Sugammadex is not associated with QT/QTc prolongation: Methodology aspects of an intravenous moxifloxacin-controlled thorough QT study

International Journal of Clinical Pharmacology and Therapeutics

Volumn 50, Issue 8, 2012, Pages 595-604

  De Kam, Pieter Jan ^a   Van Kuijk, Jacqueline ^b   Smeets, Jean ^b,d   Thomsen, Torben ^c   Peeters, Pierre ^b,e  

^a MERCK RESEARCH LABORATORIES   (United States)

^b MSD ^*  (Netherlands)

^c CRS Clinical Research Services GmbH   (Germany)

^d LAPandP Consultants BV   (Netherlands)

^e CENTRE FOR HUMAN DRUG RESEARCH   (Netherlands)

Author keywords

Moxifloxacin; QTc interval; Safety; Sugammadex

Indexed keywords

MOXIFLOXACIN; PLACEBO; SUGAMMADEX;

ADULT; AGED; ARTICLE; ATRIOVENTRICULAR BLOCK; CONTROLLED STUDY; CROSSOVER PROCEDURE; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG EFFECT; DRUG ERUPTION; DRUG HYPERSENSITIVITY; DRUG SAFETY; DYSGEUSIA; ELECTROCARDIOGRAPHY; ERYTHEMA; FEMALE; FOREIGN BODY; HEADACHE; HEART PALPITATION; HEART RATE; HEART REPOLARIZATION; HEART RIGHT BUNDLE BRANCH BLOCK; HEART VENTRICLE EXTRASYSTOLE; HOT FLUSH; HUMAN; HUMAN EXPERIMENT; HYPERSALIVATION; INJECTION SITE PRURITUS; MALE; NAUSEA; NORMAL HUMAN; ORAL PARESTHESIA; QT INTERVAL; QT PROLONGATION; RANDOMIZED CONTROLLED TRIAL; SEX DIFFERENCE; SIDE EFFECT; SINGLE DRUG DOSE; SOMNOLENCE; SUPRAVENTRICULAR TACHYCARDIA; TACHYPNEA; XEROSTOMIA;

ADOLESCENT; ADULT; AGED; ANTI-INFECTIVE AGENTS; AZA COMPOUNDS; CROSS-OVER STUDIES; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; ELECTROCARDIOGRAPHY; FEMALE; GAMMA-CYCLODEXTRINS; HUMANS; INJECTIONS, INTRAVENOUS; LONG QT SYNDROME; MALE; MIDDLE AGED; NEUROMUSCULAR AGENTS; QUINOLINES;

EID: 84864618334     PISSN: 09461965     EISSN: None     Source Type: Journal    
DOI: 10.5414/CP201693     Document Type: Article

References (29)

