Phase lib studies

In 2008, a Phase lib study of bevirimat in patients failing HIV therapy due to drug resistance was completed successfully. The results of this study demonstrated that patients who have virus with the most commonly occurring amino acids at positions 369, 370, or 371 on Gag are much more likely to respond to bevirimat treatment. In contrast, those patients whose virus has polymorphisms (variants) at these positions are less likely to respond to the drug. Furthermore, pharmacokinetic/pharmacodynamic modelling demonstrated that a trough plasma concentration of greater than 20 pg/mL bevirimat is required for a robust response. 

In the Phase lib study, the mean viral load reduction was —1.18 log10 copies/ mL after 14 days of bevirimat treatment in the patients who were free of key baseline Gag polymorphisms and who had bevirimat trough levels above the... 

Phase II investigates the compound s efficacy and safety in controlled clinical trials for a specific therapeutic indication. To eliminate as many competing factors as possible, Phase II trials are narrowly controlled. They are characterized as small—several hundred subjects with the indicated disease or symptoms—and are closely monitored. The control may be either a placebo study arm or an active control arm. The endpoint measured may be the clinical outcome of interest or a surrogate. Phase II trials may last for several months or even several years. Early pilot trials to evaluate safety and efficacy are called Phase Ila. Later trials, called Phase lib, are important tests of the compound s efficacy. These trials may constitute the pivotal trials used to establish the drug s safety and efficacy. At least one pivotal trial (most frequently a large, randomized Phase III study) is done. Only about one third of compounds entered into Phase II will begin Phase III studies [61],... 

Proof-of-efficacy trials these studies should provide, within a limited time frame and with a low-cost program, sufficient information for a go/no-go decision concerning efficacy and safety aspects of a new compound. The traditional approaches are Phase lib trials based on placebo-controlled dose-finding designs. These studies need relatively high power, which means the inclusion of several dozen to several hundred patients. 

Phase lib, typically studied in several hundred patients, establishes the dose range of the compound and may validate end point measures to be studied in later stages. Although these investigations usually last weeks to months, they can have durations of several years, particularly when the disease in question is chronic, as with osteoporosis. 

Other phase designations have also become employed in various areas, including Phase Ila, Phase lib, and Phase Illb (see Buncher and Tsay, 2006a). However, these designations are not used consistently. Therefore, two studies with the same aims may be classified into different phases, and two studies classified into the same phase may have different aims. This nomenclature, therefore, can be confusing. An alternative system has been suggested by the ICH. 

FQ (in phase lib of clinical trials) represents the first organometallic antimalarial currently in the pipe-line of promising drugs. Moreover, the pursuit of studies regarding the mechanism of action of FQ and the possible mechanisms of resistance appears promising not only for chemotherapy of malaria, but also as the basis for new concept in drug design. 

Figure 9-6 A generic strategy integrating the three facets of developmental toxicity risk assessment namely (a) the risk of pharmacologic modulation of the therapeutic target during gestation, (b) in silico, SAR and (c) in vitro screening. Abbreviations The chick embryo neural retina (CENR) embryonic stem cell test (EST), whole embryo culture (WEC), Good Laboratory Practice (GLP), Embryo/Fetal Developmental Toxicity (EFD) study. "Front-loading" is the conduct of the EFD study prior to Phase lib.

There have been specific interest and debate into the new multicomponent MenB vaccine (4CMenB). Naturally, the vaccine s impact on routine immunisation has been a question of interest. A phase lib, multicenter, open-label, parallel-group, randomised control study cf infants enrolled at age Imonths (n=1885) was randomised into four groups 4CMenB at 2, 4 and... 

Whilst the use of Taddol as an asymmetric phase-transfer catalyst for asymmetric Michael reactions was only moderately successful, it was much more enantioselec-tive in catalyzing alkylation reactions. For this study, Belokon and Kagan employed alanine derivatives lib and 16a-c as substrates, and investigated their alkylation with benzyl bromide under solid-liquid phase-transfer conditions in the presence of 10 mol % of Taddol to form a-methyl phenylalanine, as shown in Scheme 8.8. The best results were obtained using the isopropyl ester of N-benzylidene alanine 16b as substrate and sodium hydroxide as the base. Under these conditions, (R)-a-methyl phenylalanine 17 could be obtained in 81% yield and with 82% ee [19]. Under the same reaction conditions, substrate 16b reacted with allyl bromide to give (R)-Dimethyl allylglycine in 89% yield and with 69% ee, and with (l-naphthyl)methyl chloride to give (R)-a-methyl (l-naphthyl)alanine in 86% yield and with 71% ee [20]. 

Although phase explosion and the factors governing it [17] have not been studied in relation to LIBS, its threshold can be assumed to depend strongly on the laser beam spot size and wavelength. 

Figure 8.51 presents the Raman spectra of several phases important for the cement industry received with excitation by 532 nm, which is the second harmonic of industrial Nd-YAG laser and may be effectively used for simultaneous detection of LIBS and Raman signatures. The major and mostly analyzed mineral phases of cement clinker are alite and belite. Alite is characterized by the strong Raman band peaking at 845 cm range, while belite at 805 cm Tricalcium aluminate and ferrite have also been studied and exhibit the strongest Raman bands peaking at... 

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