Clinical trials INDEX

Probably the most widely adopted and well-known method for estimating the likelihood of a compound (drug) being well absorbed is the rule-of-5 described by Lipinski and co-workers [1]. In analyzing 2245 compounds from the World Drug Index (WDI) database that were either considered for, or entered into, Phase II clinical trials, these authors developed the following rules ... 

The precursor of EpoB, dEpoB, in which the 12,13-oxido linkage is lacking, also acts on microtubule assembly with a better therapeutic index than EpoB. dEpoB is currently in Phase II clinical trials. Bioassays were performed on E)-9,... 

This was a multi-centre, pan-European, randomised double-blind placebo-controlled clinical trial in acute stroke to evaluate the effect of ancrod, a natural defribrinogenating agent (Hennerici et al. (2006)). The primary endpoint was based on the Barthel Index a favourable score of 95 or 100 or a return to the pre-stroke level at three months was viewed as a success. The primary method of statistical analysis was based on a logistic model including terms for treatment, age category, baseline Scandinavian Stroke Scale and centre. 

As mentioned earlier, the clinical trials with TCAs in children and adolescents with MDD have generally been disappointing ( 120, 122,123). In addition, these medications have a less favorable adverse effect profile and thus higher patient attrition rates during the acute treatment phase compared with newer antidepressants. They also have a lower therapeutic index (i.e., difference between therapeutic and toxic dose see Chapter 7). 

The search continues for a general tumor-scanning agent. Although several radionuclides have been found to localize tumors of widely different types and regions of the body, current interest is in the use of 67 Ga-citrate, which is undergoing a wide clinical trial and may prove to be useful in the localization of lymphomas as well as some adenocarcinomas. Medical imaging techniques arc discussed in several articles of this encyclopedia. Consult alphabetical index. 

In human studies, flaxseed consumption has had positive impacts on carcinogenesis and parallel observations from animal studies. A doubleblind, placebo-controlled, prospective clinical trial involving 39 women, newly diagnosed with breast tumors, was completed to evaluate the effect of flaxseed consumption on tumor growth (Thompson et al., 2000). Subjects given flaxseed (25 g/day) diets had reduced tumor cell proliferation and c-erB-2 expression, and an increased apoptosis index compared with women who ate whole-wheat muffins. 

The success of the studies on experimental tumors and of the clinical trials prompted the synthesis of a wide range of Melphalan-related compounds such as the ortho isomer [12—15], the meta isomer [16—20], 3-alanine analogs [19], esters, N-acyl derivatives, and peptides. Despite controversial reports of greater activity or better therapeutical index, none of these analogs replaced Melphalan in clinical use. 

Based upon these observations and following Phase I safety studies, a Phase II randomized, double-blind, controlled clinical trial was undertaken to treat active ulcerative colitis with escalating doses of ISIS 2302. Based on an intent-to-treat analysis, 59% (13/22) of patients treated daily with 240 mg ISIS 2302 enema over six weeks achieved a positive response, as measured by Disease Activity Index (DAI)... 

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