A Thorough QTc Study Confirms Early Pharmacokinetics/QTc Modeling: A Supratherapeutic Dose of Omarigliptin, a Once‐Weekly DPP‐4 Inhibitor, Does Not Prolong the QTc Interval. Issue 5 (29th April 2016)

• Record Type: Journal Article
• Authors: Tatosian, Daniel A.; Cardillo Marricco, Nadia; Glasgow, Xiaoli Shirley; DeGroot, Bruce; Dunnington, Katherine; George, Laura; Gendrano, Isaias Noel; Johnson‐Levonas, Amy O.; Swearingen, Dennis; Kauh, Eunkyung
• Is Part Of: Clinical pharmacology in drug development. Volume 5:Issue 5(2016:Sep./Oct.)
• Page Start: 383
• Page End: 392
• Publication Date: 2016-04-29
• Subjects: DPP‐4 -- omarigliptin -- type 2 diabetes -- QTc -- ECG; Drugs -- Testing -- Periodicals; Drug development -- Periodicals; Clinical pharmacology -- Periodicals; 615.580724
• DOI: 10.1002/cpdd.260
• Languages: English
• ISSNs: 2160-7648

Abstract

Abstract: Omarigliptin is a dipeptidyl peptidase‐4 inhibitor being developed as a once‐weekly treatment for type 2 diabetes. This double‐blind, double‐dummy, randomized, 3‐period balanced crossover study definitively evaluated the effects of a supratherapeutic omarigliptin dose on QTc interval. Population‐specific correction of QT interval (QTcP) was used for the primary analysis. Healthy subjects (n = 60) were enrolled and received treatments separated by a ≥4‐week washout: (1) single‐dose 25 mg omarigliptin (day 1), single‐dose 175 mg omarigliptin (day 2); (2) placebo (day 1) followed by single‐dose 400 mg moxifloxacin (day 2); (3) placebo (days 1 and 2). Day 2 QTcP intervals were analyzed. The primary hypothesis was supported if the 90%CIs for the least‐squares mean differences between omarigliptin 175 mg and placebo in QTcP interval change from baseline were all < 10 milliseconds at every postdose point on day 2. The upper bounds of the 90%CIs for the differences (omarigliptin‐placebo) in QTcP change from baseline for omarigliptin 175 mg were < 10 milliseconds at all postdose times on day 2. In conclusion, a supratherapeutic dose of omarigliptin does not prolong the QTcP interval to a clinically meaningful degree relative to placebo, confirming the results of the earlier concentration‐QTc analysis.