End Stage Renal DiseasePhase 4NCT02221583
Pharmacokinetics of Immunosuppressants in Renal Transplant Candidates Who Have Undergone Laparoscopic Sleeve Gastrectomy
A Phase 4 study testing Astagraf XL, Prograf and Mycophenolate mofetil in people with End Stage Renal Disease, run by University of Cincinnati at 1 site in United States.
Trial summary
The purpose of this study is to evaluate how quickly and to what extent different immunosuppressants are absorbed into the blood (this is called pharmacokinetics) in renal transplant candidates who have undergone a laparoscopic sleeve gastrectomy. The immune system is the body's defense against diseases. Read more about this study
- Who is it for?
- Ages 19 to 75 years
- Conditions the study is for
- End Stage Renal Disease
- What is being tested?
- Astagraf XL, Prograf and Mycophenolate mofetil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- May 2014to Feb 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 19 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female or male patient aged > 18 years old.
- ESRD patient (on dialysis or preemptive) who is a potential candidate for kidney transplantation
- Undergone laparoscopic sleeve gastrectomy procedure > 3 months prior to enrollment.
- Subjects have signed and dated the informed consent to participate in the study.
Who cannot join
- Patients taking a drug known to interact with Astagraf XL, Prograf®, or MMF.
- Patients that have an allergy to Astagraf XL, Prograf®, or MMF.
- Patients currently taking Astagraf XL, Prograf®, or MMF.
- Post-surgical leak complication
- Patients failing to adhere to post laparoscopic sleeve gastrectomy follow-up recommendations and clinic visits
- Patients with any severe medical condition requiring acute or chronic treatment that in the investigator's opinion would interfere with study participation.
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- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive laboratory test
- Currently taking or planning to initiate of any medications that could interfere with tacrolimus and/or mycophenolate blood levels, including over the counter (OTC) medications, herbal supplements, grapefruit or grapefruit juice.
- Subjects who have been exposed to an investigational therapy within 30 days prior to enrollment or 5 half-lives of the investigational product, whichever is greater.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Multicenter Pilot Study to Determine the Pharmacokinetics of Astagraf XL, Prograf and Mycophenolate Mofetil in Renal Transplant Candidates Who Have Undergone Laparoscopic Sleeve Gastrectomy
The purpose of this study is to evaluate how quickly and to what extent different immunosuppressants are absorbed into the blood (this is called pharmacokinetics) in renal transplant candidates who have undergone a laparoscopic sleeve gastrectomy. The immune system is the body's defense against diseases. It also attacks "foreign" tissues such as a transplanted kidney. Immunosuppressant medications such as Astagraf sustained release (XL), Prograf, and mycophenolate mofetil may be given to suppress the immune system following kidney transplantation and prevent rejection of a transplanted kidney. This study is being performed to determine if patients who undergo laparoscopic sleeve gastrectomy need different doses of immunosuppressant medications.
Read the detailed description
Investigators propose a single dose, cross over pharmacokinetic study of Astagraf XL and Prograf® in combination with MMF in RTx candidates that have undergone LSG. Subjects at least three months post LSG and pre-renal transplant will undergo preliminary screening. The study population will consist of 24 male and female subjects, ≥ 18 years old from UC Health University Hospital and The Christ Hospital who meet the inclusion/exclusion criteria.
Two PK profiles will be obtained in each subject. Each subject will receive either Astagraf XL 8mg daily or Prograf® 4mg every 12 hours in combination with MMF 1000mg every 12 hours. A full 24 hour PK profile will be constructed. After at least a one week washout period, the patient will be crossed over to the alternative tacrolimus formulation (Astagraf XL or Prograf®) in combination with MMF 1000mg every 12 hours and the PK profile repeated. The immunosuppressants chosen reflect the regimen most commonly prescribed to transplant recipients.
Subjects participating in the study will have pharmacokinetic blood samples drawn over a 24 hour time period in order to determine the AUC, Tmax, Cmax, and half-life of tacrolimus, MMF and their metabolites. Samples would be drawn prior to dosing (C0) and at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 18, 20 and 24 hours post dosing (18 time points) by venipuncture or IV.
