Laboratory data in healthy volunteers: reference values, reference changes, screening and laboratory adverse event limits in Phase I clinical trials.

Objective: Laboratory data are key evaluation procedures for Phase I clinical pharmacology for two reasons. Firstly, laboratory data are used within the screening process to exclude subjects with asymptomatic diseases, which could result in increased danger to themselves or confuse interpretation of the study results. Secondly, during study implementation, safety evaluation and in particular maximum tolerated dose determination have to be done by a case-by-case analysis, sometimes using laboratory adverse events (LAEs).

Adverse events in phase-I studies: a report in 1015 healthy volunteers.

Objective: This report describes all clinical, laboratory and electrocardiographical adverse events detected in healthy volunteers in a phase-I centre over a 10-year period: 54 phase-I studies are involved, including 1015 healthy young volunteers (993 males) who received 1538 treatments (23 different active drugs or placebo) corresponding to 12143 days of follow-up. This updates a similar report published previously in the European Journal of Clinical Pharmacology.

Methods: Adverse events were defined as all events noted in case-report forms.

Upper limit of plasma alanine amino transferase during phase I studies.

In Phase I clinical studies, the maximum tolerated dose has to be determined by a case by case analysis sometimes using a laboratory adverse effect, e.g. an increase in alanine amino transferase (ALT).

[Critical value of bilirubin in the selection of healthy volunteers in for phase I].

10% of young male healthy volunteers have a total bilirubin value over 20 mumol/l; thus such a value appears not relevant as screening cut off point in clinical pharmacology. This study was intended to confirm if a 27 mumol/l cut off point previously defined by the authors does not support a risk. This study dealt with 487 subjects who had together measurements of total bilirubin value and lab.

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.