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 indivuduals 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 assess whether the antiviral activity (ie, fewer than 400/50 HIV-1 RNA copies per mL of plasma at week 48), of each of the 2 doses of UK-427,857 in combination with ziduvudine/lamivudine is non-inferior to a reference regimen of efavirenz plus zidovudine in antiretroviral-naïve, CCR5-tropic HIV-1 infected subjects. |
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E.2.2 | Secondary objectives of the trial |
To assess whether the antiviral activity (fewer of 400/50 HIV-1 RNA copies/mL of plasma at week 24 and 96) in each of the 2 doses of UK427,857 in combination with zidovudine/lamivudine is non-inferior to a reference regimen of efavirenz plus zidovudine/lamivudine in antiretroviral-naïve, CCR5-tropic HIV-1 infected subjects. To compare the time to loss of virological response through week 48 and 96. To compare the reduction of plasma log10 HIV-1 RNA form baseline through weeks 24, 48 and 96. To compare the differences in the magnitude of changes in the CD4 and CD8 cell counts from baseline through week 24, 48 and 96. To compare the Time Average Difference in log10 HIV-1 RNA at week 24, 48 and 96. To assess HIV-1 genotype, phenotype and tropism at baseline and at the time of failure, and the association between baseline resistance and virological response. To assess the safety and the tolerability of the 2 UK-427,857 regimens versus placebo regimen. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Men or women at least 18 years of age available of a follow up of at least 48 weeks. HIV-1 RNA viral load equal to or more than 2,000 copies of HIV-1 RNA per mL measured by Roche Amplicor HIV-1 Monitor at the screening visit. A negative urine pregnancy test at the baseline visit, prior to receiving the first dose of study medication for women of child bearing potential.
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E.4 | Principal exclusion criteria |
Suspected or document active, untreated HIV-1 related opportunistic infection (OI) or other condition requiring acute therapy (eg, hepatitis C virus infection) at the time of randomisation. Treatment for an active opportunistic infection or unexplained temperature superior to 38.5°C for 7 consecutive days, within 30 days prior to randomisation. HIV resistant to efavirenz, zidovudine or lamivudine. Prior treatment with any antiretroviral therapy for more than 14 days. Contraindicated medications being taken by the subject at the time of randomisation that must be continued during the study period, including immunomodulators (for the treatment of HIV-1 infection; interferon for the ongoing treatment of Hepatitis C infection is permitted), ketoconazole, itraconazole, miconazole, clotrimazole, troleandomycin, nefazadone, clarithromycin, rifampin and rifabutin. X4- or dual/mixed- topic virus detected by the PhenoSense viral entry assay or repeated assay failure. Primary HIV-1 infection. Renal insufficiency, increased bilirubin/AST/ALT, cytopenia. High risk of CAD/CVD. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The percentage of patients with fewer than 400 copies and the percentage of patients with fewer than 50 copies of HIV-1 RNA per milliter of plasma at 48 weeks. |
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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 | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
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 | 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) | Yes |
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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The end of the clinical trial is defined by the last patient, the last visit. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |