Envarsus® Once Daily With Everolimus in Elderly Kidney Transplant Recipients: Pharmacokinetic and Clinical Study

NCT02970630 | Completed Phase 2

• 2 other identifiers: DFIDM-15012015-005640-34
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 6

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.

Conditions

Kidney Transplantation

Keywords

prophylaxis

Outcome Measures

Primary Outcomes (4)

• Tacrolimus Area Under the curve at 24 hours (AUC24)

  10 days

• Tacrolimus Minimum whole blood concentration (Cmin)

  10 days

• Tacrolimus Cmin/daily dose

  10 days

• Tacrolimus AUC24/daily dose

  10 days

Secondary Outcomes (18)

• Tacrolimus within-patient variability of blood trough level

  from day 3 to month 6

• Time to reach therapeutic exposure to tacrolimus

  from day 3 to month 6

• Number of dose adjustments

  from day 3 to month 6

• Total daily dose

  from day 3 to month 6

• Renal function using estimated glomerular filtration rate

  from day 1 to month 6

Study Arms (1)

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.

Drug: Tacrolimus; Drug: Everolimus

Interventions

Tacrolimus DRUG

once a day

Also known as: Envarsus

Envarsus once a day, everolimus b.i.d.

Everolimus DRUG

twice daily

Also known as: Certican

Envarsus once a day, everolimus b.i.d.

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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);

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead
• Cromsource: collaborator

Study Sites (6)

Ospedale Ca' Granda - Niguarda

Milan, Italy

Location

Ospedale Maggiore Policlinico

Milan, Italy

Location

Azienda Ospedaliera di Padova

Padua, Italy

Location

Policlinico "A. Gemelli"

Rome, Italy

Location

Policlinico "Le Scotte"

Siena, Italy

Location

Azienda Ospedaliera S. Giovanni Battista

Torino, Italy

Location

Related Links

• Study Record on EU Clinical Trials Register including results

MeSH Terms

Interventions

Tacrolimus; Everolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Sirolimus

Study Officials

• Paolo Rigotti, MD

  Az Osp Padova, Osp. Civile Padova

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2016
• First Posted: November 22, 2016
• Study Start: January 1, 2017
• Primary Completion: February 22, 2018
• Study Completion: February 22, 2018
• Last Updated: March 1, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (6)