1. Adam JM, Bennett DJ, Bom A, Clark JK, Feilden H, Hutchinson EJ, Palin R, Prosser A, Rees DC, Rosair GM, Stevenson D, Tarver GJ, Zhang MQ. Cyclodextrin-derived host molecules as reversal agents for the neuromuscular blocker rocuronium bromide: synthesis and structure-activity relationships. J Med Chem. 2002; 45: 1806-1816. doi:10.1021/jm011107f PubMed (Pubitemid 34415376)
2. Bom A, Bradley M, Cameron K, Clark JK, Van Egmond J, Feilden H, MacLean EJ, Muir AW, Palin R, Rees DC, Zhang MQ. A novel concept of reversing neuromuscular block: chemical encapsulation of rocuronium bromide by a cyclodextrin- based synthetic host. Angew Chem Int Ed Engl. 2002; 41: 266-270. PubMed
3. Blobner M, Eriksson LI, Scholz J, Motsch J, Della Rocca G, Prins ME. Reversal of rocuronium-induced neuromuscular blockade with sugammadex compared with neostigmine during sevoflurane anaesthesia: results of a randomized, controlled trial. Eur J Anaesth. 2010; 27: 874-881. doi:10.1097/EJA. 0b013e32833d56b7
4. Jones RK, Caldwell JE, Brull SJ, Soto RG. Reversal of profound rocuronium-induced blockade with sugammadex: a randomized comparison with neostigmine. Anesthesiology. 2008; 109: 816-824. doi:10.1097/ALN. 0b013e31818a3fee PubMed
5. Khuenl-Brady KS, Wattwil M, Vanacker BF, Lora- Tamayo JI, Rietbergen H, Alvarez-Gómez JA. Sugammadex provides faster reversal of vecuronium- induced neuromuscular blockade compared with neostigmine: a multicenter, randomized, controlled trial. Anesth Analg. 2010; 110: 64-73. doi:10.1213/ane.0b013e3181ac53c3 PubMed
6. Lemmens HJ, El-Orbany MI, Berry J, Morte JB Jr, Martin G. Reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia: sugammadex versus neostigmine. BMC Anesthesiol. 2010; 10: 15. doi:10.1186/1471-2253-10-15 PubMed
7. Guidance for Industry E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs. 2005. Available from: URL: http://www.fda.gov/CbER/ gdlns/iche14qtc.htm [Accessed 2009 May 5].
8. Lindgren L, Yli-Hankala A, Randell T, Kirvelä M, Scheinin M, Neuvonen PJ. Haemodynamic and catecholamine responses to induction of anaesthesia and tracheal intubation: comparison between propofol and thiopentone. Br J Anaesth. 1993; 70: 306-310. doi:10.1093/bja/70.3.306 PubMed (Pubitemid 23077606)
9. Korpinen R, Saarnivaara L, Siren K. QT interval of the ECG, heart rate and arterial pressure during anaesthetic induction: comparative effects of alfentanil and esmolol. Acta Anaesthesiol Scand. 1995; 39: 809-813. doi:10.1111/j.1399-6576.1995.tb04175.x PubMed
10. Charbit B, Alvarez JC, Dasque E, Abe E, Démolis JL, Funck-Brentano C. Droperidol and ondansetron- induced QT interval prolongation: a clinical drug interaction study. Anesthesiology. 2008; 109: 206-212. doi:10.1097/ALN. 0b013e31817fd8c8 PubMed
11. Habib AS, Gan TJ. Food and drug administration black box warning on the perioperative use of droperidol: a review of the cases. Anesth Analg. 2003; 96: 1377-1379. doi:10.1213/01.ANE.00000639 23.8 7560.37 PubMed
12. Cammu G, De Kam PJ, Demeyer I, Decoopman M, Peeters PA, Smeets JM, Foubert L. Safety and tolerability of single intravenous doses of sugammadex administered simultaneously with rocuronium or vecuronium in healthy volunteers. Br J Anaesth. 2008; 100: 373-379. doi:10.1093/bja/aem402 PubMed (Pubitemid 351773650)
13. Shah A, Hajian G. A maximum likelihood approach for estimating the QT correction factor using mixed effects model. Stat Med. 2003; 22: 1901-1909. doi:10.1002/sim.1434 PubMed (Pubitemid 36603562)
14. de Kam P-J, van Kuijk J, Prohn M, Thomsen T, Peeters P. Effects of sugammadex doses up to 32 mg/kg alone or in combination with rocuronium or vecuronium on QTc prolongation: a thorough QTc study. Clin Drug Investig. 2010; 30: 599-611. doi:10.2165/11537210-000000000-00000 PubMed
