N/A
Completed N=15
Drug Interaction Study of Lopinavir/Ritonavir and Gemfibrozil
Healthy Volunteers
Source: ClinicalTrials.gov NCT00474201 ↗
Enrolled (actual)
15
Serious AEs
0.0%
Results posted
Apr 2012
Primary outcomePrimary: Gemfibrozil Area Under the Concentration vs. Time Curve (AUC) — 104; 62 ng*hr/mL — p=<0.0001
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 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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Gemfibrozil Area Under the Concentration vs. Time Curve (AUC) |
104; 62 | <0.0001 sig |
Eligibility Criteria
INCLUSION CRITERIA
- Age of 18 to 65 years.
- Healthy by medical history and physical exam.
- Test HIV negative.
- Screening laboratory values within institutional normal range.
- Negative serum pregnancy test for females of child-bearing potential within 7 days prior to the initiation of LPV/r.
- Willingness and ability of females of child-bearing potential to practice abstinence or use effective non-hormonal methods of birth control (i.e. condom, diaphragm, IUD, spermicide, etc.) during the study.
- Non-smoker for at least 6 weeks prior to study participation. Subjects who are not currently smoking must refrain from smoking during the entire study period.
EXCLUSION CRITERIA
- Concomitant routine therapy with any prescription, over-the-counter, herbal, or holistic medications, including oral contraceptives for 30 days prior to study participation.
- Subjects taking oral contraceptives currently, or within 30 days prior to study initiation.
- Intermittent (PRN) use of acetaminophen, non-steroidal antiinflammatory medications (i.e. ibuprofen), and loperamide will be allowed during the study.
- Subjects will be allowed to take a multivitamin with minerals, or equivalent, once daily if they desire to do so.
- Inability to obtain venous access for sample collection.
- Known presence of diabetes mellitus, human immunodeficiency virus (HIV) infection, active tuberculosis, cardiac disease (hypertension; congestive heart failure etc.), renal disease (chronic or acute renal failure or insufficiency), thyroid disease, hepatitis, respiratory disease (uncontrolled asthma or chronic obstructive pulmonary disease), myasthenia gravis, glaucoma, or uncontrolled peptic ulcer disease. Any other condition that may interfere with the interpretation of the study results or that may not be in the best interest of the subject in the opinion of the investigator.
- Positive pregnancy test or breastfeeding female.
- The presence of persistent diarrhea or malabsorption that would interfere with the subject's ability to absorb drugs.
- Drug or alcohol use that may impair safety or adherence.
- History of intolerance or allergic reaction (rash; hives; swollen lips; difficulty breathing) to fibric acid derivatives (e.g. gemfibrozil, fenofibrate, bezafibrate, etc.) or protease inhibitors (ritonavir, lopinavir; indinavir, nelfinavir, saquinavir, atazanavir, fosamprenavir, darunavir, tipranavir).
- Inability or unwillingness of females of child-bearing potential to use a non-hormonal (barrier) method of contraception throughout the study (e.g. condom; diaphragm, etc.).
- Non-fasting total cholesterol or triglycerides greater than or equal to 270 mg/dL.
- Participation in another study during the entire study period.
Data sourced from ClinicalTrials.gov (NCT00474201). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.