PHASE II—ASSESSMENT

Phase II Assess drug s effectiveness in treating a specific disease/disorder Limited number (200-300) patients with target disorder 2 yrs... 

The preclinical trials are performed in in vitro and animal studies to assess the biological activity of the new compound. In phase 1 of the clinical trials the safety of a new drug is examined and the dosage is determined by administering the compound to about 20 to 100 healthy volunteers. The focus in phase II is directed onto the issues of safety, evaluation of efficacy, and investigation of side effects in 100 to 300 patient volimteers. More than 1000 patient volunteers are treated with the new drug in phase 111 to prove its efficacy and safety over long-term use. 

Phase II Mass Balance. (/) Determine raw material iaputs. 2) Record water usage. 3) Assess present practice and procedures. (4) Quantify process outputs. (5) Account for emissions to atmosphere, to wastewater, and to off-site disposal. (6) Assemble iaput and output information. (7) Derive a preliminary mass balance. (8) Evaluate and refine the mass balance. 

Summarize the fmdings and recommendations in a brief pre-assessment report, and present and review this with management. This will reaffirm management s commitment to the next phase. Include in the pre-assessment report a list of actions or steps that the team intends to follow in the next phase. If some of these steps involve field measurements, then highlight these and their possible effects on production schedules and personnel assignments. Use the steps in Phase II as a guide to developing the recommended actions. 

Step 6 Write the Component Material Balances. The Phase II auditing steps define the pollutants and wastes that are among the team s focus. Its objective has always been to identify specific wastes or pollutants that the enterprise can reduce these are the components the team needs to assess in the material balances. It is important to note that once the material balance for each unit operation has been completed for raw-material inputs and waste outputs, it is necessary to repeat the procedure for each contaminant of concern. 

Samples of blood and excreta are taken for laboratory analysis. It is expected that, at the end of this phase, you will have a preliminary estimate of the maximum dose that may be safely tolerated in humans, and also a basic profile of the drug s pharmacokinetic behaviour. Depending on the availability of appropriate analytical indicators, pharmacodynamic and indicative efficacy data may also be generated. The data acquired must be carefully analysed and assessed so that, based on the findings, appropriate Phase II trials can be planned. 

GL38 Ecotoxicity Phase II Environmental Impact Assessment (EIAs) for Veterinary Medicinal Products (VMPs) -Phase II... 

Lalezari JP, DeJesus E, Northfelt DW, Richmond G, Wolfe P, Haubrich R, Henry D, Powderly W, Becker S, Thompson M, Valentine E, Wright D, Carlson M, Riddler S, Haas FF, DeMasi R, Sista PR, Salgo M, Delehanty J (2003a) A controlled Phase II trial assessing three doses of enfuvirtide (T-20) in combination with abacavir, amprenavir, ritonavir and efavirenz in nonnucleoside reverse transcriptase inhibitor-naive HIV-infected adults. Antivir Ther 8 279-287... 

Pollman CD, Porcella DB, Engstrom DR. (In preparation). Assessment of trends in mercury-related data sets and critical assessment of cause and effect for trends in mercury concentrations in Florida biota phase II. 

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). 

If the program continues and additional reductions are desired, more expensive and more complex projects begin to emerge (Phase II). These are often associated with equipment modifications, process modifications and process control and may include the addition or adaptation of auxiliary equipment for simple source treatment, possibly for recycle. This phase usually has little immediate ROI, and more inclusive approaches to assessing the economics of the operation (estimating costs for waste handling, long-term liability, risk) are needed to justify the continued pollution-prevention operation. 

Bolen, M.M., et al., Alternative Cover Assessment Program Phase II Report, Geo Engineering Report 01-10, University of Wisconsin-Madison, Madison, WI, September 2001. 

Researchers focused on the metabolically competent human hepatoma cell line HepG2 as a model of human liver. HepG2 cells are a well-known hepatoma cell line that retains many of the morphological characteristics of liver parenchymal cells. This model is often used as a useful tool for HRA/ERA-oriented chemical risk assessment due to the expression of antioxidant and xenobiotic metabolizing enzymes (in particular phase I and phase II enzymes responsible for the bioactivation/detoxification of various xenobiotics) that can be induced or inhibited by dietary and non-dietary agents [28-30]. 

A Phase II study was recently completed whereby Org-25935 was compared against placebo for the ability to improve negative symptoms in 246 subjects maintained on a stable dose of an atypical antipsychotic (data not disclosed) [46]. A second Phase II study in progress (200 patients) is designed to assess the efficacy of Org-25935 as a stand-alone therapy versus placebo, using olanzapine as the active control [46]. Org-25935 is also being investigated in separate Phase II studies as a treatment for panic disorder and for recidivism in subjects with alcohol dependence [46]. 

The Phase I NRA (Pronk 2008) made an initial assessment of the mineral potential of the area and makes recommendations for the type of survey that should be carried out for further mineral resource assessment (strategy for Phase II). 

Mills, A.J. 2008. Phase II Non-renewable Resource Assessment analysis and... 

Eplivanserin (39) is a 5-HT2A antagonist initially developed for a broader spectrum of psychiatric disorders but that has been tested recently for insomnia. Within this latter indication, phase II studies showed benefits in sleep maintenance, but not in induction [9]. Compound 39 is currently in phase III, to assess the efficacy for the treatment of sleep maintenance insomnia, evaluating both sleep and daytime functioning [96]. 

Inhibitors of MLK (MKKK) [27], MKK4, 7 and JNK [6,28,29] have been disclosed to date. CEP-1347, a semi-synthetic analog of the natural product K252a, inhibits MLKs in the JNK pathway with K = 17 nM [30-32]. This compound has shown neuroprotective effects in cellular and animal models [33]. CEP-1347, an orally available compound that was well tolerated in the clinic, was advanced to Phase II/III trials for assessing efficacy in Parkinson s disease. However, the clinical trial was stopped due to a lack of significant efficacy [34],... 

Clinical Global Impressions. Although the ECDEU Assessment Manual for Psychopharmacology (Guy, 1976) provides a formal test for the Clinical Global Impression (CGI) Scale, numerous investigators have modified the three major questions as well as the scales used in order to fit this test to their own clinical trials. The three questions, which may be apphed in almost all Phase II and Phase HI clinical trials, are... 

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