OBJECTIVE: To compare the effect of @entity3477 as a positive control in a @entity302 ( @entity302 ) study with that in a thorough QT (TQT) study. METHODS: @entity3477 was used as a positive control in a @entity302 study and a TQT study during the evaluation of the QT liability of a new drug. The @entity302 study had enrolled 24 males and the TQT study 25 males. Both studies intensively monitored electrocardiograms (ECGs) and pharmacokinetic sampling. Effect of @entity3477 on QTc interval was analysed in each study by intersection union test (IUT) and by exposure-response (ER) analysis and the results compared. Cost-effectiveness of this approach was computed. RESULTS: Analysis by IUT revealed that the maximum mean (90  % confidence interval (CI)) placebo-corrected change from baseline (    QTcF) in the @entity302 study and the TQT study were remarkably similar (10.7 (6.5; 14.9) ms vs. 9.09 (6.20; 11.98) ms, respectively). In both studies, assay sensitivity was established by the 90  % lower bound exceeding 5  ms. ER analysis revealed the slopes in both studies to be significantly different from zero and comparable. Bootstrap-predicted effects of @entity3477 at geometric mean concentrations of ~3000  ng/mL were 8.19 (90  % CI 5.86; 10.7) ms in the @entity302 study and 7.33 (90  % CI 5.69; 9.70) ms in the TQT study. CONCLUSION: @entity3477 can be integrated effectively in a @entity302 study to establish assay sensitivity, and a TQT study may be replaced by a @entity302 study which has the required assay sensitivity. Further experience is warranted to verify this conclusion.

Establishing assay sensitivity in QT studies: experience with the use of XXXX in an early phase clinical pharmacology study and comparison with its effect in a thorough QT study.

@entity302 :: ('MESH:D004827', 'Disease') :: ['SAD', 'single ascending dose'] @entity3477 :: ('MESH:C104727', 'Chemical') :: ['Moxifloxacin', 'moxifloxacin']
@entity3477 :: (MESH:C104727,Chemical) :: ['moxifloxacin']
