A Phase 2, Open-Label, Multi-Center, Randomized Trial To Demonstrate The Pharmacokinetics Of LCP-Tacro™ Tablets Once Daily and Prograf® Capsules Twice Daily In Adult De Novo Kidney Transplant Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 63
- 试验地点
- 1
- 主要终点
- Pharmacokinetics of LCP-Tacro™ Tablets in the First 14 Days After Transplantation in Adult de Novo Kidney Recipients.
研究概览
简要总结
The purpose of this study is to demonstrate the pharmacokinetics (PK, measuring the amount of medication in blood samples) and safety of a new medicine, LCP-Tacro™ tablets, and Prograf® capsules, a drug commonly taken by transplant recipients to prevent the body from rejecting a transplanted kidney. LCP-Tacro is a tablet containing the same active ingredient (tacrolimus) that is in Prograf capsules, but the tablet has been designed to release tacrolimus over an extended period so that it only has to be taken once daily. LCP-Tacro is an investigational drug.
This study will evaluate the levels of tacrolimus in the blood in the first two weeks after a kidney transplant in patients randomly assigned (by chance, like flipping a coin) to take either LCP-Tacro™ tablets (tacrolimus) once daily or Prograf® capsules twice daily. In addition, patients will remain on study drug for 360 days in order to evaluate the relative safety of LCP-Tacro™ tablets compared to Prograf over a longer period of time.
详细描述
This study was a randomized, parallel-group, open label, multicenter study in adult de novo kidney transplant patients to demonstrate the pharmacokinetics and safety of LCP-Tacro tablets and Prograf capsules in the first 2 weeks after kidney transplantation. In addition the study compared the efficacy and safety of LCP-Tacro and Prograf over an additional 50 weeks after kidney transplantation. Eligible patients were randomized (1:1 ratio) within 12 hours after transplantation (Day 0) to receive either: 1) LCP-Tacro tablets orally once daily (QD) in the morning, with an interval of 24+/- hours between doses, starting at 0.14 mg/kg (the starting daily dose for African-American patients was 0.17 mg/kg), or 2) Prograf capsules in 2 equally divided doses for African-American patients was (0.2 mg/kg total daily dose) as recommended in the U.S. Prescribing Information (Astellas Pharma US, April 2006). Day 1 was defined as the day on which the first morning dose of study medication was given which was to be within 48 hours of transplantation. Subsequent doses of study medication were adjusted to maintain target whole blood tacrolimus trough level of 7 to 20 ng/mL for the remainder of the pharmacokinetic phase of the study (Day1 through Day 14). Twenty-four-hour pharmacokinetic assessments were performed on Days 1, 7, and 14. Following completion of the third and final pharmacokinetic assessment on the morning of Day 14, patients entered the maintenance phase (Days 15 to 360) of the study and remained on their assigned study medication until Day 360. Visits for safety assessments and tacrolimus trough levels during the maintenance phase were on Days 42, 90, 120, 180, 270, and 360. On Day 360, the patients were placed on a maintenance immunosuppressive regimen determined by their treating physician.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult men and women at least 18 years of age who are recipients of a kidney transplant from a deceased donor or a live donor and who receive their first oral dose of randomized study drug within 48 hours of the transplant surgery (graft reperfusion)
排除标准
- •Recipient of any transplanted organ other than a kidney
- •Recipients of a kidney from a non-heart beating donor
- •Recipients of a kidney from an ABO incompatible donor
- •Recipients of a kidney with a cold ischemia time of ≥ 36 hours
- •Recipients of a bone marrow or stem cell transplant
- •Patients with a white blood cell count ≤ 2.8 x 109/L unless the absolute neutrophil count (ANC) is > 1.0 x 109/L
- •Patients with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) enzyme levels > 3 times the upper limit of normal during the 30 days prior to the transplant procedure
- •Patients who fail a drugs of abuse screen
- •Patients unable to swallow study medication
- •Patients incapable of understanding the purposes and risks of the study, who cannot give written informed consent, or who are unwilling to comply with the study protocol
- •Pregnant or nursing women (women of childbearing potential must have a negative serum pregnancy test within seven days prior to receiving study medication)
- •Patients with reproductive potential who are unwilling/unable to use a double barrier method of contraception throughout the duration of the study
- •Patients who were treated with any other investigational agent in the 30 days prior to enrollment
- •Patients who are hepatitis C virus (HCV) negative who have received a HCV positive (HCV RNA by polymerase chain reaction (PCR) or HCV antibody) donor kidney
- •Patients seropositive for human immunodeficiency virus (HIV)
- •Patients with a current malignancy or a history of malignancy (within the past 5 years), except basal or non-metastatic squamous cell carcinoma of the skin that has been treated successfully
- •Patients with uncontrolled concomitant infection, a systemic infection requiring treatment, or any other unstable medical condition that could interfere with the study objectives
- •Patients with severe diarrhea, vomiting, active peptic ulcer or gastrointestinal disorder that may affect the absorption of tacrolimus
- •Patients with a known hypersensitivity to tacrolimus
- •Patients with any form of current substance abuse, psychiatric disorder or a condition that, in the opinion of the Investigator, may invalidate communication with the investigator
研究组 & 干预措施
LCP-Tacro
The initial dose starting at 0.14 mg/kg (the starting daily dose for African-American patients was 0.17 mg/kg), will be administered orally in the morning (before noon) within 12 hours after transplantation. Subsequent doses adjusted to maintain a target whole blood tacrolimus trough level of 7 - 20 ng/mL for the remainder of the pharmacokinetic (PK) phase of the study (through Study Day 14). Post PK patient enter the maintenance phase of the study and remain on assigned study drug until Study Day 360. Dose of study drug was adjusted to maintain tacrolimus trough levels between 5 - 20 ng/mL from Day 15 until Day 90 and then between 5 - 15 ng/mL for the remainder of the study according to local standard of care.
干预措施: Tacrolimus (Tacro™) (Drug)
Prograf (tacrolimus)
Starting total daily dose of 0.10 mg/kg administered in two equally divided doses, morning and evening, per product labeling. Subsequent doses adjusted to maintain a target whole blood tacrolimus trough level of 7 - 20 ng/mL for the remainder of the pharmacokinetic (PK) phase of the study (through Study Day 14). Post PK patient enter the maintenance phase of the study and remain on assigned study drug until Study Day 360. Dose of study drug was adjusted to maintain tacrolimus trough levels between 5 - 20 ng/mL from Day 15 until Day 90 and then between 5 - 15 ng/mL for the remainder of the study according to local standard of care.
Other name: tacrolimus
干预措施: Prograf (Drug)
结局指标
主要结局
Pharmacokinetics of LCP-Tacro™ Tablets in the First 14 Days After Transplantation in Adult de Novo Kidney Recipients.
时间窗: 14 days
Comparison of the proportion of patients achieving sufficient tacrolimus whole blood trough levels (7 to 20 ng/mL) during the first 14 days post-transplantation
次要结局
- Comparative Pharmacokinetics Between LCP-Tacro and Prograf Within 14 Days After Kidney Transplantation.(14 days)
- Evaluation of Safety and Efficacy of LCP-Tacro Compared to Prograf in Adult de Novo Kidney Transplant Patients.(12 months)