tmc125-tidp2-c238: an exploratory pharmacokinetics, safety and anti-hiv activity study of etravirine (etr) when given with boosted atazanavir (atv/rtv) at two different doses and 1 nucleoside reverse transcriptase inhibitor (nrti) in treatment experienced hiv patients

Conditions: HIV Infections; Acquired Immunodeficiency Syndrome

Summary: the purpose of this study is to determine the pharmacokinetics (how the body absorbs, distributes, metabolizes and eliminates a drug) (pk) of etr when given with atv/rtv and 1 nrti in treatment experienced hiv-1 infected patients. in addition, safety, tolerability and anti-hiv effect of this regimen will also be studied. a total of 46 patients will be enrolled.

this is a randomized (study drug assigned by chance), exploratory, open-label (all involved people know the identity of the intervention) trial to evaluate the pharmacokinetics (pk), safety, tolerability and anti-hiv (anti human immunodeficiency virus) activity of etravirine (etr ) when given with atazanavir/ritonavir (atv/rtv) and 1 nucleoside reverse transcriptase inhibitor (nrti) in 46 treatment experienced hiv-1 infected patients. the trial will consist of : 4 weeks of screening period, 2 weeks pre-treatment phase, 48-week treatment period, and a final visit followed by a 4-week follow-up period (only for patients not continuing treatment with etr in another trial or program). safety evaluations (ae reporting, labs, vital signs, etc.) will be monitored at each study visit. a pk substudy (included in the protocol, with optional participation) with tenofovir (tdf) added to the antiretroviral regimen for 7 days will be conducted in patients with \> 24 weeks of treatment with suppressed hiv-1 viral load. in pre-treatment phase, all patients will receive atv/rtv 300/100 mg once daily to be taken following a meal each morning + 2 nrtis (dose as specified in the labels) for 14 days. in treatment phase, patients will receive etr 200 mg twice daily in addition to atv/rtv (300/100 mg or 400/100 mg) once daily with meals + 1 investigator-selected nrti for 48 weeks. in substudy tdf 300 mg once daily will be added to the treatment regimen x 7 days.

Eligibility criteria:
inclusion criteria: - documented hiv-1 infection * failing on a stable art (anti retroviral therapy) with hiv-1 plasma viral load above 500 hiv-1 rna copies/ml * presence of at least 1 documented nnrti mutation * demonstrated sensitivity to atv, etr and at least one of the selected nrtis based on the resistance test at screening * general medical condition, in the investigator's opinion, does not interfere with the assessments and completion of the trial * substudy: patients who have been treated in c238 for more than 24 weeks and are currently suppressed (defined as patients with at least 2 most recent and consecutive viral loads less than 50 cp/ml) will be considered eligible for the substudy exclusion criteria: * primary hiv-1 infection * previously documented hiv-2 infection * previously failed 2 or more hiv pi-containing regimens * previous diagnosis of hereditary hyperbilirubinemia (eg. gilbert's syndrome, crigler-najjar syndrome). grade 3 or 4 toxicities (according to daids grading) * acute and chronic viral hepatitis * receipt of an investigational drug or investigational vaccine within 30 days prior to the trial drug administration * pregnant or breastfeeding female

Keywords: hiv infections acquired immunodeficiency syndrome tmc125-tidp2-c238 tmc125-c238 etravirine intelence hiv hiv-1 pharmacokinetics