The Influence of Ritonavir, Alone and in Combination With Lopinavir, on Fenofibric Acid Pharmacokinetics in Healthy Volunteers

NCT01148004 | Completed Phase 1

• 2 other identifiers: 10012410-CC-0124
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Patients infected with the human immunodeficiency virus (HIV) are often treated with protease inhibitors that help fight HIV infection. However, these medications often increase blood cholesterol levels, particularly triglycerides and low-density lipoproteins, and can lead to heart disease and other problems. Patients may take drugs known as fibrates (such as gemfibrozil (Lopid )) to lower triglyceride levels, but even with maximum approved doses patients often cannot reach goal triglyceride levels. Research suggests that fibrates and certain HIV medications, such as ritonavir and lopinavir/ritonavir, may interact and decrease the effectiveness of the fibrate treatment. More research is needed to determine the best drug to lower triglyceride levels in HIV patients who are receiving protease inhibitor therapy. Objectives: \- To evaluate the drug-drug interaction between fenofibrate and protease inhibitors lopinavir/ritonavir and ritonavir. Eligibility: \- Healthy individuals between 18 and 60 years of age. Design:

• This study will require a screening visit and 18 study visits. The screening visit will take 3 to 4 hours, and can occur 7 to 30 days before starting the study. The rest of the study, not including the screening visit, is 48 days. Three of the visits will take about 12 hours, and the remaining 15 visits will take about 1 hour.
• For study days 1 to 7, participants will take fenofibrate alone. Participants will keep a daily record of medication doses and any side effects.
• For study days 8 to 27, participants will take fenofibrate and ritonavir. Participants will keep a daily record of medication doses and any side effects.
• For study days 29 to 48, participants will take fenofibrate and lopinavir/ritonavir. Participants will keep a daily record of medication doses and any side effects.
• Participants will have regular study visits to provide blood samples for research and monitoring.

Conditions

HIV; Fenofibrate; Protease Inhibitors; Hypertriglyceridemia; Glucuronosyltransferase

Keywords

HIV; Hypertriglyceridemia; Protease Inhibitors; Healthy Volunteer; HV

Outcome Measures

Primary Outcomes (1)

• Fenofibratae pharmacokinetic parameter values

  48 days from study day 1 (after screening has been completed)

Interventions

Fenofibrate DRUG

Ritonavir DRUG

Lopinavir/Ritonavir DRUG

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• A subject will be considered eligible for this study only if all of the following criteria are met:
• Between the ages of 18 and 60 years
• Healthy according to medical history and physical examination
• Laboratory values: normal liver function tests (ALT less than or equal to 41 units/L, AST less than or equal to 34 units/L, total bilirubin less than or equal to 1.0 mg/dL, and direct bilirubin less than or equal to 0.2 mg/dL); serum creatinine less than or equal to ULN; hemoglobin greater than or equal to 12 g/dL (for both males and females)
• a. For patients with a history of Gilbert's Syndrome, patients with a total bilirubin that is greater than 1.0 mg/dL will be considered eligible for study participation if direct bilirubin is within normal limits (direct bilirubin \< 0.2 mg/dL)
• Normal ECG with no history of cardiac arrhythmias or conduction abnormalities
• Females of child bearing potential who are able and willing to prevent pregnancy by
• a. practicing abstinence or
• b. using non hormonal effective methods of birth control, such as condoms or
• diaphragms during the study period and for 1 month after study completion

You may not qualify if:

• A subject will be ineligible for this study if 1 or more of the following criteria are met:
• Concomitant routine therapy with any prescription, over the counter, herbal, or holistic medications, including hormonal contraceptives by any route and any investigational drugs for 30 days prior to study participation
• Concomitant therapy (chronic or intermittent) with any prescription, over the counter, or herbal drugs will not be allowed during the study duration
• Intermittent use of acetaminophen, non-steroidal anti-inflammatory medications (i.e., ibuprofen), and loperamide will be allowed to be taken according to each manufacturer s recommendations during the study, but will not be allowed on the days of PK blood sampling
• A daily multivitamin with minerals will be allowed during the study, according to the subject s wishes
• Inability to obtain venous access for blood sample collection
• The presence or history of any of the following:
• Diabetes mellitus (clinical diagnosis based on current guidelines)
• HIV infection
• Pulmonary disease (e.g. uncontrolled asthma, chronic obstructive pulmonary disease, etc.)
• Cardiac disease (e.g. heart failure, history of arrhythmia, or abnormal ECG results during screening, etc.)
• Hypertension (systolic blood pressure greater than 145 mmHG or diastolic blood pressure greater than 90 mmHg)
• Renal disease (chronic or acute renal failure or insufficiency)
• Hepatitis (as assessed by patient interview) or hepatic impairment
• Pancreatitis

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 (3)

• Penzak SR, Chuck SK. Management of protease inhibitor-associated hyperlipidemia. Am J Cardiovasc Drugs. 2002;2(2):91-106. doi: 10.2165/00129784-200202020-00003.

  PMID: 14727985 BACKGROUND

• Grunfeld C, Tien P. Difficulties in understanding the metabolic complications of acquired immune deficiency syndrome. Clin Infect Dis. 2003;37 Suppl 2:S43-6. doi: 10.1086/375886.

  PMID: 12942373 BACKGROUND

• Sax PE. Strategies for management and treatment of dyslipidemia in HIV/AIDS. AIDS Care. 2006 Feb;18(2):149-57. doi: 10.1080/09540120500161843.

  PMID: 16338773 BACKGROUND

MeSH Terms

Conditions

Hypertriglyceridemia

Interventions

Fenofibrate; Ritonavir; Lopinavir

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Fibric Acids; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Phenyl Ethers; Ethers; Benzophenones; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols; Ketones; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidinones; Pyrimidines

Study Officials

• Scott R Penzak, Pharm.D.

  National Institutes of Health Clinical Center (CC)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2010
• First Posted: June 22, 2010
• Study Start: May 13, 2010
• Primary Completion: July 29, 2013
• Study Completion: July 29, 2013
• Last Updated: December 9, 2019

Record last verified: 2013-07-29

Locations

US (1)