No QTc Prolongation with Semaglutide: A Thorough QT Study in Healthy Subjects

Autor: Valentin Demmel, Jonas Pettersson, Anne Sandberg-Schaal, Georg Golor, Anne Flint, Jacob Bonde Jacobsen
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Diabetes Therapy
ISSN: 1869-6961
1869-6953
Popis: Introduction Semaglutide is a glucagon-like peptide-1 (GLP-1) analog approved for the once-weekly treatment of type 2 diabetes. The objective of this 16-week, double-blind, single-center thorough QT study was to confirm that semaglutide treatment does not prolong cardiac repolarization versus placebo. Prolongation of the QT interval is a biomarker for ventricular tachyarrhythmia. Methods In a parallel design, 168 healthy subjects were randomized to the treatment or placebo arms, of whom 166 were treated with subcutaneous semaglutide (N = 83; escalated to a supratherapeutic dose of 1.5 mg) or placebo (N = 83). The subjects (60% males) had a mean age of 38.2 years and body mass index of 25.1 kg/m2. To assess QT assay sensitivity, subjects in the placebo group received a single 400 mg moxifloxacin dose as positive control, and placebo in a crossover fashion. The primary endpoint was the time-matched change from baseline in QT interval corrected individually for heart rate (ΔQTcI), calculated from 11 electrocardiogram recordings from 0 to 48 h after the last 1.5 mg dose. Similar assessments were made for the therapeutic 0.5 and 1.0 mg semaglutide dose levels. Results No QTcI prolongation occurred with any semaglutide dose; the upper limits of two-sided 90% confidence intervals of the placebo-subtracted ΔQTcI were < 10 ms at all doses and time points. Exposure–response analysis showed no dependence of QTcI on semaglutide concentration. QT assay sensitivity was confirmed. The semaglutide safety profile was similar to that of other GLP-1 receptor agonists. Conclusion Based on investigations of QT/QTc, no concern with regard to ventricular arrhythmias was raised as semaglutide did not prolong the cardiac repolarization duration in healthy subjects. Trial Registration ClinicalTrials.gov identifier: NCT 02064348. Funding Novo Nordisk. Electronic supplementary material The online version of this article (10.1007/s13300-018-0442-0) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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