HIV-1 Infection Study of Once a Day Versus Twice a Day Protease Inhibitor in Antiretroviral Treatment Naive Adults

NCT00450580 | Completed Phase 3 Results

• 1 other identifier: APV109141
• Study Type: interventional
• Target: 212
• Locations: 9 countries
• Sites: 69

Brief Summary

This is a Phase IIIB, 48 Week, multicentre, randomized, open-label, parallel group study comparing the safety and efficacy of fosamprenavir plus ritonavir 1400mg/100mg once-daily to fosamprenavir plus ritonavir 700mg/100mg twice-daily, both administered with abacavir/lamivudine 600mg/300mg once-daily in antiretroviral-naive HIV-1 infected adults. This study utilizes a group-sequential design with two stages: 1) an interim 24 week cohort analysis of approximately 200 subjects and 2) if study continuation criteria are met at this interim analysis, further enrolment of an additional 528 subjects, followed over a minimum of 48 weeks. The objectives of the study are to demonstrate 1) non-inferior antiviral activity of fosamprenavir/ritonavir 1400mg/100mg QD compared to fosamprenavir/ritonavir 700mg/100mg BID and 2) a superior fasting non-HDL lipid profile in subjects receiving fosamprenavir/ritonavir 1400mg/100mg QD.

Conditions

Infection, Human Immunodeficiency Virus I; HIV-1 Infection

Keywords

protease inhibitor,; HIV-1,; Fosamprenavir,; non-HDL cholesterol; ritonavir,; naive,

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With HIV-1 RNA <400 and >=400 Copies/mL Over 48 Weeks

  A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at week 48. The percentage of participants with HIV-1 RNA \<400 copies/mL at Week 48 was determined by the Time to Loss Of Virologic Response (TLOVR) algorithm.

  Week 48

Secondary Outcomes (7)

• Percentage of Participants With HIV-1 RNA <50 and >=50 Copies/mL by Visit Over 48 Weeks

  Week 48

• Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline Viral Load, TLOVR Analysis

  Week 48

• Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline CD4+ Count, TLOVR Analysis

  Week 48

• Change From Baseline in Non-HDL Cholesterol at Week 48

  Week 48

• Number of Protocol-defined Virological Failures With Genotypic and Phenotypic Resistance Changes

  Time to virologic failure; Week 4 up to Week 48

Study Arms (2)

Arm A

EXPERIMENTAL

Fosamprenavir/ritonavir 1400mg/100mg QD + ABC/3TC FDC 600/300mg QD

Drug: fosamprenavir/ritonavir

Arm B

ACTIVE COMPARATOR

Fosamprenavir/ritonavir 700mg/100mg BID + ABC/3TC FDC 600/300mg QD

Drug: fosamprenavir/ritonavir

Interventions

fosamprenavir/ritonavir DRUG

Fosamprenavir (FPV, TELZIR) is currently licensed in Europe for twice daily (BID) dosing in combination with ritonavir (RTV, Norvir) as a boosting agent

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is ≥18 years of age.
• Subject is antiretroviral-naïve (defined as having ≤14 days of prior therapy with any antiretroviral agent).
• Subject has plasma HIV-1 RNA ≥1,000 copies/mL at screening.
• Subject is willing and able to understand and provide written informed consent prior to participation in this study.
• A female is eligible to enter and participate in the study if she is of:
• Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal); or,
• Child-bearing potential, has a negative pregnancy test (serum b-HCG) at screen and agrees to one of the following methods of contraception (any contraception method must be used consistently and correctly, i.e., in accordance with both the approved product label and the instructions of a physician):
• Complete abstinence from intercourse from 2 weeks prior to administration of the investigational products, throughout the study, and for at least 2 weeks after discontinuation of all study medications
• Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide). Hormonal contraception will not be permitted in this study
• Any intrauterine device (IUD) with published data showing that the expected failure rate is \<1% per year.
• Sterilization (female subject or male partner of female subject). All subjects participating in the study should be counselled on the practice of safer sex.
• Prior to randomization, subjects entering Stage 2 must have been screened and be negative for the HLA-B\*5701 allele. Test may be performed by local laboratory and results must be available for source document verification according to local practices.

