776C85 is a potent inactivator of dihydropyrimidine dehydrogenase (DPD), the first enzyme in the degradative pathway of 5-fluorouracil (5-FU). In preclinical studies, doses of 776C85 sufficient to inactivate greater than 99 percent of endogenous DPD were non-toxic and exhibited no antiproliferative activity. Pretreatment with 776C85 significantly increased the bioavailability and reduced the pharmacokinetic variability of oral 5-FU in animal models. 776C85 also increased the antitumor efficacy of 5-FU and increased the therapeutic index of 5-FU by up to six-fold in three rodent tumor models. Based on these data and on promising preliminary results from phase I trials, it is hypothesized that combination 776C85 and 5-FU may be effective therapy. The combination of 776C85 and 5-FU tablets is also desirable for patients' safety and compliance. 776C85 has been shown to significantly increase the bioavailability and reduce the pharmacokinetic variability of oral 5-FU. 776C85 has also been shown to increase the antitumor efficacy of 5-FU. Based on recent preliminary data, it is hypothesized that the combination of 5-FU and 776C85 may be effective therapy. The combination of 776C85 and 5-FU tablets is desirable for patients safety and compliance. This study will determine the bioequivalence of a 776C85/5-FU combination tablet to the individual 776C85 and 5-FU tablets. The primary objective of this study is to determine the bioequivalence of each strength of the combination 776C85/5-FU tablet to the separate 776C85 and 5-FU tablets used in Phase II and III clinical trials.
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