NCT02970630已完成2 期
Envarsus® Tablets Administered Once Daily in Combination With Everolimus in Elderly De-novo Kidney Transplant Recipients: Open-label, Multicentre, Single-arm, Pharmacokinetic and Clinical Study
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 6
- 主要终点
- Tacrolimus Area Under the curve at 24 hours (AUC24)
研究概览
简要总结
Prospective, single-arm, open-label, multicentre study with the principal aim to estimate tacrolimus pharmacokinetic parameters in elderly de-novo kidney transplant recipients of ECD (Extended Criteria Donor) kidney grafts treated with Envarsus® prolonged release tablets in combination with everolimus tablets.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject's written informed consent obtained prior to transplant intervention and prior to any study-related procedures;
- •Caucasian male or female subjects aged 60 or older who are receiving a primary or secondary single or dual renal transplant from a blood group compatible deceased donor;
- •Patients who are planned to receive a renal allograft by Extended Criteria Donor (ECD);
- •Patients capable of understanding the purposes and risks of the study, who can give written informed consent and who are willing to participate in and comply with the study;
- •Patients with low to standard immunological risk, who had a PRA (Panel Reactive Antibody) ≤ 20% (PRA testing according to centre's practice);
- •Body Mass Index (BMI) between 15 and 35 kg/m2 extremes inclusive;
- •Women must be postmenopausal (physiologic menopause defined as "12 consecutive months of amenorrhea") or permanently sterilized (e.g. tubal occlusion, hysterectomy or bilateral salpingectomy) to be enrolled in the study.
排除标准
- •Recipients of any transplanted organ other than a single or dual kidney;
- •Patients unable or unwilling to provide informed consent;
- •Male subjects with females partner of childbearing potential UNLESS they or their partner are willing to use a reliable method of contraception (see below for details) from the time of first dose administration and until 8 weeks after the last dose of study drugs. Male subjects with partners of non-childbearing potential are not required to use contraception.
- •Reliable methods of contraception for male subjects and their partner of childbearing potential must be one of the following:
- •Placement of an intrauterine device or intrauterine system
- •Hormonal contraception (implantable, patch, oral)
- •Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical vaults/caps) with spermicidal foam/gel/film/cream/suppository.
- •Male sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate "True abstinence" is acceptable only if it is in line with the preferred and usual lifestyle of the subject.
- •Recipients of a bone marrow or stem cell transplant;
- •Recipients of a kidney from a cardiac death donor;
- •Recipients of a kidney from an ABO (0, A and blood cell types) incompatible donor;
- •Recipients having pre-transplant donor specific anti-HLA (Human leukocyte antigen antibodies) (DSA) or who lost the first kidney transplant because of acute rejection;
- •Recipients of a kidney with an anticipated cold ischemia time ≥ 24 hours;
- •Recipients positive for Hepatitis C virus (HCV-RNA positive) and/or Hepatitis B Virus (HBV-DNA or HBsAg positive);
- •Recipients positive for Human Immunodeficiency Virus (HIV-Ab positive);
- •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 diarrhoea, vomiting, active peptic ulcer or gastrointestinal disorder that may affect the absorption of study drugs;
- •Patients with a white blood cell count ≤ 2.8x109/L unless the absolute neutrophil count (ANC) is ≥ 1.0x109/L;
- •Patients with a platelet count ≤ 50.0x109/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 were treated with any other investigational agent in the three months prior to enrolment;
- •Patients who received any investigational new drug, or participated in clinical study within the last 8 weeks;
- •Patient planned to receive an induction therapy different from rabbit ATG (Anti-thymocyte globulin) alone or patients who did not start rabbit ATG induction therapy after transplant;
- •Patients who are already on immunosuppressive drugs the day before transplantation, except ATG as per protocol;
- •Patients who are planned to receive therapy with any immunosuppressive agent other than those prescribed in the study;
- •Patients with a known hypersensitivity to corticosteroids, tacrolimus or everolimus or sirolimus or any of the excipients present in study drugs formulations;
- •Patients with hypersensitivity to macrolides;
- •Patients with any form of substance abuse, psychiatric disorder or a condition that, in the opinion of the Investigator, may invalidate communication with the Investigator;
- •Subjects unlikely to comply with the study protocol or unable to understand the nature and scope of the study but also the possible benefits or unwanted effects of the study treatments;
- •Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
研究组 & 干预措施
Envarsus once a day, everolimus b.i.d.