This study proposal represents a simple and expeditious method to achieve PK information in patients that have undergone LSG. If desired, study could be expanded to evaluate PK in additional patient groups such as pre and post LSG and/or pre and post renal transplant. The exact sample collection time will be recorded in the case report form. All deviations from the scheduled sampling time of more than 5 minutes for the first 4 hours after the AM dose (predose-4 hr) and first 4 hours of the PM dose (12 hr-16 hr), and more than 10 minutes for all remaining samples (6 hr-8 hr; 18 hr-24 hr) will be reported as a protocol deviation.
- Conditions
- End Stage Renal Disease
- Being tested
- Astagraf XL, Prograf, Mycophenolate mofetil
- Keywords
- End stage renal disease, Renal transplant candidate, Laparoscopic sleeve gastrectomy, Immunosuppressants
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Astagraf XLDrug
Also called Tacrolimus sustained release
Two PK profiles will be obtained in each subject. Each subject will receive either Astagraf XL 8mg daily or Prograf® 4mg every 12 hours in combination with MMF 1000mg every 12 hours. A full 24 hour PK profile will be constructed. After at least a one week washout period, the patient will be crossed over to the alternative tacrolimus formulation (Astagraf XL or Prograf®) in combination with MMF 1000mg every 12 hours and the PK profile repeated.
PrografDrug
Also called Tacrolimus
Two PK profiles will be obtained in each subject. Each subject will receive either Astagraf XL 8mg daily or Prograf® 4mg every 12 hours in combination with MMF 1000mg every 12 hours. A full 24 hour PK profile will be constructed. After at least a one week washout period, the patient will be crossed over to the alternative tacrolimus formulation (Astagraf XL or Prograf®) in combination with MMF 1000mg every 12 hours and the PK profile repeated.
Also called Cellcept
Two PK profiles will be obtained in each subject. Each subject will receive either Astagraf XL 8mg daily or Prograf® 4mg every 12 hours in combination with MMF 1000mg every 12 hours. A full 24 hour PK profile will be constructed. After at least a one week washout period, the patient will be crossed over to the alternative tacrolimus formulation (Astagraf XL or Prograf®) in combination with MMF 1000mg every 12 hours and the PK profile repeated.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Astagraf XL + Mycophenolate mofetil then cross over to Prograf + Mycophenolate Receives: Drug: Astagraf XL; Drug: Prograf; Drug: Mycophenolate mofetil |
| Group 2 | Experimental | Prograf + Mycophenolate mofetil then cross over to Astagraf XL + Mycophenolate Receives: Drug: Astagraf XL; Drug: Prograf; Drug: Mycophenolate mofetil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under Curve (AUC)
AUC of tacrolimus, MMF and their metabolites will be measured at 18 timepoints within 24 hour period on Study Day 1 and Day 8
Measured: Prior to dosing (CO), and at 1, 1.5, 2, 2.5, 3, 4, 6, 8,12, 12.5, 13, 14, 15, 16, 18, 20 and 24 hours post dosing
Maximum concentration (Cmax)
Cmax of tacrolimus, MMF and their metabolites will be measured at 18 timepoints within 24 hour period on Study Day 1 and Day 8
Measured: Prior to dosing (CO), and at 1, 1.5, 2, 2.5, 3, 4, 6, 8,12, 12.5, 13, 14, 15, 16, 18, 20 and 24 hours post dosing
Time to maximum concentration (Tmax)
Tmax of tacrolimus, MMF and their metabolites will be measured at 18 timepoints within 24 hour period on Study Day 1 and Day 8
Measured: Prior to dosing (CO), and at 1, 1.5, 2, 2.5, 3, 4, 6, 8,12, 12.5, 13, 14, 15, 16, 18, 20 and 24 hours post dosing
Half life (T 1/2)
Half-life of tacrolimus, MMF and their metabolites will be measured at 18 timepoints within 24 hour period on Study Day 1 and Day 8
Measured: 24 hours
Secondary outcomes (1)
Adverse events (serious and non-serious)
All serious adverse events and non-serious adverse events as reported by the subject will be recorded
Measured: Study Day 1 and Day 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2014 (estimated)
- Study startMay 2014
- Primary completionFeb 2015
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for End Stage Renal DiseaseStudies of the same condition, open and under way.
