Comparison of a Tacrolimus Hexal® Based Regimen Versus a Prograf® Based Regimen in de Novo Renal Transplant Recipients (Spartacus)

Multi-center, Open-label, Prospective, Randomized, Parallel Group Study Investigating a Tacrolimus Hexal® Based Regimen Versus a Prograf® Based Regimen in de Novo Renal Transplant Recipients

The purpose of this study was to investigate if Tacrolimus Hexal® has similar pharmacokinetic properties compared to Prograf® in de novo renal transplant patients and whether the comparable exposure resulted in similar renal function.

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics Study in de Novo Kidney Transplantation
• Intervention / Treatment: Drug: Prograf; Drug: Tacrolimus Hexal

Detailed Description

In Phase II of this study there was a high patient drop-out rate and an associated long recruitment timespan. Eighty-one patients were recruited to Phase I and only 45 of the required 54 patients were available for PK analysis. To complete Phase II, 245 (in addition to 81) patients were to be required to achieve calculated sample size. Therefore the protocol was amended to stop recruitment and analyze Phase I patient data of CERL080ADE27 (PK-Phase I). Patients that were still ongoing were scheduled for an end of study (EOS) visit. During this visit patients were informed by the investigator about the end of study and advised about further treatment course.

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10098
    • Novartis Investigative Site
  • Bochum, Germany, 44892
    • Novartis Investigative Site
  • Duesseldorf, Germany, 40225
    • Novartis Investigative Site
  • Kaiserslautern, Germany, 67655
    • Novartis Investigative Site
  • Koeln-Merheim, Germany, 51109
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion:

primary or sec. kidney transplanted patiens, written consent, cold ischemia < 24 h

Exclusion:

multi organ, immunological risc pts., PRA >20%, Antibodys against HLA-type of donor organ, hypersensitivity against Tacro or MMF,

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prograf; Control therapy: one capsule containing 0.5 mg, 1mg or 5mg Prograf®, one tablet containing 180mg or 360mg Myfortic®, corticosteroids and one vial containing 20mg lyophilisate Simulect®	Drug: Prograf; Prograf® capsules were supplied as capsules of 0.5 mg, 1 mg and 1.5 mg dose strengths.
Experimental: Tacroliums Hexal; Investigational therapy: one capsule containing 0.5mg, 1mg or 5mg Tacrolimus Hexal®, one tablet containing 180mg or 360mg Myfortic®, corticosteroids and one vial containing 20mg lyophilisate Simulect®	Drug: Tacrolimus Hexal; Tacrolimus Hexal® capsules were supplied to the investigators at dose strengths of 0.5 mg, 1 mg and 1.5 mg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ANCOVA Model for Change in Nankivell GFR (mL/Min) at Month 6, Without Replacement of Missing Values (Full Analysis Set)	Change in Nankivell glomerular filtration rate (GFR) from baseline to 6 months Glomerular Filtration Rate (GFR): The GFR is the best clinical estimate of renal function in health and disease, and correlates well with the clinical severity of renal function disturbances. Several studies have shown that in patients with progressive renal disease, GFR declines or reciprocal serum creatinine levels elevate linearly over time in a predictable manner. With the help of the serum creatinine values, the GFR was calculated via Nankivell formula.	baseline to month 6
ANOVA for Dose-normalized Tacrolimus 12-h-AUC (h/103*L) at Month 1	Compares the PK of Tacrolimus Hexal® assessed by the ratio of the AUC0-12h over one month period post transplantation vs. Prograf® in renal transplant patients	end of month 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Incidence of Biopsy-proven Acute Rejection (BPAR), Graft Loss and Death Until Month 12 (Full Analysis Set) (Full Analysis Set)	The key secondary objective was to assess the incidence of individual endpoints BPAR, graft loss and death until month 6 post-transplantation.	baseline to month 12
ANCOVA Model for Change in CKD-EPI GFR (Chronic Kidney Disease Epidemiology Collaboration Glomerular Filtration Rate) at Month 6 Post-transplantation	ANCOVA model for change in CKD-EPI Glomerular Filtration Rate (GFR)[ml/min] without replacement of missing values	baseline to Month 6
ANCOVA Model for Change in MDRD GFR (ml/Min) at Month 6, Without Replacement of Missing Values	MDRD GFR	least square (LS) mean change from baseline to Month 6
ANCOVA Model for Change in Cockcroft-Gault GFR (ml/Min) at Month 6, Without Replacement of Missing Values	change in Cockcroft-Gault GFR	least square (LS) mean change from baseline to Month 6

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2012
• Primary Completion (Actual): August 20, 2015
• Study Completion (Actual): August 20, 2015

Study Registration Dates

• First Submitted: July 20, 2012
• First Submitted That Met QC Criteria: July 24, 2012
• First Posted (Estimate): July 25, 2012

Study Record Updates

• Last Update Posted (Actual): June 17, 2019
• Last Update Submitted That Met QC Criteria: March 18, 2019
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: kidney; renal transplant; allograft rejection; xenograft rejection; host vs graft disease; Pharmacokinetics Study; Tacroliums; GFR; transplant rejection
• 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: CERL080ADE27

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com