The study known as VS411-C201 is a five-arm, dose-ranging, proof of principle study. Investigators in four countries, Italy, Russia, Uganda, and Argentina, will enroll 60 patients into five randomized blinded arms containing varying dosages of enterically-coated didanosine and hydroxyurea, the two components of VS411.
VS411 has been designed to yield lower peak plasma concentrations of didanosine with improved dosing flexibility to investigate lower doses of hydroxyurea to further reduce toxicity and enhance efficacy. The VS411-C201 study will investigate hydroxyurea doses between 300mg and 900mg/day in combination with 200 mg or 400 mgs of enterically-coated didanosine administered over a four-week period using traditional measures of efficacy, pharmacokinetic parameters, safety, and tolerability.
In addition, two non-traditional tests will be also used to further differentiate between the five arms. Intense intracellular pharmacokinetics will be performed to investigate the interaction between low dose hydroxyurea and the conversion of didanosine to its active form, dideoxyadenosine triphosphate, within CD4 cells and novel immunological tests will study the conservation of immune system cells with high proliferative capacity.