Pharmacokinetics Study in de Novo Kidney TransplantationPhase 4SpartacusNCT01649427

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

A Phase 4 study testing Prograf and Tacrolimus Hexal in people with Pharmacokinetics Study in de Novo Kidney Transplantation, run by Novartis Pharmaceuticals at 5 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 18 to 64 years
Conditions the study is for: Pharmacokinetics Study in de Novo Kidney Transplantation
What is being tested?: Prograf and Tacrolimus Hexal
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 73 participants
Where: 5 sitesGermany
Study dates: 17 Oct 2012to 20 Aug 2015
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 64 years
All sexes
No healthy volunteers
Adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

Germany5 sites

Novartis Investigative Site
Berlin, 10098
Novartis Investigative Site
Bochum, 44892
Novartis Investigative Site
Düsseldorf, 40225
Novartis Investigative Site
Kaiserslautern, 67655
Novartis Investigative Site
Koeln-Merheim, 51109

Other trials in Germany

About this study

Official title: 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

Read the 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.

Conditions: Pharmacokinetics Study in de Novo Kidney Transplantation
Being tested: Prograf, Tacrolimus Hexal
Keywords: Pharmacokinetics Study, Tacroliums, GFR, kidney, transplant rejection, allograft rejection, xenograft rejection, host vs graft disease, renal transplant
Medical subject headings: Graft vs Host Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PrografDrug
Prograf® capsules were supplied as capsules of 0.5 mg, 1 mg and 1.5 mg dose strengths.
Tacrolimus HexalDrug
Tacrolimus Hexal® capsules were supplied to the investigators at dose strengths of 0.5 mg,
1 mg and 1.5 mg.

Study groups in NCT01649427
Study group	Role	What they receive
Prograf	Experimental	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® Receives: Drug: Prograf
Tacroliums Hexal	Experimental	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® Receives: Drug: Tacrolimus Hexal

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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
Measured: end of month 1

Secondary outcomes (4)

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.
Measured: 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
Measured: baseline to Month 6
ANCOVA Model for Change in MDRD GFR (ml/Min) at Month 6, Without Replacement of Missing Values
MDRD GFR
Measured: 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
Measured: least square (LS) mean change from baseline to Month 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

17 Oct 201220 Aug 2015

First posted25 Jul 2012 (estimated)
Study start17 Oct 2012
Primary completion20 Aug 2015
Study completion20 Aug 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Pharmacokinetics Study in de Novo Kidney TransplantationStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 73 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01649427
Sponsor's protocol ID: CERL080ADE27
Acronym: Spartacus
Status last verified: Nov 2017
First submitted: 20 Jul 2012
Last updated: 17 Jun 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Undecided: 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

Study at a glance

From the registry record, last updated by the sponsor on 17 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT01649427
Acronym / sponsor ID: Spartacus / CERL080ADE27
Conditions: Pharmacokinetics Study in de Novo Kidney Transplantation
Keywords: Pharmacokinetics Study, Tacroliums, GFR, kidney, transplant rejection, allograft rejection, xenograft rejection, host vs graft disease
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 73 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 17 Oct 2012 (actual)
Primary completion: 20 Aug 2015 (actual)
Study completion: 20 Aug 2015 (actual)
First posted: 25 Jul 2012 (estimated)
Results: Posted 17 Jun 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Prograf	Experimental	Drug: PrografControl 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®
Tacroliums Hexal	Experimental	Drug: Tacrolimus HexalInvestigational 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®

Who may qualify

Ages: 18 to 64 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (1 listed)

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

Key exclusion criteria (2 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PrografPrograf® capsules were supplied as capsules of 0.5 mg, 1 mg and 1.5 mg dose strengths.	Drug	Prograf
Tacrolimus HexalTacrolimus Hexal® capsules were supplied to the investigators at dose strengths of 0.5 mg, 1 mg and 1.5 mg.	Drug	Tacroliums Hexal

Primary outcome

ANCOVA Model for Change in Nankivell GFR (mL/Min) at Month 6, Without Replacement of Missing Values (Full Analysis Set)
Time frame: 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.
ANOVA for Dose-normalized Tacrolimus 12-h-AUC (h/103*L) at Month 1
Time frame: 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

4 secondary outcomes

The Incidence of Biopsy-proven Acute Rejection (BPAR), Graft Loss and Death Until Month 12 (Full Analysis Set) (Full Analysis Set)
Time frame: 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
Time frame: baseline to Month 6
ANCOVA Model for Change in MDRD GFR (ml/Min) at Month 6, Without Replacement of Missing Values
Time frame: 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
Time frame: least square (LS) mean change from baseline to Month 6

Results and safety

Results posted to the registry on 17 Jun 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Tacrolimus Hexal®	35	24
Prograf®	38	26

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

Time frame: baseline to month 6. Least squares mean (95% Confidence Interval). Unit: mL/min

Measure	Tacrolimus Hexal® n = 24	Prograf® n = 27
Value	47.65 (20.24)	38.60 (18.83)

Tacrolimus Hexal® vs Prograf®: p = 0.0003, ANCOVA

Population analysed: The Full Analysis Set (FAS) consisted of all patients in whom study treatment was assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization

Primary outcome: ANOVA for Dose-normalized Tacrolimus 12-h-AUC (h/103*L) at Month 1

Time frame: end of month 1. Least squares mean (90% Confidence Interval). Unit: h/10^3*L

Measure	Tacrolimus Hexal® n = 23	Prograf® n = 20
Adjusted, log-transformed Estimates (ANOVA)	2.944 (2.783 to 3.105)	3.020 (2.811 to 3.228)
Adjusted, back-transformed Estimates (ANOVA)	18.991 (16.163 to 22.314)	20.484 (16.630 to 25.231)

4 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Tacrolimus Hexal	19 of 35 (54.3%)	34 of 35 (97.1%)	Not reported
Prograf	17 of 39 (43.6%)	38 of 39 (97.4%)	Not reported

Limitations and caveats (from the sponsor): 1 patient was randomized to Prograf but didn't get treatment and was excluded from efficacy analyses but kept for safety reporting. Phase 2 was not started due to high drop-out rate. 73 enrolled; 43 of the planned 54 were available for PK analysis

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Undecided. 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

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Prograf and Tacrolimus Hexal in people with Pharmacokinetics Study in de Novo Kidney Transplantation, run by Novartis Pharmaceuticals at 5 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

ANCOVA Model for Change in Nankivell GFR (mL/Min) at Month 6, Without Replacement of Missing Values (Full Analysis Set) (time frame: baseline to month 6). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01649427.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2019.