Lopinavir/r or Fosamprenavir/r Switch to Atazanavir/r or Darunavir/r

HIV Infections Clinical Trial

— LARD  

Official title:

Randomized, Open-label Study of Switch From Lopinavir/Ritonavir (LPV/r) or Fosamprenavir/Ritonavir (FPV/r) to Either Once Daily Atazanavir/Ritonavir (ATV/r) or Once Daily Darunavir/Ritonavir (DRV/r) (Plus Background Nucleoside Reverse Transcriptase Inhibitors) in Patients Experiencing Triglyceride Elevations While Receiving LPV/r or FPV/r.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00756730
• Other study ID #: 08-09
• Status: Completed
• Phase: Phase 4
• First received: September 18, 2008
• Last updated: October 23, 2012
• Start date: September 2008
• Est. completion date: June 2011

Study information

• Verified date: October 2012
• Source: Community Research Initiative of New England
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

For participants with HIV taking either lopinavir or fosamprenavir who have elevated triglycerides, this trial will study the change in triglycerides after switching protease inhibitors.

Description:

This Phase IV trial will look at lipid and virologic responses after a switch to a more lipid-friendly antiretroviral regimen. Participants will be randomized to receive either boosted atazanavir or boosted darunavir given once daily, along with background NRTIs. This 24-week study will require 4 visits after randomization for evaluation, monitoring, and lab studies.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: June 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Currently receiving Antiretroviral Therapy (ART) regimen including LPV/r or FPV/r and > or equal to 2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs). Patient must be on a stable regimen containing LPV/r or FPV/r for at least 12 weeks prior to screening.

• Documentation of an undetectable Human Immunodeficiency Virus (HIV) viral load (VL<400 copies/ml) using an FDA approved assay for a minimum of twelve weeks prior to screening AND undetectable HIV viral load using an FDA approved ultrasensitive assay at screening.

• No evidence of HIV protease resistance as defined by the Stanford HIV database

• Currently receiving first protease inhibitor unless switch to LPV/r or FPV/r was for non-virologic reasons

• Fasting triglycerides > 200 mg/dL

• No ongoing issues that in the opinion of the investigator would lead to decreased ability to comply with the study procedures

• If currently receiving a proton pump inhibitor, the dose is < omeprazole 20 mg or the equivalent dose of another proton pump inhibitor

• If patient is receiving another lipid lowering medication, it must be at a stable dose

Exclusion Criteria:

• Currently receiving an ART regimen other than > or equal to two NRTIs and either LPV/r or FPV/r

• Prior use of darunavir or atazanavir

• CDC Class C Illness diagnosed within 30 days of screening

• Patient is currently receiving the following Hydroxamethylglutaryl-coA (HMGCoA) reductase inhibitor medications (statins): pravastatin, lovastatin, simvastatin

• Patient is currently receiving a bile acid sequestrant (cholestyramine, colestipol, and colesevelam)

• Grade 3 or 4 Laboratory abnormalities as defined by a standardized grading scheme based on the DAIDS table with the following exceptions:

1. Pre-existing diabetes mellitus with asymptomatic, nonfasting glucose grade 3 elevations

2. Subjects with asymptomatic grade 3 fasting triglyceride or cholesterol elevations

• Clinical or laboratory evidence of clinically significant liver impairment/dysfunction disease or cirrhosis

• Note: Individuals co-infected with chronic hepatitis B or C viruses will be allowed to enter the trial if their condition is clinically stable and they will not require therapy during the course of the study. Individuals diagnosed with acute viral hepatitis at screening will not be allowed to enroll during acute phase

• Active substance abuse or significant psychiatric illness that in the opinion of the investigator might interfere with study compliance

• Use of any investigational agents 30 days prior to screening

• Life expectancy < 6 months in the opinion of the investigator

• Pregnancy or breast feeding

• Female subject of childbearing potential (i.e., heterosexually active, and not surgically sterile or at least two years post-menopausal) not using effective non-hormonal birth control methods or not willing to continue practicing these birth control methods from screening until the last trial related activity

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• ATV/r
Switch to ATV/r at a dose of 300mg/100mg QD for 24 weeks. Subjects will continue to maintain their background NRTI drugs throughout the screening period and during the entire study.
• DRV/r
We designed a study to determine if switching virologically suppressed patients on a regimen containing LPV/r or FPV/r to either DRV/r or ATV/r would result in improved TGs while maintaining virological suppression. Switch to DRV/r at a dose 800mg/100mg QD for 24 weeks. Subjects will continue to maintain their background NRTI drugs throughout the screening period and during the entire study.

Locations

Country	Name	City	State
United States	Community Research Initiative	Boston	Massachusetts
United States	David M. Lee, M.D., P.A., a/b/a Uptown Physicians Group	Dallas	Texas
United States	Nicholaos C. Bellos, MD, PA	Dallas	Texas
United States	AIDS Healthcare Foundation	Los Angeles	California
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Abbott Northwestern Infectious Disease and Travel Clinic	Minneapolis	Minnesota
United States	Orlando Immunology Center	Orlando	Florida
United States	Philadelphia Fight	Philadelphia	Pennsylvania
United States	Spectrum Medical Group	Phoenix	Arizona
United States	AIDS Community Health Center	Rochester	New York
United States	Community Research Initiative - West	Springfield	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Daniel Skiest, MD	Tibotec Pharmaceutical Limited

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Patients That Experience 10% Decline in Triglycerides From Baseline to Week 24.	A 10% decline in triglycerides (TGs) was determined to be clinically significant. The percentage of people that experienced a 10% decline was calculated by dividing the number who had a decline of 10% TGs by the total number of participants in the arm.	baseline, 24 weeks	No
Primary	At Week 24 the Percentage of Subjects That Had Triglycerides Less Than 200 mg/dL		24 weeks	No
Primary	The Change in Fasting Triglyceride Level From Baseline to Week 24		Baseline to week 24	No
Secondary	Percent of Patients With HIV VL <200 Copies/mL at Week 4, 12 & 24		Week 4, 12 & 24	Yes
Secondary	Difference in CD4 From Baseline to Week 24		baseline to Week 24	No
Secondary	Total Cholesterol in the Two Study Groups at 24 Weeks		Week 24	No
Secondary	LDL Cholesterol at Week 24		week 24	No
Secondary	HDL Cholesterol at Week 24		24 weeks	No