You may not qualify if:

• Subject is in the initial acute phase of a CDC Clinical Category C infection at Baseline. Subjects may be enrolled provided they are receiving treatment for such infections and are clinically improving at the Baseline visit.
• Subject is enrolled in one or more investigational drug protocols, which may impact HIV RNA suppression.
• Subject is, in the opinion of the Investigator, unable to complete the study dosing period and protocol evaluations and assessments.
• Subject is either pregnant or breastfeeding.
• Subject suffers from any serious medical condition (such as pancreatitis, diabetes, congestive heart failure, cardiomyopathy or other cardiac dysfunction) which in the opinion of the Investigator would compromise the safety of the subject.
• Subject has a pre-existing mental, physical, or substance abuse disorder which, in the opinion of the Investigator, may interfere with the subject's ability to comply with the dosing schedule and protocol evaluations and assessments.
• Subject has a history of inflammatory bowel disease or intestinal malignancy, intestinal ischemia, malabsorption, or other gastrointestinal dysfunction, which, in the opinion of the Investigator, may interfere with drug absorption or render the subject unable to take oral medication.
• Subject has any acute laboratory abnormality at screening, which, in the opinion of the Investigator, would preclude the subject's participation in the study of an investigational compound. If subjects are found to have an acute Grade 4 laboratory abnormality at screening, this test may be repeated once within the 45-day screening window. Any verified Grade 4 laboratory abnormality would exclude a subject from study participation.
• Subject has an estimated creatinine clearance \< 50 mL/min via the Cockcroft-Gault method \[Cockcroft, 1976\]. This test may be repeated once within the 45-day screening window.
• NOTE: Creatinine clearance should be estimated using the following formula:
• For serum creatinine concentration in mg/dL:
• For serum creatinine concentration in µmol/L:
• Alanine aminotransferase (ALT) \>5 times the upper limit of normal (ULN) or hepatic impairment as determined by Child-Pugh Score ≥ 5.
• Subject is receiving, or has received within 90 days prior to screen, any lipid lowering agent, including drugs from the following classes: HMG-CoA reductase inhibitors (statins), niacin, fibrates, bile acid sequestrants, and/or fish oil supplements. Subjects anticipated to require initiation of therapy with these agents within 12 weeks of Baseline are not eligible to participate.
• Subject has received treatment with radiation therapy or cytotoxic chemotherapeutic agents within 28 days prior to Screening, or has an anticipated need for these agents within the study period.

Sponsors & Collaborators

• ViiV Healthcare: lead
• GlaxoSmithKline: collaborator

Study Sites (69)

