A Study To Assess GW433908 (Fosamprenavir) Containing Regimens In HIV-1 Infected Subjects

An Open-Label Phase III Study to Assess the Long Term Safety Profile of GW433908 Containing Regimens in HIV-1 Infected Subjects

GW433908 (fosamprenavir; FPV)is a pro-drug of amprenavir (APV) which is more water soluble and can be formulated into a tablet with a reduced pill burden (four 700mg tablets of FPV versus sixteen 150mg capsules daily for APV. This study is designed to provide additional information on long term safety and tolerability of FPV containing regimens for those subjects who received FPV in previous GlaxoSmithKline studies.

Study Overview

• Status: Completed
• Conditions: Infection, Human Immunodeficiency Virus
• Intervention / Treatment: Drug: ritonavir; Drug: fosamprenavir (GW433908)

Detailed Description

ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship.

• Study Type: Interventional
• Enrollment (Actual): 753
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • São Paulo
    • Campinas, São Paulo, Brazil, 13083970
      • GSK Investigational Site
• Chile
  • Región Metro De Santiago
    • Santiago, Región Metro De Santiago, Chile
      • GSK Investigational Site
• France
  • Le Kremlin Bicêtre Cedex, France, 94275
    • GSK Investigational Site
  • Marseille, France, 13005
    • GSK Investigational Site
  • Paris Cedex 10, France, 75475
    • GSK Investigational Site
  • Paris Cedex 20, France, 75970
    • GSK Investigational Site
  • Vandoeuvre Les Nancy Cedex, France, 54511
    • GSK Investigational Site
  • Villejuif Cedex, France, 94805
    • GSK Investigational Site
• Italy
  • Liguria
    • Genova, Liguria, Italy, 16128
      • GSK Investigational Site
• Portugal
  • Coimbra, Portugal, 3000-075
    • GSK Investigational Site
• Spain
  • Badajoz, Spain, 6080
    • GSK Investigational Site
  • Barcelona, Spain, 08036
    • GSK Investigational Site
• United Kingdom
  • London, United Kingdom, SE1 7EH
    • GSK Investigational Site
  • London, United Kingdom, NW3 2QG
    • GSK Investigational Site
• United States
  • California
    • Fountain Valley, California, United States, 92708
      • GSK Investigational Site
    • San Francisco, California, United States, 94115-1931
      • GSK Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80262
      • GSK Investigational Site
  • Florida
    • Fort Lauderdale, Florida, United States, 33145
      • GSK Investigational Site
    • Orlando, Florida, United States, 32804
      • GSK Investigational Site
    • Orlando, Florida, United States, 32806
      • GSK Investigational Site
    • Sarasota, Florida, United States, 34239
      • GSK Investigational Site
    • Tampa, Florida, United States, 33614
      • GSK Investigational Site
  • New York
    • Manhasset, New York, United States, 11030
      • GSK Investigational Site
  • Texas
    • Galveston, Texas, United States, 77555-1188
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or non-pregnant/non-lactating females >/=13 years of age (or >/= 18 years of age according to local requirements).
• Received fosamprenavir through prior participation in APV20001, APV30002, APV30003 or PRO30017 or have participated in APV30001 or other studies as deemed appropriate by the project team.

Exclusion Criteria:

