PMID- 15906587
OWN - NLM
STAT- MEDLINE
DCOM- 20050714
LR  - 20190608
IS  - 0946-1965 (Print)
IS  - 0946-1965 (Linking)
VI  - 43
IP  - 5
DP  - 2005 May
TI  - Adverse events in volunteers participating in phase I clinical trials: a 
      single-center five-year survey in 1,559 subjects.
PG  - 217-26
AB  - OBJECTIVE: This report analyzes all adverse events (AEs) which occurred in 
      healthy volunteers in a phase I center over a five-year period. It included 142 
      phase I studies with a total of 1,559 participants receiving 2,955 treatments 
      with 32 different active drugs and placebo (ratio 6.5 : 1 in terms of follow-up 
      days). The observation period covered a total of 29,664 follow-up days. METHODS: 
      All adverse events (AEs) as well as clinically relevant laboratory findings were 
      counted. The incidence of AEs was defined as the ratio between the number of AEs 
      and the number of follow-up days. Severity of AEs was classified as mild, 
      moderate and severe; serious AEs were analyzed separately. A chi2-test was used 
      to compare incidence rates of the AEs. Statistical tests based on the normal 
      distribution were used for comparison of demographic data and relative 
      frequencies; p < 0.05 was defined as the minimum level of significance. RESULTS: 
      There were 2,604 AEs and 291 different types of AEs with headache (2.23%), 
      diarrhea (1.37%) and common cold (0.72%) being the most frequent. The overall 
      incidence of AEs was 8.8% with no significant difference between those occurring 
      with active drug and those on placebo when the studies were taken as a whole 
      (8.5% vs. 9.1%), but the incidence of AEs in the active treatment groups was 
      higher than under placebo (14.1% vs. 9.1%; p < 0.001) in placebo-controlled 
      studies. The overall rate of AEs was 1.7 per subject and 0.9 per treatment. The 
      vast majority of AEs were of mild or moderate intensity (99.2%). Only six AEs 
      were serious as defined by GCP but two, a pseudoallergic reaction and a prolonged 
      orthostatic dysregulation were rated as possibly or probably drug-related and 
      these resolved completely. The incidence of AEs was three-fold (all AEs) and 
      six-fold (AEs with probable relationship to study medication) higher (p < 0.001) 
      in multiple-dose studies than in single-dose trials, and within multiple-dose 
      trials the difference between AEs on active drug and on placebo was also 
      significant (22.9% vs. 12.5%; p < 0.001). Irrespective of whether on active drug 
      or placebo, AEs occurred with a significantly higher incidence on the first day 
      of the study drug administration, in the first study period, with respect to the 
      overall population in elderly subjects and in volunteers with a high body weight. 
      CONCLUSION: AEs in phase I studies are common, but usually of mild or moderate 
      intensity. Placebo effects and study conditions contribute significantly to the 
      rate of their occurrence. Multiple-dose placebo-controlled studies are of 
      particular importance in determining the substance-specific AE profile.
FAU - Lutfullin, A
AU  - Lutfullin A
AD  - Institute of Clinical Pharmacology, Bayer Health Care AG, Wuppertal, Germany.
FAU - Kuhlmann, J
AU  - Kuhlmann J
FAU - Wensing, G
AU  - Wensing G
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PL  - Germany
TA  - Int J Clin Pharmacol Ther
JT  - International journal of clinical pharmacology and therapeutics
JID - 9423309
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Body Mass Index
MH  - Clinical Trials as Topic/*adverse effects
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Incidence
MH  - Male
MH  - Middle Aged
MH  - Research Design
EDAT- 2005/05/24 09:00
MHDA- 2005/07/15 09:00
CRDT- 2005/05/24 09:00
PHST- 2005/05/24 09:00 [pubmed]
PHST- 2005/07/15 09:00 [medline]
PHST- 2005/05/24 09:00 [entrez]
AID - 10.5414/cpp43217 [doi]
PST - ppublish
SO  - Int J Clin Pharmacol Ther. 2005 May;43(5):217-26. doi: 10.5414/cpp43217.