
| |
| Renal injury | Injury, poisoning and procedural complications | MedDRA (6.1) | Systematic Assessment |
| |
| Tibia fracture | Injury, poisoning and procedural complications | MedDRA (6.1) | Systematic Assessment |
| |
| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA (6.1) | Systematic Assessment |
| |
| Localised osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Aseptic necrosis bone | Musculoskeletal and connective tissue disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Myopathy | Musculoskeletal and connective tissue disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Pelvic mass | General disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Malignant hypertension | Vascular disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Gangrene | Vascular disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Peripheral ischaemia | Vascular disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Angina unstable | Cardiac disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Atrial Fibrillation | Cardiac disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Cardiac arrest | Cardiac disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Cardiac failure congestive | Cardiac disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA (6.1) | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (6.1) | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Amyloidosis | Immune system disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Kidney transplant rejection | Immune system disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Ectopic pregnancy | Pregnancy, puerperium and perinatal conditions | MedDRA (6.1) | Systematic Assessment |
| |
| Vulvar Dysplasia | Reproductive system and breast disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Pregnancy of partner | Social circumstances | MedDRA (6.1) | Systematic Assessment |
| |
| Renal transplant | Surgical and medical procedures | MedDRA (6.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper respiratory tract infection | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Escherichia urinary tract infection | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Urinary tract infection bacterial | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Urinary tract infection enterococcal | Infections and infestations | MedDRA (6.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Pharyngolaryngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Oedema Peripheral | General disorders | MedDRA (6.1) | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA (6.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (6.1) | Systematic Assessment |
|
Company makes no warranties or representations of any kind as to the posting, expressed or implied, including warranties of merchantability and fitness for a particular purpose, and shall not be liable for any damages.
Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data or until 18 months have elapsed following study completion. Sponsor must receive a site's manuscript at least 30 days prior to publication to ensure that no confidential information of Sponsor is included in the document.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Vice President, Therapeutic Area Head, Transplantation | Astellas Pharma Global Development, Inc. | ClinicalTrials.Disclosure@us.astellas.com |
| ID | Term |
|---|---|
| D016559 | Tacrolimus |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
Not provided
Not provided
| Lost to Follow-up |
|
| Asian |
|
| Hypertensive Nephrosclerosis |
|
| Immunoglobulin A Nephropathy |
|
| Diabetes |
|
| Systemic Lupus Erythematosis |
|
| Focal Segmental Glomerulonephritis |
|
| Tubular and Interstitial Disease |
|
| Unknown |
|
| Other |
|
| Living Nonrelated Donor |
|
| Title | Measurements |
|---|---|
|
| Day 21: Tacrolimus MR |
|
If the 90% Confidence Interval for the ratio of the natural log-transformed pharmacokinetic parameters fell within an 80% to 125% range, then the exposure between the two formulations was considered to be equivalent. |
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