Phase I-III trials

All CTs (phase IV ones included) need ethical approval by independent central or regional ethics committees, as specified by a Decree of the Minister of Health in 1987, to be issued in an amended form in 1999. Phase I-III trials also need authorization by the competent medicine regulatory authority (the NIP or the Executive Office of the National Chief Medical Officer). The documentation needed for authorization does not differ from that in the EU. In short, it consists of the following (if not specified, it may be in English German may also be accepted) ... 

Once patients are recruited, retaining them becomes the next hurdle. Data suggest that only 70% of subjects enrolled in phases I-III trials complete those trials (Lamberti, 2005). That retention figure is likely to increase if study volunteers are satisfied with the care and treatment they are receiving (Miskin and Neuer, 2002). Proper treatment starts from the beginning, from the minute volunteers enter the site, extends to follow-up reminder telephone calls or postcards about upcoming visits... 

In a meta-analysis of all prospective phase I-III trials published up to December 2008 of bevacizumab, grade 3-4 hypertension occurred in 9.2%, grade 3-4 left ventricular systolic dysfunction in 0.3%, and grade 3-4 thromboembolism in 9.6% [92 ]. 

EribuUn Eribulin mesylate is a nontaxane microtubule dynamics inhibitor that is currently under development in phase I-III trials for the treatment of solid tumours. The effects of ketoconazole on eribulin pharmacokinetics were evaluated in a randomised crossover study in 12 patients [52f. Ketoconazole had no effect on eribulin pharmacokinetics and suggest that cytochrome P450 3A inhibitors do not interfere eribulin metabolism. 

Phase IV trials, like trials in Phases I-III, must be genuine investigations that are properly conducted and the data analysed. Free drug may not be given to doctors solely for them to use as they think fit. The restrictions do, however, reduce the chances for physicians to assess the new medicine personally and thus to form a roimded view of the product. The argument must therefore rest on clinical and scientific merit. 

In November 2005, a phase II/III study in NSCLC patients started in Australia and Canada, hi February 2006, Cediranib was undergoing a UK phase II/III trials in colorectal cancer. At that time, US phase II trials were underway in patients with advanced solid tumors, mesothelioma, melanoma, fiver, ovarian, peritoneal, fallopian tube, kidney, and breast cancers, hi May 2006, a US phase II trial began for neurofibromatosis type I and plexiform neurofibroma. 

Phase IV trials must be conducted according to the same ethical, scientific and Good Clinical Practice standards as those required in Phase I III studies. A more detailed account on PMS studies can be found in a chapter by Hollister et al (1994). 

Based on the results from these three trials, BioCryst has initiated a multicenter Phase III trial for the treatment of CTCL, as well as a large, multicenter Phase II trial for psoriasis. In addition to the two clinical trials using the topical formulation, a Phase I clinical trial in CTCL and T-cell lymphoma/leukemia has begun using an oral formulation of BCX-34. In the future, a number of other T-cell mediated diseases or processes are possible targets for BCX-34, including rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and organ transplant rejection. 

Clinical Trial See Phase I Clinical Trials, along with definitions for Phase II, Phase III and Phase IV. 

Alvocidib (flavopiridol, HMR 1275) 66 (Sanofi-Aventis) is being evaluated in Phase II/III trials for the treatment of chronic lymphocytic leukaemia in collaboration with Ohio State University and the US National Cancer Institute (NCI).124 Alvocidib 66 is also being evaluated in Phase I and II trials against... 

Plasmapheresis is effective in patients with severe neuropsychiatric SLE refractory to conventional treatment. Intrathecal methotrexate and dexamethasone is also beneficial to those patients (Dong et al., 2001 Baca et al., 1999). Positive results of a phase I/II trial of autologous hematopoietic stem cell transplantation (AHSCT) at Northwestern University in Chicago, UL has led to a phase III ASCT trial. As with other similar trials involving autoimmune disease, the ASCT trial is designed to include standard of care IV pulse cyclophosphamide (Burt et al., 2003b). 

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