A Study of an Investigational Regimen Combining FDA Approved HIV Drugs in HIV-Infected Subjects

See Detailed Description.

This is a 24-week study to evaluate the efficacy and safety of a once-daily ritonavir-boosted fosamprenavir regimen (1400mg/100mg QD) to a 200mg ritonavir-boosted fosamprenavir regimen administered either twice-daily or once-daily.

Study Overview

• Status: Completed
• Conditions: HIV Infection; Infection, Human Immunodeficiency Virus
• Intervention / Treatment: Drug: Full Boosted Fosamprenavir; Drug: Half-boosted Fosamprenavir

Detailed Description

A Phase IIIB, randomized, open-label, parallel group, multi-center, non-inferiority, 24-week study to evaluate the safety, efficacy and tolerability of switching from a 200mg ritonavir-boosted regimen of LEXIVA (700mg/100mg BID or 1400mg/200mg QD) to a once-daily, 100mg ritonavir-boosted regimen of LEXIVA (1400mg/100mg QD)

• Study Type: Interventional
• Enrollment (Actual): 211
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • Ponce, Puerto Rico, 00731
    • GSK Investigational Site
  • San Juan, Puerto Rico, 00909-1711
    • GSK Investigational Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • GSK Investigational Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72207
      • GSK Investigational Site
  • California
    • Beverly Hills, California, United States, 90211
      • GSK Investigational Site
    • Fountain Valley, California, United States, 92708
      • GSK Investigational Site
    • Garden Grove, California, United States, 92845
      • GSK Investigational Site
    • Los Angeles, California, United States, 90022
      • GSK Investigational Site
    • Newport Beach, California, United States, 92663
      • GSK Investigational Site
    • Tarzana, California, United States, 91356
      • GSK Investigational Site
    • West Hollywood, California, United States, 90069
      • GSK Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80220
      • GSK Investigational Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • GSK Investigational Site
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • GSK Investigational Site
    • Fort Lauderdale, Florida, United States, 33308
      • GSK Investigational Site
    • Fort Myers, Florida, United States, 33901
      • GSK Investigational Site
    • Hollywood, Florida, United States, 33020
      • GSK Investigational Site
    • Miami, Florida, United States, 33136
      • GSK Investigational Site
    • Oakland Park, Florida, United States, 33334
      • GSK Investigational Site
    • Orlando, Florida, United States, 32804
      • GSK Investigational Site
    • Sarasota, Florida, United States, 34243
      • GSK Investigational Site
    • Tampa, Florida, United States, 33614
      • GSK Investigational Site
    • West Palm Beach, Florida, United States, 33408
      • GSK Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30339
      • GSK Investigational Site
    • Macon, Georgia, United States, 31201
      • GSK Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60612
      • GSK Investigational Site
    • Chicago, Illinois, United States, 60613
      • GSK Investigational Site
    • Chicago, Illinois, United States, 60657
      • GSK Investigational Site
    • Maywood, Illinois, United States, 60153
      • GSK Investigational Site
  • Indiana
    • Indianapolis, Indiana, United States, 46280
      • GSK Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • GSK Investigational Site
    • Baltimore, Maryland, United States, 21229-5299
      • GSK Investigational Site
  • Massachusetts
    • Springfield, Massachusetts, United States, 01107
      • GSK Investigational Site
    • Springfield, Massachusetts, United States, 01103
      • GSK Investigational Site
  • Michigan
    • Detroit, Michigan, United States, 48202
      • GSK Investigational Site
    • Lansing, Michigan, United States, 48910
      • GSK Investigational Site
  • New Jersey
    • Hillsborough, New Jersey, United States, 08844
      • GSK Investigational Site
    • Somers Point, New Jersey, United States, 08244
      • GSK Investigational Site
  • New York
    • New York, New York, United States, 10011
      • GSK Investigational Site
    • Valhalla, New York, United States, 10595
      • GSK Investigational Site
  • Ohio
    • Akron, Ohio, United States, 44304
      • GSK Investigational Site
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18102
      • GSK Investigational Site
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • GSK Investigational Site
  • Texas
    • Dallas, Texas, United States, 75246
      • GSK Investigational Site
    • Dallas, Texas, United States, 75204
      • GSK Investigational Site
    • Fort Worth, Texas, United States, 76104
      • GSK Investigational Site
    • Harlingen, Texas, United States, 78550
      • GSK Investigational Site
    • Houston, Texas, United States, 77030
      • GSK Investigational Site
    • Houston, Texas, United States, 77027
      • GSK Investigational Site
  • Virginia
    • Hampton, Virginia, United States, 23666
      • GSK Investigational Site
  • Washington
    • Spokane, Washington, United States, 99204
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Subjects with HIV-1 infection.
• Are willing and able to understand and provide written consent prior to participation in this study.

