A Study to Assess the Pharmacokinetics of a Modified-release Tacrolimus Based Immunosuppression Regimen in Stable Liver Transplant Patients
2013년 8월 1일 업데이트: Astellas Pharma Inc
A Phase 2, Open-Label, Multi-Center Study to Assess the Pharmacokinetics, Long-term Safety and Tolerability of Tacrolimus in Stable Liver Transplant Patients Converted From a Prograf® Based Immunosuppression Regimen to a Modified Release (MR) Tacrolimus Based Immunosuppression Regimen
A study to assess the pharmacokinetics, safety and effectiveness of tacrolimus in stable liver transplant patients converted from a tacrolimus (Prograf®) based immunosuppression regimen to a modified release tacrolimus based immunosuppression regimen.
연구 개요
상세 설명
A one arm study to assess the pharmacokinetics, safety and effectiveness of tacrolimus in stable liver transplant patients converted from a tacrolimus (Prograf®) based immunosuppression regimen to a modified release tacrolimus based immunosuppression regimen.
연구 유형
중재적
등록 (실제)
70
단계
- 2 단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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California
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Palo Alto, California, 미국
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Colorado
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Denver, Colorado, 미국, 80262
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Maryland
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Baltimore, Maryland, 미국, 21287
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Michigan
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Ann Arbor, Michigan, 미국, 48109
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Minnesota
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Minneapolis, Minnesota, 미국, 55455
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Rochester, Minnesota, 미국, 55905
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New York
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New York, New York, 미국, 10029
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Ohio
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Cincinnati, Ohio, 미국, 45267
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Texas
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Dallas, Texas, 미국, 75246
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Wisconsin
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Madison, Wisconsin, 미국, 53792
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
18년 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
Inclusion Criteria:
- Patient is currently receiving Prograf ® based immunosuppressive therapy for liver transplantation.
- Patient has stable whole blood trough level concentrations of Prograf® and is clinically stable
Exclusion Criteria:
- Patient has previously received an organ transplant other than a liver
- Patient is currently receiving sirolimus immunosuppression therapy.
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 방지
- 할당: 무작위화되지 않음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: Tacrolimus MR
After enrollment in the pharmacokinetic period, patients were maintained on their usual dose of tacrolimus twice daily on Day 1 through Day 14 and on Day 15 were converted to tacrolimus modified release (MR) once-daily in the morning for 14 days, converted back to tacrolimus twice daily for 14 days and then converted back to tacrolimus MR formulation once-daily in the morning for 14 days, all based on a 1:1 mg for mg total daily dose conversion. The extended treatment period began on day 57 and consisted of a single dose of tacrolimus extended-release formulation once every morning through the end of the study. Dose adjustments were allowed in order to maintain the target tacrolimus trough level within the range of 5 to 20 ng/mL and for clinical reasons. |
경구
다른 이름들:
경구
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) for Tacrolimus
기간: Days 14 and 42 (tacrolimus) and Days 28 and 56 (tacrolimus MR), pre-dose 0.5, 1, 2, 3, 4, 6, 8, 12 (pre-dose for tacrolimus only), 12.5, 13, 14, 15, 16, 18, 20, and 24 hours post-dose.
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The area under the concentration-time curve was calculated from whole blood tacrolimus concentrations for both the tacrolimus and tacrolimus MR treatment periods at steady state using the linear trapezoidal rule.
The AUC0-24 for tacrolimus was calculated as the sum of the AUC0-12 for the morning (0-12 hour) and afternoon (12-24 hour) doses.
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Days 14 and 42 (tacrolimus) and Days 28 and 56 (tacrolimus MR), pre-dose 0.5, 1, 2, 3, 4, 6, 8, 12 (pre-dose for tacrolimus only), 12.5, 13, 14, 15, 16, 18, 20, and 24 hours post-dose.
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Minimum Observed Concentration of Tacrolimus (Cmin)
기간: Days 14 and 42 at 12 hours post-dose (tacrolimus) and Days 28 and 56 at 24 hours post-dose (for tacrolimus MR).
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The trough (minimum) concentration of tacrolimus determined from the tacrolimus whole blood concentration value at the 12 hour post-dose concentration based on the evening dose (i.e., the 8 am concentration) for tacrolimus and the 24-hour time point post-dose for tacrolimus MR, prior to receiving the next dose.
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Days 14 and 42 at 12 hours post-dose (tacrolimus) and Days 28 and 56 at 24 hours post-dose (for tacrolimus MR).
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Patient Survival
기간: From enrollment until the end of study (up to 60 months).
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Patient survival was defined as any participant known to be alive at the time of analysis.
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From enrollment until the end of study (up to 60 months).
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Graft Survival
기간: From enrollment until the end of study (up to 60 months).
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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 participant death.
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From enrollment until the end of study (up to 60 months).
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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여러 번의 거부 에피소드가 있는 참가자 수
기간: 등록부터 학업 종료까지(최대 60개월).
