Drug Interaction Study of Lopinavir/Ritonavir and Gemfibrozil (GEM-PK)
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 gemfibrozil's 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, 1.5, 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.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
|Official Title:||The Influence of Lopinavir/Ritonavir on Gemfibrozil Pharmacokinetics in Healthy Volunteers|
- Gemfibrozil Area Under the Concentration vs. Time Curve (AUC) [ Time Frame: 22 days per subject (approximately 1 year for entire study completion) ] [ Designated as safety issue: No ]AUC (ng*hr/mL) of gemfibrozil when given as a 600 mg dose by itself compared to gemfibrozil AUC after 14.5 days of lopinavir-ritonavir (400mg/100mg) twice daily.
|Study Start Date:||May 2007|
|Study Completion Date:||July 2008|
|Primary Completion Date:||July 2008 (Final data collection date for primary outcome measure)|
No Intervention: Gemfibrozil PK without LPV/r
Subjects received a single 600 mg dose of gemfibrozil without concurrent lopinavir-ritonavir 400mg/100mg; this is the "control" arm of a crossover study design.
Control arm (no intervention used in this arm)
Other Name: gemfibrozil (Teva Pharmaceuticals)
Experimental: Gemfibrozil PK after 2 weeks of LPV/r
Single dose (600 mg) Gemfibrozil pharmacokinetics (i.e. plasma concentrations collected over time to calculate area under the concentration vs. time curve) assessed after 14.5 days of lopinavir/ritonavir (400/100 mg twice daily) administration.
lopinavir 400 mg + ritonavir 100 mg twice daily for 2 weeks
Other Name: lopinavir/ritonavir = Kaletra(TM)
Please refer to this study by its ClinicalTrials.gov identifier: NCT00474201
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Scott R Penzak, Pharm.D.||CC Pharmacy Department|