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| Name | Class |
|---|---|
| Astellas Pharma Inc | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1 | Experimental | Astagraf XL + Mycophenolate mofetil then cross over to Prograf + Mycophenolate |
|
| Group 2 | Experimental | Prograf + Mycophenolate mofetil then cross over to Astagraf XL + Mycophenolate |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Astagraf XL | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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 | 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 | 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 | 24 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse events (serious and non-serious) | All serious adverse events and non-serious adverse events as reported by the subject will be recorded | Study Day 1 and Day 8 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Tayyab Diwan, MD | University of Cincinnati | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Cincinnati | Cincinnati | Ohio | 45267 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28342282 | Derived | 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. |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Jun 30, 2016 | |
| Reset | Aug 9, 2016 | |
| Release | Aug 20, 2016 | |
| Reset | Oct 13, 2016 | |
| Release | Oct 26, 2016 | |
| Reset | Dec 27, 2016 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Jun 30, 2016 | Aug 9, 2016 | |||
| Aug 20, 2016 |
| ID | Term |
|---|---|
| D007676 | Kidney Failure, Chronic |
| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
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| ID | Term |
|---|---|
| D016559 | Tacrolimus |
| D009173 | Mycophenolic Acid |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D002208 | Caproates |
| D000144 |
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|
| Prograf | Drug | 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. |
|
|
| Mycophenolate mofetil | Drug | 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. |
|
|
| Oct 13, 2016 |
| Oct 26, 2016 | Dec 27, 2016 |
| D052776 |
| Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |