E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
UK-427,857 is an antagonist of the human chemokine receptor, and is intended to help prevent the development and progression of AIDS in individuals HIV-1 positive. |
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MedDRA Classification |
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 confirm that the hypothesis that UK-427,857 added to Optimised Background Therapy (OBT) provides an additional reduction in plasma HIV-1 RNA compared to OBT alone, as measured by the difference between each of the two UK-427,857 regimens versus the placebo regimen in the mean changes from baseline in plasma HIV-1 RNA at week 24. |
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E.2.2 | Secondary objectives of the trial |
To assess whether UK-427,857 added to OBT provides an additional reduction in plasma HIV-1 RNA compared to OBT alone, as measured by the difference between each of the 2 UK-427,857 regimens versus placebo regimen in the mean changes from baseline in plasma HIV-1 RNA at week 48. To compare at week 24 and 48, in the 2 UK-427,857 regimens versus placebo regimen: - the percentage of subjects with HIV-1 RNA less than 400 and 50 copies/mL . - the percentage of subjects who achieve a 0.5 log10 and 1.0 log10 reduction in HIV-1 RNA. - the differences in the magnitude of changes in CD4 and CD8. - the time-averaged difference in log10 HIV RNA. To compare at week 48 the time-to-loss of virologic response. To assess the association between baseline resistance and virologic response. To compare safety and tolerability of UK-427,857 when added to OBT versus OBT alone. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
HIV-1 RNA superior to or equal to 5000 copies/mL measured by Roche Amplicor HIV-1 monitor at screening visit. CCR5-tropic HIV-1 by PhenoSense entry Assay. Stable pre-study antiretroviral regimen, or on no antiretroviral agents, for at least 4 weeks. Treatment experience criteria as defined in the protocol. A negative urine pregnancy test at the baseline visit prior to receiving the first dose of study medication for women child bearing protential. |
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E.4 | Principal exclusion criteria |
Patient requiring treatment with more than 6 antiretroviral agents (excluded low dose ritonavir). Prior treatment with UK-427,857 or another experimental HIV entry inhibitor for more than 14 days. Suspected or documented active, untreated HIV-1related opportunistic infection (OI) or other conditions requiring acute therapy (eg Hepatitis C virus infection) at the time of randomisation. R5 virus phenotype only, as determined by PhenoSense viral entry assay. Renal insufficiency, increased bilirubin/AST/ALT, cytopenia. High risk for CAD/CVD. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline to 24 weeks in HIV-1 RNA measured on a logarithmic (based 10) scale. |
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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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |