Clinical oedema phase

Diller describes three main phases associated with phosgene induced lung injury as the initial reflex syndrome, the clinical latent phase and the clinical oedema phase. ... 

Ruboxistaurin (LY333531) 41 (Eli Lilly) is being evaluated in a Phase III trial for the treatment of diabetic macular oedema.224 Lilly had submitted an NDA in February 2006 to the FDA for the treatment of diabetic retinopathy and received an Approvable Letter in September 2006 that requested another Phase III trial for additional efficacy data. The EMEA also required further clinical data and, as a consequence, Lilly withdrew its European MAA. Ruboxistaurin 41225 228 competitively inhibits adenosine triphosphate (ATP) binding to PKC/i and is a synthetic analogue of staurosporine 42. 

Since recombinant human IL-12 had no biological activity in the mouse, the homologous recombinant murine IL-12 had to be employed for efficacy and toxicity studies in mice. Safety studies in rodents and non-human primates with IL-12 demonstrated a small therapeutic window with hepato- and splenomegaly, myelodepression, and lung oedema (Ryffel, 1997). Phase I clinical trials confirmed the toxic potential of IL-12 (Hall, 1995). The toxicity observed was non-specific. In view of the preclinical results, the adverse effects were not a surprise (Lotze and Gately, 1996). 

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