Lopinavir/r or Fosamprenavir/r Switch to Atazanavir/r or Darunavir/r (LARD)

This study has been completed.
Sponsor:
Collaborator:
Tibotec Pharmaceutical Limited
Information provided by (Responsible Party):
Daniel Skiest, MD, Community Research Initiative of New England
ClinicalTrials.gov Identifier:
NCT00756730
First received: September 18, 2008
Last updated: October 23, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: ATV/r
Drug: DRV/r
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Community Research Initiative of New England:

Primary Outcome Measures:
  • Percentage of Patients That Experience 10% Decline in Triglycerides From Baseline to Week 24. [ Time Frame: baseline, 24 weeks ] [ Designated as safety issue: No ]
    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.

  • At Week 24 the Percentage of Subjects That Had Triglycerides Less Than 200 mg/dL [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • The Change in Fasting Triglyceride Level From Baseline to Week 24 [ Time Frame: Baseline to week 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percent of Patients With HIV VL <200 Copies/mL at Week 4, 12 & 24 [ Time Frame: Week 4, 12 & 24 ] [ Designated as safety issue: Yes ]
  • Difference in CD4 From Baseline to Week 24 [ Time Frame: baseline to Week 24 ] [ Designated as safety issue: No ]
  • Total Cholesterol in the Two Study Groups at 24 Weeks [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • LDL Cholesterol at Week 24 [ Time Frame: week 24 ] [ Designated as safety issue: No ]
  • HDL Cholesterol at Week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Enrollment: 49
Study Start Date: September 2008
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Switch to DRV/r (800mg/100mg) QD
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. For this arm the sbject switched 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.
Drug: 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.
Switch to ATV/r (300mg/100mg QD)
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. For this are the subject switched 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
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.
Other Name: Atazanavir/r

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00756730

Locations
United States, Arizona
Spectrum Medical Group
Phoenix, Arizona, United States, 85012
United States, California
AIDS Healthcare Foundation
Los Angeles, California, United States, 02319
United States, Florida
Orlando Immunology Center
Orlando, Florida, United States, 32803
United States, Massachusetts
Community Research Initiative
Boston, Massachusetts, United States, 02215
Community Research Initiative - West
Springfield, Massachusetts, United States, 01107
United States, Minnesota
Abbott Northwestern Infectious Disease and Travel Clinic
Minneapolis, Minnesota, United States, 55404
United States, New York
AIDS Community Health Center
Rochester, New York, United States, 14804
United States, Pennsylvania
Philadelphia Fight
Philadelphia, Pennsylvania, United States, 19107
United States, Texas
David M. Lee, M.D., P.A., a/b/a Uptown Physicians Group
Dallas, Texas, United States, 75204
Nicholaos C. Bellos, MD, PA
Dallas, Texas, United States, 75204
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Daniel Skiest, MD
Tibotec Pharmaceutical Limited
Investigators
Principal Investigator: Daniel J Skiest, MD Community Research Initiative
  More Information

No publications provided

Responsible Party: Daniel Skiest, MD, Associate Research Director, Community Research Initiative of New England
ClinicalTrials.gov Identifier: NCT00756730     History of Changes
Other Study ID Numbers: 08-09
Study First Received: September 18, 2008
Results First Received: February 21, 2012
Last Updated: October 23, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Community Research Initiative of New England:
lopinavir
ritonavir
atazanavir
fosamprenavir
darunavir
anti-retroviral
AIDS
HIV
LARD
triglyceride
protease inhibitors
treatment Experienced

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Reverse Transcriptase Inhibitors
Ritonavir
Lopinavir
Atazanavir
Fosamprenavir
Darunavir
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
HIV Protease Inhibitors
Protease Inhibitors
Anti-HIV Agents

ClinicalTrials.gov processed this record on August 18, 2014