A Study to Assess the Pharmacokinetics of a Modified-release Tacrolimus Based Immunosuppression Regimen in Stable Liver Transplant Patients
2013年8月1日 更新者：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.
調査の概要
詳細な説明
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.
研究の種類
介入
入学 (実際)
70
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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California
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Palo Alto、California、アメリカ
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Colorado
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Denver、Colorado、アメリカ、80262
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Maryland
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Baltimore、Maryland、アメリカ、21287
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Michigan
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Ann Arbor、Michigan、アメリカ、48109
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Minnesota
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Minneapolis、Minnesota、アメリカ、55455
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Rochester、Minnesota、アメリカ、55905
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New York
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New York、New York、アメリカ、10029
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Ohio
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Cincinnati、Ohio、アメリカ、45267
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Texas
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Dallas、Texas、アメリカ、75246
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Wisconsin
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Madison、Wisconsin、アメリカ、53792
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年～65年 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：防止
- 割り当て：非ランダム化
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：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. |
オーラル
他の名前：
オーラル
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) for Tacrolimus
時間枠：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)
時間枠：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
時間枠：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
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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複数の拒否エピソードがある参加者の数
時間枠：入学から学習終了まで（最長60か月）。
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この分析には、臨床現場の病理学者による生検によって確認された、または臨床的に治療された拒絶反応エピソードが含まれます。
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入学から学習終了まで（最長60か月）。
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臨床治療を受けた急性拒絶症状のある参加者の数
時間枠：入学から学習終了まで（最長60か月）。
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臨床的に治療された急性拒絶エピソードとは、生検で確認された、または疑いのある拒絶エピソードであり、免疫抑制療法で治療されたものです。
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入学から学習終了まで（最長60か月）。
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慢性拒絶反応を示す参加者の数
時間枠：入学から学習終了まで（最長60か月）。
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生検で急性拒絶反応が確認された参加者の数が少ないため、慢性拒絶反応は分析されませんでした。
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入学から学習終了まで（最長60か月）。
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治療が失敗した参加者の数
時間枠：入学から学習終了まで（最長60か月）。
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治療失敗は、何らかの理由による治験薬の中止として定義されました。
スポンサーによる研究の中止のため、治療の失敗は分析されませんでした。
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入学から学習終了まで（最長60か月）。
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Maximum Observed Concentration of Tacrolimus (Cmax)
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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)
時間枠：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)
時間枠：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
時間枠：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
時間枠：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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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
捜査官
- スタディディレクター：Central Contact、Astellas Pharma US, Inc.
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- 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.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2003年2月1日
一次修了 (実際)
2008年10月1日
研究の完了 (実際)
2008年10月1日
試験登録日
最初に提出
2006年1月24日
QC基準を満たした最初の提出物
2006年1月24日
最初の投稿 (見積もり)
2006年1月26日
学習記録の更新
投稿された最後の更新 (見積もり)
2013年9月30日
QC基準を満たした最後の更新が送信されました
2013年8月1日
最終確認日
2013年8月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。