Exclusion criteria:

• Are pregnant or breastfeeding.
• Have an active AIDS condition, pancreatitis, poor kidney function, or clinically relevant hepatitis.
• Have certain medical conditions that may make participation unsafe.
• Take medication that may interact with the study medication.
• Have a history of allergy to any of the study drugs or any excipients therein.
• Other inclusion/exclusion criteria to be evaluated by the physician.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: FPV/r200; Fosamprenavir/ritonavir (either 700/100mg BID or 1400/200mg QD)	Drug: Full Boosted Fosamprenavir; Full ritonavir-boosted fosamprenavir; Other Names: ritonavir; Fosamprenavir
Experimental: FPV/r100; Fosamprenavir/ritonavir 1400/100mg QD	Drug: Half-boosted Fosamprenavir; Once daily, reduced dose ritonavir-boosted fosamprenavir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Not Meeting the Definition of Virologic Failure at or Prior to Week 24	Virologic failure was defined as two consecutive plasma HIV-1 RNA measures greater than 400 copies/milliliter (mL) separated by at least 2 to 4 week. The percentage of participants not meeting the virologic failure definition was estimated with stratification by the six randomization strata using Mantel-Haenszel weights and the missing/discontinuation equals failure (MD=F) analysis. Missing/discontinuation values were considered failures.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Plasma Human Immunodeficiency Virus, Type 1, Ribonucleic Acid (HIV-1 RNA) <400 Copies/mL at Week 24, Time to Loss of Virologic Response (TLOVR) Analysis	A blood sample was drawn to determine the amount of plasma HIV-1 RNA virus in copies/mL at week 24. The percentage of participants with plasma HIV-1 RNA <400 copies/mL at Week 24 were determined by the TLOVR algorithm with stratification by the six randomization strata.	Week 24
Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL at Week 24, TLOVR Analysis	A blood sample was drawn to determine the amount of plasma HIV-1 RNA virus in copies/mL at week 24. The percentage of participants plasma with HIV-1 RNA <50 copies/mL at Week 24 were determined by the TLOVR algorithm with stratification by the six randomization strata.	Week 24
Mean Change From Baseline of log10 Copies/mL Plasma HIV-1 RNA Levels at Week 24, Observed Analysis	A blood sample was drawn to determine the amount of plasma HIV-1 RNA virus in copies/mL at week 24. Change from baseline was defined as plasma HIV-1 RNA level at Week 24 minus plasma HIV-1 RNA level at baseline.	Baseline and Week 24
Median Change From Baseline of CD4+ Cell Count at Week 24, Observed Analysis	A blood sample was drawn to determine the CD4+ cell count at week 24. Change from baseline was defined as CD4+ cell count at Week 24 minus CD4+ cell count at baseline.	Baseline and Week 24
Number of Participants Who Discontinued Treatment Due to Adverse Events Through Week 24	The number of participants who prematurely discontinued study drug due to adverse events was tabulated. Data are summarized by individual adverse event. Adverse events were defined as any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	Baseline through Week 24
Number of Participants With Grade 2-4 Adverse Events Occurring in Greater Than or Equal to 2% of Subjects Through Week 24	The number of participants who experienced any grades 2 to 4 adverse events was tabulated. Adverse events were graded based on the Division of Acquired Immunodeficiency Syndrome (AIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events.	Baseline through Week 24
Percent Change From Baseline in Total Cholesterol, High Density Lipoprotein (HDL), and Triglycerides at Week 24	A blood sample was drawn to determine the cholesterol, HDL, triglycerides levels at Week 24. Percent change in total blood cholesterol, HDL, and triglycerides was defined as (lipid level at Week 24 minus level at baseline) divided by level at baseline x 100%.	Baseline and Week 24
Percent Change From Baseline in Low Density Lipoprotein (LDL) at Week 24	A blood sample was drawn to determine the LDL level at Week 24. Percent change in LDL was defined as (LDL level at Week 24 minus level at baseline) divided by level at baseline x 100%.	Baseline and Week 24
Number of Participants With Plasma HIV-1 RNA Genotypic Mutations and Phenotypic Resistance at Time of Virologic Failure Not Present at Baseline	A blood sample was drawn for subjects failing to respond to therapy and the mutations present in the virus were identified. For each subject, the mutations found at the time of failure were compared with any mutations found in the blood sample at baseline. New mutations that developed at the time of virologic failure were tabulated by drug class.	Baseline through Week 24
Steady-State Plasma Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 12 and 24	Blood samples were drawn at weeks 12 and 24 to determine the plasma levels of APV and RTV. Concentration at the end of the dosing interval at steady state (Ctau) was presented.	Weeks 12 and 24

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Cohen C, Dejesus E, Lamarca A, Young B, Yau L, Patel L, Vavro C, Wire MB, Wannamaker P, Shaefer M. Similar virologic and immunologic efficacy with fosamprenavir boosted with 100 mg or 200 mg of ritonavir in HIV-infected patients: results of the LESS trial. HIV Clin Trials. 2010 Sep-Oct;11(5):239-47. doi: 10.1310/hct1105-239.

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: August 11, 2006
• First Submitted That Met QC Criteria: August 11, 2006
• First Posted (Estimate): August 15, 2006

Study Record Updates

• Last Update Posted (Estimate): November 5, 2010
• Last Update Submitted That Met QC Criteria: October 21, 2010
• Last Verified: October 1, 2010

More Information

Terms related to this study

• Keywords: HIV-1 LEXIVA Ritonavir Once-daily
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Slow Virus Diseases; HIV Infections; Infections; Communicable Diseases; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Fosamprenavir
• Other Study ID Numbers: LEX106430