A multicentre, randomised, double-blind, placebo-controlled trial of a novel CCR5 antagonist, UK-427,857 in combination with optimised background therapy versus optimised background therapy alone for the treatment of antiretroviral-experienced HIV-1 infected subjects

INTERVENTION: Product Name: UK‐427,857 Product Code: UK‐427,857 Pharmaceutical Form: Coated tablet INN or Proposed INN: Maraviroc CAS Number: 376348‐65‐1 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 150‐ Pharmaceutical form of the placebo: Coated tablet Route of administration of the placebo: Oral use CONDITION: 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. PRIMARY OUTCOME: Main Objective: To confirm the hypothesis that UK‐247,857 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 48. An interim analysis will be performed at week 24. Primary end point(s): Change from baseline to 48 weeks in HIV‐1 RNA measured on a logarithmic (base 10) scale.; An interim analysis will be performed at week 24. Secondary Objective: To compare the percentage of subjects with HIV‐RNA less than 400 copies/mL and 5O copies/mL at week 24 and 48.; To compare the percentage of subjects who achieve at least a 0.5 log10 and 1log10 reduction in HIV‐RNA from baseline at week 24 and 48.; To compare the time to loss of virological response through week 48.; To compare the differences in the magnitude of changes in the CD4 and CD8 cell counts from baseline through week 24 and 48.; To compare the Time Average Difference in log10 HIV‐1 RNA at week 24 and 48.; 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. INCLUSION CRITERIA: HIV‐1 RNA superior to or equal to 5000 copies/mL measured by Roche Amplicor HIV‐1 monitor at screening visit. Stable pre‐study antiretroviral regimen, or on no antiretroviral agents, for at least 4 weeks. Documented genotypic or phenotypic resistance to two fo 4 antiretroviral drug classes. A negative urine pregnancy test at the baseline visit prior to receiving the first dose of study medication for women child bearing protential. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range