Kidney TransplantationPhase 2NCT00282568

A Study to Assess the Pharmacokinetics of a Modified-release Tacrolimus Based Immunosuppression Regimen in Stable Kidney Transplant Patients

A Phase 2 study testing Tacrolimus Modified Release (MR) and tacrolimus in people with Kidney Transplantation, run by Astellas Pharma Inc at 9 sites in 2 countries.

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

A study to assess the pharmacokinetics, safety and effectiveness of tacrolimus in stable kidney transplant patients converted from a Prograf® based immunosuppression regimen to a modified release tacrolimus based immunosuppression regimen. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Kidney Transplantation
What is being tested?: Tacrolimus Modified Release (MR) and tacrolimus
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 70 participants
Where: 9 sitesin 2 countries
Study dates: Aug 2002to Oct 2008
Phase: Phase 2
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 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patient is currently receiving Prograf ® based immunosuppressive therapy for kidney transplantation.
Patient has stable whole blood trough level concentrations of Prograf® and is clinically stable

Who cannot join

Patient has previously received an organ transplant other than a kidney
Patient is currently receiving sirolimus immunosuppression therapy.

Trial locations and contacts

9 sites in 2 countries.

Country

City, postcode or hospital

9 sites in 2 countries

United States7 sites

Study site
Cincinnati, Ohio, 45267
Study site
Madison, Wisconsin, 53792
Study site
Miami, Florida, 33136
Study site
Milwaukee, Wisconsin, 53226
Study site
Minneapolis, Minnesota, 55455
Study site
Portland, Oregon, 97239
Study site
San Diego, California

Other trials in United States

Canada2 sites

Study site
Edmonton, Alberta, T6G 2B7
Study site
Toronto, Ontario, M5C 2T2

Other trials in Canada

About this study

Official title: A Phase 2, Open-Label, Multi-center Study to Assess the Pharmacokinetics, Safety and Tolerability of Tacrolimus in Stable Kidney Transplant Patients Converted From a Prograf® Based Immunosuppression Regimen to a Modified Release (MR) Tacrolimus Based Immunosuppression Regimen

Read the detailed description

This is a Phase II open-label, multi-center conversion study in stable, adult kidney transplant recipients to assess the pharmacokinetics, safety and effectiveness of tacrolimus in stable kidney transplant patients converted from a Prograf® based immunosuppression regimen to a modified release tacrolimus based immunosuppression regimen.

Conditions: Kidney Transplantation
Being tested: Tacrolimus Modified Release (MR), tacrolimus
Keywords: Pharmacokinetics, Therapy, Immunosuppression, Drugs, Investigational, Adult

What participants receive

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

Tacrolimus Modified Release (MR)Drug
Also called Advagraf, Astagraf XL, FK506E, FKMR
Oral
tacrolimusDrug
Also called Prograf®, FK506
Oral

Study groups in NCT00282568
Study group	Role	What they receive
Tacrolimus Modified Release	Experimental	Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons. Receives: Drug: Tacrolimus Modified Release (MR); Drug: tacrolimus

What is being measured

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

Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) for Tacrolimus
The area under the concentration-time curve was calculated from whole blood tacrolimus concentrations for both tacrolimus and tacrolimus MR at steady state using the trapezoidal rule.
Measured: For tacrolimus, Days 1 and 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Days 14 and 21 pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.
Maximum Observed Concentration (Cmax) of Tacrolimus
The maximum concentration was calculated from whole blood tacrolimus concentrations for both tacrolimus and tacrolimus MR at steady state, without interpolation.
Measured: For tacrolimus, Days 1 and 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Days 14 and 21 pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.
Minimum Concentration of Tacrolimus (Cmin)
The trough (minimum) concentration of tacrolimus determined from the tacrolimus whole blood concentration value at the 24-hour time point post- dose, prior to receiving the next dose.
Measured: Days 1 and 7 (tacrolimus) and Days 14 and 21 (tacrolimus MR), 24 hours post-dose.
Time to Maximum Observed Concentration of Tacrolimus (Tmax)
The time to reach the maximum concentration of tacrolimus was calculated from whole blood tacrolimus concentrations for both tacrolimus and tacrolimus MR at steady state, without interpolation.
Measured: For tacrolimus, Days 1 and 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Days 14 and 21 pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.
Patient Survival
Patient Survival defined as any participant who did not die by the time of analysis.
Measured: From enrollment until the end of study (up to 60 months).
Graft Survival
Graft survival was defined as any participant who did not meet the definition of graft loss, where graft loss was defined as graft failure (re-transplant or permanent return to dialysis (for more than 30 days)) or participants death.
Measured: From enrollment until the end of study (up to 60 months).

