E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of HIV-1 infection. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008922 |
E.1.2 | Term | Chronic infection with HIV |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate non-inferior antiviral response of fosamprenavir/ritonavir 1400mg/100mg QD compared to fosamprenavir/ritonavir 700mg/100mg BID, both administered with ABC/3TC FDC QD. |
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E.2.2 | Secondary objectives of the trial |
•To demonstrate a superior fasting non-HDL lipid profile in subjects receiving fosamprenavir/ritonavir (FPV/rtv) 1400mg/100mg QD compared to FPV/rtv 700mg/100mg BID, both administered with ABC/3TC FDC QD. • To compare fasting lipid profiles in subjects receiving FPV/rtv 1400mg/100mg QD compared to FPV/rtv 700mg/100mg BID, both administered with ABC/3TC FDC QD. • To compare virologic and immunologic responses in subjects receiving FPV/rtv 1400mg/100mg QD compared to fosamprenavir/ritonavir 700mg/100mg BID, both administered with ABC/3TC FDC QD. • To compare safety and tolerability in subjects receiving FPV/rtv 1400mg/100mg QD compared to FPV/rtv 700mg/100mg BID, both administered with ABC/3TC FDC QD. • To evaluate viral genotypic and phenotypic resistance patterns in subjects experiencing virologic failure • To characterize steady-state plasma amprenavir and ritonavir trough concentrations in subjects receiving FPV/rtv 1400mg/100mg QD or FPV/rtv 700/100mg BID |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject is ≥18 years of age 2. Subject is antiretroviral-naïve (defined as having ≤14 days of prior therapy with any antiretroviral agent). 3. Subject has plasma HIV-1 RNA ≥1,000 copies/mL at screening. 4. Subject is willing and able to understand and provide written informed consent prior to participation in this study. 5. A female is eligible to enter and participate in the study if she is of: a. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal); or, b. Child-bearing potential, has a negative pregnancy test (serum β-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). 6. 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. |
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E.4 | Principal exclusion criteria |
1. 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. 2. Subject is enrolled in one or more investigational drug protocols, which may impact HIV RNA suppression. 3. Subject is either pregnant or breastfeeding. 4. 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. 5. Alanine aminotransferase (ALT) >5 times the upper limit of normal (ULN) or hepatic impairment as determined by Child-Pugh Score ≥ 5. 6. 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. 7. 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects with HIV-1 RNA <400c/mL over 48 weeks by ITT-E, TLOVR analysis |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 88 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of the last subject |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |