Renal FailurePhase 3ASTCOFFNCT02339246

Pharmacokinetic Comparison Of All FK-506 Formulations

A Phase 3 study testing Prograf vs Envarsus XR vs Astagraf XL and Prograf vs Astagraf XL vs Envarsus XR in people with Renal Failure, run by Veloxis Pharmaceuticals at 1 site in United States.

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 the study is to compare the pharmacokinetic parameters of three different formulations of tacrolimus. Eligible patients will be treated with all three formulations in a pre-defined sequence. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Renal Failure
What is being tested?: Prograf vs Envarsus XR vs Astagraf XL and Prograf vs Astagraf XL vs Envarsus XR
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 32 participants
Where: 1 siteUnited States
Study dates: Jan 2015to Mar 2015
Phase: Phase 3
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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Renal transplant recipients, males or females, of 18 years of age or above.
Able to participate and willing to give written informed consent and to comply with study visits and restrictions.
Able to understand English.
Patients having received a primary or secondary renal transplant

Who cannot join

Evidence of acute rejection episode within the past three months prior to screening.
Recipients of organ transplants other than kidney.
Patients who are known to be HIV positive.

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Cincinnati
Cincinnati, Ohio, 45267-2827

Other trials in United States

About this study

Official title: A Steady-state Pharmacokinetic Comparison Of All FK-506 Formulations

The purpose of the study is to compare the pharmacokinetic parameters of three different formulations of tacrolimus.

Eligible patients will be treated with all three formulations in a pre-defined sequence.

Read the detailed description

The pharmacokinetic parameters T(max), C(max) and AUC(0-24) will be compared between the three formulations Envarsus XR once daily, Astagraf XL once daily and Prograf Twice daily.

Conditions: Renal Failure
Being tested: Prograf vs Envarsus XR vs Astagraf XL, Prograf vs Astagraf XL vs Envarsus XR
Medical subject headings: Renal Insufficiency

What participants receive

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

Prograf vs Envarsus XR vs Astagraf XLDrug
Also called Tacrolimus
prograf vs Envarsus XR vs Astagraf XL
Prograf vs Astagraf XL vs Envarsus XRDrug
Also called Tacrolimus
Prograf vs Astagraf XL vs Envarsus XR

Study groups in NCT02339246
Study group	Role	What they receive
Prograf vs Envarsus XR vs Astagraf XL	Active comparator	Prograft capsules Twice daily for 7 days, followed by Envarsus XR tablets once daily for 7 days followed by Astagraf XL capsules once daily for 7 days. Receives: Drug: Prograf vs Envarsus XR vs Astagraf XL
Prograf vs Astagraf XL vs Envarsus XR	Active comparator	Prograf capsules twice daily for 7 days followed by Astagraf XL capsules once daily for 7 days followed by Envarsus XR tablets once daily. Receives: Drug: Prograf vs Astagraf XL vs Envarsus XR

What is being measured

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

Evaluation of T(Max) for Envarsus XR, Astagraf XL and Prograf.
Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling times was used to calculate T(max).
Nominal time points used were:
Prograf sampling strategy (21 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20, and 24.
Envarsus XR sampling strategy (18 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, 24, and 27.
Astagraf XL sampling strategy (17 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, and 24.
Measured: 8 days
Evaluation of C(Max) for Envarsus XR, Astagraf XL and Prograf.
Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling times was used to calculate C(max).
Nominal time points used were:
Prograf sampling strategy (21 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20, and 24.
Envarsus XR sampling strategy (18 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, 24, and 27.
Astagraf XL sampling strategy (17 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, and 24.
Measured: 8 days
Evaluation of AUC(0-24) for Envarsus XR, Astagraf XL and Prograf.
Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling times was used to calculate AUC(0-24).
Nominal time points used were:
Prograf sampling strategy (21 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20, and 24.
Envarsus XR sampling strategy (18 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, 24, and 27.
Astagraf XL sampling strategy (17 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, and 24.
Measured: 8 days

