Proof-of-principle studies

Similarly, the number and types of tests completed will influence the cost in ways that can be very complex. Recently, the author was involved in designing a proof-of-principle study intended to assess the ability of a dietary supplement to enhance weight loss among subjects instructed to follow a reduced energy diet. Sample size calculations were run for two scenarios, the first using change in body weight as the primary outcome variable, the... 

Liu, J. Li, Q. Yang, X. van Breemen, R. B. Bolton, J. L. Thatcher, G. R. Analysis of protein covalent modification by xenobiotics using a covert oxidatively activated tag raloxifene proof-of-principle study. Chem. Res. Toxicol. 2005, 18, 1485-1496. 

Bettuzzi S, Brausi M, Rizzi F, Castagnetti G, Peracchia G and Corti A. 2006. Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia a preliminary report from a one-year proof-of-principle study. Cancer Res 66(2) 1234—1240. 

In 2000 the Miller group provided a proof-of-principle study of Pd pi-allyl chemistry for library selection in the presence of a biomolecule [44]. In this approach, Pd(0) chemistry was employed to generate a library of cyclopentene-1,4-diesters in halogenated solvent (Fig. 1.10). This was allowed to equilibrate across a dialysis membrane with an enzyme target (pepsin) in buffered aqueous solution. LC-MS analysis of the library allowed identification of compound 24 as a library member amplified in the presence... 

Willis, C. M., Church, S. M., Guest, C. M., etal. (2004). Olfactory detection of human bladder cancer by dogs proof of principle study. British Medical Journal 329,712. 

Of particular interest is a proof of principle study showing that cardiac-specific overexpression of the A3 receptor can protect the murine myocardium against ischemia/reperfusion (Cross et al. 2002 Black et al. 2002). Although some raised the question that the widely used prototypical agonist Cl-IBMECA (2-chloro-iV6-(3-iodobenzyl)adenosine-5 -/V-methyluronamide) may not be selective at the adenosine A3 receptor in intact heart, Cl-IBMECA could not exert a cardio-protective effect in A3R-knockout mice, pointing to an essential role of the A3 receptor in... 

Initial proof of principle studies of ocular carotenoid RRS employed a laboratory-grade high-resolution Raman spectrometer and flat-mounted human cadaver retinas and eyecups. In Fig. 12.10, typical Raman spectra are shown for an excised eyecup, in which the excitation laser was aimed at the center of the macula, the fovea, and at two locations with increased eccentricities. In all cases, RRS spectra are obtained that display the... 

Another interesting application motivated by medicine is the use of the three-spin effect to determine lithium concentration solely through 1H DNP measurements. In a proof of principle study by Zeghib et al., an increased concentration of 7LiOH in aqueous solution with trityl radicals resulted in a decreased H DNP enhancement at 6.8 mT due to a competing three-spin effect.96 This was proposed to allow lithium monitoring... 

The first tolerability studies in early clinical development always provide pharmacokinetic (PK) data over a considerable dose range. Especially the explorative first-in-man study with escalating single doses, or an explorative proof of principle study with escalating multiple doses provides a valuable basis for an exploratory assessment of dose linearity/ proportionality of drugs in humans. In addition such an assessment can directly help within the same study to optimize the dose selection and dose progression. Already in this early phase of the development, these data are going to support exposure-response relationships, and thus a potential submission (US FDA 2003, ICH E4 1994). 

The first tolerability studies early in a clinical development always provide pharmacokinetic (PK) data over a range of doses, mostly with a single-dose approach. In situations where an explorative proof of principle study... 

PURPOSE AND RATIONALE In early clinical development the steps before entering into larger patient studies are typically an explorative first-in-man study with escalating single doses in healthy volunteers, an explorative proof-of-principle study with escalating multiple doses in healthy volunteers, and then a proof-of-concept with escalating... 

Koutsky LA, Ault KA, Wheeler CM, Brown DR, Barr E, Alvarez FB, Chiacchierini LM, Jansen KU Proof of Principle Study Investigators. A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med 2002 347(21) 1645-51. 

Targeting lAPs in Cancer—Proof of Principle Studies... 

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