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

Journal of Clinical Pharmacology

Volumn 49, Issue 11, 2009, Pages 1353-1362

  Chatterjee, Dhruba J ^a   Khutoryansky, Naum ^a   Zdravkovic, Milan ^b   Sprenger, Craig R ^c   Litwin, Jeffrey S ^d  

^a NOVO NORDISK INC   (United States)

^b NOVO NORDISK A S   (Denmark)

^c PRACS Institute Ltd   (United States)

^d eResearchTechnology   (United States)

Author keywords

Drug safety; GLP 1; Liraglutide; Qtc interval

Indexed keywords

GLUCAGON LIKE PEPTIDE 1; LIRAGLUTIDE; MOXIFLOXACIN; PLACEBO;

ADULT; ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DECREASED APPETITE; DIARRHEA; DOUBLE BLIND PROCEDURE; DRUG EXPOSURE; DRUG SAFETY; ELECTROCARDIOGRAM; FEMALE; GASTROINTESTINAL SYMPTOM; HEADACHE; HUMAN; MAJOR CLINICAL STUDY; MALE; NAUSEA; NON INSULIN DEPENDENT DIABETES MELLITUS; QT INTERVAL; QT PROLONGATION; RANDOMIZED CONTROLLED TRIAL;

ADOLESCENT; ADULT; AZA COMPOUNDS; CROSS-OVER STUDIES; DIABETES MELLITUS, TYPE 2; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG EVALUATION, PRECLINICAL; ELECTROCARDIOGRAPHY; FEMALE; GLUCAGON-LIKE PEPTIDE 1; HEART CONDUCTION SYSTEM; HUMANS; INJECTIONS, SUBCUTANEOUS; MALE; MIDDLE AGED; MODELS, STATISTICAL; QUINOLINES; TIME FACTORS;

EID: 70350430650     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1177/0091270009339189     Document Type: Article

References (24)

1. Vilsboll T. Liraglutide: a once-daily GLP-1 analogue for the treatment of type 2 diabetes mellitus. Expert Opin Investig Drugs. 2007 ; 16: 231-237.
2. Frias JP, Edelman SV Incretins and their role in the management of diabetes. Curr Opin Endocrinol Diabetes Obes. 2007 ; 14: 269-276.
3. Deacon CF, Nauck MA, Toft-Nielsen M., et al. Both subcutaneously and intravenously administered glucagon-like peptide I are rapidly degraded from the NH2-terminus in type II diabetic patients and in healthy subjects. Diabetes. 1995 ; 44: 1126-1131.
4. Deacon CF, Nauck MA, Meier J., et al. Degradation of endogenous and exogenous gastric inhibitory polypeptide in healthy and in type 2 diabetic subjects as revealed using a new assay for the intact peptide. J Clin Endocrinol Metab. 2000 ; 85: 3575-3581.
5. Vilsboll T., Agerso H., Krarup T., et al. Similar elimination rates of glucagon-like peptide-1 in obese type 2 diabetic patients and healthy subjects. J Clin Endocrinol Metab. 2003 ; 88: 220-224.
6. Agerso H., Jensen LB, Elbrond B., et al. The pharmacokinetics, pharmacodynamics, safety and tolerability of NN2211, a new long-acting GLP-1 derivative, in healthy men. Diabetologia. 2002 ; 45: 195-202.
7. Degn KB, Juhl CB, Sturis J., et al. One weekĝ€™s treatment with the long-acting glucagon-like peptide 1 derivative liraglutide (NN2211) markedly improves 24-h glycemia and alpha- and beta-cell function and reduces endogenous glucose release in patients with type 2 diabetes. Diabetes. 2004 ; 53: 1187-1194.
8. Damholt B., Golor G., Wierich W., et al. An open-label, parallel group study investigating the effects of age and gender on the pharmacokinetics of the once-daily glucagon-like peptide-1 analogue liraglutide. J Clin Pharmacol. 2006 ; 46: 635-641.
9. Declaration of Helsinki. Recommendations guiding medical physicians in biomedical research involving human subjects. JAMA. 1997 ; 277: 925-926.
10. Bloomfield DM, Kost JT, Ghosh K., et al. The effect of moxifloxacin on QTc and implications for the design of thorough QT studies. Clin Pharmacol Ther. 2008 ; 84: 679-683.
11. Darpo B., Nebout T., Sager PT Clinical evaluation of QT/QTc prolongation and proarrhythmic potential for nonantiarrhythmic drugs: the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use E14 guideline. J Clin Pharmacol. 2006 ; 46: 498-507.
12. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. The Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs: E14. Geneva, Switzerland: International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use; 2005. http://www.ich.org/LOB/media/MEDIA1476.pdf
13. Malhotra BK, Glue P., Sweeney K., et al. Thorough QT study with recommended and supratherapeutic doses of tolterodine. Clin Pharmacol Ther. 2007 ; 81: 377-385.
14. Sarapa N., Nickens DJ, Raber SR, et al. Ritonavir 100 mg does not cause QTc prolongation in healthy subjects: a possible role as CYP3A inhibitor in thorough QTc studies. Clin Pharmacol Ther. 2007 ; 83: 153-159.
15. Horowitz M., Vilsboll T., Zdravkovic M., et al. Patient-reported rating of gastrointestinal adverse effects during treatment of type 2 diabetes with the once-daily human GLP-1 analogue, liraglutide. Diabetes Obes Metab. 2008 ; 10: 593-596.
16. Vilsboll T., Zdravkovic M., Le Thi T., et al. Liraglutide, a once-daily GLP-1 analog, given as monotherapy significantly improves glycaemic control and lowers body weight without risk of hypoglycemia in patients with type 2 diabetes mellitus. Diabetes Care. 2007 ; 30: 1608-1610.
17. Dmitrienko A., Smith B. Analysis of the QT interval in clinical trials. Drug Info J. 2002 ; 36: 269-279.
18. US Food and Drug Administration (FDA). Guidance for Industry: E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs. Rockville, MD: FDA ; 2005. http://www.fda.gov/ cber/gdlns/iche14qtc.pdf
19. Garber A., Henry R., Ratner R., et al. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet. 2009 ; 373: 473-481.
20. Nauck M., Frid A., Hermansen K., et al. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care. 2008 ; 32: 84-90.
21. Nelson HS, Gross NJ, Levine B., et al. Cardiac safety profile of nebulized formoterol in adults with COPD: a 12-week, multicenter, randomized, double- blind, double-dummy, placebo- and active-controlled trial. Clin Ther. 2007 ; 29: 2167-2178.
22. Peeters M., Janssen K., Kakuda TN, et al. Etravirine has no effect on QT and corrected QT interval in HIV-negative volunteers. Ann Pharmacother. 2008 ; 42: 757-765.
23. Morganroth J. A definitive or thorough phase 1 QT ECG trial as a requirement for drug safety assessment. J Electrocardiol. 2004 ; 37: 25-29.
24. US Food and Drug Administration. Patient information sheet: moxifloxacin hydrochloride (marketed as Avelox). www.fda.gov/Cder/drug/InfoSheets/patient/ moxifloxacin-hclPIS.htm. Accessed August 15, 2008.