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Infection, Human Immunodeficiency Virus IPhase 3NCT00450580

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

A Phase 3 study testing fosamprenavir/ritonavir in people with Infection, Human Immunodeficiency Virus I and HIV-1 Infection, run by ViiV Healthcare at 69 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
fosamprenavir/ritonavir
Could I receive a placebo?
No, everyone receives an active treatment
How many people
212 participants
Where
69 sitesin 9 countries
Study dates
Mar 2007to Aug 2008
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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,
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  • 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.

Who cannot join

  • 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.
Show all 26Show fewer
  • 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.
  • Subject has received treatment with an HIV-1 immunotherapeutic vaccine or any agents with documented activity against HIV-1 in vitro within 28 days prior Screening, or an anticipated need during the study.
  • Subjects who require treatment with any of the following medications within 28 days of commencement of investigational product, or an anticipated need during the study:
  • Amiodarone, astemizole, bepridil, cisapride, dihydroergotamine, ergonovine, ergotamine, flecainide, halofantrine, lidocaine, lovastatin, methylergonovine, midazolam, pimozide, propafenone, quinidine, simvastatin, terfenadine, triazolam.
  • Carbamazepine, dexamethasone, phenobarbital, phenytoin, primidone, rifampin, St Johns Wort (Hypericum perforatum), troglitazone.
  • Systemic interleukins or interferons.
  • Subject has a history of allergy to any of the investigational products or any excipients therein.
  • Subject has evidence of genotypic (as defined by the current ANRS AC-11 algorithm) resistance at screening or prior documented evidence of genotypic and/or phenotypic (above threshold for reduced susceptibility) resistance to amprenavir/ritonavir, abacavir or lamivudine.
  • Subjects recruited at sites in France will be excluded if:
  • The subject is not affiliated with or a beneficiary of a social security.
  • The subject has previously participated in an experimental drug and/or vaccine trial(s) within 60 days or 5 half-lives, or twice the duration of the biological effect of the experimental drug or vaccine - whichever is longer, prior to screening for the study.
  • The subject will participate simultaneously in another clinical study. Notwithstanding these minimum inclusion and exclusion criteria, investigators are urged to follow country specific guidelines where they exist when making decisions about subjects who are eligible for study participation.

Trial locations and contacts

69 sites in 9 countries.

