Changes in Triglyceride and Other Lipids (Levels of Fats Found in Blood) When Taking Darunavir Compared to Atazanavir in HIV-Infected Patients That Have Never Received Treatment.

Condition(s) targeted: HIV

Intervention: darunavir;emtricitabine [FTC]/tenofovir [TDF];ritonavir (Drug); atazanavir;emtricitabine [FTC]/tenofovir [TDF];ritonavir (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Tibotec, Inc

Official(s) and/or principal investigator(s):
Tibotec, Inc. Clinical Trial, Study Director, Affiliation: Tibotec, Inc

Overall contact:
Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions:, Email: info1@veritasmedicine.com

The purpose of this research study is to compare changes in triglyceride and other lipids (levels of fats found in the blood) from Baseline (Day 1) to Week 12 for darunavir/ritonavir 800/100 mg once daily versus atazanavir/ritonavir 300/100 mg once daily in combination with a fixed background regimen consisting of emtricitabine [FTC]/tenofovir [TDF] 200/300 mg). This study will also evaluate the safety (adverse events), effectiveness, and tolerability of darunavir/ritonavir and atazanivir/ritonavir over 48 weeks.

Official title: A Multicenter, Open-Label, Randomized Study to Assess the Metabolics, Efficacy, and Safety of Once-Daily Darunavir Versus Atazanavir in HIV-Infected Treatment-naïve Adult Patients

Study design: Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study

Primary outcome: To assess change from baseline in triglyceride (TG) level at week 12 for darunavir versus atazanavir. The primary objective of the substudy is to assess the effect on insulin sensitivity at 12 weeks using the hyperinsulinemic clamp technique.

Secondary outcome: Assess change from baseline in lipids, glucose, insulin, insulin resistance, adipose tissue, body habitus & inflammatory markers. Assess virologic suppression, immunologic response & safety. Assess endothelial function, insulin sensitivity for substudy.

Detailed description: The purpose of this study is to expand our understanding of the metabolic effects of darunaivr/ritonavir (DRV/r) in HIV-infected patients. This is a phase 4, multicenter, open-label, randomized (study drug assigned by chance), comparative study designed to compare changes in lipid, glucose, and insulin parameters in HIV-infected, anti-retroviral (ARV) naïve patients treated with DRV/r 800/100 mg once daily (QD) versus atazanavir/ritonavir (ATV/r) 300/100 mg QD in combination with a common background of tenofovir (FTC)/ emtricitabine (TDF) 200/300 mg QD. In addition, changes in inflammatory markers will be measured. A substudy of the parent study TMC114HIV4023 will evaluate insulin sensitivity and endothelial function in a subset of patients. The study will be conducted at up to 12 study sites in the United States. Approximately 60 HIV-1 infected, treatment-naïve adult patients will be enrolled in the study. Screening will take place during a 4-week period. At the baseline visit, eligible patients will be randomized in a 1: 1 ratio to receive DRV/r 800/100 mg QD or ATV/r 300/100 mg QD administered in combination with a fixed-dose background regimen consisting of tenofovir (FTC)/emtricitabine (TDF) 200/300 mg. The treatment period is 48 weeks. Study assessments will be performed at clinic visits at the end of weeks 2, 4, 12, 24, 36, and 48. The primary endpoint will be assessed at week 12. All patients will return for follow up visits 1 week and 4 weeks after the completion of study treatment. During the treatment period, the patient will be seen at regular visits during which the investigator will assess the patient's medical condition, any Adverse Events and study drug compliance. Laboratory evaluations for efficacy and safety will be done at regular visits as well as blood pressure monitoring. Twenty patients (10 randomized to receive DRV/r and 10 randomized to receive ATV/r) who meet additional entry criteria will be enrolled in the substudy. The study hypothesis is the change in triglycerides and other lipids from baseline to week 12 will be similar in the DRV/r arm versus the ATV/r arm. The substudy hypothesis is that DRV/r will not adversely affect insulin sensitivity or endothelial function during 12 weeks of therapy, and the change from baseline in insulin sensitivity and endothelial function will be similar in the DRV/r arm versus the ATV/r arm. During the treatment period, the patient will be seen at regular visits during which the investigator will assess the patient's medical condition, any Adverse Events and study drug compliance. Laboratory evaluations for efficacy and safety will be done at regular visits as well as blood pressure monitoring.

Patients will be randomized in a 1: 1 ratio to receive darunavir/ritonavir 800/100 mg once daily (QD) plus emtricitabine (FTC)/tenofovir (TDF) 200/300 mg QD or atazanavir/ritonavir 300/100 mg QD plus emtricitabine (FTC)/tenofovir (TDF) for 48 weeks..

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- HIV-1 RNA of 1000 copies/mL or more

- No previous treatment with antiretroviral drugs

- Demonstrated sensitivity [Fold Change (FC) ≤ lower Clinical Cut Off (CCO)] to

tenofovir, darunavir and atazanavir

- Demonstrated sensitivity to emtricitabine defined as absence of M184V/I mutation

- Any CD4 cell count

Exclusion Criteria:

- Body mass index >30 kg/m2

- Presence of diabetes mellitus or hyperlipidemia as defined by: fasting insulin >12

U/mL, fasting glucose >126 mg/dL, total cholesterol >260 mg/dL, LDL cholesterol >160 mg/dL, triglycerides >400 mg/dL

- Presence of any currently active AIDS-defining illness

- Treatment for primary HIV infection or postexposure prophylaxis for HIV

- Subjects with acute or chronic hepatitis A, B or C infection

Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions:, Email: info1@veritasmedicine.com

Orange Coast Medical Group, Newport Beach, California 92663, United States; Recruiting
Jorge Rodriguez, Principal Investigator

Los Angeles, California 90033, United States; Not yet recruiting

Peter J. Ruane MD, Inc., Los Angeles, California 90036, United States; Recruiting
Peter Ruane, Phone: 323-954-1072
Peter Ruane, Principal Investigator

Capital Medical Associates, PC, Washington, District of Columbia 20036, United States; Recruiting
Kelly Davis, Phone: 202-822-6311
Bruce Rashbaum, Principal Investigator

Miami, Florida 33136, United States; Not yet recruiting

Orlando Immunology Center, Orlando, Florida 32803, United States; Recruiting
Jeffrey Dinsmore, Phone: 407-647-3960
Edwin De Jesus, Principal Investigator

North Broward Hospital District (HIV Clinical Research), Ft Lauderdale, Florida 33311, United States; Recruiting
Michael Sension, Phone: 954-467-0880
Michael Sension, Principal Investigator

Indianapolis, Indiana 46202, United States; Not yet recruiting

Boston, Massachusetts 02115, United States; Not yet recruiting

Saint Louis, Missouri 63110, United States; Not yet recruiting

New York, New York 10025, United States; Not yet recruiting

New York, New York 10016, United States; Not yet recruiting

Philadelphia, Pennsylvania 19104, United States; Not yet recruiting

To learn how to participate in this trial please click here.

Starting date: September 2008
Ending date: March 2010
Last updated: January 29, 2009