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

Study Overview
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Brief Summary
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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.

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

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

Conditions
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Infection, Human Immunodeficiency Virus

Intervention / Treatment
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* Drug: fosamprenavir (GW433908)
* Drug: ritonavir


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 13 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: fosamprenavir (GW433908)|nan|
|Drug: ritonavir|nan|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antiretroviral therapy naive subjects, fosamprenavir, HIV-1, protease inhibitor, pro-drug, antiretroviral therapy, LEXIVA, AGENERASE, GW433908, amprenavir