Cognitive testing in early phase clinical trials: outcome according to adverse event profile in a Phase I study

Human Psychopharmacology - Tập 21 Số 7 - Trang 481-488 - 2006
Alex Collie1,2, Paul Maruff2,3, Peter J. Snyder4, Miss Amanda Darekar5, John P. Huggins5
1Centre for Neuroscience, The University of Melbourne, Australia
2CogState Limited, Melbourne, Australia
3Department of Psychology, La Trobe University, Melbourne, Australia
4Department of Psychology, The University of Conneticut, USA
5Pfizer, Global Research & Development, Sandwich, United Kingdom

Tóm tắt

AbstractBackgroundIt has been proposed that objective cognitive testing provides additional information to that collected via adverse event (AE) recordings. However, in clinical trials of compounds with potentially negative effects on cognition, the results of cognitive testing may overlap with AE recordings.AimsTo examine cognitive function in subjects who do and do not report sedation‐related AEs in a Phase I clinical trial.MethodsFive computerized cognitive tasks were administered to 28 healthy male volunteers enrolled in a simulated Phase I study using midazolam to induce sedation‐related AEs and cognitive dysfunction. For each subject, the magnitude of cognitive change between pre‐dose and 1 hr post‐dose assessments was calculated. Group and individual level cognitive outcome was compared between subjects who did and did not report sedation‐related AEs following administration of 1.75 and 5.25 mg midazolam.ResultsAt both doses of midazolam, cognitive dysfunction was observed in both subject groups (i.e., those who did and did not report AEs). Analysis of individual outcomes identified consistent cognitive dysfunction among subjects who reported sedation‐related AEs. Further, in the 5.25 mg condition a subset of individuals (66.7%) who did not report sedation‐related AEs nevertheless displayed substantial cognitive dysfunction.ConclusionsFollowing administration of oral midazolam, there is a dissociation between sedation‐related AE recordings and performance on computerized cognitive tests of motor function, attention, strategy use and problem solving, learning and delayed recall. Inclusion of computerized cognitive tests in early phase trials may allow identification of subtle cognitive change, beyond that which is possible by self‐report and clinical observation. Copyright © 2006 John Wiley & Sons, Ltd.

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Tài liệu tham khảo

10.1177/0269881104040248

10.1016/j.acn.2004.12.003

10.1097/01.jcp.0000155822.51962.b4

10.1136/bmj.313.7059.744

Cohen J, 1988, Statistical power analysis for the behavioural sciences

10.1017/S1355617703930074

CollieA DarekarA WeissgerberG et al.2005.Cognitive testing in early phase clinical trials: Development of a rapid computerised test battery and application in a simulated Phase I study. Manuscript submitted for publication.

10.1111/j.1365-2869.2003.00363.x

10.1046/j.1365-2044.2002.02785.x

10.1385/JMN:18:3:283

10.1037/0894-4105.10.1.120

10.1002/j.1875-9114.1985.tb03411.x

10.1017/S1041610205001638

10.1200/JCO.2000.18.3.646

10.1002/hup.624

10.1016/S0736-4679(97)00022-X

10.1034/j.1399-6576.2001.045003275.x

10.1067/mcp.2002.128866

10.1002/hup.692

10.1038/sj.bdj.4800330a

10.1111/j.1528-1157.1992.tb02324.x

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Human Psychopharmacology

Tập 21 Số 7

481-488

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