Phase III clinical trials

The clinical development of new drugs usually takes place in steps or phases conventionally described as clinical pharmacology phase I), clinical investigation (phase II), clinical trials (phase III), and postmarketing studies (phase IV). Table 1.1 summarizes the four phases of clinical evaluation. 

Halofantrine was an important antimalarial drug. It is now infrequently used because of worldwide strain resistance phenomena. Tafenoquine is a new 8-amino-quinoline currently in clinical trials (Phase III) (Figure 8.26). ... 

During the clinical trial phase, the sponsor and FDA will meet on one or more occasions. A particularly important meeting is often the end of phase II meeting. This aims primarily to evaluate and agree upon phase III plans and protocols. This is particularly important, as phase III trials are the most costly and generate the greatest quantity of data, used later to support the drug approval application. 

Pharmacogenetics and Pharmacogenomics in Late Clinical Development (Phase III Trials)... 

Refer to Section 6.3 to describe the phases of a clinical trial. Phase IV trials are necessary to maintain a close watch on the efficacy and adverse events of an approved drug when it is administered to the population at large. For example, even a small percentage of adverse events in Phase III trial for several thousand people may translate into a substantial number when a drug is made available to milhons of people. A case in point is Vioxx and Bextra (see Section 2.9). 

Phase I, II, and III Trials An IND is submitted for each phase of clinical trial. Phases I to III. At any stage of the trial, the FDA has the authority to put clinical hold on the trial until deficiencies or safety issues are resolved. The Sponsor can request meetings with the FDA at various stages ... 

Clinical trials Phase I, II, and III trials" with increasing numbers of human volunteers... 

VIII. Clinical evaluation Humans Phase I Safety and pharmacokinetics Phase II Initial clinical efficacy Phase III Clinical efficacy Phase IV Post-marketing trials... 

Phase II clinical trial studies are designed primarily to explore the relationship between the dose level and frequency of administration and the efficacy and safety observed in patients with a particular therapeutic indication or disorder. Normally, a primary endpoint is selected to evaluate the efficacy however, secondary endpoints are often included to establish criteria for monitoring patients in the more definitive phase III clinical trials. Phase II clinical trials are commonly... 

This proof of safety and efficacy takes the form of adequate and well-controUed clinical trials (Phase 111 studies), which can require thousands of patients, are time-consuming, and expensive. The cost of a Phase III study alone can easily exceed 10 million and can take several years. 

In phase II of treatment hepatic failure, renal failure, pancytopenia, and rhabdomyolysis were eommon adverse effects. Pharmacokinetic and pharmacodynamic studies show that biliary function can be served as reference parameter to indicate whether patient receive full dose of trabectedin or not. It is also reported that alkaline phosphatase and bilirubin can be served as a high risk indicator in full dose treatment. Phase II clinical trials show that trabectedin has greater efficacy in patient who suffered from breast and ovarian cancer and refractory soft tissue sarcoma. A search in Pubmed shows that there are several studies reporting the results of clinical trials (phase I, II and III) on the efficacy of trabectedin against ovarian cancer. Ferrandina et al. [38] performed retrospective, multicenter study to determine the potential efficacy of trabectedin as single agent in 98 patients (67 platinum sensitive, and 31 platinum refractory/resistant) who suffered from heavily relapsed ovarian cancer. They found that trabectedin treatment can prolong the survival of patients (18 month for treatment vs. 14 month for SD). They also found that hepatotoxicity and rare cardiotoxicity were the most important adverse effects of trabectedin treatment [38]. 

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