69 sites in 9 countries

France17 sites

  • GSK Investigational Site

    Besançon, 25030

  • GSK Investigational Site

    Bordeaux, 33000

  • GSK Investigational Site

    Clamart, 92140

  • GSK Investigational Site

    La Roche-sur-Yon, 85025

  • GSK Investigational Site

    Levallois-Perret, 92300

  • GSK Investigational Site

    Lyon, 69437

  • GSK Investigational Site

    Nantes, 44093

  • GSK Investigational Site

    Nice, 06202

  • GSK Investigational Site

    Orléans, 45100

  • GSK Investigational Site

    Paris, 75010

  • GSK Investigational Site

    Paris, 75018

  • GSK Investigational Site

    Paris, 75475

  • GSK Investigational Site

    Paris, 75651

  • GSK Investigational Site

    Saint-Denis, 93205

  • GSK Investigational Site

    Strasbourg, 67000

  • GSK Investigational Site

    Suresnes, 92151

  • GSK Investigational Site

    Tourcoing, 59208

Other trials in France

Spain16 sites

  • GSK Investigational Site

    A Coruña, 15006

  • GSK Investigational Site

    Barcelona, 08025

  • GSK Investigational Site

    Barcelona, 08036

  • GSK Investigational Site

    Barcelona, 08907

  • GSK Investigational Site

    Barcelona, 8400

  • GSK Investigational Site

    Elche (Alicante), 03202

  • GSK Investigational Site

    Madrid, 28029

  • GSK Investigational Site

    Madrid, 28040

  • GSK Investigational Site

    Madrid, 28041

  • GSK Investigational Site

    Madrid, 28046

  • GSK Investigational Site

    Málaga, 29010

  • GSK Investigational Site

    Marid, 28040

  • GSK Investigational Site

    Mataró, 08034

  • GSK Investigational Site

    Santiago de Compostela, 15706

  • GSK Investigational Site

    Seville, 41013

  • GSK Investigational Site

    Valencia, 46015

Other trials in Spain

Germany15 sites

  • GSK Investigational Site

    Cologne, North Rhine-Westphalia, 50937

  • GSK Investigational Site

    Dortmund, North Rhine-Westphalia, 44137

  • GSK Investigational Site

    Frankfurt am Main, Hesse, 60311

  • GSK Investigational Site

    Frankfurt am Main, Hesse, 60590

  • GSK Investigational Site

    Frankfurt am Main, Hesse, 60596

  • GSK Investigational Site

    Freiburg im Breisgau, Baden-Wurttemberg, 79098

  • GSK Investigational Site

    Freiburg im Breisgau, Baden-Wurttemberg, 79106

  • GSK Investigational Site

    Fürth, Bavaria, 90762

  • GSK Investigational Site

    Hamburg, Free and Hanseatic City of Hamburg, 20146

  • GSK Investigational Site

    Hamburg, Free and Hanseatic City of Hamburg, 20246

  • GSK Investigational Site

    Hanover, Lower Saxony, 30159

  • GSK Investigational Site

    Hanover, Lower Saxony, 30625

  • GSK Investigational Site

    Munich, Bavaria, 80801

  • GSK Investigational Site

    Osnabrück, Lower Saxony, 49090

  • GSK Investigational Site

    Stuttgart, Baden-Wurttemberg, 70197

Other trials in Germany

Italy8 sites

  • GSK Investigational Site

    Brescia, Lombardy, 25125

  • GSK Investigational Site

    Busto Arsizio (VA), Lombardy, 21052

  • GSK Investigational Site

    Catanzaro, Calabria, 88100

  • GSK Investigational Site

    Grosseto, Tuscany, 58100

  • GSK Investigational Site

    Milan, Lombardy, 20127

  • GSK Investigational Site

    Milan, Lombardy, 20142

  • GSK Investigational Site

    Rome, Lazio, 00161

  • GSK Investigational Site

    Rome, Lazio, 00185

Other trials in Italy

Romania4 sites

  • GSK Investigational Site

    Bucharest, 021105

  • GSK Investigational Site

    Bucharest, 030303

  • GSK Investigational Site

    Constanța, 900709

  • GSK Investigational Site

    Iași, 700116

Other trials in Romania

Belgium3 sites

  • GSK Investigational Site

    Antwerp, 2000

  • GSK Investigational Site

    Brussels, 1090

  • GSK Investigational Site

    Ghent, 9000

Other trials in Belgium

United Kingdom3 sites

  • GSK Investigational Site

    London, NW3 2QG

  • GSK Investigational Site

    London, SE1 7EH

  • GSK Investigational Site

    London, SW10 9TH

Other trials in United Kingdom

Russia2 sites

  • GSK Investigational Site

    Saint Petersburg, 196645

  • GSK Investigational Site

    Volgograd, 400040

Other trials in Russia

Switzerland1 site

  • GSK Investigational Site

    Sankt Gallen, 9007

Other trials in Switzerland

About this study

Official title: Study of Once-Daily Versus Twice-Daily Fosamprenavir Plus Ritonavir, Administered With Abacavir/Lamivudine Once-Daily in Antiretroviral-Naive HIV-1 Infected Adult Subjects.

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.

Being tested
fosamprenavir/ritonavir
Keywords
protease inhibitor,, HIV-1,, Fosamprenavir,, non-HDL cholesterol, ritonavir,, naive,
Medical subject headings
Infections, Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • fosamprenavir/ritonavirDrug

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

Study groups in NCT00450580
Study groupRoleWhat they receive
Arm AExperimentalFosamprenavir/ritonavir 1400mg/100mg QD + ABC/3TC FDC 600/300mg QD
Receives: Drug: fosamprenavir/ritonavir
Arm BActive comparatorFosamprenavir/ritonavir 700mg/100mg BID + ABC/3TC FDC 600/300mg QD
Receives: Drug: fosamprenavir/ritonavir

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Week 48

Secondary outcomes (7)

  1. Percentage of Participants With HIV-1 RNA <50 and >=50 Copies/mL by Visit 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 <50 copies/mL at Week 48 was determined by the TLOVR algorithm

    Measured: Week 48

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

    The number of participants with HIV-1 RNA <400 copies/mL at Week 48 was determined (by analysis of blood draw) and categorised by baseline viral load (BVL).

    Measured: Week 48

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

    The number of participants with HIV-1 RNA <400 copies/mL at week 48 was determined (by analysis of blood draw) and categorised by baseline CD4+ count.

    Measured: Week 48

  4. Change From Baseline in Non-HDL Cholesterol at Week 48

    Blood samples were drawn to determine the non-HDL cholesterol levels at Week 48. The mean absolute change in non-HDL cholesterol was defined as the Week 48 levels minus levels at baseline.

    Measured: Week 48

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

    A blood sample was drawn at the time of confirmation of virological failure, and mutations present in the virus were identified and compared to those found in the blood sample at baseline. New mutations were tabulated by drug class. RT, reverse transcriptase. Virological failure could occur anytime from Week 4 to Week 48.

    Measured: Time to virologic failure; Week 4 up to Week 48

  6. Steady-state Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 4, 12, and 24

    Blood samples were drawn at Weeks 4, 12, and 24 to determine plasma concentrations (Ctau) of APV and RTV

    Measured: Weeks 4, 12, and 24

  7. Study Endpoints for a Subset of Subjects Receiving Study Drug Beyond 48 Weeks

    Adaptive two-stage design study up to 48 weeks. N=200, expanding to 728 if continuation criteria were achieved based on a 24-week interim analysis. The initial 200 participants would continue until the last subject of the expanded cohort reached 48 weeks and would constitute the subset. As continuation criteria were not achieved, the study did not proceed to the second stage, and full analysis was performed on the initial 200 participants only.

    Measured: Up to 60 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Mar 2007 (estimated)
  2. Study startMar 2007
  3. Primary completionAug 2008
  4. Study completionAug 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
212 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00450580
Sponsor's protocol ID
APV109141
Status last verified
Apr 2012
First submitted
21 Mar 2007
Last updated
7 Jun 2012

Publications

  • 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):

  • 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.

  • 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.

    PubMed 20133266

  • 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.

    PubMed 18383194

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing fosamprenavir/ritonavir in people with Infection, Human Immunodeficiency Virus I and HIV-1 Infection, run by ViiV Healthcare at 69 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 69 sites in France, Spain, Germany, Italy, Romania and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Sep 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With HIV-1 RNA <400 and >=400 Copies/mL Over 48 Weeks (time frame: Week 48). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00450580, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2012.

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