Drug Interaction Study of Lopinavir/Ritonavir and Gemfibrozil

NCT00474201 | Completed Results

• 2 other identifiers: 07014907-CC-0149 CL006000-01 CC
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Healthy Volunteers

Keywords

Pharmacokinetic; HIV; Drug-Drug Interaction; Lopinavir/Ritonavir; Gemfibrozil; Healthy Volunteer; HV

Outcome Measures

Primary Outcomes (1)

• Gemfibrozil Area Under the Concentration vs. Time Curve (AUC)

  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.

  22 days per subject (approximately 1 year for entire study completion)

Study Arms (2)

Gemfibrozil PK without LPV/r

SHAM COMPARATOR

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.

Drug: Gemfibrozil

Gemfibrozil PK after 2 weeks of LPV/r

EXPERIMENTAL

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.

Drug: Lopinavir/Ritonavir

Interventions

Lopinavir/Ritonavir DRUG

lopinavir 400 mg + ritonavir 100 mg twice daily for 2 weeks

Also known as: lopinavir/ritonavir = Kaletra(TM)

Gemfibrozil PK after 2 weeks of LPV/r

Gemfibrozil DRUG

Control arm (no intervention used in this arm)

Also known as: gemfibrozil (Teva Pharmaceuticals)

Gemfibrozil PK without LPV/r

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Busse KH, Hadigan C, Chairez C, Alfaro RM, Formentini E, Kovacs JA, Penzak SR. Gemfibrozil concentrations are significantly decreased in the presence of lopinavir-ritonavir. J Acquir Immune Defic Syndr. 2009 Oct 1;52(2):235-9. doi: 10.1097/QAI.0b013e3181b0610e.

  PMID: 19648824 RESULT

MeSH Terms

Interventions

Lopinavir; Gemfibrozil

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fibric Acids; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Pentanoic Acids; Valerates; Phenyl Ethers; Ethers; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Fatty Acids, Volatile; Fatty Acids; Lipids

Results Point of Contact

• Title: Scott Penzak
• Organization: National Institutes of Health

sp286u@nih.gov

301-496-2997

Study Officials

• Scott R Penzak, Pharm.D.

  CC Pharmacy Department

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Clinical Pharmacokinetics research Laboratory

Study Record Dates

• First Submitted: May 15, 2007
• First Posted: May 16, 2007
• Study Start: May 1, 2007
• Primary Completion: July 1, 2008
• Study Completion: July 1, 2008
• Last Updated: September 26, 2016
• Results First Posted: April 9, 2012

Record last verified: 2012-03

Locations

US (1)