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이 분석에는 임상 현장 병리학자에 의한 생검에 의해 확인되었거나 임상적으로 치료된 거부 에피소드가 포함됩니다.
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등록부터 학업 종료까지(최대 60개월).
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임상적으로 치료된 급성 거부 반응 에피소드가 있는 참가자 수
기간: 등록부터 학업 종료까지(최대 60개월).
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임상적으로 치료된 급성 거부 반응 에피소드는 면역억제 요법으로 치료된 모든 생검 확인 또는 의심되는 거부 반응 에피소드였습니다.
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등록부터 학업 종료까지(최대 60개월).
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만성 거부 반응이 있는 참여자 수
기간: 등록부터 학업 종료까지(최대 60개월).
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생검으로 확인된 급성 거부 반응 사례가 있는 참가자 수가 적기 때문에 만성 거부 반응은 분석되지 않았습니다.
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등록부터 학업 종료까지(최대 60개월).
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치료 실패 참가자 수
기간: 등록부터 학업 종료까지(최대 60개월).
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치료 실패는 어떤 이유로든 연구 약물을 중단하는 것으로 정의되었습니다.
후원자의 연구 중단으로 인해 치료 실패는 분석되지 않았습니다.
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등록부터 학업 종료까지(최대 60개월).
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Maximum Observed Concentration of Tacrolimus (Cmax)
기간: Days 14 and 42 (tacrolimus) and Days 28 and 56 (tacrolimus MR), pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 (pre-dose for tacrolimus only), 12.5, 13, 14, 15, 16, 18, 20, and 24 hours post-dose.
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The maximum concentration was calculated from whole blood tacrolimus concentrations for both the tacrolimus and tacrolimus MR treatment periods at steady state, without interpolation.
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Days 14 and 42 (tacrolimus) and Days 28 and 56 (tacrolimus MR), pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 (pre-dose for tacrolimus only), 12.5, 13, 14, 15, 16, 18, 20, and 24 hours post-dose.
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Time to Maximum Observed Concentration of Tacrolimus (Tmax)
기간: Days 14 and 42 (tacrolimus) and Days 28 and 56 (tacrolimus MR), pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 (pre-dose for tacrolimus only), 12.5, 13, 14, 15, 16, 18, 20, and 24 hours post-dose.
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Time to the first occurrence to reach the maximum concentration of tacrolimus was calculated from whole blood tacrolimus concentrations for both the tacrolimus and tacrolimus MR treatment periods at steady state, without interpolation.
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Days 14 and 42 (tacrolimus) and Days 28 and 56 (tacrolimus MR), pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 (pre-dose for tacrolimus only), 12.5, 13, 14, 15, 16, 18, 20, and 24 hours post-dose.
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Percentage of Participants With Biopsy-confirmed Acute Rejection
기간: From enrollment until the end of study (up to 60 months).
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Biopsy-confirmed acute rejection (BCAR) is defined as an episode of acute liver allograft rejection that was confirmed by biopsy results and was Banff grade ≥ I. Biopsies were graded by the pathologist at the clinical site according to the 1997 Banff criteria for grading of acute liver allograft rejection: Indeterminate: Portal inflammatory infiltrate that fails to meet the criteria for diagnosis of acute rejection; Grade I (Mild): Rejection infiltrate in a minority of the triads that is generally mild and confined within the portal spaces; Grade II (Moderate): Rejection infiltrate, expanding to most or all of the triads; Grade III (Severe): Rejection infiltrate, expanding to most or all of the triads, with spillover into periportal areas and moderate to severe perivenular inflammation that extends into the hepatic parenchyma and is associated with perivenular hepatocyte necrosis.
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From enrollment until the end of study (up to 60 months).
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Time to Event for Patient Non-survival
기간: From enrollment until the end of study (up to 60 months).
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For participants who died on study, the median number of days from first dose of study drug to death due to any cause.
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From enrollment until the end of study (up to 60 months).
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Time to Event for Graft Non-survival
기간: From enrollment until the end of study (up to 60 months).
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For participants with graft loss, the median number of days from the first dose of study drug to graft loss.
Graft loss was defined as graft failure (re-transplant) or participant death.
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From enrollment until the end of study (up to 60 months).
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Time to First Biopsy-confirmed Acute Rejection
기간: From enrollment until the end of study (up to 60 months).
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For participants with a biopsy-confirmed acute rejection (BCAR), the median number of days from the first dose of study drug to the date of biopsy confirmation.
BCAR is defined as an episode of acute liver allograft rejection that was confirmed by biopsy results and was Banff grade ≥ I. Biopsies were graded by the clinical site pathologist according to the 1997 Banff criteria for grading acute liver allograft rejection: Indeterminate: Portal inflammatory infiltrate that fails to meet the criteria for diagnosis of acute rejection; Grade I: Rejection infiltrate in a minority of the triads that is generally mild and confined within the portal spaces; Grade II: Rejection infiltrate, expanding to most or all of the triads; Grade III: Rejection infiltrate, expanding to most or all of the triads, with spillover into periportal areas and moderate to severe perivenular inflammation that extends into the hepatic parenchyma and is associated with perivenular hepatocyte necrosis.
