Phase II clinical testing

KC706 stabilizes the inactive conformation of the mitogen-activated protein kinase p38a, a protein kinase involved in inflammatory reactions and cardiovascular functions. KC706 therefore holds the potential to treat conditions such as rheumatoid arthritis, psoriasis, inflammatory bowel disease and cardiovascular disease. This compound is currently being tested in phase II clinical trials with patients suffering from rheumatoid arthritis. 

The definitive identifieation of a therapeutie raison d etre for H3 antagonists will happen in the elinie. A handful of H3 ligands are reported to have entered elinieal testing. ABT-834 entered Phase-I trials for the indieation of cognitive disorders in May 2003 but no news has been reported since that time. GT-2331 (11) was approved for Phase-II clinical trials in 1999 but no news has been reported since then [4]. At this point, there are no data available to assess the therapeutic potential in human disease (See Table 5.1). 

Several diverse, potent, and selective GlyT-1 inhibitors have appeared in the literature and many are reported to be efficacious in animal psychosis models. Several of these have advanced into Phase I and Phase II clinical studies. Recent Phase II results from a double-blind, 320-patient study with the investigational GlyT-1 inhibitor RG1678 (33) [17] demonstrated that the compound improved negative symptoms and social functioning of stable patients currently on atypical antipsychotic therapy and was well tolerated at all doses tested [18]. 

Alzheimer s Disease The vaccine being tested contains a small protein called jS-amyloid (AjS). This protein forms abnormal deposits, or plaques, in the brains of people with Alzheimer s disease. Researchers believe that Kji deposition causes loss of mental function by killing the brain neurons. The strategy of Aji vaccination is to stimulate the immune system to clean up plaques and prevent further A deposits. Although preclinical and Phase I studies showed the potential of the vaccine, the Phase II clinical trial was halted because 15 of 360 patients developed severe brain inflammation. Further studies showed that the A did generate the desired... 

PVC s alone with Class IC drugs was not sufficient to reduce mortality in the specific post-infarction population chosen for the CAST study. The failure of Class IC agents in the CAST study and their low efficacy in preventing induction of SVT during electrophysiological testing has increased the interest in alternative approaches to antiarrhythmic therapy, particularly towards Class III agents, a number of which are in Phase II clinical evaluation. 

The phase I clinical testing of enalapril began in 1980 in a study in which its efficacy to inhibit intravenously administered angiotensin I was determined. Oral doses as low as 2.5 mg produced a substantial decrease in ACE, activity and lowering was evident even 21-24 hours after the drug was given (129). Phase II and phase III trials began in 1981, and the first approval to use enalapril in hypertension came in 1984 and in heart failure in 1986. 

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