The Safety and Effectiveness of PMPA Prodrug in HIV-Infected Patients

To evaluate the safety of single and multiple doses (28 daily doses) of 9-\[2-(R)-\[\[bis\[\[(isopropoxycarbonyl)- oxy\]methoxy\]phosphinoyl\]methoxy\]propyl\]adenine fumarate (PMPA) prodrug administered orally to HIV-infected patients. To determine the pharmacokinetics of single and multiple doses of PMPA prodrug when administered orally to HIV-infected patients. To evaluate the anti-HIV activity of PMPA prodrug, as demonstrated by increases in CD4 cell counts and decreases in HIV RNA, when administered orally as a single dose and daily for 4 weeks to HIV-infected patients with CD4 cell counts of 200 or more cells/mm3.

In this double-blind, placebo-controlled study, a total of 60 patients are randomized to receive PMPA prodrug at 1 of 5 doses or matching placebo tablets. Part A (Days 1-7): Patients receive a single dose of PMPA prodrug or matching placebo tablets administered orally followed by a 1-week observation period. Patients who complete Part A without a dose-limiting toxicity begin Part B. Part B (Days 8-35): Patients receive either PMPA prodrug or matching placebo tablets administered orally qd for 4 weeks at the same dosage level administered in Part A.