title: Effect of Therapeutic and Supratherapeutic Doses of Vonoprazan on the QT/QTc Interval in a Phase I Randomized Study in Healthy Subjects.
abstract: This phase I, randomized, 4-period, 4-sequence, double-blind, active- and placebo-controlled, crossover study assessed the effects of vonoprazan on the QT/QTc interval in healthy subjects. Subjects received single oral doses of vonoprazan 40 mg, vonoprazan 120 mg, moxifloxacin 400 mg (positive control/open label), and placebo. The primary end point was time-matched, placebo-corrected, baseline-adjusted mean Fridericia-corrected QT interval (ddQTcF). Of 64 subjects (mean age, 37.8 years; 50% male), 63 received all four regimens. One subject discontinued due to nondrug-related adverse event of tonsillitis. Assay sensitivity was established; lower bound of the one-sided 95% confidence interval (CI) for ddQTcF was >5 ms between 1.5 and 12 h following moxifloxacin administration. For both doses of vonoprazan, the one-sided upper 95% CI ddQTcF did not exceed 10 ms. There was no correlation between plasma vonoprazan concentrations and increases in ddQTcF. Vonoprazan was well tolerated. No severe adverse events/deaths were reported. (European Clinical Trials Database Registry: 2011-004003-20.).
authors.affiliation: Biotrial S.A., Rennes, France.
authors.forename: B
authors.initials: B
authors.lastname: Astruc
authors.affiliation: Takeda Development Centre Europe Ltd, London, UK.
authors.forename: H
authors.initials: H
authors.lastname: Jenkins
authors.affiliation: Takeda Development Centre Europe Ltd, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Jenkins
mesh_terms: D000328:Adult; D003710:Demography; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D011758:Pyrroles / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013449:Sulfonamides / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: C552956:1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine; D011758:Pyrroles; D013449:Sulfonamides