Deferasirox does not induce QT/QTc-prolongation in healthy subjects
Abstract
UNLABELLED: The International Conference on Harmonization (ICH) E14 guidance recommends that almost all drugs should undergo careful clinical testing in a thorough QT/QTc study. Deferasirox (Exjade, ICL670) is a once-daily oral iron chelator, developed for the treatment of blood transfusion-related iron overload.
OBJECTIVE: This study was designed to investigate the effect of deferasirox on the QT/QTc interval.
METHODS: A randomized, single-dose, placebo- and positive-controlled, parallel-group study was conducted in a total of 182 healthy subjects. Study participants were randomized to four treatments arms: deferasirox 20 mg/kg (n = 46), deferasirox 40 mg/kg (n = 46), placebo (n = 46) or moxifloxacin 400 mg (n = 44). Moxifloxacin tablets were taken in an open-label fashion, while the subjects and investigator staff remained blinded for the other treatments. Electrocardiograms, obtained at various time points during a 24-h period, were evaluated centrally in a blinded fashion. The primary endpoint was the average change from baseline in QT/QTc over the 24-h period following intake of study medication. It was prospectively defined that deferasirox will be considered devoid of inducing QT/QTc-prolongation if the upper bound of the 95% 2-sided confidence interval (CI) for the difference to placebo is below 8 milliseconds (i.e., being noninferior to placebo).
RESULTS: Deferasirox 20 and 40 mg/kg were noninferior to placebo with respect to the average change from baseline in…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 182 participants or records.
Read the paper
Related studies
- Synthesis, In Vitro and In Silico Molecular Docking Studies of Novel Phthalimide–Pyrimidine Hybrid Analogues to Thalidomide as Potent Antitubercular Agents
- Exploring the inhibitory performance of expired moxifloxacin and norfloxacin on copper corrosion in saline environment
- Molecular investigation of antimicrobial peptides against Helicobacter pylori proteins using a peptide-protein docking approach
- Screening of novel narrow-spectrum benzofuroxan derivatives for the treatment of multidrug-resistant tuberculosis through in silico, in vitro, and in vivo approaches
- Synthesis, Characterization, Anticancer, Antioxidant, and In Silico Evaluation of Semicarbazides and Thiosemicarbazides
- Fast and accurate prediction of drug induced proarrhythmic risk with sex specific cardiac emulators
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.