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NCT01649427: Spartacus

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

Completed Phase 4 Results posted Last updated 17 June 2019
What this trial tests

Phase 4 trial testing Prograf in Pharmacokinetics Study in de Novo Kidney Transplantation in 73 participants. Completed in 20 August 2015.

Timeline
17 October 2012
Primary endpoint
20 August 2015
20 August 2015

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 4
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposebasic science
Enrollment73
Start date17 October 2012
Primary completion20 August 2015
Estimated completion20 August 2015
Sites5 locations across Germany

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Adults 18 to 64, any sex, with Pharmacokinetics Study in de Novo Kidney Transplantation. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

ANCOVA Model for Change in Nankivell GFR (mL/Min) at Month 6, Without Replacement of Missing Values (Full Analysis Set) Primary · baseline to month 6

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.

GroupValue95% CI
Tacrolimus Hexal®47.6541.70 – 53.60
Prograf®38.6031.32 – 45.89
The Incidence of Biopsy-proven Acute Rejection (BPAR), Graft Loss and Death Until Month 12 (Full Analysis Set) (Full Analysis Set) Secondary · baseline to month 12

The key secondary objective was to assess the incidence of individual endpoints BPAR, graft loss and death until month 6 post-transplantation.

Biopsy proven acute rejection (BPAR)
GroupValue95% CI
Tacrolimus Hexal®20.70 – 19.16
Prograf®31.66 – 21.38
Graft loss
GroupValue95% CI
Tacrolimus Hexal®00.00 – 10.00
Prograf®10.07 – 13.81
Death
GroupValue95% CI
Tacrolimus Hexal®00.00 – 10.00
Prograf®10.07 – 13.81
Composite: BPAR, graft loss or death
GroupValue95% CI
Tacrolimus Hexal®20.70 – 19.16
Prograf®42.94 – 24.80
ANCOVA Model for Change in CKD-EPI GFR (Chronic Kidney Disease Epidemiology Collaboration Glomerular Filtration Rate) at Month 6 Post-transplantation Secondary · baseline to Month 6

ANCOVA model for change in CKD-EPI Glomerular Filtration Rate (GFR)\[ml/min\] without replacement of missing values

GroupValue95% CI
Tacrolimus Hexal®48.33± 3.84
Prograf®39.77± 4.61
ANOVA for Dose-normalized Tacrolimus 12-h-AUC (h/103*L) at Month 1 Primary · end of 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

Adjusted, log-transformed Estimates (ANOVA)
GroupValue95% CI
Tacrolimus Hexal®2.9442.783 – 3.105
Prograf®3.0202.811 – 3.228
Adjusted, back-transformed Estimates (ANOVA)
GroupValue95% CI
Tacrolimus Hexal®18.99116.163 – 22.314
Prograf®20.48416.630 – 25.231
ANCOVA Model for Change in MDRD GFR (ml/Min) at Month 6, Without Replacement of Missing Values Secondary · least square (LS) mean change from baseline to Month 6

MDRD GFR

GroupValue95% CI
Tacrolimus Hexal®46.2037.62 – 54.79
Prograf®38.5228.64 – 48.41
ANCOVA Model for Change in Cockcroft-Gault GFR (ml/Min) at Month 6, Without Replacement of Missing Values Secondary · least square (LS) mean change from baseline to Month 6

change in Cockcroft-Gault GFR

GroupValue95% CI
Tacrolimus Hexal®60.4552.48 – 68.41
Prograf®46.4536.89 – 56.02

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Tacrolimus Hexal
Serious: 19/35 (54%)
Deaths:
Prograf
Serious: 17/39 (44%)
Deaths:

Serious adverse events (58 terms)

