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Pharmacogenetics to Predict Drug Interactions in Kidney Transplant Recipients

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ClinicalTrials.gov Identifier: NCT01288521
Recruitment Status : Completed
First Posted : February 2, 2011
Results First Posted : March 9, 2018
Last Update Posted : March 9, 2018
Sponsor:
Collaborator:
American College of Clinical Pharmacy
Information provided by (Responsible Party):
Sony Tuteja, University of Iowa

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Basic Science
Condition Kidney Transplantation
Interventions Drug: Tacrolimus + Ketoconazole, Then Tacrolimus alone
Drug: Tacrolimus alone, Then Tacrolimus + Ketoconazole
Enrollment 8
Recruitment Details Kidney transplant recipients were recruited from the transplant clinic from 10/2008 to 6/2010.
Pre-assignment Details Assignment to the treatment group was based on CYP3A5 genotype and subjects were eligible only if they had the *3/*3 genotype. 22 subjects were consented to participate. Based on genotype, 3 subjects were ineligible to complete the study. Of the 19 eligible subjects, 11 declined to participate. 8 subjects completed the study.
Arm/Group Title Tacrolimus + Ketoconazole, Then Tacrolimus Alone Tacrolimus Alone, Then Tacrolimus + Ketoconazole
Hide Arm/Group Description

Randomized, cross over design

Tacrolimus + Ketoconazole : Pharmacokinetic profiling of tacrolimus (AUC0-24h) in subjects receiving tacrolimus + keotconazole 200 mg every 12 hours x 3 doses.

Tacrolimus alone : Pharmacokinetic profiling of subjects on a stable dose of tacrolimus (AUC 0-24h)

Randomized, cross over design

Tacrolimus + Ketoconazole : Pharmacokinetic profiling of tacrolimus (AUC0-24h) in subjects receiving tacrolimus + keotconazole 200 mg every 12 hours x 3 doses.

Tacrolimus alone : Pharmacokinetic profiling of subjects on a stable dose of tacrolimus (AUC 0-24h)

Period Title: Overall Study
Started 3 5
Completed 3 5
Not Completed 0 0
Arm/Group Title Tacrolimus + Ketoconazole, Then Tacrolimus Alone Tacrolimus Alone, Then Tacrolimus + Ketoconazole Total
Hide Arm/Group Description

Randomized, cross over design

Tacrolimus + Ketoconazole : Pharmacokinetic profiling of tacrolimus (AUC0-24h) in subjects receiving tacrolimus + keotconazole 200 mg every 12 hours x 3 doses.

Tacrolimus alone : Pharmacokinetic profiling of subjects on a stable dose of tacrolimus (AUC 0-24h)

Randomized, cross over design

Tacrolimus + Ketoconazole : Pharmacokinetic profiling of tacrolimus (AUC0-24h) in subjects receiving tacrolimus + keotconazole 200 mg every 12 hours x 3 doses.

Tacrolimus alone : Pharmacokinetic profiling of subjects on a stable dose of tacrolimus (AUC 0-24h)

Total of all reporting groups
Overall Number of Baseline Participants 3 5 8
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 5 participants 8 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
2
  66.7%
5
 100.0%
7
  87.5%
>=65 years
1
  33.3%
0
   0.0%
1
  12.5%
[1]
Measure Description: Information gathered through self-report and medical records review
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3 participants 5 participants 8 participants
53  (12.5) 57  (5.5) 55.6  (8.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 5 participants 8 participants
Female
1
  33.3%
1
  20.0%
2
  25.0%
Male
2
  66.7%
4
  80.0%
6
  75.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 3 participants 5 participants 8 participants
3 5 8
1.Primary Outcome
Title Tacrolimus Bioavailability (F)
Hide Description Tac bioavailability alone vs. Tac bioavailability with Keto. To determine F we took the ratio of area under the curve of the oral dose divided by the area under the curve of the IV dose. F was determined by fitting a model that considered the plasma concentration of tac with IV vs. oral dosing.
Time Frame baseline and 2 weeks
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Hide Analysis Population Description
Stable kidney transplant recipients
Arm/Group Title Tacrolimus Alone Tacrolimus + Ketoconazole
Hide Arm/Group Description:

cross over design

Tacrolimus alone : Pharmacokinetic profiling of subjects on a stable dose of tacrolimus (AUC 0-24h)

Tacrolimus + Ketoconazole : Pharmacokinetic profiling of tacrolimus (AUC0-24h) in subjects receiving tacrolimus + keotconazole 200 mg every 12 hours x 3 doses.
Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: ratio of oral to IV
0.224  (0.107) 0.681  (0.308)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tacrolimus Alone, Tacrolimus + Ketoconazole
Comments The bioavailability of Tac alone vs. Tac +keto was compared using a general linear model including sex and creatinine clearance as covariates.
Type of Statistical Test Superiority
Comments The null hypothesis is that the tacrolimus biovailability alone is equal to the tacrolimus bioavailability when given with ketoconazole.
Statistical Test of Hypothesis P-Value 0.006
Comments [Not Specified]
Method Regression, Linear
Comments The bioavailability with Tac alone vs. Tac +keto was compared using linear model adjusting for sex and creatinine clearance.
Time Frame Data collected over 6 months of the PK intervention
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Tacrolimus Alone Tacrolimus + Ketoconazole
Hide Arm/Group Description Tacrolimus alone : Pharmacokinetic profiling of subjects on a stable dose of tacrolimus (AUC 0-24h) Tacrolimus + Ketoconazole : Pharmacokinetic profiling of tacrolimus (AUC0-24h) in subjects receiving tacrolimus + keotconazole 200 mg every 12 hours x 3 doses.
All-Cause Mortality
Tacrolimus Alone Tacrolimus + Ketoconazole
Affected / at Risk (%) Affected / at Risk (%)
Total   0/8 (0.00%)   0/8 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Tacrolimus Alone Tacrolimus + Ketoconazole
Affected / at Risk (%) Affected / at Risk (%)
Total   0/8 (0.00%)   0/8 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Tacrolimus Alone Tacrolimus + Ketoconazole
Affected / at Risk (%) Affected / at Risk (%)
Total   0/8 (0.00%)   0/8 (0.00%) 
Early termination leading to small numbers of subjects analyzed.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Sony Tuteja, Pharmd
Organization: University of Iowa
Phone: 215-573-7834
EMail: sony.tuteja@gmail.com
Layout table for additonal information
Responsible Party: Sony Tuteja, University of Iowa
ClinicalTrials.gov Identifier: NCT01288521     History of Changes
Other Study ID Numbers: 200806718
First Submitted: February 9, 2010
First Posted: February 2, 2011
Results First Submitted: March 31, 2017
Results First Posted: March 9, 2018
Last Update Posted: March 9, 2018