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From enrollment until the end of study (up to 60 months).
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Grade of Biopsy-confirmed Acute Rejection Episodes
기간: From enrollment until the end of study (up to 60 months).
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Biopsy-confirmed acute rejection (BCAR) is defined as an episode of acute liver allograft rejection that was confirmed by biopsy results and was Banff grade ≥ I. Biopsies were graded by the clinical site pathologist according to the 1997 Banff criteria for grading of acute liver allograft rejection: Indeterminate: Portal inflammatory infiltrate that fails to meet the criteria for diagnosis of acute rejection; Grade I (Mild): Rejection infiltrate in a minority of the triads that is generally mild and confined within the portal spaces; Grade II (Moderate): Rejection infiltrate, expanding to most or all of the triads; Grade III (Severe): Rejection infiltrate, expanding to most or all of the triads, with spillover into periportal areas and moderate to severe perivenular inflammation that extends into the hepatic parenchyma and is associated with perivenular hepatocyte necrosis.
For participants with more than one biopsy-confirmed acute rejection episode, the worst case grade is reported.
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From enrollment until the end of study (up to 60 months).
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Number of Participants Receiving Anti-lymphocyte Antibody Therapy for Acute Rejection
기간: From enrollment until the end of study (up to 60 months).
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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.
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From enrollment until the end of study (up to 60 months).
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Primary Reason for Graft Loss
기간: From enrollment until the end of study (up to 60 months).
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The primary reason for graft loss was recorded by the Investigator.
Graft loss was defined as graft failure (re-transplant) or participant death.
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From enrollment until the end of study (up to 60 months).
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Change From Baseline in Alanine Aminotransferase (ALT)
기간: Baseline (the last day of tacrolimus on Day 14 prior to the first conversion to tacrolimus MR), Day 56 (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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Hepatic function was assessed by measuring alanine aminotransferase levels over the course of the study.
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Baseline (the last day of tacrolimus on Day 14 prior to the first conversion to tacrolimus MR), Day 56 (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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Change From Baseline in Aspartate Aminotransferase (AST)
기간: Baseline (the last day of tacrolimus on Day 14 prior to the first conversion to tacrolimus MR), Day 56 (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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Hepatic function was assessed by measuring aspartate aminotransferase levels over the course of the study.
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Baseline (the last day of tacrolimus on Day 14 prior to the first conversion to tacrolimus MR), Day 56 (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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Change From Baseline in Total Bilirubin
기간: Baseline (the last day of tacrolimus on Day 14 prior to the first conversion to tacrolimus MR), Day 56 (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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Hepatic function was assessed by measuring total bilirubin over the course of the study.
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Baseline (the last day of tacrolimus on Day 14 prior to the first conversion to tacrolimus MR), Day 56 (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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Safety as Assessed by Adverse Events, Laboratory Parameters and Vital Signs
기간: From the first dose of tacrolimus MR formulation through the last dose day plus 10 days (approximately 60 months).
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An adverse event is 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:
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From the first dose of tacrolimus MR formulation through the last dose day plus 10 days (approximately 60 months).
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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
수사관
- 연구 책임자: Central Contact, Astellas Pharma US, Inc.
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
일반 간행물
- Florman S, Alloway R, Kalayoglu M, Punch J, Bak T, Melancon J, Klintmalm G, Busque S, Charlton M, Lake J, Dhadda S, Wisemandle K, Wirth M, Fitzsimmons W, Holman J, First MR. Once-daily tacrolimus extended release formulation: experience at 2 years postconversion from a Prograf-based regimen in stable liver transplant recipients. Transplantation. 2007 Jun 27;83(12):1639-42. doi: 10.1097/01.tp.0000265445.09987.f1.
- Florman S, Alloway R, Kalayoglu M, Lake K, Bak T, Klein A, Klintmalm G, Busque S, Brandenhagen D, Lake J, Wisemandle K, Fitzsimmons W, First MR. Conversion of stable liver transplant recipients from a twice-daily Prograf-based regimen to a once-daily modified release tacrolimus-based regimen. Transplant Proc. 2005 Mar;37(2):1211-3. doi: 10.1016/j.transproceed.2004.11.086.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작
2003년 2월 1일
기본 완료 (실제)
2008년 10월 1일
연구 완료 (실제)
2008년 10월 1일
연구 등록 날짜
최초 제출
2006년 1월 24일
QC 기준을 충족하는 최초 제출
2006년 1월 24일
처음 게시됨 (추정)
2006년 1월 26일
연구 기록 업데이트
마지막 업데이트 게시됨 (추정)
2013년 9월 30일
QC 기준을 충족하는 마지막 업데이트 제출
2013년 8월 1일
마지막으로 확인됨
2013년 8월 1일
추가 정보
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .