Inside Clinical Trial

Inside Clinical Trials Testing Medical Products in People... 

IFN-y may also prove valuable in treating a variety of other conditions, and clinical trials for various indications are currently underway. This cytokine shows promise in treating leishmaniasis, a disease common in tropical and subtropical regions. The causative agent is a parasitic protozoan of the genus Leishmania. The disease is characterized by the presence of these protozoa inside certain immune cells, particularly macrophages. IFN-y appears to stimulate the infected macrophage to produce nitric oxide, which is toxic for the parasite. 

Doxil , of which I had the pleasure of being one of the inventors (1-12), serves as an example of successful passive targeting to tumors in animals and humans (1,3,4,13). The ammonium sulfate (AS) transmembrane inside high/outside low gradient-driven loading is also the basis for doxorubicin (DOX) loading for Targeted Doxil (14), which soon will be tested in clinical trials. 

Similarly, synthetic modification of castanospermine showed that the lipophilic 6-0-acyl derivatives were more potent inhibitors of HIV than the natural product. In particular, the 6-0-butanoyl derivative (MDL 28,574) was approximately twenty times more active than castanospermine and fifty times more active than A-butyl-DNJ. However, once inside cells, 6-0-butanoylcastanospermine appeared to be hydrolysed to release castanospermine and hence this compound can also be considered to be a pro-dmg. " Recently, this compound was reported to be tolerated well by patients during a phase II clinical trial. ° Studies in vitro have shown synergistic activity against HIV type 1 and 2 replication when castanospermine (and its 6-C>-butanoyI derivative) are combined with AZT and other similar dideoxynucleoside drags. ... 

Basically, it is aU abont balance between risk and certainty. If 11 of the 12 compounds that enter clinical trials are going to fail, it makes sense to find ways to reduce this attrition rate. This message in-honse is no longer new, and more and more outside companies are developing commercial tools to make better predictions for compounds based on the ADMET parameters. The mood inside pharmaceutical companies is serious in taking a close look at compounds in the library that could not be considered druglike and removing them from the file. 

Adenosine deaminase (ADA) deficiency is a very rare autosomal recessive disease and is responsible for 20-30% of recessively inherited cases of SCID. It causes ATP and dATP to accumulate, which feed-back to inhibit ribonucleotide reductase in thymocytes and peripheral blood B-ceUs. This in turn restricts the formation of DNA and hence the production of T- and B-ceUs (SCID). Infants are extremely vulnerable to infection as exempUfled by the case in the 1970s of David Vetter who spent his entire life of 12 years protected inside a plastic bubble and is immortalised in the film The Boy in the Plastic Bubble. Clinical trials of gene therapy for ADA-SCID are encouraging. 

Biomedical research and, in particular, clinical trials are very complex and well regulated. Administrative procedures have two objectives to provide help in obtaining correct and unambiguous results, and to prove that experiments were performed as described, according to high scientific and ethical standards, and therefore to increase confidence in the conclusions obtained. Administrative procedures also involve various controls (inside and outside the institute performing the study). 

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