Secondary outcomes (15)

Percentage of Participants With Biopsy-confirmed Acute Rejection
Biopsy-confirmed acute rejection (BCAR) is defined as an episode of acute allograft rejection that was confirmed by biopsy results and was Banff grade ≥ IA. Biopsies were graded by the pathologist at the clinical site according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis; Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel.
Measured: From enrollment until the end of study (up to 60 months).
Change From Baseline in Serum Creatinine
Renal function was assessed using serum creatinine levels over the course of the study.
Measured: Baseline (the last day of tacrolimus on Day 7), Day 35 (end of the pharmacokinetic phase) and end of treatment (EOT; the last observed value during treatment, maximum time on study was 60 months).
Change From Baseline in Creatinine Clearance
Renal function was assessed using creatinine clearance levels calculated using the Cockcroft-Gault formula, over the course of the study.
Measured: Baseline (the last day of tacrolimus on Day 7), Day 35 (end of the pharmacokinetic phase) and end of treatment (EOT; the last observed value during treatment, maximum time on study was 60 months).
Time to Event for Patient Non Survival
For participants who died on study, the median number of days from enrollment to death due to any cause.
Measured: From enrollment until the end of study (up to 60 months).
Time to Event for Graft Non Survival
For participants with graft loss, the median number of days from enrollment to graft loss. Graft loss was defined as graft failure (re-transplant or permanent return to dialysis (for more than 30 days)) or participant death.
Measured: From enrollment until the end of study (up to 60 months).
Time to First Biopsy-confirmed Acute Rejection
For participants with a biopsy-confirmed acute rejection, the median number of days from enrollment to the date of biopsy confirmation. Biopsy-confirmed acute rejection (BCAR) is defined as an episode of acute allograft rejection that was confirmed by biopsy results and was Banff grade ≥ IA. Biopsies were graded by the pathologist at the clinical site according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis; Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel.
Measured: From enrollment until the end of study (up to 60 months).
Grade of Biopsy-confirmed Acute Rejection Episodes
Biopsy-confirmed acute rejection (BCAR) is defined as an episode of acute allograft rejection that was confirmed by biopsy results and was Banff grade ≥ IA. Biopsies were graded by the pathologist at the clinical site according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis; Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel.
For participants with more than one biopsy-confirmed acute rejection episode, the worst case grade is reported.
Measured: From enrollment until the end of study (up to 60 months).
Number of Participants Receiving Anti-lymphocyte Antibody Therapy for Acute Rejection
Steroid-resistant rejection episodes were treated with anti-lymphocyte antibodies. If a participant had a histologically proven Banff Grade II or III rejection, they could be initiated on anti-lymphocyte antibody treatment per institutional practice. Biopsies were graded by the pathologist at the clinical site according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis; Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel.
Measured: From enrollment until the end of study (up to 60 months).
Number of Participants With Multiple Rejection Episodes
This analysis includes rejection episodes that were either confirmed by biopsy by the clinical site pathologist or were clinically treated.
Measured: From enrollment until the end of study (up to 60 months).
Number of Participants With Clinically Treated Acute Rejection Episodes
A clinically treated acute rejection episode was any biopsy-confirmed or suspected rejection episode that was treated with immunosuppressive therapy.
Measured: From enrollment until the end of study (up to 60 months).
Number of Participants With Chronic Rejection
Due to the low number of participants with biopsy-confirmed acute rejection episodes, chronic rejection was not analyzed.
Measured: From enrollment until the end of study (up to 60 months).
Number of Participants With Treatment Failure
Treatment failure was defined as discontinuation of study drug for any reason. Due to discontinuation of the study by the sponsor, treatment failure was not analyzed.
Measured: From enrollment until the end of study (up to 60 months).
Primary Reason for Graft Loss
The primary reason for graft loss was recorded by the Investigator. Graft loss was defined as graft failure (re-transplant or permanent return to dialysis) or death. GBM = glomerular basement membrane.
Measured: From enrollment until the end of study (up to 60 months).
Number of Participants Returning to Permanent Dialysis
Permanent dialysis defined as dialysis for longer than 30 days.
Measured: From enrollment until the end of study (up to 60 months).
Safety as Assessed by Adverse Events, Laboratory Parameters and Vital Signs
An adverse event was defined as any reaction, side effect or other untoward medical occurrence, regardless of the relationship to study drug which occurred during the conduct of a clinical study. Clinically significant adverse changes in clinical status, routine laboratory studies or physical examinations were considered adverse events.
A serious adverse event was any adverse event occurring at any dose that resulted in any of the following outcomes:
- Death
- Life-threatening adverse event
- Inpatient hospitalization or prolongation of existing hospitalization
- Persistent or significant disability or incapacity
- Congenital abnormality or birth defect
- Important medical event.
Measured: From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months).