- More trials run by University of CincinnatiThe 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
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- Astellas Pharma Inc
- Responsible party
- Principal investigator, Tayyab Diwan, University of Cincinnati
- Investigators
- Tayyab Diwan, MD, Principal investigator, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02221583
- Sponsor's protocol ID
- ASTA-14B02
- Status last verified
- May 2015
- First submitted
- 13 Aug 2014
- Last updated
- 12 May 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Diwan TS, Lichvar AB, Leino AD, Vinks AA, Christians U, Shields AR, Cardi MA, Fukuda T, Mizuno T, Kaiser T, Woodle ES, Alloway RR. Pharmacokinetic and pharmacogenetic analysis of immunosuppressive agents after laparoscopic sleeve gastrectomy. Clin Transplant. 2017 Jun;31(6). doi: 10.1111/ctr.12975. Epub 2017 May 2.
PubMed 28342282
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Pilot Study to Determine the Pharmacokinetics of Astagraf XL, Prograf and Mycophenolate Mofetil in Renal Transplant Candidates Who Have Undergone Laparoscopic Sleeve Gastrectomy
- ClinicalTrials.gov ID
- NCT02221583
- Acronym / sponsor ID
- ASTA-14B02
- Conditions
- End Stage Renal Disease
- Keywords
- End stage renal disease, Renal transplant candidate, Laparoscopic sleeve gastrectomy, Immunosuppressants
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Collaborators
- Astellas Pharma Inc
- Study start
- May 2014
- Primary completion
- Feb 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 20 Aug 2014 (estimated)
- Results
- Not posted in the source record
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 this study is to evaluate how quickly and to what extent different immunosuppressants are absorbed into the blood (this is called pharmacokinetics) in renal transplant candidates who have undergone a laparoscopic sleeve gastrectomy. The immune system is the body's defense against diseases. It also attacks "foreign" tissues such as a transplanted kidney. Immunosuppressant medications such as Astagraf sustained release (XL), Prograf, and mycophenolate mofetil may be given to suppress the immune system following kidney transplantation and prevent rejection of a transplanted kidney. This study is being performed to determine if patients who undergo laparoscopic sleeve gastrectomy need different doses of immunosuppressant medications.
Detailed description
Investigators propose a single dose, cross over pharmacokinetic study of Astagraf XL and Prograf® in combination with MMF in RTx candidates that have undergone LSG. Subjects at least three months post LSG and pre-renal transplant will undergo preliminary screening. The study population will consist of 24 male and female subjects, ≥ 18 years old from UC Health University Hospital and The Christ Hospital who meet the inclusion/exclusion criteria.
Two PK profiles will be obtained in each subject. Each subject will receive either Astagraf XL 8mg daily or Prograf® 4mg every 12 hours in combination with MMF 1000mg every 12 hours. A full 24 hour PK profile will be constructed. After at least a one week washout period, the patient will be crossed over to the alternative tacrolimus formulation (Astagraf XL or Prograf®) in combination with MMF 1000mg every 12 hours and the PK profile repeated. The immunosuppressants chosen reflect the regimen most commonly prescribed to transplant recipients.
Subjects participating in the study will have pharmacokinetic blood samples drawn over a 24 hour time period in order to determine the AUC, Tmax, Cmax, and half-life of tacrolimus, MMF and their metabolites. Samples would be drawn prior to dosing (C0) and at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 18, 20 and 24 hours post dosing (18 time points) by venipuncture or IV.
This study proposal represents a simple and expeditious method to achieve PK information in patients that have undergone LSG. If desired, study could be expanded to evaluate PK in additional patient groups such as pre and post LSG and/or pre and post renal transplant. The exact sample collection time will be recorded in the case report form. All deviations from the scheduled sampling time of more than 5 minutes for the first 4 hours after the AM dose (predose-4 hr) and first 4 hours of the PM dose (12 hr-16 hr), and more than 10 minutes for all remaining samples (6 hr-8 hr; 18 hr-24 hr) will be reported as a protocol deviation.
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: Astagraf XL, Drug: Prograf, Drug: Mycophenolate mofetilAstagraf XL + Mycophenolate mofetil then cross over to Prograf + Mycophenolate |
| Group 2 | Experimental | Drug: Astagraf XL, Drug: Prograf, Drug: Mycophenolate mofetilPrograf + Mycophenolate mofetil then cross over to Astagraf XL + Mycophenolate |
Who may qualify
- Ages
- 19 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Female or male patient aged > 18 years old.
- ESRD patient (on dialysis or preemptive) who is a potential candidate for kidney transplantation
- Undergone laparoscopic sleeve gastrectomy procedure > 3 months prior to enrollment.
- Subjects have signed and dated the informed consent to participate in the study.
Key exclusion criteria (9 listed)
- Patients taking a drug known to interact with Astagraf XL, Prograf®, or MMF.
