Drug trials phases

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. 

Diet drugs that are in development take years to be approved and marketed in the United States. First, these compounds are studied in the laboratory. Then, they are tested in animals. The next step is to be tested in people. There are three rounds of study—called Phases 1,11, and III trials—to establish safety and effectiveness of the drug in humans. Drugs that are in Phase III trials are closest to approval and are usually available in the United States within a couple of years if they prove to be safe and effective. Drugs in Phase II trials are a little further behind in the approval process. 

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. 

Phase 1 drug trials, 89-90, 154 Phase 2 drug trials, 90-91,154 Phase 3 drug trials, 91-94, 154, 177-178 Phase 4 drug trials, postmarketing, 325 Phenotypes, localization of, 34 Phenylketonuria, 76 Physical characteristics, group... 

Choosing Laboratory Tests. There is no standardized series of laboratory parameters that are evaluated in all clinical trials, nor is there a single standard for drugs in Phases I, 11, or HI. There are, however, broad general guidelines for laboratory tests that reperformed at each stage of clinical development. 

O Grady, J. and Joubert, P.H. (1997). Phase //// Clinical Drug Trials. CRC Press, New York. 

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). 

DKP drugs, which were developed as analgesics and anti-Parkinson s agents, have entered the clinical trial phase. ... 

Phase II trials in breast cancer and head and neck cancer were underway in Japan by November 2005 and in brain cancer by December 2005. By July 2005, a phase III trial in solid tumors had started. In February 2006, the company listed the drug in phase III trials for NSCLC. AstraZeneca plans to file Vandetanib for marketing authorization apphcation (MAA) in Europe and new drug application (NDA) in the USA not earlier then 2007. 

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. 

O Grady J and Joubert PH (eds.). Handbook of Phase I/II Clinical Drug Trials. Boca Raton, FL CRC, 1997. 

Early clinical trials (Phases I and II) are something of a special case in drug development in that no definite clinical benefit can be imputed the risk-benefit balance, therefore, consists entirely of risk for healthy volunteer trials and of only theoretical benefit for Phase II trials. For this reason, it is imperative that the nonclinical data be described accurately and any potential risks have been identified. 

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). ... 

Namjoshi and coworkers (297) reported the results of an extension phase study comparing olanzapine with placebo. The initial reduction achieved in YMS scores continued during this period and by the end of the extension phase reached a mean reduction of 18-points. The authors also conducted an economic analysis of the drug trial (excluding the acute treatment period) and found that the cost per month seen in the open-label extension phase (i.e., 649) was about half of that observed during the 12 months before entering the study (i.e., 1,533.)... 

Clinical trials are planned experiments involving human subjects, designed to answer a clinically relevant question concerning treatment. Many involve the evaluation of drugs. In a clinical trial one uses resu ts from a limited sample of subjects to make inferences about the general population. Drug trials are by convention classified into four phases ... 

Preliminary Testing Data Any data generated during the developmental and clinical trial phases of the drug may be useful to determine the expected manufacturing process variability. The process variability is an important factor to define the sampling plan to be used in the stability study. 

In the October 10, 1988 issue of Chemical Engineering News there appeared a brief report from the Israel Institute for Biological Research about an acetylcholine analog, cis-2-methylspiro(1,3-oxathiolane-5,3 )quinuclidine, which seems to be very specific for brain Ach receptors involved in AD. In the same report another drug in Phase I clinical trials was mentioned. Produced by Bristol-Myers it is meant to be used for a variety of cognitive memory disorders including AD. 

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