Timeline

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

Aug 2002Oct 2008

First posted27 Jan 2006 (estimated)
Study startAug 2002
Primary completionOct 2008
Study completionOct 2008

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 Kidney TransplantationStudies 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 2
Primary purpose: Prevention
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 70 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00282568
Sponsor's protocol ID: 02-0-131
Status last verified: Jul 2013
First submitted: 25 Jan 2006
Last updated: 26 Sep 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Alloway R, Steinberg S, Khalil K, Gourishankar S, Miller J, Norman D, Hariharan S, Pirsch J, Matas A, Zaltzman J, Wisemandle K, Fitzsimmons W, First MR. Two years postconversion from a prograf-based regimen to a once-daily tacrolimus extended-release formulation in stable kidney transplant recipients. Transplantation. 2007 Jun 27;83(12):1648-51. doi: 10.1097/01.tp.0000264056.20105.b4.
PubMed 17589351
Alloway R, Steinberg S, Khalil K, Gourishankar S, Miller J, Norman D, Hariharan S, Pirsch J, Matas A, Zaltzman J, Wisemandle K, Fitzsimmons W, First MR. Conversion of stable kidney transplant recipients from a twice daily Prograf-based regimen to a once daily modified release tacrolimus-based regimen. Transplant Proc. 2005 Mar;37(2):867-70. doi: 10.1016/j.transproceed.2004.12.222.
PubMed 15848559

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?

See locations

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All Kidney Transplantation trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2, Open-Label, Multi-center Study to Assess the Pharmacokinetics, Safety and Tolerability of Tacrolimus in Stable Kidney Transplant Patients Converted From a Prograf® Based Immunosuppression Regimen to a Modified Release (MR) Tacrolimus Based Immunosuppression Regimen
ClinicalTrials.gov ID: NCT00282568
Acronym / sponsor ID: 02-0-131
Conditions: Kidney Transplantation
Keywords: Pharmacokinetics, Therapy, Immunosuppression, Drugs, Investigational, Adult
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 70 participants (actual)
Lead sponsor: Astellas Pharma IncIndustry (pharma, biotech, devices)
Study start: Aug 2002
Primary completion: Oct 2008 (actual)
Study completion: Oct 2008 (actual)
First posted: 27 Jan 2006 (estimated)
Results: Posted 26 Sep 2013

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: Prevention
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Tacrolimus Modified Release	Experimental	Drug: Tacrolimus Modified Release (MR), Drug: tacrolimusParticipants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Patient is currently receiving Prograf ® based immunosuppressive therapy for kidney transplantation.
Patient has stable whole blood trough level concentrations of Prograf® and is clinically stable

Key exclusion criteria (2 listed)

Patient has previously received an organ transplant other than a kidney
Patient is currently receiving sirolimus immunosuppression therapy.

