Ignite Creation Date:
2024-05-05 @ 5:31 PM
Last Modification Date:
2024-10-26 @ 9:33 AM
Study NCT ID:
NCT00474201
Status:
COMPLETED
Last Update Posted:
2016-09-26
First Post:
2007-05-15
Brief Title:
Drug Interaction Study of LopinavirRitonavir and Gemfibrozil
Sponsor:
National Institutes of Health Clinical Center CC
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
The Influence of LopinavirRitonavir on Gemfibrozil Pharmacokinetics in Healthy Volunteers
Status:
COMPLETED
Status Verified Date:
2012-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
GEM-PK
Brief Summary:
This study will determine whether the protease inhibitor lopinavir ritonavir Kaletra Trademark which is used to treat HIV disease lowers blood levels of the lipid-regulating drug gemfibrozil Lopid Trademark in HIV-negative healthy volunteers Many patients with HIV infection who take protease inhibitors have abnormally high lipids cholesterol and triglycerides Gemfibrozil commonly used to treat high triglycerides often is not effective in HIV-infected patients taking protease inhibitors possibly because of an interaction between the two medicines that causes a lowering of gemfibrozils levels in the blood Results from this study will give researchers information on whether lopinavir ritonavir affects the blood levels of gemfibrozil
Healthy normal volunteers between 18 and 65 years old who test negative for HIV may be eligible for this study
On study day 1 subjects have a blood sample drawn from a catheter inserted into a vein in the arm to determine pre-dosing blood levels of gemfibrozil They then take a gemfibrozil tablet and are given breakfast 30 minutes after taking the drug Blood samples are obtained through the catheter at 0 1 15 2 3 4 6 8 12 and 24 hours after dosing to determine gemfibrozil levels at those intervals At the end of 12 hours the catheter is removed and the subject is discharged from the clinic The next morning subjects return to the clinic for another blood sample collected through a vein in the arm
Subjects begin taking lopinavir ritonavir between 7 and 35 days after their first dose depending on their schedule and the clinic schedule On the fourteenth day of dosing subjects come to the clinic and are given a single dose of gemfibrozil as on study day 1 and have breakfast 30 minutes later Blood samples are collected to determine gemfibrozil levels just like on study days 1 and 2 An additional sample is collected for routine lab tests
Healthy normal volunteers between 18 and 65 years old who test negative for HIV may be eligible for this study
On study day 1 subjects have a blood sample drawn from a catheter inserted into a vein in the arm to determine pre-dosing blood levels of gemfibrozil They then take a gemfibrozil tablet and are given breakfast 30 minutes after taking the drug Blood samples are obtained through the catheter at 0 1 15 2 3 4 6 8 12 and 24 hours after dosing to determine gemfibrozil levels at those intervals At the end of 12 hours the catheter is removed and the subject is discharged from the clinic The next morning subjects return to the clinic for another blood sample collected through a vein in the arm
Subjects begin taking lopinavir ritonavir between 7 and 35 days after their first dose depending on their schedule and the clinic schedule On the fourteenth day of dosing subjects come to the clinic and are given a single dose of gemfibrozil as on study day 1 and have breakfast 30 minutes later Blood samples are collected to determine gemfibrozil levels just like on study days 1 and 2 An additional sample is collected for routine lab tests
Detailed Description:
Hyperlipidemia continues to be a common problem in individuals with HIV particularly those receiving HIV protease inhibitors PIs or the nucleoside reverse transcriptase inhibitor stavudine PI-treated patients have been noted to have increases in low-density lipoprotein LDL triglycerides TG and total cholesterol compared to PI-treatment naive individuals The prevalence of lipid abnormalities in patients receiving PI-containing therapy has been estimated at 27-57 percent moreover cardiovascular complications have begun to be revealed Triglyceride elevations in particular are not only an independent risk factor for the development of coronary artery disease but may also lead to pancreatitis Despite treatment with fibric acid derivatives such as gemfibrozil TGs typically remain elevated above the upper limit of normal in HIV-infected subjects One possible reason for persistently elevated TGs in these patients is reduced efficacy of their fibric acid therapy which may result from an unrecognized drug-drug interaction Fibric acid derivatives are metabolized in the liver via uridine 5-diphosphate-glucuronosyl transferase enzymes UGT which are induced by the HIV PI ritonavir Indeed ritonavir significantly lowers plasma concentrations of other drugs metabolized by this enzymatic system by 40-50 percent As UGT activity is induced the metabolism of UGT substrates gemfibrozil will increase resulting in a decrease in their plasma concentrations Preliminary data in non-HIV-infected subjects suggest that reduced plasma concentrations of gemfibrozil are likely to result in reduced efficacy of the drug Despite the fact that many HIV-infected patients with hypertriglyceridemia are likely to be receiving triglyceride-lowering therapy with a fibric acid derivative while simultaneously receiving antiretroviral therapy that includes ritonavir ie lopinavir ritonavir LPVr these two drugs have not been studied in combination to determine whether or not they interact The objective of this study is to characterize the impact of LPVr on the pharmacokinetic PK profile of gemfibrozil after a single 600 mg oral dose administered to healthy volunteers In a longitudinal study design fifteen subjects will receive a single 600 mg dose of gemfibrozil before and after 13 days of LPVr 400100 mg twice daily Gemfibrozil pharmacokinetics will be determined on days one and 14 and compared using the student t-test Results from this study will provide or refute the rationale for further studies designed to assess the possibility of dose-adjusting gemfibrozil when it is given in combination with ritonavir in order to maximize the pharmacologic effects of gemfibrozil
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 07-CC-0149 CL006000-01 CC | OTHER | Clinical Center Z number | None |