Transaminase elevation on placebo during phase I trials: prevalence and significance.
OBJECTIVE
To evaluate the prevalence of transaminase elevation on placebo during Phase I trials.


METHODS
Retrospective review of pooled transaminase data collected on placebo during 13 Phase I trials in 93 healthy volunteers hospitalized for 14 days, with determination of the prevalence of abnormally high values.


RESULTS
20.4% of the 93 subjects showed at least one ALT value above the upper limit of the normal range (ULN), and 7.5% had at least one value twice ULN.


CONCLUSIONS
Laboratory safety results of Phase I trials should be interpreted with caution, in the light of data on placebo, to avoid premature discontinuation of the development of safe drugs wrongly believed to be hepatotoxic.
Rosenzweig
P
P
Department of Clinical Pharmacology, Synthélabo Recherche, 31 avenue Paul Vaillant-Couturier, 92225 Bagneux Cedex, France.
Miget
N
N
Brohier
S
S
D000410:Alanine Transaminase / Q000378:metabolism*; D017321:Clinical Trials, Phase I as Topic; D016208:Databases, Factual; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D010919:Placebos / Q000494:pharmacology*; D012189:Retrospective Studies
D010919:Placebos; D000410:Alanine Transaminase