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
Tacrolimus Modified Release (MR)Also: Advagraf, Astagraf XL, FK506E, FKMROral	Drug	Tacrolimus Modified Release
tacrolimusAlso: Prograf®, FK506Oral	Drug	Tacrolimus Modified Release

Primary outcome

Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) for Tacrolimus
Time frame: For tacrolimus, Days 1 and 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Days 14 and 21 pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.
The area under the concentration-time curve was calculated from whole blood tacrolimus concentrations for both tacrolimus and tacrolimus MR at steady state using the trapezoidal rule.
Maximum Observed Concentration (Cmax) of Tacrolimus
Time frame: For tacrolimus, Days 1 and 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Days 14 and 21 pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.
The maximum concentration was calculated from whole blood tacrolimus concentrations for both tacrolimus and tacrolimus MR at steady state, without interpolation.
Minimum Concentration of Tacrolimus (Cmin)
Time frame: Days 1 and 7 (tacrolimus) and Days 14 and 21 (tacrolimus MR), 24 hours post-dose.
The trough (minimum) concentration of tacrolimus determined from the tacrolimus whole blood concentration value at the 24-hour time point post- dose, prior to receiving the next dose.
Time to Maximum Observed Concentration of Tacrolimus (Tmax)
Time frame: For tacrolimus, Days 1 and 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Days 14 and 21 pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.
The time to reach the maximum concentration of tacrolimus was calculated from whole blood tacrolimus concentrations for both tacrolimus and tacrolimus MR at steady state, without interpolation.
Patient Survival
Time frame: From enrollment until the end of study (up to 60 months).
Patient Survival defined as any participant who did not die by the time of analysis.
Graft Survival
Time frame: From enrollment until the end of study (up to 60 months).
Graft survival was defined as any participant who did not meet the definition of graft loss, where graft loss was defined as graft failure (re-transplant or permanent return to dialysis (for more than 30 days)) or participants death.

15 secondary outcomes

Percentage of Participants With Biopsy-confirmed Acute Rejection
Time frame: From enrollment until the end of study (up to 60 months).
Change From Baseline in Serum Creatinine
Time frame: Baseline (the last day of tacrolimus on Day 7), Day 35 (end of the pharmacokinetic phase) and end of treatment (EOT; the last observed value during treatment, maximum time on study was 60 months).
Change From Baseline in Creatinine Clearance
Time frame: Baseline (the last day of tacrolimus on Day 7), Day 35 (end of the pharmacokinetic phase) and end of treatment (EOT; the last observed value during treatment, maximum time on study was 60 months).
Time to Event for Patient Non Survival
Time frame: From enrollment until the end of study (up to 60 months).
Time to Event for Graft Non Survival
Time frame: From enrollment until the end of study (up to 60 months).
Time to First Biopsy-confirmed Acute Rejection
Time frame: From enrollment until the end of study (up to 60 months).
Grade of Biopsy-confirmed Acute Rejection Episodes
Time frame: From enrollment until the end of study (up to 60 months).
Number of Participants Receiving Anti-lymphocyte Antibody Therapy for Acute Rejection
Time frame: From enrollment until the end of study (up to 60 months).
Number of Participants With Multiple Rejection Episodes
Time frame: From enrollment until the end of study (up to 60 months).
Number of Participants With Clinically Treated Acute Rejection Episodes
Time frame: From enrollment until the end of study (up to 60 months).
Number of Participants With Chronic Rejection
Time frame: From enrollment until the end of study (up to 60 months).
Number of Participants With Treatment Failure
Time frame: From enrollment until the end of study (up to 60 months).
Primary Reason for Graft Loss
Time frame: From enrollment until the end of study (up to 60 months).
Number of Participants Returning to Permanent Dialysis
Time frame: From enrollment until the end of study (up to 60 months).
Safety as Assessed by Adverse Events, Laboratory Parameters and Vital Signs
Time frame: From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months).

