Assessment of adverse events during drug development: experience with temafloxacin

Abstract

The safety of temafloxacin was evaluated in 753 subjects in phase I trials and in 2602 patients included in phase II and III studies. Comparative treatment was given to 153 subjects in phase I who received placebo and to 2031 patients in phase II and III trials who were given other quinolones (n = 1169) or non-quinolone comparators (n = 862). Adverse events were collated by spontaneous reporting by the patients or observations by investigators and, additionally in some studies, by the use of diary cards filled in by the patients. The results showed that temafloxacin was at least as safe as the comparators. Dose related gastrointestinal adverse reactions were found only in patients with reduced renal function who received a high temafloxacin dose. There was a low incidence of quinolone-related adverse reactions (photosensitivity, CNS-toxicity, or theophylline drug-drug interactions). The most common adverse reactions were gastrointestinal ones which occurred in 13.4% of the patients included in phase II and III trials. The corresponding frequencies in patients randomized to quinolone and non-quinolone comparators were 15.7% and 11.6% (P less than 0.05) [corrected], respectively. In conclusion, temafloxacin was shown to be at least as safe as the comparators used in the extensive phase I to III programme for evaluation of this new quinolone.