- Patients that have an allergy to Astagraf XL, Prograf®, or MMF.
- Patients currently taking Astagraf XL, Prograf®, or MMF.
- Post-surgical leak complication
- Patients failing to adhere to post laparoscopic sleeve gastrectomy follow-up recommendations and clinic visits
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 |
|---|---|---|
| Astagraf XLAlso: Tacrolimus sustained releaseTwo PK profiles will be obtained in each subject. Each subject will receive either Astagraf XL 8mg daily or Prograf® 4mg every 12 hours in combination with MMF 1000mg every 12 hours. A full 24 hour PK profile will be constructed. After at least a one week washout period, the patient will be crossed over to the alternative tacrolimus formulation (Astagraf XL or Prograf®) in combination with MMF 1000mg every 12 hours and the PK profile repeated. | Drug | Group 1, Group 2 |
| PrografAlso: TacrolimusTwo PK profiles will be obtained in each subject. Each subject will receive either Astagraf XL 8mg daily or Prograf® 4mg every 12 hours in combination with MMF 1000mg every 12 hours. A full 24 hour PK profile will be constructed. After at least a one week washout period, the patient will be crossed over to the alternative tacrolimus formulation (Astagraf XL or Prograf®) in combination with MMF 1000mg every 12 hours and the PK profile repeated. | Drug | Group 1, Group 2 |
| Mycophenolate mofetilAlso: CellceptTwo PK profiles will be obtained in each subject. Each subject will receive either Astagraf XL 8mg daily or Prograf® 4mg every 12 hours in combination with MMF 1000mg every 12 hours. A full 24 hour PK profile will be constructed. After at least a one week washout period, the patient will be crossed over to the alternative tacrolimus formulation (Astagraf XL or Prograf®) in combination with MMF 1000mg every 12 hours and the PK profile repeated. | Drug | Group 1, Group 2 |
Primary outcome
Area Under Curve (AUC)
Time frame: Prior to dosing (CO), and at 1, 1.5, 2, 2.5, 3, 4, 6, 8,12, 12.5, 13, 14, 15, 16, 18, 20 and 24 hours post dosing
AUC of tacrolimus, MMF and their metabolites will be measured at 18 timepoints within 24 hour period on Study Day 1 and Day 8
Maximum concentration (Cmax)
Time frame: Prior to dosing (CO), and at 1, 1.5, 2, 2.5, 3, 4, 6, 8,12, 12.5, 13, 14, 15, 16, 18, 20 and 24 hours post dosing
Cmax of tacrolimus, MMF and their metabolites will be measured at 18 timepoints within 24 hour period on Study Day 1 and Day 8
Time to maximum concentration (Tmax)
Time frame: Prior to dosing (CO), and at 1, 1.5, 2, 2.5, 3, 4, 6, 8,12, 12.5, 13, 14, 15, 16, 18, 20 and 24 hours post dosing
Tmax of tacrolimus, MMF and their metabolites will be measured at 18 timepoints within 24 hour period on Study Day 1 and Day 8
Half life (T 1/2)
Time frame: 24 hours
Half-life of tacrolimus, MMF and their metabolites will be measured at 18 timepoints within 24 hour period on Study Day 1 and Day 8
1 secondary outcome
Adverse events (serious and non-serious)
Time frame: Study Day 1 and Day 8
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2015.
- Derived from this study: PubMed 28342282Diwan TS, Lichvar AB, Leino AD, Vinks AA, Christians U, Shields AR, Cardi MA, Fukuda T, Mizuno T, Kaiser T, Woodle ES, Alloway RR. Pharmacokinetic and pharmacogenetic analysis of immunosuppressive agents after laparoscopic sleeve gastrectomy. Clin Transplant. 2017 Jun;31(6). doi: 10.1111/ctr.12975. Epub 2017 May 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.
Tayyab Diwan, MD 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 4 study testing Astagraf XL, Prograf and Mycophenolate mofetil in people with End Stage Renal Disease, run by University of Cincinnati 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 9 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 12 May 2015. 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 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 Curve (AUC) (time frame: Prior to dosing (CO), and at 1, 1.5, 2, 2.5, 3, 4, 6, 8,12, 12.5, 13, 14, 15, 16, 18, 20 and 24 hours post dosing). The study lists 4 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 NCT02221583, which also lists 1 linked publication.
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 12 May 2015.