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Central Nervous System (CNS)-related safety concerns are major contributors to delays and failure during the development of new candidate drugs (CDs). CNS-related safety data on 141 small molecule CDs from five pharmaceutical companies were analyzed 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, namely headache, nausea, dizziness, fatigue/somnolence and pain. In the context of this analysis, the FOB/IT did not predict the occurrence of these particular AEs in man. For AEs such as headache, nausea, dizziness and pain the results are perhaps unsurprising, as the FOB/IT were not originally designed to predict these AEs. More unexpected was that the FOB/IT are not adequate for predicting ‘somnolence/fatigue’ nonclinically. In drug …