AzTrials
AzTrials

HIVPhase 1NCT01148004

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

A Phase 1 study testing Fenofibrate, Ritonavir and Lopinavir/Ritonavir in people with HIV and Fenofibrate, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
HIV, Fenofibrate, Protease Inhibitors
What is being tested?
Fenofibrate, Ritonavir and Lopinavir/Ritonavir
How many people
25 participants
Where
1 siteUnited States
Study dates
13 May 2010to 29 Jul 2013
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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)
  • 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
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  • 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

Who cannot join

  • 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
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  • 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
  • Bleeding disorders (e.g. hemophilia, gastrointestinal or intracranial bleeding)
  • Organ transplant
  • Seizure disorders, with the exception of childhood febrile seizures in the past
  • Schizophrenia or other psychiatric illnesses that may interfere with the subject s ability to participate in the study
  • Any condition that may interfere with the interpretation of the study results or not be in the best interest of the subject in the opinion of the investigators
  • Positive serum or urine 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 abuse that may impair safety or adherence
  • History of intolerance or allergic reaction to LPV/r, RTV, or fenofibrate
  • Fasting total cholesterol greater than 240 mg/dL or fasting triglycerides greater than 400 mg/dL
  • Fasting glucose greater than 100 mg/dL
  • Use of tobacco products, including cigarettes and chewing tobacco

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

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.
Read more

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.
Read the detailed description

Highly active antiretroviral therapy (HAART) has enhanced the life expectancy of human immunodeficiency virus (HIV) infected patients, making HIV a manageable chronic disease for many patients. Patients with HIV are prone to lipid abnormalities secondary to HIV infection and antiretroviral therapy, particularly HIV protease inhibitors (PI). PI containing regimens that contain boosting doses of ritonavir (RTV) (i.e., 100 200 mg once or twice daily) often cause significant increases in total cholesterol, low density lipoprotein cholesterol, and triglycerides. Therapy for isolated hypertriglyceridemia includes fibric acid derivatives, such as gemfibrozil (GFZ) or fenofibrate; however, despite treatment with these agents, triglyceride levels often remain elevated in HIV infected patients treated with HAART. Many factors likely contribute to the incomplete effectiveness of fibrates in these patients. One possible contributing factor may be a clinically significant interaction between HAART and fibrates. We recently reported a mean 41 percent decrease in GFZ area under the curve when administered with the PI combination lopinavir/ritonavir (LPV/r). To determine whether a similar interaction exists with fenofibrate, this study will characterize the impact of RTV and LPV/r on the pharmacokinetic (PK) profile of fenofibrate (Tricor formulation), after a single 145 mg oral dose, administered to healthy volunteers. In a single sequence study design, 13 subjects will receive a single 145 mg dose of fenofibrate on three occasions: before and after 14 days of RTV 100 mg twice daily, and after 14 days of LPV/r 400/100 mg twice daily. With the exclusion of the screening period, the total duration of the study will be 48 days. Fenofibric acid (FFA) PK will be determined for all 3 sampling periods and compared. Results from this study will inform us about a potentially clinically relevant drug drug interaction between fenofibrate and RTV boosted PI combinations. This information may therefore assist clinicians in choosing triglyceride lowering therapy for their HIV infected patients.

Being tested
Fenofibrate, Ritonavir, Lopinavir/Ritonavir
Keywords
HIV, Hypertriglyceridemia, Protease Inhibitors, Healthy Volunteer, HV
Medical subject headings
Hypertriglyceridemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FenofibrateDrug

  • RitonavirDrug

  • Lopinavir/RitonavirDrug

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Fenofibratae pharmacokinetic parameter values

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jun 2010 (estimated)
  2. Study start13 May 2010
  3. Primary completion29 Jul 2013
  4. Study completion29 Jul 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Non-randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01148004
Sponsor's protocol ID
100124
Other IDs
10-CC-0124
Status last verified
29 Jul 2013
First submitted
18 Jun 2010
Last updated
9 Dec 2019
Results posted
No

Publications

  • 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.

    PubMed 14727985

  • 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.

    PubMed 12942373

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

    PubMed 16338773

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Fenofibrate, Ritonavir and Lopinavir/Ritonavir in people with HIV and Fenofibrate, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Fenofibratae pharmacokinetic parameter values (time frame: 48 days from study day 1 (after screening has been completed)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01148004, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2019.

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