Journal article
A Randomized, Placebo- and Positive-Controlled, Single-Dose, Crossover Thorough QT/QTc Study Assessing the Effect of Daprodustat on Cardiac Repolarization in Healthy Subjects
Clinical pharmacology in drug development, v 6(6), pp 627-640
01 Nov 2017
PMID: 28419747
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Daprodustat (GSK1278863) is a prolyl hydroxylase inhibitor in phase 3 clinical studies for the treatment of anemia associated with chronic kidney disease. This study was conducted to evaluate the effect of daprodustat on cardiac repolarization and enrolled 55 healthy adult male (29) and female (26) subjects who received single-dose 75 and 500mg daprodustat, 400mg moxifloxacin, and placebo. Mean placebo-corrected change from baseline QT interval for daprodustat showed no statistically significant increase. However, statistically significant decreases in the Delta Delta QTcF were observed for both doses of daprodustat, reaching a lowest value of -2.74 milliseconds for 75mg and -5.93milliseconds for 500mg daprodustat; this minor shortening effect is not considered clinically significant. The moxifloxacin group showed a statistically significant increase in the Delta Delta QTcF value, reaching a maximal increase of 11.47 milliseconds at 4 hours. Forty subjects (73%) reported at least I adverse event, with the highest incidence with 500 mg daprodustat. This group had a higher incidence of gastrointestinal adverse events compared to the other treatment groups. These results suggest that 500 mg daprodustat was not well tolerated; however, daprodustat at 75 mg was generally well tolerated. No new safety concerns were identified in subjects who received 500 mg daprodustat.
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Details
- Title
- A Randomized, Placebo- and Positive-Controlled, Single-Dose, Crossover Thorough QT/QTc Study Assessing the Effect of Daprodustat on Cardiac Repolarization in Healthy Subjects
- Creators
- Stephen Caltabiano - Metabolic Pathways and Cardiovascular, GlaxoSmithKline, Collegeville, PA, USA.Jon Collins - Research Triangle Park FoundationGul Serbest - GlaxoSmithKlineLisa Morgan - GlaxoSmithKlineDeborah A. Smith - Research Triangle Park FoundationRamiya Ravindranath - Clinical Statistics, GlaxoSmithKline, Bangalore, India.Alexander R. Cobitz - Metabolic Pathways and Cardiovascular, GlaxoSmithKline, Collegeville, PA, USA.
- Publication Details
- Clinical pharmacology in drug development, v 6(6), pp 627-640
- Publisher
- Wiley
- Number of pages
- 14
- Grant note
- GlaxoSmithKline
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000414941900012
- Scopus ID
- 2-s2.0-85018541796
- Other Identifier
- 991019176647404721
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- Collaboration types
- International collaboration
- Web of Science research areas
- Pharmacology & Pharmacy