Results and safety

Results posted to the registry on 26 Sep 2013, 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 Modified Release	70	67

Primary outcome: Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) for Tacrolimus

Time frame: For tacrolimus, Days 1 and 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Days 14 and 21 pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.. Mean (Standard Deviation). Unit: ng*hr/mL

Measure	Tacrolimus Modified Release n = 66
Day 1: Tacrolimus	215.1 (59.4)
Day 7: Tacrolimus	206.6 (58.4)
Day 14: Tacrolimus MR	200.7 (57.5)
Day 21: Tacrolimus MR	197.6 (47.5)

Tacrolimus Modified Release: Ratio of means: 94.97 (90% CI 90.72 to 99.41)

Population analysed: The number of participants analyzed represents the Pharmacokinetic evaluable set, defined as patients with all five complete pharmacokinetic profiles (two tacrolimus and three tacrolimus MR).

Primary outcome: Maximum Observed Concentration (Cmax) of Tacrolimus

Measure	Tacrolimus Modified Release n = 66
Day 1: Tacrolimus	17.2 (7.2)
Day 7: Tacrolimus	16.0 (6.5)
Day 14: Tacrolimus MR	14.3 (4.7)
Day 21: Tacrolimus MR	14.2 (5.1)

Tacrolimus Modified Release: Ratio of means: 88.15 (90% CI 82.69 to 93.96)

Population analysed: The number of participants analyzed represents the Pharmacokinetic evaluable set.

Primary outcome: Minimum Concentration of Tacrolimus (Cmin)

Time frame: Days 1 and 7 (tacrolimus) and Days 14 and 21 (tacrolimus MR), 24 hours post-dose.. Mean (Standard Deviation). Unit: ng/mL

Measure	Tacrolimus Modified Release n = 66
Day 1: Tacrolimus	6.96 (1.90)
Day 7: Tacrolimus	6.73 (1.99)
Day 14: Tacrolimus MR	6.08 (1.80)
Day 21: Tacrolimus MR	5.83 (1.63)

Tacrolimus Modified Release: Ratio of means: 87.20 (90% CI 82.72 to 91.93)

Population analysed: The number of participants analyzed represents the trough evaluable set defined as all patients with replicate trough measurements for both tacrolimus and tacrolimus MR.

Primary outcome: Time to Maximum Observed Concentration of Tacrolimus (Tmax)

Measure	Tacrolimus Modified Release n = 66
Day 1: Tacrolimus	1.9 (1.8)
Day 7: Tacrolimus	2.0 (1.7)
Day 14: Tacrolimus MR	3.1 (2.3)
Day 21: Tacrolimus MR	2.7 (2.1)

Population analysed: The number of participants analyzed represents the trough evaluable set defined as all patients with replicate trough measurements for both tacrolimus and tacrolimus MR.

15 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Tacrolimus Modified Release	39 of 67 (58.2%)	48 of 67 (71.6%)	Not reported

Limitations and caveats (from the sponsor): Company makes no warranties or representations of any kind as to the posting, expressed or implied, including warranties of merchantability and fitness for a particular purpose, and shall not be liable for any damages.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 17589351Alloway R, Steinberg S, Khalil K, Gourishankar S, Miller J, Norman D, Hariharan S, Pirsch J, Matas A, Zaltzman J, Wisemandle K, Fitzsimmons W, First MR. Two years postconversion from a prograf-based regimen to a once-daily tacrolimus extended-release formulation in stable kidney transplant recipients. Transplantation. 2007 Jun 27;83(12):1648-51. doi: 10.1097/01.tp.0000264056.20105.b4.
Background: PubMed 15848559Alloway R, Steinberg S, Khalil K, Gourishankar S, Miller J, Norman D, Hariharan S, Pirsch J, Matas A, Zaltzman J, Wisemandle K, Fitzsimmons W, First MR. Conversion of stable kidney transplant recipients from a twice daily Prograf-based regimen to a once daily modified release tacrolimus-based regimen. Transplant Proc. 2005 Mar;37(2):867-70. doi: 10.1016/j.transproceed.2004.12.222.

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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.

Central Contact study director

Astellas Pharma US, Inc.

9 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tacrolimus Modified Release (MR) and tacrolimus in people with Kidney Transplantation, run by Astellas Pharma Inc at 9 sites in 2 countries.

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 2 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 26 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, Canada. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 26 Sep 2013). 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?

Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) for Tacrolimus (time frame: For tacrolimus, Days 1 and 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Days 14 and 21 pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.). The study lists 6 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 NCT00282568, 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 26 Sep 2013.