• Permanent discontinuation of GW433908 in a previous study due to intolerance.
• An active CDC Class C Event.
• Any condition which, in the opinion of the investigator, would preclude a subject from participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Any Adverse Event (AE): Interim Analysis	An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A list of all adverse events is reported in the "Other (Non-Serious) Adverse Events" section.	Baseline (Day 1) up to 31 January 2006 (up to Week 264)
Number of Participants With Any Adverse Event (AE): Final Analysis	An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A list of all adverse events is reported in the "Other (Non-Serious) Adverse Events" section.	Post January 2006; for up to 241 weeks
Change From Baseline in the Indicated Clinical Chemistry Parameters at Weeks 48, 96, 120, 132, 168, 180, 204, and 216	Fasting blood samples of participants were collected for the assessment of triglycerides (Tri.), cholesterol (Chol.), high density cholesterol (HDL), low density cholesterol (LDL), and fasting blood glucose (FBG). Change from Baseline at Weeks (W) 48, 96, 120, 132, 168, 180, 204, and 216 was calculated as the value at that particular week minus the value at Baseline (Day 1).	Baseline (Day 1) and Weeks 48, 96, 120, 132, 168, 180, 204, and 216
Median Values of the Indicated Clinical Chemistry Parameters at Weeks 120, 180, 204, 216, and 432	Fasting blood samples of participants were collected for the assessment of triglycerides, cholesterol, high density cholesterol (HDL), low density cholesterol (LDL), and fasting blood glucose (FBG).	Weeks 120, 180, 204, 216, and 432
Change From Baseline in the Total Cholesterol/HDL Ratio at Weeks 48, 120, 180, 204, and 216	blood samples of participants were collected for the assessment of the total cholesterol/HDL ratio. The ratio of total cholesterol/HDL was calculated by dividing the value of total cholesterol by the value of HDL. Change from Baseline at Weeks 48, 120, 180, 204, and 216 was calculated as the value at that particular week minus the value at Baseline (Day 1).	Baseline (Day 1) and Weeks 48, 120, 180, 204, and 216
Change From Baseline in the Total Cholesterol/HDL Ratio at Weeks 48, 96, 132, and 168	Fasting blood samples of participants were collected for the assessment of the total cholesterol/HDL ratio. The ratio of total cholesterol/HDL was calculated by dividing the value of total cholesterol by the value of HDL. Change from Baseline at Weeks 48, 96, 132, and 168 was calculated as the value at that particular week minus the value at Baseline (Day 1).	Baseline (Day 1) and Weeks 48, 96, 132, and 168
Median Value of the Total Cholesterol/HDL Ratio at Weeks 120, 180, 204, 216, and 432	Fasting blood samples of participants were collected for the assessment of the total cholesterol/HDL ratio. The ratio of total cholesterol/HDL was calculated by dividing the value of total cholesterol by the value of HDL.	Weeks 120, 180, 204, 216, and 432
Change From Baseline in Aspartate Aminotransferase (AST), Alanine Transaminase (ALT), and Serum Lipase at Weeks 48, 120, 180, 204, and 216	Blood samples of participants were collected for the assessment of AST, ALT, and serum lipase. Change from Baseline at Weeks 48, 120, 180, 204, and 216 was calculated as the value at that particular week minus the value at Baseline (Day 1).	Baseline (Day 1) and Weeks 48, 120, 180, 204, and 216
Change From Baseline in Aspartate Aminotransferase (AST), Alanine Transaminase (ALT), and Serum Lipase at Weeks 48, 96, 132, and 168	Blood samples of participants were collected for the assessment of AST, ALT, and serum lipase. Change from Baseline at Weeks 48, 96, 132, and 168 was calculated as the value at that particular week minus the value at Baseline (Day 1).	Baseline (Day 1) and Weeks 48, 96, 132, and 168
Median Aspartate Aminotransferase (AST), Alanine Transaminase (ALT), and Serum Lipase Values at Weeks 120, 180, 204, 216, and 432	Blood samples of participants were collected for the assessment of AST, ALT, and serum lipase.	Weeks 120, 180, 204, 216, and 432

