This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.ABSTRACT There is an acute medical need for novel and potent antiretroviral therapy for HIV-infected patients who are experiencing resistance, suffer from toxicities on other possible regimens, or are failing their current antiretroviral regimen. These patients are often heavily pre-treated and have very limited or no remaining therapeutic options. The purpose of this pediatric study is to gain dosage, short and long term safety data, intensive and population PK data, drug interactions, and efficacy experience with raltegravir in HIV-1 infected children with which to guide potential usage in children ages two through adolescence. IMPAACT P1066 is a Phase I/II, multi-center, open-label, noncomparative study of approximately 120 to 140 HIV-1 infected children and adolescents ages =2 years to less than 19 years of age to evaluate the safety, tolerability, pharmacokinetic parameters and efficacy of raltegravir. The primary objectives are: In Stage I, to evaluate the short term safety and tolerability of raltegravir added to an initial stable background therapy which will then be optimized in children and adolescents in the age groups of =2 to less than 6, =6 to less than 12 and =12 to less than 19 years; In Stage I, to evaluate the steady state plasma concentration profiles and pharmacokinetic parameters of raltegravir added to stable background therapy* in children and adolescents in the age groups of =2 to less than 6, =6 to less than 12 and =12 to less than 19 years; and In chronic dosing, to evaluate the safety and tolerability of raltegravir at the selected dose in combination with optimized background therapy (OBT) in children and adolescents in the age groups =2 to less than 6, =6 to less than 12 and =12 to less than 19 years, as assessed by review of the accumulated safety data over 24 weeks. I. HYPOTHESIS Dosage data, short and long term safety data, intensive and population PK data, drug interactions, and efficacy experience of Raltegravir (MK-0518) will help guide potential usage in HIV infected children ages two through adolescence. II.
SPECIFIC AIMS Primary 1. In Stage I, to evaluate the short term safety and tolerability of raltegravir added to an initial stable background therapy* which will then be optimized in children and adolescents in the age groups of =2 to <6, =6 to less than 12 and =12 to less than 19 years. 2. In Stage I, to evaluate the steady state plasma concentration profiles and pharmacokinetic parameters of raltegravir added to stable background therapy* in children and adolescents in the age groups =2 to less than 6, =6 to less than 12 and =12 to less than 19 years.3. In chronic dosing, to evaluate the safety and tolerability of raltegravir at the selected dose in combination with optimized background therapy (OBT) in children and adolescents in the age groups =2 to less than 6, =6 to less than 12 and =12 to less than 19 years, as assessed by review of the accumulated safety data over 24 weeks. * Stable background therapy defined as unchanged therapeutic regimen for at least 12 weeks, or treatment experienced (not including therapy to interrupt maternal-infant transmission) but on no treatment for =4 weeks. See section 4.13. Secondary 1. In chronic dosing, to evaluate the safety and tolerability of raltegravir at the selected dose in combination with optimized background therapy (OBT) in study subjects, as assessed by review of the accumulated safety data over 48 weeks. 2. To evaluate the antiretroviral activity of raltegravir at study weeks 24 and 48 at the selected dose in combination with OBT in study subjects, as measured by the proportion of subjects achieving HIV RNA below 400 copies/mL, or maintaining a 1-log drop in HIV RNA from baseline.3. To evaluate the immunological activity of raltegravir at the selected dose in combination with OBT in study subjects, as measured by changes in CD4 cell count and changes in CD4 % over 24 and 48 weeks. 4. To describe pediatric raltegravir exposure over time, using a population pharmacoknetic modeling approach
Showing the most recent 10 out of 459 publications
