Study to Evaluate Pharmacokinetic and Bioavailability of Envarsus® vs. Advagraf® in Liver Transplant Recipients

Single Center, Open-label, Randomized, Controlled, Cross Over Study to Evaluate the Pharmacokinetic and Bioavailability of Envarsus® in Comparison to Advagraf® in de Novo Liver Transplant Recipients

Single centre, open-label, randomized, controlled, cross over study to evaluate the pharmacokinetic and bioavailability of Envarsus® in comparison to Advagraf® in de novo liver transplant recipients

Study Overview

• Status: Completed
• Conditions: Liver Transplantation
• Intervention / Treatment: Drug: Treatment 2 weeks Envarsus followed by 2 weeks Advagraf; Drug: Treatment 2 weeks Advagraf followed by 2 weeks Envarsus

Detailed Description

Using an open-label, randomized, controlled, 2-period cross-over design, two treatments (Envarsus® and Advagraf®) will be compared (with regard to PK profile and bioavailability) after administration of IMP to 20 de novo transplanted recipients. The patients will be randomly assigned to one of the two treatments as treatment period 1 and afterwards switched to treatment period 2 (Group 1: Envarsus® - Advagraf®; Group 2: Advagraf® - Envarsus®).

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Hamburg, Germany
    • University Hospital Hamburg-Eppendorf

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Ability to understand the patient information and to personally sign and date the informed consent to participate in the clinical trial, before completing any clinical trial related procedures.
2. Male or female recipients ≥ 18 years of a liver graft from a deceased or living donor
3. The patient must receive a twice daily Tacrolimus based immunosuppression treatment.
4. Females of child-bearing potential who agree to comply with any applicable contraceptive requirements of the protocol or females who are permanently sterilized (at least 6 weeks post sterilization).
5. Non-pregnant, non-lactating female.
6. Recipients of a first or re-liver transplant in the last 30 days
7. The patient is co-operative and available for the entire clinical trial.

Exclusion Criteria:

1. Patients with a known hypersensitivity to any of the drugs used in the study.
2. Patients who are not able to take oral medication at the time point of randomization.
3. Recipients of combined organ transplants.
4. Patients who are recipients of AB0 incompatible transplant grafts.
5. Currently participation in a clinical trial and any IMP intake within the last four weeks.
6. Patients who use drugs known to strongly interact with the cytochrome P-450 3A4 pathway and therefore influence the tacrolimus blood level are not allowed during Envarsus®/Advagraf® treatment period.
7. Patient with renal impairment with need of dialysis treatment at the time point of randomization.
8. Patient with a quick value < 30 %
9. Patient with a thrombocytopenia <20 Mrd./L
10. Patients with a leukopenia < 1.0 Mrd. / L
11. Patients with inability of oral food intake.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Envarsus - Advagraf	Drug: Treatment 2 weeks Envarsus followed by 2 weeks Advagraf
Active Comparator: Advagraf - Envarsus	Drug: Treatment 2 weeks Advagraf followed by 2 weeks Envarsus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
DAV (average cumulative dose) = cumulative dose per study period/ period days	20 month
C0/doses (trough level at steady state / daily dose at steady state)	20 month
AUC0-24/doses	20 month

Collaborators and Investigators

• Sponsor: Universitätsklinikum Hamburg-Eppendorf
• Investigators: Principal Investigator: Herden, Universitätsklinikum Hamburg-Eppendorf

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Actual): April 1, 2019
• Study Completion (Actual): April 1, 2019

Study Registration Dates

• First Submitted: September 12, 2016
• First Submitted That Met QC Criteria: August 2, 2017
• First Posted (Actual): August 7, 2017

Study Record Updates

• Last Update Posted (Actual): May 4, 2021
• Last Update Submitted That Met QC Criteria: May 3, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Pharmacokinetic study; Comparing Envarsus versus Advagraf
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: PAKT CTC 151043