Table 12 Subacute or chronic toxicology studies required to support human clinical testing of orally administered drugs

Clinical trial duration

Duration of repeated dose toxicology studies



Single dose p 2 weeks p 1 month p3 months p 6 months >6 months p4 weeks p4 weeks p3 months p6 months 6 months 6 months

2 weeks p4 weeks p4 weeks p3 months p 12 months p 12 months

Figure 15 The process from idea to IND.

metabolism, and excretion (ADME), and toxicity (ADMET), as well as formulation, among other steps, (3) to filing of an IND, requires the interplay of many different groups and disciplines (Figure 15).

If suitable data have been obtained to support human clinical testing and all regulatory hurdles have been cleared, the drug enters clinical pharmacology studies - first in man (FIM) or Phase I. FIM may be conducted in normal volunteers or in patients, depending on the disease target, with rising dose PKand tolerability (safety), and occasionally with biomarker endpoints.

To accelerate the entry of new drugs into clinical trials, as well as to select the best lead for advancement, microdosing or Phase 0 studies have been devised to determine human metabolism data on very small quantities of material. Accelerator mass spectrometry (AMS) has been used to provide pharmacokinetic data, and positron emission tomography (PET) has been used to generate pharmacodynamics information.121

There are various types of clinical trial design, each with its own set of strengths and weaknesses (Figure 16). Some of the common terms used to describe clinical studies are given in Table 13. For example, a nonrandomized intervention study using historical controls ensures that every patient receives therapy (no one receives placebo). It can be easier to recruit patients into these studies and less expensive to run the trial. However, the lack of a concurrent control can lead to incorrect conclusions, particularly when the current patient population differs from the historical population or when disease management has evolved to a new standard of care. While different diseases and special circumstances may sometimes dictate otherwise, for most Phase III trials the gold standard is a double-blind,

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