Timeline

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

Jan 2015Mar 2015

First posted15 Jan 2015 (estimated)
Study startJan 2015
Primary completionMar 2015
Study completionMar 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.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Renal FailureStudies of the same condition, open and under way.
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 3
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 32 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02339246
Sponsor's protocol ID: Envarsus 3006
Acronym: ASTCOFF
Status last verified: Nov 2015
First submitted: 19 Dec 2014
Last updated: 18 Jan 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Philosophe B, Leca N, West-Thielke PM, Horwedel T, Culkin-Gemmell C, Kistler K, Stevens DR. Evaluation of Flexible Tacrolimus Drug Concentration Monitoring Approach in Patients Receiving Extended-Release Once-Daily Tacrolimus Tablets. J Clin Pharmacol. 2018 Jul;58(7):891-896. doi: 10.1002/jcph.1082. Epub 2018 Feb 20.
PubMed 29462506
Tremblay S, Nigro V, Weinberg J, Woodle ES, Alloway RR. A Steady-State Head-to-Head Pharmacokinetic Comparison of All FK-506 (Tacrolimus) Formulations (ASTCOFF): An Open-Label, Prospective, Randomized, Two-Arm, Three-Period Crossover Study. Am J Transplant. 2017 Feb;17(2):432-442. doi: 10.1111/ajt.13935. Epub 2016 Aug 2.
PubMed 27340950

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 18 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Steady-state Pharmacokinetic Comparison Of All FK-506 Formulations
ClinicalTrials.gov ID: NCT02339246
Acronym / sponsor ID: ASTCOFF / Envarsus 3006
Conditions: Renal Failure
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 32 participants (actual)
Lead sponsor: Veloxis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Jan 2015
Primary completion: Mar 2015 (actual)
Study completion: Mar 2015 (actual)
First posted: 15 Jan 2015 (estimated)
Results: Posted 18 Jan 2016

Clinical summary

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

The purpose of the study is to compare the pharmacokinetic parameters of three different formulations of tacrolimus.

Eligible patients will be treated with all three formulations in a pre-defined sequence.

Detailed description

The pharmacokinetic parameters T(max), C(max) and AUC(0-24) will be compared between the three formulations Envarsus XR once daily, Astagraf XL once daily and Prograf Twice daily.

Study design

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

Arm	Type	Receives
Prograf vs Envarsus XR vs Astagraf XL	Active comparator	Drug: Prograf vs Envarsus XR vs Astagraf XLPrograft capsules Twice daily for 7 days, followed by Envarsus XR tablets once daily for 7 days followed by Astagraf XL capsules once daily for 7 days.
Prograf vs Astagraf XL vs Envarsus XR	Active comparator	Drug: Prograf vs Astagraf XL vs Envarsus XRPrograf capsules twice daily for 7 days followed by Astagraf XL capsules once daily for 7 days followed by Envarsus XR tablets once daily.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Renal transplant recipients, males or females, of 18 years of age or above.
Able to participate and willing to give written informed consent and to comply with study visits and restrictions.
Able to understand English.
Patients having received a primary or secondary renal transplant

Key exclusion criteria (3 listed)

Evidence of acute rejection episode within the past three months prior to screening.
Recipients of organ transplants other than kidney.
Patients who are known to be HIV positive.

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
Prograf vs Envarsus XR vs Astagraf XLAlso: Tacrolimusprograf vs Envarsus XR vs Astagraf XL	Drug	Prograf vs Envarsus XR vs Astagraf XL
Prograf vs Astagraf XL vs Envarsus XRAlso: TacrolimusPrograf vs Astagraf XL vs Envarsus XR	Drug	Prograf vs Astagraf XL vs Envarsus XR

