Adverse Events Associated with Oral First-in-Man Administration of New Chemical Entities Compared with Placebo – An Analysis of 14 Single- and Multi-Dosing, Double-Blind, Placebo-Controlled Studies

Abstract

This investigation is a retrospective analysis of the adverse events (AEs) associated with oral administration of new chemical entities (NCEs)for the first time in humans. We gathered data from 14 single- and multiple-dosings of FIM NCE studies conducted in our centre over a period of 5 years. In total, 452 subjects were dosed. A total of 2280 doses were administered. Active medication was given on 1763 dosing occasions and placebo was given on 517 dosing. 74.9% of AEs of active and 95.6% of AEs on placebo were mild. The most common AE (incidence of more than 2%) on active medication and placebo were headache, nausea, dizziness, diarrhoea, dry mouth, fatigue, tachycardia, insomnia, abnormal dreams and abdominal pain. Except for nausea and diarrhoea, which was more in the active group, there was no statistically significant difference for other AEs between active and placebo.

Keywords: AE, placebo effect, nocebo effect