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Description
Phase
0 approaches — which include microdosing — evaluate subtherapeutic exposures of
new drugs in first-in-human studies known as exploratory clinical trials.
Recent progress extends phase 0 benefits beyond assessment of pharmacokinetics
to include understanding of mechanism of action and pharmacodynamics. Indeed, phase
0 approaches have the potential to improve preclinical candidate selection and
enable safer, cheaper, quicker and more accurate developmental decisions. Here,
we discuss phase 0 methods and applications, highlight their advantages over
traditional strategies and address concerns related to extrapolation and
developmental timelines. Although challenges remain, we propose that phase 0 approaches be considered for application in current drug development scenarios.
Reducing attrition in
clinical development is the single most important challenge in increasing
pharmaceutical industry productivity. A key strategy to reducing attrition rates
is to improve the quality of candidates entering clinical development. A phase
0 stage, so named because it is positioned between preclinical and phase I
stages (Table 1), has the potential to improve preclinical candidate selection
by applying approaches such as subtherapeutic microdosing (100 µg or less) to
provide human in vivo data on pharmacokinetics, pharmacodynamics and target
engagement earlier in the development process than with traditional approaches.
Phase 0 approaches also have the potential to provide data that is not readily acquired
via traditional approaches. These include first-in-human testing in patients,
simultaneous testing of multiple drug candidates (known as cassette
microdosing), intravenous administration of oral drugs and intratarget
microdosing (ITM; the administration of
microdoses locally to generate momentarily therapeutic level exposures in
targets of interest). These advantages allow triaging of preclinical candidates
for entry into clinical development in a more informed, timely and effective
manner. Overall, this webinar will provide state-of-the-art perspective on
phase 0 drug development strategies and their utility in improving therapeutic
development and reducing clinical candidate attrition rates.
Learning Objectives:
1. Understand the
strategy of phase 0 methods and their application in the drug development
process
2. Highlight advantages
of phase 0 strategies over traditional strategies.
3. Address
concerns related to extrapolation and developmental timelines.
4. Discuss how
phase 0 approaches can contribute to reduced attrition of clinical drug
candidates.