NCT02970630
Completed
Phase 2
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
Chiesi Farmaceutici S.p.A.6 sites in 1 country28 target enrollmentStarted: January 2017Last updated:
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Chiesi Farmaceutici S.p.A.
- Enrollment
- 28
- Locations
- 6
- Primary Endpoint
- Tacrolimus Area Under the curve at 24 hours (AUC24)
Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 60 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
Exclusion Criteria
- •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;
Arms & Interventions
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.
Intervention: 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.
Intervention: Everolimus (Drug)
Outcomes
Primary Outcomes
Tacrolimus Area Under the curve at 24 hours (AUC24)
Time Frame: 10 days
Tacrolimus Minimum whole blood concentration (Cmin)
Time Frame: 10 days
Tacrolimus Cmin/daily dose
Time Frame: 10 days
Tacrolimus AUC24/daily dose
Time Frame: 10 days
Secondary Outcomes
- 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)
Investigators
Study Sites (6)
Loading locations...
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