Join Us for the First SPS Member Webinar of the Year—January 19, 11AM ET

Dear Colleagues,

The Safety Pharmacology Society is pleased to invite you to a webinar presentation, to be held on January 19, 2017 from 11:00 am –12:00 Noon ET.

Title: Assessing the Predictive Value of the Rodent Neurofunctional Assessment for Commonly Reported Adverse Events in Phase I Clinical Trials

Presenter: Samuel Jackson, PhD, National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs)

Description: Central Nervous System (CNS)-related safety concerns are major contributors to delays and failure during the development of new candidate drugs (CDs). Preclinical CNS-related safety data on 141 small molecule CDs from five pharmaceutical companies were analysed to identify the concordance between rodent multi-parameter neurofunctional assessments (Functional Observational Battery: FOB, or Irwin test: IT) and the five most common adverse events (AEs) in Phase I clinical trials that could have plausible preclinical correlates that are measured in the FOB/IT, namely headache, nausea, dizziness, fatigue/somnolence and pain.

In the context of this analysis, the FOB/IT did not predict these particular AEs. For AEs such as headache, nausea, dizziness and pain the results are perhaps unsurprising, as the FOB/IT were not originally designed or intended to predict these AEs and these are events that are subjective in nature. The most unexpected result was that the FOB/IT are not adequate for detecting 'somnolence/fatigue' as this event terms might more readily manifest in parameters of the FOB/IT that measure decreased arousal, handling reactivity, activity, rearing or grip strength, and/or hunched posture, for example. In drug development, these five most common AEs are rarely responsible for delaying or stopping further progression of CDs, unless the frequency or severity of the events confers an unfavourable benefit/risk ratio. More overt CNS AEs that occur with lower frequency in CD development occurred at too low an incidence rate in our clinical dataset to enable translational analysis.

These results indicate that care should be taken in generalizing the interpretation of the FOB/IT lack of translation to these common 5 AEs, when its utility has been more broadly established in integrated assessment of overall CNS activity rather than predictive value for common Phase 1 adverse events. In addition, analysis of a much larger dataset is required to fully evaluate the predictive value of the FOB/IT for less common CNS-related AEs.

Moderator: Simon Authier, DVM, MBA, PhD, DSP, Director Safety Pharmacology, CiToxLAB

We look forward to your participation.


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