A Phase I study is a safety trial in a small number of healthy human volunteers
or patients. It is typically the first human exposure to a New Chemical Entity
(NCE) and takes place in a controlled clinical setting. To be granted permission
by the regulatory bodies to perform such a study, a comprehensive package of
toxicology data, demonstrating safety at many times the human dose in animals,
must be submitted.
Damage at the gene or chromosomal level can be investigated
using in vitro tests in dividing cells. Toxicology investigations
require data in two animal species, usually one rodent species, and
one non-rodent species. Animals must be dosed in a similar way to human
volunteers and for a duration that is equal to or exceeds the clinical
protocol. In addition, safety pharmacology studies must be performed
to evaluate possible effects on the cardiovascular, respiratory and
central nervous systems.
Exposure must be quantified through pharmacokinetic analysis
with a bioanalytical method validated to the requirements of Good Laboratory
Practice (GLP).
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