Ignite Creation Date:
2024-05-05 @ 11:13 PM
Last Modification Date:
2024-10-26 @ 10:31 AM
Study NCT ID:
NCT01288521
Status:
COMPLETED
Last Update Posted:
2018-03-09
First Post:
2010-02-09
Brief Title:
Pharmacogenetics to Predict Drug Interactions in Kidney Transplant Recipients
Sponsor:
Sony Tuteja
Organization:
University of Iowa
Study Overview
Official Title:
Utilizing Pharmacogenetics to Predict Drug Interactions in Kidney Transplant Recipients
Status:
COMPLETED
Status Verified Date:
2018-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Solid organ transplant recipients would greatly benefit from pharmacogenetic evaluation since immunosuppressive drug regimens consist of multiple medications with narrow therapeutic ranges and toxic adverse event profiles Tacrolimus is a potent immunosuppressive agent utilized for rejection prophylaxis Intensive pharmacokinetic monitoring must be performed following organ transplantation to ensure therapeutic drug concentrations due to its highly variable pharmacokinetics profile and narrow therapeutic index Tacrolimus is a substrate for CYP450 3A and for the membrane transporter p-glycoprotein Pgp Polymorphisms in the gene encoding for CYP3A5 have been extensively studied and have been found to influence the dosing of tacrolimus The effect of ABCB1 gene polymorphisms which encodes for Pgp upon tacrolimus pharmacokinetics has been more difficult to establish
This study will determine if haplotypes derived from three frequent polymorphisms in the ABCB1 gene C1236T G2677T C3435T can predict the degree of drug interaction between tacrolimus CYP3A5Pgp substrate and ketoconazole CYP3A5Pgp inhibitor in patients who are CYP3A5 nonexpressors
This prospective pharmacokinetic and pharmacogenomic study will enroll 20 stable renal transplant recipients with the CYP3A5 33 genotype and grouped by ABCB1 haplotype CGC vs TTT Pharmacokinetics of tacrolimus will be assessed on 2 occasions with and without ketoconazole coadministration separated by 1 week The order of study occasions will be randomized in a crossover design
The results of this study may identify a genomic marker for predicting drug-drug interactions Knowing this information a priori will aid clinicians in modifying drug dosing and alleviate patients of the burden of significant drug toxicities
This study will determine if haplotypes derived from three frequent polymorphisms in the ABCB1 gene C1236T G2677T C3435T can predict the degree of drug interaction between tacrolimus CYP3A5Pgp substrate and ketoconazole CYP3A5Pgp inhibitor in patients who are CYP3A5 nonexpressors
This prospective pharmacokinetic and pharmacogenomic study will enroll 20 stable renal transplant recipients with the CYP3A5 33 genotype and grouped by ABCB1 haplotype CGC vs TTT Pharmacokinetics of tacrolimus will be assessed on 2 occasions with and without ketoconazole coadministration separated by 1 week The order of study occasions will be randomized in a crossover design
The results of this study may identify a genomic marker for predicting drug-drug interactions Knowing this information a priori will aid clinicians in modifying drug dosing and alleviate patients of the burden of significant drug toxicities
Detailed Description:
Two mL of blood will be obtained for pharmacogenomic screening for CYP3A5 and ABCB1 genotypes Patients with the CYP3A533 genotype will be consented for the pharmacokinetic portion of the study Volunteers from this patient cohort will participate in 2 overnight visits to the General Clinical Research Center GCRC
Patients will report to the GCRC on the evening before each study visit They will be required to fast from midnight the night before until 1 hour after tacrolimus administration which will be in the morning approximately at 8 am
Pharmacokinetics of tacrolimus will be assessed on 2 occasions with and without ketoconazole coadministration separated by 1 week The order of study occasions will be randomized in a crossover design Each patient will take their take their usual oral dose of tacrolimus and have whole blood levels obtained immediately before C0 and at 05 1 15 2 3 4 6 hours after the tacrolimus dose They will then receive tacrolimus by intravenous infusion a therapeutic dose over four hours The IV dose will take the place of the patients usual evening dose of tacrolimus Additional blood will be drawn for tacrolimus at 025 05 1 15 2 3 4 6 8 12 18 hours after the intravenous dose During the ketoconazole visit tacrolimus doses will be decreased by one-half to account for the drug interaction and avoid potential tacrolimus-induced toxicities Ketoconazole 200 mg will be administered orally every 12 hours for a total of 3 doses the first ketoconazole dose will be given 13 hours before tacrolimus administration
Patients will report to the GCRC on the evening before each study visit They will be required to fast from midnight the night before until 1 hour after tacrolimus administration which will be in the morning approximately at 8 am
Pharmacokinetics of tacrolimus will be assessed on 2 occasions with and without ketoconazole coadministration separated by 1 week The order of study occasions will be randomized in a crossover design Each patient will take their take their usual oral dose of tacrolimus and have whole blood levels obtained immediately before C0 and at 05 1 15 2 3 4 6 hours after the tacrolimus dose They will then receive tacrolimus by intravenous infusion a therapeutic dose over four hours The IV dose will take the place of the patients usual evening dose of tacrolimus Additional blood will be drawn for tacrolimus at 025 05 1 15 2 3 4 6 8 12 18 hours after the intravenous dose During the ketoconazole visit tacrolimus doses will be decreased by one-half to account for the drug interaction and avoid potential tacrolimus-induced toxicities Ketoconazole 200 mg will be administered orally every 12 hours for a total of 3 doses the first ketoconazole dose will be given 13 hours before tacrolimus administration
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None