Adverse events in phase one studies: a study in 430 healthy volunteers.
All the clinical, laboratory and electrocardiographic adverse events detected during 24 Phase I studies in the same unit over a 5 y period are reported here. 430 healthy male volunteers were involved, corresponding to 5488 days of follow-up. The overall incidence of adverse events was 13.5%, with a significant difference between active drug (15.3%) and placebo (7.4%) treatments. There were 69 distinct types of adverse events. Headache was the most frequent symptom (2%). There were severe adverse events in 20 cases (0.36%), with an incidence of 20/430 per subject (4.6%). There were no deaths or life-threatening events. Although the main objective of Phase I studies is to determine the maximum dose tolerated, cause-effect relationships with adverse events are hard to establish, because of the frequency of adverse events with placebo, and because of the limited number of subjects included such studies.
Sibille
M
M
Rhône-Poulenc-Rorer, Lyon Sud, France.
Deigat
N
N
Olagnier
V
V
Durand
D V
DV
Levrat
R
R
D004341:Drug Evaluation; D016903:Drug Monitoring; D064420:Drug-Related Side Effects and Adverse Reactions; D006261:Headache / Q000209:etiology; D006801:Humans; D008297:Male; D010919:Placebos; D012107:Research Design
D010919:Placebos