Pharmacokinetic of Everolimus and Atorvastatin Co-administration

Not Applicable

Completed

• Conditions: Difference of 12-hour AUC
• Interventions: Drug: Atorvastatin 20 mg; Drug: Everolimus

• Registration Number: NCT01780948
• Lead Sponsor: Chulalongkorn University

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.

Study Timeline

• Study Start: 2012-09
• Primary Completion: 2013-01
• Study Completion: 2013-01
• Study First Submitted: 2013-01-29
• Study First Submitted QC: 2013-01-29
• Study First Posted: 2013-01-31
• Status Verified: 2013-02
• Last Update Submitted: 2013-02-07
• Last Update Posted: 2013-02-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
everolimus	Atorvastatin 20 mg	Everolimus administration with adjusted dose to target C trough (C0) level between 3-12 ng/mL
everolimus with atorvastatin 20 mg	Everolimus	Co-administration of everolimus and atorvastatin. Everolimus administration with adjusted dose to target C trough (C0)level between 3-12 ng/mL. Atorvastatin 20 mg/day (fixed dose)

Primary Outcome Measures

Name	Time	Method
12-hour area under the time concentration curve of everolimus	3 months	compare when taking only everolimus to coadministered with atorvastatin

Secondary Outcome Measures

Name	Time	Method
Renal function	3 months	Renal function : serum creatinine, 24 hour creatinine clearance 24 hour urine protein, Urinalysis Sample take at month 0,1,2,3
Liver function test	3 month	Total protein, Albumin, total bilirubin, direct bilirubin, AST, ALT, Alkaline phosphatase at month 0,1,2,3
Lipid profile	3 month	Total cholesterol, Triglyceride, HDL, LDL at month 0,1,2,3
Rhabdomyolysis	3 month	Adverse drug reaction from atorvastatin by measured CPK at month 0,1,2,3

Trial Locations

Locations (1)

King Chulalongkorn Memorial Hospital; 🇹🇭 Bangkok, Thailand