Primary outcome

Evaluation of T(Max) for Envarsus XR, Astagraf XL and Prograf.
Time frame: 8 days
Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling times was used to calculate T(max). Nominal time points used were: Prograf sampling strategy (21 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20, and 24. Envarsus XR sampling strategy (18 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, 24, and 27. Astagraf XL sampling strategy (17 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, and 24.
Evaluation of C(Max) for Envarsus XR, Astagraf XL and Prograf.
Time frame: 8 days
Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling times was used to calculate C(max). Nominal time points used were: Prograf sampling strategy (21 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20, and 24. Envarsus XR sampling strategy (18 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, 24, and 27. Astagraf XL sampling strategy (17 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, and 24.
Evaluation of AUC(0-24) for Envarsus XR, Astagraf XL and Prograf.
Time frame: 8 days
Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling times was used to calculate AUC(0-24). Nominal time points used were: Prograf sampling strategy (21 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20, and 24. Envarsus XR sampling strategy (18 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, 24, and 27. Astagraf XL sampling strategy (17 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, and 24.

Results and safety

Results posted to the registry on 18 Jan 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Envarsus XR	0	0
Astagraf XL	0	0
Prograf	31	31

Primary outcome: Evaluation of T(Max) for Envarsus XR, Astagraf XL and Prograf.

Time frame: 8 days. Median (95% Confidence Interval). Unit: hour

Measure	Envarsus XR n = 30	Astagraf XL n = 30	Prograf n = 30
Value	5.91 (1.45 to 13.95)	1.93 (0.92 to 5.92)	1.48 (0.93 to 19.97)

Population analysed: One patient in the Envarsus XR arm was excluded from the analysis due to non compliance.

Primary outcome: Evaluation of C(Max) for Envarsus XR, Astagraf XL and Prograf.

Time frame: 8 days. Mean (Standard Deviation). Unit: ng/mL

Measure	Envarsus XR n = 30	Astagraf XL n = 30	Prograf n = 30
Value	13.88 (5.331)	13.17 (12.49)	14.54 (13.60)

Population analysed: One patient in the Envarsus XR arm was excluded from the analysis due to non compliance.

Primary outcome: Evaluation of AUC(0-24) for Envarsus XR, Astagraf XL and Prograf.

Time frame: 8 days. Mean (Standard Deviation). Unit: hr*ng/mL

Measure	Envarsus XR n = 30	Astagraf XL n = 30	Prograf n = 30
Value	213.41 (83.095)	165.02 (48.910)	176.52 (50.799)

Population analysed: One patient in the Envarsus XR arm was excluded from the analysis due to non compliance.

Adverse events

Time frame: Adverse events were collected from time of first dose of study drug and until last visit which was approximately 1 month.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Envarsus XR	0 of 31 (0%)	2 of 31 (6.5%)	Not reported
Astagraf XR	0 of 31 (0%)	10 of 31 (32.3%)	Not reported
Prograf	0 of 31 (0%)	3 of 31 (9.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 29462506Philosophe B, Leca N, West-Thielke PM, Horwedel T, Culkin-Gemmell C, Kistler K, Stevens DR. Evaluation of Flexible Tacrolimus Drug Concentration Monitoring Approach in Patients Receiving Extended-Release Once-Daily Tacrolimus Tablets. J Clin Pharmacol. 2018 Jul;58(7):891-896. doi: 10.1002/jcph.1082. Epub 2018 Feb 20.
Derived from this study: PubMed 27340950Tremblay S, Nigro V, Weinberg J, Woodle ES, Alloway RR. A Steady-State Head-to-Head Pharmacokinetic Comparison of All FK-506 (Tacrolimus) Formulations (ASTCOFF): An Open-Label, Prospective, Randomized, Two-Arm, Three-Period Crossover Study. Am J Transplant. 2017 Feb;17(2):432-442. doi: 10.1111/ajt.13935. Epub 2016 Aug 2.

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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.

Rita Alloway, PharmD principal investigator

University of Cincinnati

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

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Prograf vs Envarsus XR vs Astagraf XL and Prograf vs Astagraf XL vs Envarsus XR in people with Renal Failure, run by Veloxis Pharmaceuticals at 1 site in United States.

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 4 inclusion and 3 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 18 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 18 Jan 2016). 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?

Evaluation of T(Max) for Envarsus XR, Astagraf XL and Prograf. (time frame: 8 days). The study lists 3 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 NCT02339246, which also lists 2 linked publications.

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 18 Jan 2016.