15. Sparr HJ, Vermeyen KM, Beaufort AM, Rietbergen H, Proost JH, Saldien V, Velik-Salchner C, Wierda JM. Early reversal of profound rocuronium- induced neuromuscular blockade by sugammadex in a randomized multicenter study: efficacy, safety, and pharmacokinetics. Anesthesiology. 2007; 106: 935-943. doi:10.1097/01.anes.0000265 152.78943.74 PubMed
16. Saarnivaara L, Simola M. Effects of four anticholinesterase- anticholinergic combinations and tracheal extubation on QTc interval of the ECG, heart rate and arterial pressure. Acta Anaesthesiol Scand. 1998; 42: 460-463. doi:10.1111/j.1399-657 6.1 998.tb05142.x PubMed
17. van Vlymen JM, Parlow JL. The effects of reversal of neuromuscular blockade on autonomic control in the perioperative period. Anesth Analg. 1997; 84: 148-154. PubMed (Pubitemid 27020975)
18. Bloomfield DM, Kost JT, Ghosh K, Hreniuk D, Hickey LA, Guitierrez MJ, Gottesdiener K, Wagner JA. The effect of moxifloxacin on QTc and implications for the design of thorough QT studies. Clin Pharmacol Ther. 2008; 84: 475-480. doi:10.1038/clpt.2008.33 PubMed
19. Démolis JL, Kubitza D, Tennezé L, Funck-Brentano C. Effect of a single oral dose of moxifloxacin (400 mg and 800 mg) on ventricular repolarization in healthy subjects. Clin Pharmacol Ther. 2000; 68: 658-666. doi:10.1067/mcp.2000.111482 PubMed (Pubitemid 32059992)
20. Shah RR. Drug-induced prolongation of the QT interval: regulatory dilemmas and implications for approval and labelling of a new chemical entity. Fundam Clin Pharmacol. 2002; 16: 147-156. doi:10.1046/j.1472-8206.2002.00083.x PubMed (Pubitemid 34587799)
21. Peeters M, Janssen K, Kakuda TN, Schöller- Gyüre M, Lachaert R, Hoetelmans RM, Woodfall B, De Smedt G. Etravirine has no effect on QT and corrected QT interval in HIV-negative volunteers. Ann Pharmacother. 2008; 42: 757-765. doi:10.1345/aph.1K681 PubMed (Pubitemid 351778082)
22. Hulhoven R, Rosillon D, Letiexhe M, Meeus MA, Daoust A, Stockis A. Levocetirizine does not prolong the QT/QTc interval in healthy subjects: results from a thorough QT study. Eur J Clin Pharmacol. 2007; 63: 1011-1017. doi:10.1007/s00228-007-0366-5 PubMed (Pubitemid 47561809)
23. Lasseter KC, Dilzer SC, Smith N. Intravenous conivaptan: effects on the QTc interval and other electrocardiographic parameters in healthy volunteers. Adv Ther. 2007; 24: 310-318. doi:10.1007/BF02849899 PubMed (Pubitemid 46988374)
24. Malik M, Hnatkova K, Schmidt A, Smetana P. Electrocardiographic QTc changes due to moxifloxacin infusion. J Clin Pharmacol. 2009; 49: 674-683. doi:10.1177/0091270008330984 PubMed
25. Nakagawa M, Ooie T, Takahashi N, Taniguchi Y, Anan F, Yonemochi H, Saikawa T. Influence of menstrual cycle on QT interval dynamics. Pacing Clin Electrophysiol. 2006; 29: 607-613. doi:10.1111/j.1540-8159.2006.00407.x PubMed (Pubitemid 43886612)
26. Zhang L, Dmitrienko A, Luta G. Sample size calculations in thorough QT studies. J Biopharm Stat. 2008; 18: 468-482. doi:10.1080/105 4340080 1993002 PubMed
27. Tyl B, Kabbaj M, Fassi B, De Jode P, Wheeler W. Comparison of semiautomated and fully automated methods for QT measurement during a thorough QT/QTc study: variability and sample size considerations. J Clin Pharmacol. 2009; 49: 905-915. doi:10.1177/0091270009337944 PubMed
28. Piccirillo G, Viola E, Nocco M, Santagada E, Durante M, Bucca C, Marigliano V. Autonomic modulation and QT interval dispersion in hypertensive subjects with anxiety. Hypertension. 1999; 34: 242-246. PubMed (Pubitemid 29409222)
29. Peeters P, Passier P, Smeets J et al. Single intravenous high-dose sugammadex (up to 96 mg/kg) is generally safe and well tolerated in healthy volunteers. In: the Annual Meeting of the European Society of Anaesthesiology; 2008 May 31-Jun 3; Copenhagen, Denmark. Eur J Anaesthesiol. 2008; 25 (Suppl 44): 132.