Experimental
Tacrolimus tablets at starting dose of 0.07 mg/kg/day will be administered once daily in the morning.
Everolimus tablets at starting dose of 2 mg/day (1 mg b.i.d.) will be administered twice daily, every 12 hours.
干预措施: Tacrolimus (Drug)
Envarsus once a day, everolimus b.i.d.
Experimental
Tacrolimus tablets at starting dose of 0.07 mg/kg/day will be administered once daily in the morning.
Everolimus tablets at starting dose of 2 mg/day (1 mg b.i.d.) will be administered twice daily, every 12 hours.
干预措施: Everolimus (Drug)
结局指标
主要结局
Tacrolimus Area Under the curve at 24 hours (AUC24)
时间窗: 10 days
Tacrolimus Minimum whole blood concentration (Cmin)
时间窗: 10 days
Tacrolimus Cmin/daily dose
时间窗: 10 days
Tacrolimus AUC24/daily dose
时间窗: 10 days
次要结局
- Number of dose adjustments(from day 3 to month 6)
- Treatment failure rate(from day 1 to month 6)
- Tacrolimus within-patient variability of blood trough level(from day 3 to month 6)
- Renal function using estimated glomerular filtration rate(from day 1 to month 6)
- Acute rejection requiring treatment(from day 1 to month 6)
- Time to reach therapeutic exposure to tacrolimus(from day 3 to month 6)
- Total daily dose(from day 3 to month 6)
- Tacrolimus Maximum whole blood concentration (Cmax)(10 days)
- Tacrolimus Tmax (time that the drug is present at the maximum concentration in serum)(10 days)
- Tacrolimus % fluctuation(10 days)
- Biopsy proven acute rejections(from day 1 to month 6)
- Tacrolimus Average whole blood drug concentration (Cave)(10 days)
- Tacrolimus linear correlation coefficient between Cmin and AUC24(10 days)
- Serious Adverse Events(from screening to month 6)
- Number of opportunistic infections(from screening to month 6)
- Delayed graft function(from day 1 to month 6)
- Tacrolimus % swing(10 days)
- Adverse Events(from screening to month 6)
研究者
研究点 (6)
Loading locations...
相似试验
已完成
4 期
Envarsus XR Compared to Immediate Release TacrolimusKidney Transplant RecipientsNCT03979365Mayo Clinic261
已完成
4 期
Multicentre, Open Label, Randomized, Two-arm, Parallel-group Study to Assess Efficacy and Safety of ENVARSUS® Compared With Tacrolimus Used as Per Current Clinical Practice in the Initial Maintenance Setting in de Novo Kidney Transplant PatientsEnd Stage Renal DiseaseNCT02432833Chiesi Farmaceutici S.p.A.428
已完成
不适用
Once-daily Regimen With Envarsus® to Optimize Immunosuppression Management and Outcomes in Kidney Transplant RecipientsImmunosuppressionNCT02954198Medical University of South Carolina40
招募中
3 期
Pharmacokinetics, Effectiveness and Tolerability of Prolonged-release Tacrolimus After Paediatric Kidney TransplantationPediatric Kidney DiseaseNCT06057545University Hospital, Essen30
已完成
4 期
Study to Evaluate the Efficacy and Safety of Once-Daily Tacrolimus in Kidney Transplant RecipientsKidney TransplantNCT03749356Chong Kun Dang Pharmaceutical141