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) <400 and <50 Copies Per Milliliter at Baseline and Weeks 48, 120, 180, and 216 (MD=F and Observed)	Blood samples of participants were collected for the assessment of HIV-1RNA copies in plasma. Viral load, measured in RNA copies per milliliter of plasma, is an efficacy measure for antiretroviral drugs. In the MD=F analysis, participants who had missing data at or had discontinued the study prior to a certain time point are classified as non-responders. In the observed analysis (OA), data are presented for the number of participants still enrolled in the study at a certain time point. Participants in the NFV populations had received antiretroviral therapy prior to Baseline.	Baseline and Weeks 48, 120, 180, and 216
Percentage of Participants With Plasma HIV-1RNA <400 and <50 Copies Per Milliliter at Baseline and Weeks 12, 24, 48, 60, 96, and 132 (MD=F and Observed)	Blood samples of participants were collected for the assessment of HIV-1RNA copies in plasma. Viral load, measured in RNA copies per milliliter of plasma, is an efficacy measure for antiretroviral drugs. In the MD=F analysis, participants who had missing data at or had discontinued the study prior to a certain time point are classified as non-responders. In the observed analysis (OA), data are presented for the number of participants still enrolled in the study at a certain time point.	Baseline and Weeks 12, 24, 48, 60, 96, and 132
Percentage of Participants With Plasma HIV-1RNA <50 Copies Per Milliliter at Baseline and Weeks 120, 180, 240, 300, 360, 420, and 432 (Observed)	Blood samples of participants were collected for the assessment of HIV-1RNA copies in plasma. Viral load, measured in RNA copies per milliliter of plasma,is an efficacy measure for antiretroviral drugs.	Baseline and Weeks 120, 180, 240, 300, 360, 420, and 432
Cluster of Differentiation Antigen 4 (CD4+) Cell Count at Baseline and Weeks 48, 120, 168, 180, 204, and 216: Observed Analysis	Blood samples of participants were collected for the assessment of CD4+ cell count. CD4+ cells are white blood cells that are important in fighting infection. HIV infects CD4+ cells, replicates in them, and destroys them. CD4+ cell count provides a measure of the status of the immune system and to what extent it is affected by HIV.	Baseline and Weeks 48, 120, 168, 180, 204, and 216
Cluster of Differentiation Antigen 4 (CD4+) Cell Count at Baseline and Weeks 24, 48, 96, 132, and 168: Observed Analysis	Blood samples of participants were collected for the assessment of CD4+ cell count. CD4+ cells are white blood cells that are important in fighting infection. HIV infects CD4+ cells, replicates in them, and destroys them. CD4+ cell count provides a measure of the status of the immune system and to what extent it is affected by HIV.	Baseline and Weeks 24, 48, 96, 132, and 168
Median Plasma HIV-1 RNA at Baseline and Weeks 24, 48, 72, 96, 120, 144, 168, 180, 204, and 216	Blood samples of participants were collected for the assessment of plasma HIV-1 RNA.	Baseline and Weeks 24, 48, 72, 96, 120, 144, 168, 180, 204, and 216
Median Plasma HIV-1 RNA at Baseline and Weeks 12, 24, 48, 72, 96, 132, and 168	Blood samples of participants were collected for the assessment of plasma HIV-1 RNA.	Baseline and Weeks 12, 24, 48, 72, 96, 132, and 168
Median Plasma HIV-1 RNA at Weeks 180, 240, 300, 360, 420, and 432	Blood samples of participants were collected for the assessment of plasma HIV-1 RNA.	Weeks 180, 240, 300, 360, 420, and 432
Number of Participants With HIV-1 Disease Progression to CDC Class C, or New CDC Class C or Death, From Baseline	The number of participants with progression of HIV-1 disease were assessed using the CDC classification of HIV-1: class A, asymptomatic or lymphadenopathy; class B: symptomatic, but not AIDS; class C, AIDS. A participant is considered to have had a disease progression if they report a CDC Class C event for the first time, if they report a new CDC Class C event, or if they experience any fatal adverse event during the study.	Baseline (Day 1) up to 31 January 2006 (up to Week 264)
Number of Participants Enrolled in Studies APV30001 and APV300002 With the Indicated HIV-associated Conditions	The number of participants with the indicated HIV-associated conditions were assessed, excluding recurrences.	Baseline (Day 1) up to 31 January 2006 (up to Week 264)
Number of Participants Enrolled in Study APV30003 and Other Studies With the Indicated HIV-associated Conditions	The number of participants with the indicated HIV-associated conditions were assessed.	Baseline (Day 1) up to 31 January 2006 (up to Week 264)

Collaborators and Investigators

• Sponsor: ViiV Healthcare
• Collaborators: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: November 1, 2001
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: February 24, 2006
• First Submitted That Met QC Criteria: February 24, 2006
• First Posted (Estimate): February 27, 2006

Study Record Updates

• Last Update Posted (Estimate): April 19, 2013
• Last Update Submitted That Met QC Criteria: April 11, 2013
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: HIV-1; protease inhibitor; antiretroviral therapy; antiretroviral therapy naive subjects; fosamprenavir; pro-drug; LEXIVA; AGENERASE; GW433908; amprenavir
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; 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: APV30005