Pharmacokinetic of Everolimus and Atorvastatin Co-administration

This study has been completed.
Sponsor:
Collaborator:
Ratchadapiseksompotch Research Fund
Information provided by (Responsible Party):
ANOCHA WANITCHANONT, Chulalongkorn University
ClinicalTrials.gov Identifier:
NCT01780948
First received: January 29, 2013
Last updated: February 7, 2013
Last verified: February 2013

January 29, 2013
February 7, 2013
September 2012
January 2013   (final data collection date for primary outcome measure)
12-hour area under the time concentration curve of everolimus [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
compare when taking only everolimus to coadministered with atorvastatin
Same as current
Complete list of historical versions of study NCT01780948 on ClinicalTrials.gov Archive Site
  • Renal function [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    Renal function : serum creatinine, 24 hour creatinine clearance 24 hour urine protein, Urinalysis Sample take at month 0,1,2,3
  • Liver function test [ Time Frame: 3 month ] [ Designated as safety issue: Yes ]
    Total protein, Albumin, total bilirubin, direct bilirubin, AST, ALT, Alkaline phosphatase at month 0,1,2,3
  • Lipid profile [ Time Frame: 3 month ] [ Designated as safety issue: Yes ]
    Total cholesterol, Triglyceride, HDL, LDL at month 0,1,2,3
  • Rhabdomyolysis [ Time Frame: 3 month ] [ Designated as safety issue: Yes ]
    Adverse drug reaction from atorvastatin by measured CPK at month 0,1,2,3
Renal function, lipid profile, liver function [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
Renal function : serum creatinine, 24 hour creatinine clearance Liver function test Lipid profile : total cholesterol, triglyceride, HDL,LDL Sample take at month 1,2,3
Correlation of 12-hour AUC and point of everolimus level [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
To correlate between 12-hour AUC and point of everolimus level
Same as current
 
Pharmacokinetic of Everolimus and Atorvastatin Co-administration
Drug Interaction and Pharmacokinetic Assessment of Everolimus When Coadministered With Atorvastatin in Renal Transplantation Recipient

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.

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.
Interventional
Not Provided
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Difference of 12-hour AUC
  • Drug: Atorvastatin 20 mg
    Add atorvastatin 20 mg and compare 12-hour AUC of everolimus between Arm everolimus and everolimus with atorvastatin 20 mg
    Other Name: Lipitor 20 mg
  • Drug: Everolimus
    Administration only everolimus, no atorvastatin. Everolimus administration with adjusted dose to target C trough (C0)level between 3-12 ng/mL.
    Other Name: Everolimus alone
  • Placebo Comparator: everolimus
    Everolimus administration with adjusted dose to target C trough (C0) level between 3-12 ng/mL
    Intervention: Drug: Atorvastatin 20 mg
  • Experimental: everolimus with atorvastatin 20 mg

    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)

    Intervention: Drug: Everolimus
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
18
January 2013
January 2013   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Thailand
 
NCT01780948
A7478
No
ANOCHA WANITCHANONT, Chulalongkorn University
Chulalongkorn University
Ratchadapiseksompotch Research Fund
Principal Investigator: Anocha Wanitchanont, MD. Chulalongkorn University
Chulalongkorn University
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP