Phase 0 clinical trials

A large and rapidly growing number of clinical trials (phase I and phase II) evaluating the potential of DNA vaccines to treat and prevent a variety of human diseases are currently being performed ( http // clinicaltrials.gov) however, there is yet no licensed DNA vaccine product available for use in humans. The clinical trials include the treatment of various types of cancers (e.g., melanoma, breast, renal, lymphoma, prostate, and pancreas) and also the prevention and therapy of infectious diseases (e.g., HIV/ABDS, malaria, Hepatitis B vims, Influenza vims, and Dengue vims). So far, no principally adverse effects have been reported from these trials. The main challenge for the development of DNA vaccines for use in humans is to improve the rather weak potency. DNA vaccines are already commercially available for veterinary medicine for prevention of West Nile Vims infections in horses and Infectious Hematopoetic Necrosis Vims in Salmon. 

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. 

The complexity of a sample matrix increases if the sample is derived from a biological system. Note that the number of analyses per compound dramatically increases as the complexity of determining compound properties increases, while the number of individual compounds decreases by filtering out unsuitable structures. At the end of a clinical trial phase, perhaps 100,000 LC/MS analyses may have been performed for one compound (Figure 3.2). 

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 ... 

Confirmatory clinical trials (Phase 111, including published review articles)... 

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

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. 

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). ... 

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

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. 

Osiris overcomes the ethical, health and practical concerns that hamper the development of other stem cell products because of its stem cell source and the great care taken to ensure safety and quality of the material. Stem cell donors are monitored for up to five years after donation to ensure their health status. This is the primary reason that Osiris has progressed into the human clinical trial phase faster than any other stem cell company [www. stemcellsinc. com]. 

The first clinical trials (Phase I trials) are usually conducted on small groups of healthy volunteers, which do not include children and the elderly. These... 

SL65.0155 Currently under clinical trial (phase II). SL65.0155 and a cholinesterase inhibitor, rivastigmine, had a synergic effect in the object recognition task and in linear maze performances in aged rats. 108... 

Obviously, the inclusion/exclusion criteria should result in a patient population that is as large as is scientifically justifiable and desirable (i.e., large enough to detect the desired difference at the stated probability levels.) In the earliest clinical trial (phase 1), the potential risk entailed in administering a new... 

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