Absence of QTc prolongation in a thorough QT study with subcutaneous liraglutide, a once-daily human GLP-1 analog for treatment of type 2 diabetes
| Autor: | Milan Zdravkovic, Craig R. Sprenger, Jeffrey S. Litwin, Naum Khutoryansky, Dhruba J. Chatterjee |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Time Factors Adolescent Injections Subcutaneous Moxifloxacin Drug Evaluation Preclinical Placebo QT interval law.invention Electrocardiography Randomized controlled trial law Glucagon-Like Peptide 1 Heart Conduction System Clinical endpoint Medicine Humans Pharmacology (medical) Dosing Pharmacology Aza Compounds Cross-Over Studies Models Statistical Dose-Response Relationship Drug business.industry Liraglutide Middle Aged Crossover study Confidence interval Diabetes Mellitus Type 2 Anesthesia Quinolines Female business medicine.drug Fluoroquinolones |
| Zdroj: | Journal of clinical pharmacology. 49(11) |
| ISSN: | 1552-4604 |
| Popis: | The objective of this study was to establish effects of liraglutide on the QTc interval. In this randomized, placebo-controlled, double-blind crossover study, 51 healthy participants were administered placebo, 0.6, 1.2, and 1.8 mg liraglutide once daily for 7 days each. Electrocardiograms were recorded periodically over 24 hours at the end of placebo and highest dosing periods. Four different models for QT correction were used: QTci, as the primary endpoint, and QTciL, QTcF, and QTcB as secondary endpoints. The upper bound of the 1-sided 95% confidence interval for time-matched, baseline-corrected, placebo-subtracted QTc intervals was10 ms for all 4 correction methods. Moxifloxacin (400 mg) increased QTc intervals by 10.6 to 12.3 ms at 2 hours. There was no concentration-exposure dependency on QTc interval changes by liraglutide and no QTc thresholds above 500 ms or QTc increases60 ms. The authors conclude that liraglutide caused no clinically relevant increases in the QTc interval. |
| Databáze: | OpenAIRE |
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