Since then, clinical data challenging this assumption have been accumulating. Unfortunately, two limitations have arisen
to date: limited data evaluating inter-ethnic differences in baseline, drug-free QT intervals MS-275 supplier exist and evidence from TQT studies has been collected mostly from Caucasian subjects or subjects that do not adequately represent ethnic differences . A known debate concerning which QT interval correction method should be used in TQT studies also exists . QT intervals are influenced by the individual’s heart rate and should be corrected (heart rate-corrected QT; QTc) for investigational purposes. Formulae that reflect individual heart rate include Bazett’s formula, Fridericia’s formula, and a correction using the individual QT/RR regression model. There was previously no consensus regarding which method to use in TQT studies , but as the data accumulated, it is now encouraged that newer correction formulae
such as individual correction should be used . In addition, TQT studies may use either the time-matched baseline method or the pre-dose baseline method. ICH guideline E14 recommends the use of the time-matched method for parallel studies and the use of the pre-dose method for crossover studies ; however, few studies have addressed the differences between the two baseline measurement methods. Comparing the two methods may provide some insight into whether using different baseline Nintedanib (BIBF 1120) measurement methods significantly affects the results of TQT studies. At present, no comparable published data collected from Korean subjects exist that can be used to evaluate check details an investigational product’s effects on QT interval during the drug development phase. Furthermore, the effects of moxifloxacin 400 or 800 mg (supratherapeutic dose) on QT prolongation have not been fully assessed in healthy Korean subjects, nor has the known diurnal variation been evaluated in this population . Hence, an investigation is required to
evaluate whether the usual positive control dose for TQT studies, moxifloxacin 400 mg, is adequate for Korean subjects and to determine whether moxifloxacin can be used as a positive control in Koreans, as outlined by ICH guideline E14. Therefore, the aims of the present study were to evaluate QTc prolongation in healthy Korean male subjects (both at therapeutic and supratherapeutic doses of moxifloxacin), to assess the use of moxifloxacin as an adequate positive control, to compare QT interval correction methods, and to compare baseline measurement methods in Korean subjects. 2 Methods 2.1 Subjects Healthy Korean male subjects, aged 20–40 years with body this website weight over 50 kg and within ±20 % of ideal body weight (calculated as: (height in cm − 100) × 0.9), were recruited to participate in this study and written informed consent was obtained prior to participation.