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

Study Overview
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Brief Summary
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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.

Detailed Description
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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)

Official Title
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See Detailed Description.

Conditions
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HIV Infection, Infection, Human Immunodeficiency Virus

Intervention / Treatment
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* Drug: Half-boosted Fosamprenavir
* Drug: Full Boosted Fosamprenavir


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1 LEXIVA Ritonavir Once-daily