All seven drugs were tested at both a pharmacologic dose and at a microdose (one hundredth of the pharmacologic dose, not
to exceed 100 μg). For six of the seven drugs, an intravenous (IV) microdose was compared with an IV therapeutic dose from
data generated within EUMAPP and with the literature or from EUMAPP data alone. For all seven drugs, an oral microdose was
compared with an oral therapeutic dose. For five of the seven drugs, the comparison was made from data generated from EUMAPP
and the literature. For two drugs, the comparison was with the literature only.
» Xceleron has conducted its own microdosing research. Can you share these results and results from the Consortium for Resourcing
and Evaluating AMS Microdosing (CREAM) study?
A total of 25 drugs (that we know of) have been tested at both a microdose and pharmacologic dose. This total consists of
several compounds from the peer-reviewed literature and a number of molecules that are not yet in the public domain as they
are either Xceleron research projects or sponsor studies that are confidential. Of the 25 drugs, 21 exhibited linear PK, and
4 drugs exhibited some nonlinearity. Thus, 84% of the drugs examined showed linear PK between a microdose and therapeutic
Table I: Pharmacokinetic data of select drugs in microdosing.
Tables I and II are a compilation of the published data and the data that we are aware of that is not currently in the public
domain. The data includes fexofenadine (an EUMAPP molecule) as data on this drug was published by a Japanese group, but the
listing excludes the other six EUMAPP molecules. The drugs tested in the CREAM trial (4) are also listed.
Table II. Pharmacokinetic (PK) data for select drugs and drug types in microdosing.
» How are microdosing studies conducted? Are there any limitations in the type of the active ingredient that can be tested?
Microdosing studies are normally conducted as a two-way crossover design with an oral microdose, followed by an appropriate
wash-out period, then the IV microdose. The number of human volunteers is usually between four and six subjects per molecule.
It is most common to test multiple molecules in parallel groups of subjects within one human Phase 0 clinical study. A microdose
is categorized as a hundredth of the pharmacologic dose (or predicted pharmacologic dose) and cannot exceed 100 μg. The dose
contains only the active ingredient, which has a radiolabelled tag incorporated into the compound structure, most commonly
14 C. To date, microdosing has been conducted predominantly on small molecules. Xceleron's research and development team is
currently researching ways to label biologics without altering the activity of the compound. A significant amount of work
has been conducted on biologics in preclinical studies; however, there are no published data from microdose testing of biologics
in humans as yet.