ReactionSystemTacrolimus HexalPrograf
URINARY TRACT INFECTIONInfections and infestations
COMPLICATIONS OF TRANSPLANTED KIDNEYInjury, poisoning and procedural complications
BLOOD CREATININE INCREASEDInvestigations
DIARRHOEAGastrointestinal disorders
ACUTE KIDNEY INJURYRenal and urinary disorders
PROTEINURIARenal and urinary disorders
THROMBOTIC MICROANGIOPATHYBlood and lymphatic system disorders
KIDNEY TRANSPLANT REJECTIONImmune system disorders
UROSEPSISInfections and infestations
INCISIONAL HERNIAInjury, poisoning and procedural complications
FOCAL SEGMENTAL GLOMERULOSCLEROSISRenal and urinary disorders
RENAL IMPAIRMENTRenal and urinary disorders
LEUKOPENIABlood and lymphatic system disorders
ACUTE MYOCARDIAL INFARCTIONCardiac disorders
CORONARY ARTERY DISEASECardiac disorders
COLITISGastrointestinal disorders
ENTERITISGastrointestinal disorders
LARGE INTESTINE PERFORATIONGastrointestinal disorders
PANCREATIC PSEUDOCYSTGastrointestinal disorders
PANCREATITIS CHRONICGastrointestinal disorders
IMPAIRED HEALINGGeneral disorders
IMPLANT SITE EXTRAVASATIONGeneral disorders
OEDEMA PERIPHERALGeneral disorders
PYREXIAGeneral disorders
BACTERIAL SEPSISInfections and infestations
Other adverse events (66 terms — click to expand)

ReactionSystemTacrolimus HexalPrograf
HYPERTENSIONVascular disorders
WOUND COMPLICATIONInjury, poisoning and procedural complications
URINARY TRACT INFECTIONInfections and infestations
COMPLICATIONS OF TRANSPLANTED KIDNEYInjury, poisoning and procedural complications
HYPERKALAEMIAMetabolism and nutrition disorders
HYPERURICAEMIAMetabolism and nutrition disorders
ANAEMIABlood and lymphatic system disorders
LEUKOPENIABlood and lymphatic system disorders
OEDEMA PERIPHERALGeneral disorders
HYPOMAGNESAEMIAMetabolism and nutrition disorders
CONSTIPATIONGastrointestinal disorders
BLOOD CREATININE INCREASEDInvestigations
VITAMIN D DEFICIENCYMetabolism and nutrition disorders
INSOMNIAPsychiatric disorders
NEPHROGENIC ANAEMIABlood and lymphatic system disorders
DIARRHOEAGastrointestinal disorders
NAUSEAGastrointestinal disorders
HYPOCALCAEMIAMetabolism and nutrition disorders
HYPOKALAEMIAMetabolism and nutrition disorders
BLADDER PAINRenal and urinary disorders
FLATULENCEGastrointestinal disorders
KIDNEY TRANSPLANT REJECTIONImmune system disorders
CYTOMEGALOVIRUS INFECTIONInfections and infestations
RENAL LYMPHOCELEInjury, poisoning and procedural complications
HEADACHENervous system disorders
RENAL HYPERTENSIONRenal and urinary disorders
HIATUS HERNIAGastrointestinal disorders
VOMITINGGastrointestinal disorders
PYREXIAGeneral disorders
NASOPHARYNGITISInfections and infestations
POST PROCEDURAL HAEMATOMAInjury, poisoning and procedural complications
HEPATIC ENZYME INCREASEDInvestigations
DIABETES MELLITUSMetabolism and nutrition disorders
HYPERLIPIDAEMIAMetabolism and nutrition disorders
HYPOPHOSPHATAEMIAMetabolism and nutrition disorders
METABOLIC ACIDOSISMetabolism and nutrition disorders
TREMORNervous system disorders
SLEEP DISORDERPsychiatric disorders
BLADDER SPASMRenal and urinary disorders
LEUKOCYTOSISBlood and lymphatic system disorders

Most-reported serious reactions: URINARY TRACT INFECTION, COMPLICATIONS OF TRANSPLANTED KIDNEY, BLOOD CREATININE INCREASED, DIARRHOEA, ACUTE KIDNEY INJURY, PROTEINURIA, THROMBOTIC MICROANGIOPATHY, KIDNEY TRANSPLANT REJECTION.

Data from ClinicalTrials.gov NCT01649427 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.

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