Pharmacokinetic of Everolimus and Atorvastatin Co-administration

Difference of 12-hour AUC Clinical Trial

Official title:

Drug Interaction and Pharmacokinetic Assessment of Everolimus When Coadministered With Atorvastatin in Renal Transplantation Recipient

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01780948
• Other study ID #: A7478
• Status: Completed
• Phase: N/A
• First received: January 29, 2013
• Last updated: February 7, 2013
• Start date: September 2012
• Est. completion date: January 2013

Study information

• Verified date: February 2013
• Source: Chulalongkorn University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Thailand: Ethical Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Difference of 12-hour AUC

Intervention

Drug:
• Atorvastatin 20 mg
Add atorvastatin 20 mg and compare 12-hour AUC of everolimus between Arm everolimus and everolimus with atorvastatin 20 mg
• Everolimus
Administration only everolimus, no atorvastatin. Everolimus administration with adjusted dose to target C trough (C0)level between 3-12 ng/mL.

Locations

Country	Name	City	State
Thailand	King Chulalongkorn Memorial Hospital	Bangkok

Sponsors (2)

Lead Sponsor	Collaborator
Chulalongkorn University	Ratchadapiseksompotch Research Fund

Country where clinical trial is conducted

Thailand, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Correlation of 12-hour AUC and point of everolimus level	To correlate between 12-hour AUC and point of everolimus level	3 months	Yes
Primary	12-hour area under the time concentration curve of everolimus	compare when taking only everolimus to coadministered with atorvastatin	3 months	Yes
Secondary	Renal function	Renal function : serum creatinine, 24 hour creatinine clearance 24 hour urine protein, Urinalysis Sample take at month 0,1,2,3	3 months	Yes
Secondary	Liver function test	Total protein, Albumin, total bilirubin, direct bilirubin, AST, ALT, Alkaline phosphatase at month 0,1,2,3	3 month	Yes
Secondary	Lipid profile	Total cholesterol, Triglyceride, HDL, LDL at month 0,1,2,3	3 month	Yes
Secondary	Rhabdomyolysis	Adverse drug reaction from atorvastatin by measured CPK at month 0,1,2,3	3 month	Yes