GSK Investigational Site

Antwerp, 2000, Belgium

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GSK Investigational Site

Brussels, 1090, Belgium

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GSK Investigational Site

Ghent, 9000, Belgium

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GSK Investigational Site

Besançon, 25030, France

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GSK Investigational Site

Bordeaux, 33000, France

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GSK Investigational Site

Clamart, 92140, France

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GSK Investigational Site

La Roche-sur-Yon, 85025, France

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GSK Investigational Site

Levallois-Perret, 92300, France

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GSK Investigational Site

Lyon, 69437, France

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GSK Investigational Site

Nantes, 44093, France

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GSK Investigational Site

Nice, 06202, France

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GSK Investigational Site

Orléans, 45100, France

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GSK Investigational Site

Paris, 75010, France

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GSK Investigational Site

Paris, 75018, France

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GSK Investigational Site

Paris, 75475, France

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GSK Investigational Site

Paris, 75651, France

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GSK Investigational Site

Saint-Denis, 93205, France

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GSK Investigational Site

Strasbourg, 67000, France

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GSK Investigational Site

Suresnes, 92151, France

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GSK Investigational Site

Tourcoing, 59208, France

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GSK Investigational Site

Freiburg im Breisgau, Baden-Wurttemberg, 79098, Germany

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GSK Investigational Site

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

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GSK Investigational Site

Stuttgart, Baden-Wurttemberg, 70197, Germany

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GSK Investigational Site

Fürth, Bavaria, 90762, Germany

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GSK Investigational Site

Munich, Bavaria, 80801, Germany

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GSK Investigational Site

Hamburg, Hamburg, 20146, Germany

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GSK Investigational Site

Hamburg, Hamburg, 20246, Germany

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GSK Investigational Site

Frankfurt am Main, Hesse, 60311, Germany

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GSK Investigational Site

Frankfurt am Main, Hesse, 60590, Germany

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GSK Investigational Site

Frankfurt am Main, Hesse, 60596, Germany

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GSK Investigational Site

Hanover, Lower Saxony, 30159, Germany

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GSK Investigational Site

Hanover, Lower Saxony, 30625, Germany

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GSK Investigational Site

Osnabrück, Lower Saxony, 49090, Germany

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GSK Investigational Site

Cologne, North Rhine-Westphalia, 50937, Germany

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GSK Investigational Site

Dortmund, North Rhine-Westphalia, 44137, Germany

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GSK Investigational Site

Catanzaro, Calabria, 88100, Italy

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GSK Investigational Site

Rome, Lazio, 00161, Italy

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GSK Investigational Site

Rome, Lazio, 00185, Italy

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GSK Investigational Site

Brescia, Lombardy, 25125, Italy

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GSK Investigational Site

Busto Arsizio (VA), Lombardy, 21052, Italy

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GSK Investigational Site

Milan, Lombardy, 20127, Italy

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GSK Investigational Site

Milan, Lombardy, 20142, Italy

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GSK Investigational Site

Grosseto, Tuscany, 58100, Italy

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GSK Investigational Site

Bucharest, 021105, Romania

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GSK Investigational Site

Bucharest, 030303, Romania

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GSK Investigational Site

Constanța, 900709, Romania

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GSK Investigational Site

Iași, 700116, Romania

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GSK Investigational Site

Saint Petersburg, 196645, Russia

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GSK Investigational Site

Volgograd, 400040, Russia

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GSK Investigational Site

A Coruña, 15006, Spain

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GSK Investigational Site

Barcelona, 08025, Spain

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GSK Investigational Site

Barcelona, 08036, Spain

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GSK Investigational Site

Barcelona, 08907, Spain

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GSK Investigational Site

Barcelona, 8400, Spain

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GSK Investigational Site

Elche (Alicante), 03202, Spain

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GSK Investigational Site

Madrid, 28029, Spain

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GSK Investigational Site

Madrid, 28040, Spain

Location

GSK Investigational Site

Madrid, 28041, Spain

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GSK Investigational Site

Madrid, 28046, Spain

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GSK Investigational Site

Marid, 28040, Spain

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GSK Investigational Site

Mataró, 08034, Spain

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GSK Investigational Site

Málaga, 29010, Spain

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GSK Investigational Site

Santiago de Compostela, 15706, Spain

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GSK Investigational Site

Seville, 41013, Spain

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GSK Investigational Site

Valencia, 46015, Spain

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GSK Investigational Site

Sankt Gallen, 9007, Switzerland

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GSK Investigational Site

London, NW3 2QG, United Kingdom

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GSK Investigational Site

London, SE1 7EH, United Kingdom

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GSK Investigational Site

London, SW10 9TH, United Kingdom

Location

Related Publications (4)

• Ross LL, Robinson MD, Carosi G, et al. Impact of HIV subtype on response and resistance in antiretroviral-naïve adults comparing treatment with once daily versus twice daily Ritonavir boosted Fosamprenavir in combination with Abacavir/Lamivudine. [Drugs Ther Stud]. 2012;2(e1):

  BACKGROUND

• Carosi G, Lazzarin A, Stellbrink H, et al. Efficacy and Safety of Fosamprenavir + Ritonavir (FPV/RTV) 700mg/100mg Twice Daily (BID) Versus FPV/RTV 1400mg/100mg Once Daily (QD) with ABC/3TC QD over 24 Weeks. Abstract H-1244, 48th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC, 2008.

  BACKGROUND

• Carosi, Lazzarin, Stellbrink, Moyle, Rugina, Staszewski, Givens, Ross, Granier, Ait-Khaled, Leather, Nichols. Study of once-daily versus twice-daily fosamprenavir plus ritonavir administered with abacavir/lamivudine once daily in antiretroviral-naive HIV-1-infected adult subjects. HIV Clin Trials. 2009 Nov-Dec;10(6):356-67. doi: 10.1310/hct1006-356.

  PMID: 20133266 DERIVED

• Hughes S, Cuffe RL, Lieftucht A, Garrett Nichols W. Informing the selection of futility stopping thresholds: case study from a late-phase clinical trial. Pharm Stat. 2009 Jan-Mar;8(1):25-37. doi: 10.1002/pst.323.

  PMID: 18383194 DERIVED

MeSH Terms

Conditions

Infections; Acquired Immunodeficiency Syndrome

Interventions

fosamprenavir; Ritonavir

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2007
• First Posted: March 22, 2007
• Study Start: March 1, 2007
• Primary Completion: August 1, 2008
• Study Completion: August 1, 2008
• Last Updated: June 7, 2012
• Results First Posted: September 2, 2009

Record last verified: 2012-04

Locations

ES (16); BE (3); DE (15); CH (1); RO (4); FR (17); GB (3); RU (2); IT (8)