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Review of the Fialuridine (FIAU) Clinical Trials (1995) / Chapter Skim
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Appendix F: FIAC and FIAU Preclinical Toxicity Studies
Pages 246-250

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From page 246...
... Decreased food intake, weight loss, intestinal changes and hematopoietic depression were noted at 48 mg/kg/day. Mutagenicity Studies FIAC is reported to be devoid of mutagenic activity in an Ames test study.
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From page 247...
... A 1-month subchronic study was performed in cynomolgus monkeys, where 3 or 4 animals per dose level, treated orally twice daily, received 5, 20, or 80 mg/kg/day. Three of four SO-mg/kg/day animals were moribund and sacrificed on days 23, 25, and 27; clinical signs of toxicity included weight loss, diarrhea, hypoactivity, and hypothermia.
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From page 248...
... Drug-related histological changes were observed mostly in the high-dose and some of the intermediate-dose groups; these included hematopoietic changes, vacuolation and presence of pigment in hepatocytes, renal cortical tubular dilatation, cytostatic enteropathy of the large intestine and acinar cell atrophy in the salivary gland, giant cell formations in the testes, and myocardial degeneration. All, except the heart, were considered reversible.
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From page 249...
... At the two higher dosages, depression of food consumption and body weight gain were observed, but no apparent adverse effects on sperm production, sperm quality, mating performance, or fertility occurred in this study. The potential to produce developmental toxicity was evaluated in rabbits at dosages of 2, 10, or 50 mg/kg/day on gestation days 6-~.
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From page 250...
... Furthermore, dose-dependent relationships were generally clear, and the toxic effects usually occurred at dosages near the maximum tolerated range in each species. There was nothing in the preclinical toxicity studies that was suggestive of the tragic episode that transpired in the PPPC clinical trial.
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Key Terms

  • body weight
  • toxicity studies
  • preclinical toxicity
  • cynomolgus monkeys
  • urea nitrogen

  • clinical trial
  • aminotransferase activity
  • male mice
  • lethal dose
  • toxic effects

  • recovery period
  • dose level
  • nitrogen concentration
  • weight gain
  • multiple dose

  • pppc clinical
  • hematopoietic tissues
  • male rats
  • clinical signs
  • food consumption

  • weight loss
  • weight losses
  • myocardial degeneration
  • monkeys treated
  • mutagenicity studies

  • female mice
  • dose studies
  • studies performed
  • bone marrow
  • various clinical


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