Clinical trial NCT01780948: Pharmacokinetic of Everolimus and Atorvastatin Co-administration
Official title: Drug Interaction and Pharmacokinetic Assessment of Everolimus When Coadministered With Atorvastatin in Renal Transplantation Recipient
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Difference of 12-hour AUC
Keywords: Drug Interaction
Pharmacokinetics
Everolimus
Atorvastatin
Lead sponsor: Chulalongkorn University
Sponsor class: OTHER
Collaborators: name: Ratchadapiseksompotch Research Fund
First posted: 2013-01-31
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Hypothesis : In renal transplantation recipient who received immunosuppressive drug "certican" and have hypercholesterolemia will get lipid lower drug-HMG Co-A reductase inhibitors. Because atorvastatin and everolimus have metabolism via Cytochrome P450 subfamily 3A4 both, so investigator made the hypothesis that when patients received everolimus with atorvastatin will change area under the time concentration curve of everolimus.

Detailed description: Population : Thai postrenal transplantation recipient who received everolimus and have hypercholesterolemia in posttransplantation clinic at Faculty of Medicine, Chulalongkorn University.

Study Design : Experimental study, Two-sample crossover study Sample size calculation :N = 18 Primary outcome : 12-hour area under the time concentration curve of everolimus Secondary outcome : renal function (serum creatinine, creatinine clearance)

Method :

1. Patients will random to everolimus or everolimus with atorvastatin 20 mg arm for 1 month.
2. Take blood sample for everolimus concentration at time 0,0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 hour
3. After first blood sample, patients will received everolimus only for 1 month (wash out period)
4. Patients will switch to another arm eg.patient who had received everolimus will switch to everolimus with atorvastatin 20 mg for 1 month
5. Take blood sample for everolimus concentration at time 0,0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 hour
6. Everolimus level will analyse for 12-hour AUC of everolimus.

Eligibility criteria: Inclusion Criteria:

* Post renal transplantation recipient who received immunosuppressive drug Everolimus and has hypercholesterolemia
* Co everolimus level within 3-12 ng/mL
* Informed consent
* Patient can follow research methodology

Exclusion Criteria:

* Patient don't want to participate in the study
* Post renal transplantation recipient who have normal lipid profile

Primary outcomes:
measure: 12-hour area under the time concentration curve of everolimus
timeFrame: 3 months
Secondary outcomes:
measure: Renal function
timeFrame: 3 months
measure: Liver function test
timeFrame: 3 month
measure: Lipid profile
timeFrame: 3 month
measure: Rhabdomyolysis
timeFrame: 3 month
Other outcomes:
measure: Correlation of 12-hour AUC and point of everolimus level
timeFrame: 3 months
Locations:
city: Bangkok
country: Thailand
facility: King Chulalongkorn Memorial Hospital
Study officials:
affiliation: Chulalongkorn University
name: Anocha Wanitchanont, MD.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kovarik JM, Hartmann S, Hubert M, Berthier S, Schneider W, Rosenkranz B, Rordorf C. Pharmacokinetic and pharmacodynamic assessments of HMG-CoA reductase inhibitors when coadministered with everolimus. J Clin Pharmacol. 2002 Feb;42(2):222-8. doi: 10.1177/00912700222011148.