A Randomized, Prospective Study of the Efficacy, Safety and Tolerability of Two Doses of GW433908Ritonavir Given With Abacavir/Lamivudine Fixed Dose Combination
Drug: fos-amprenavir calcium, ritonavir
Drug: abacavir/lamivudine as Epzicom
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Randomized, Prospective Study of the Efficacy, Safety and Tolerability of Two Doses of GW433908Ritonavir Given With Abacavir/Lamivudine Fixed Dose Combination|
- Proportion of subjects with plasma HIV 1 RNA <400 copies at week 48
- Proportion of subjects who experience drug related discontinuations at Week 48
- Proportion of subjects who achieve plasma HIV 1 RNA<400 copies/mL at Weeks 24 and 96
- Proportion of subjects who achieve plasma HIV-1 RNA <50 copies/mL at Weeks 24, 48, and 96.
- Absolute values and change from baseline in plasma HIV-1 RNA and CD4+ cell counts at Weeks 24, 48, and 96.
- Development and identification of genotypic resistance mutations and phenotypic resistance at virologic failure.
- Incidence of Grades 2 to 4 AEs, treatment-limiting AEs, and serious adverse events (SAEs) over 24, 48, and 96 weeks.
- Change from baseline in fat distribution as determined by percent change in body fat using whole body DEXA scans at Weeks 48, 72, and 96.
- Change from baseline in subject's self-report of body fat distribution using the Body Image Questionnaire and the investigator's assessment of subject's body fat distribution using FRAM 2 PE (Grunfeld et al., 2003) at Weeks 48, 72, and 96.
- Change from baseline in fasting lipids (total cholesterol, HDL cholesterol, direct LDL cholesterol, and triglycerides), fasting glucose and insulin measurements at Weeks 12, 24, 48, and 96.
- Measurements of plasma APV trough concentrations at Weeks 4, 8, 24, and 48
- To assess relationships between plasma APV trough concentrations and outcomes, including safety, efficacy and the development of resistance.
- Adherence to each treatment regimen using pill counts of unused study drugs and subject self-assessment adherence questionnaire.
|Study Start Date:||March 2006|
|Estimated Study Completion Date:||December 2007|
|Primary Completion Date:||December 2007 (Final data collection date for primary outcome measure)|
The optimal long-term management of HIV-1 infection necessitates the chronic use of highly effective, well-tolerated antiretroviral (ARV) combination therapy, which ideally can preserve future treatment options. Current preferred standard treatment for HIV consists of a regimen composed of a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs). A recent trend that may contribute to improving rates of treatment response is to use regimens with fewer pills and once daily dosing. This study is designed to assess two PI options that consist of four or five pills taken once daily - these options may also offer advantages in terms of metabolic consequences.
The primary objective of this multi-center, open-label, randomized, two-arm, pilot study is to evaluate the antiretroviral efficacy, safety, and tolerability (adverse events and metabolic profile) of fos-amprenavir (fAPV) boosted with either of two doses of ritonavir (RTV) when administered in combination with ABC/3TC (abacavir/lamivudine, Epzicom®) FDC (fixed dose combination) in a once-daily regimen over 48 weeks in ART-naïve, HIV-infected adults. Approximately 100 subjects will be enrolled from about 10 sites in the United States. Subjects must be >18 years of age, be ART-naïve (<7 days of prior therapy with any licensed or investigational ARV drugs) and have a plasma HIV-1 RNA>1,000 copies/mL. A CD4+ cell count >50 cells/mm3 was initially required for eligibility. Amendment 1 has dropped this as a requirement. Subjects will be stratified at entry according to their screening plasma HIV-1 RNA level (<100,000 copies/mL or >100,000 copies/mL). Eligible subjects will be randomized (1:1) to one of the following two treatment arms for 96 weeks; fAPV 1400 mg/RTV 100 mg QD plus ABC 600 mg/3TC 300 mg FDC QD (Treatment Arm A) or fAPV 1400 mg/RTV 200 mg QD plus ABC 600 mg/3TC 300 mg FDC QD (Treatment Arm B).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00335270
|United States, Florida|
|University of Miami School of Medicine|
|Miami, Florida, United States, 33136|
|Principal Investigator:||Charles Hicks, MD||Duke University|
|Principal Investigator:||Rafael E Campo, MD||University of Miami|
|Principal Investigator:||Jason Flamm, MD||Medicine 4|
|Principal Investigator:||Jeffrey Lennox, MD||Emory University|
|Principal Investigator:||Rodger MacArthur, MD||Wayne State University|
|Principal Investigator:||Jeffrey P Nadler, MD||Hillsborough County Health Department|
|Principal Investigator:||John H. Schrank, MD||Greenville Hospital System|
|Principal Investigator:||Louis Sloan, MD||North Texas Infectious Disease Consultants|
|Principal Investigator:||Jeffrey Stephens, MD||Mercer University School of Medicine|
|Principal Investigator:||David A Wohl, MD||University of North Carolina, Chapel Hill|