title: Investigation of parameters highlighting drug induced small changes of the T-wave's morphology for drug safety studies.
abstract: In guideline E14, the American Food and Drug Administration (FDA) requests for clinical studies to investigate the prolongation of the heart rate corrected QT-interval (QTc) of the ECG. As drug induced QT-prolongation can be caused by changes in the repolarisation of the ventricles, it is so far a thorough ECG biomarker of risk for ventricular tachyarrhythmias and Torsade de Pointes (TdP). Ventricular repolarisation changes not only change QT but also influence the morphology of the T-wave. In a (400 mg single dose) Moxifloxacin positive control study both, QTc and several descriptors describing the T-wave morphology have been measured. Moxifloxacin is changing two shape dependent descriptors significantly (P<0.05) about 3 to 4 hours after a 400 mg oral single dose of Moxifloxacin.
authors.affiliation: Karlsruhe Institute of Technology, Institute of Biomedical Engineering, 76131 Karlsruhe, Germany.Tobias.baas@kit.edu
authors.forename: Tobias
authors.initials: T
authors.lastname: Baas
authors.forename: Ksenija
authors.initials: K
authors.lastname: Gräfe
authors.forename: Antoun
authors.initials: A
authors.lastname: Khawaja
authors.forename: Olaf
authors.initials: O
authors.lastname: Dössel
mesh_terms: D000890:Anti-Infective Agents / Q000009:adverse effects*; D001372:Aza Compounds / Q000009:adverse effects*; D004562:Electrocardiography / Q000379:methods*; D005260:Female; D024841:Fluoroquinolones; D006801:Humans; D008297:Male; D000077266:Moxifloxacin; D011804:Quinolines / Q000009:adverse effects*; D017180:Tachycardia, Ventricular / Q000503:physiopathology; D016171:Torsades de Pointes / Q000503:physiopathology; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin