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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
History of Changes
  Purpose

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.


Condition Intervention
Difference of 12-hour AUC
 Drug: Atorvastatin 20 mg
Drug: Everolimus

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Drug Interaction and Pharmacokinetic Assessment of Everolimus When Coadministered With Atorvastatin in Renal Transplantation Recipient

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Chulalongkorn University:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Other Outcome Measures:
  • 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


Enrollment: 18
Study Start Date: September 2012
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: everolimus
Everolimus administration with adjusted dose to target C trough (C0) level between 3-12 ng/mL
 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
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)

 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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01780948

Locations
Thailand
King Chulalongkorn Memorial Hospital
Bangkok, Thailand, 10330
Sponsors and Collaborators
Chulalongkorn University
Ratchadapiseksompotch Research Fund
Investigators
Principal Investigator: Anocha Wanitchanont, MD. Chulalongkorn University
  More Information

Publications:

Responsible Party: ANOCHA WANITCHANONT, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Chulalongkorn University
ClinicalTrials.gov Identifier: NCT01780948     History of Changes
Other Study ID Numbers: A7478
Study First Received: January 29, 2013
Last Updated: February 7, 2013
Health Authority: Thailand: Ethical Committee

Keywords provided by Chulalongkorn University:
Drug Interaction
Pharmacokinetics
Everolimus
Atorvastatin

Additional relevant MeSH terms:
Everolimus
Sirolimus
Atorvastatin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
 Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Lipid Regulating Agents

ClinicalTrials.gov processed this record on May 22, 2013