Human studies drug trials

The primary objective of a Phase I trial is to assess the safety of the drug in humans. Studies are normally conducted in healthy male volunteers, although specific categories of subject may be used in certain cases. For example, to avoid the risk of low blood pressure, subjects with mild hypertension would be more appropriate for the evaluation of antihypertensive drugs, while patients are likely to be used in the case of drugs that are expected to produce significant toxic effects (e.g. anti-cancer cytotoxic drugs). Remuneration may be offered for participation in the study. The number of subjects is normally between 10 and 100 people. 

It should be noted that our proposal goes considerably beyond the current proposal of FDA to create a looser Phase 0 stage for first-in-man pharmacokinetic and similar activities. Our proposal would cover all early human studies through clinical proof-of-concept, which usually occurs in Phase 2a. Only in the large pivotal studies (Phases 2b-3), when there is more assurance that the drug candidate has a solid chance of getting to an NDA submission, would the full formal IND filing be necessary. (These proposals are the opposite of what has been introduced by the EC Clinical trial Directive, see Chapter 17.)... 

Food and Drug Administration (FDA)—U.S. government agency responsible for approving drugs for sale based on information from laboratory, animal, and human studies. Human studies, called clinical trials, can begin only after the FDA reviews the laboratory and animal studies. 

Human studies are designed to determine Does the drug work To provide an answer, pharmaceutical companies, through a series of controlled clinical trials, must, according to the FDA, collect and submit substantial evidence of effectiveness, as well as confirmation of relative safety in terms of the risk-to-benefit ratio for the disease that is to be treated. It is critical from the outset to design clinical studies that pose the right question and provide an answer to the question in the intended patient population. 

Most human evidence concerning chemical effects on health comes from case-confrol and convenience-cohort studies rather than drug trials. But such studies can have serious flaws. ... 

The best evidence about the effects of chemical exposure on human health would come from clinical trials, but they are generally not used because of ethical concerns about experimentation on humans. Even when clinical drug trials are conducted, the prohibitive cost of large studies means that the smallest incidence change that can be detected is about 1 percent. 

Recent research using NMR has revealed novel noninvasive biomarkers for peroxisomal proliferation. These are two breakdown products of NAD detectable in plasma by HPLC. These reflect the increased demand and production of NAD for oxidation metabolism such as (3-oxidation of fatty acids. This biomarker will be useful in studies in humans, especially clinical trials of more potent lipid-lowering drugs. 

Phase II Chemical Trials Controlled studies are carried out on 200 to 300 volunteer patients to test drug efficacy together with animal and human studies for safety. This stage requires about two years. 

Nasal spray 18 healthy volunteers in Bristol-Myers first time in humans study withdrawal not seen when drug discontinued after 16 days92 Nasal spray Bristol-Myers clinical trial in post-Caesarian-section pain no assessment of abuse liability or withdrawal93 Continued... 

Before a drug may be tested on humans, it must first be tested on animals. Tests on humans are called clinical trials, and animal trials are often referred to as preclinical trials. Preclinical trials differ from the animal tests mentioned earlier in this chapter. The previously discussed animal tests help the drug discovery team determine and optimize the pharmacodynamic and pharmacokinetic behavior of a hit or lead. Preclinical trials, in contrast, are standardized, industrywide tests. The preclinical tests have technical names such as Segment II Reproductive Study in Rabbits or 6-Month Toxicity Study in Rats. The specific names suggest the exact nature of each study. Each trial seeks to answer predefined safety questions concerning a drug candidate. Preclinical trials do not address the therapeutic effectiveness of the drug candidate in any way. Preclinical trials examine exclusively safety issues. 

The nomenclature for early clinical studies is not fully standardized. In addition to first-in-human evaluations, Phase I trials are appropriate throughout the drug development process as specific issues arise that require clinical pharmacologic investigation. Further, some exploratory hrst-in-human studies are currently being described as "Phase Zero," in which the goals are somewhat different from classic Phase I trials. 

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