Lack of a clinically relevant effect of sugammadex on anti-Xa activity or activated partial thromboplastin time following pretreatment with either unfractionated or low-molecular-weight heparin in healthy subjects

• Published in: International journal of clinical pharmacology and therapeutics Vol. 52; no. 8; p. 631
• Main Authors: De Kam, Pieter-Jan, Kruithof, Annelieke C, van Lierop, Marie-José, Moerland, Matthijs, Dennie, Justin, Troyer, Matthew D, Langdon, Ronald B, Gutstein, David E, Burggraaf, Jacobus, El Galta, Rachid
• Format: Journal Article
• Language: English
• Published: Germany 01.08.2014
• Subjects: Adolescent; Adult; Anticoagulants - pharmacology; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Interactions; Enoxaparin - pharmacology; Factor Xa Inhibitors; gamma-Cyclodextrins - administration & dosage; gamma-Cyclodextrins - pharmacology; Heparin - pharmacology; Humans; Male; Middle Aged; Partial Thromboplastin Time; Young Adult
• ISSN: 0946-1965
• DOI: 10.5414/CP202091

To investigate the potential effect of sugammadex on anti-Xa anticoagulantactivity of enoxaparin and the activated partial thromboplastin time (APTT) of unfractionated heparin (UFH). This two-part, randomized, double-blind, placebocontrolled, four-period cross-over study was performed in healthy males (18 - 45 years). In each period, subjects received 40 mg enoxaparin (in part 1), 5,000 units UFH (in part 2), or placebo followed by 4 or 16 mg/kg sugammadex, or placebo. Treatments were separated by ≥ 4 days. Primary endpoints were anti-Xa activity and APTT both time-averaged from 3 to 30 minutes post-dose. Geometric mean ratios (GMRs) and their two-sided 90% confidence limits were calculated for anticoagulant plus sugammadex (4 or 16 mg/kg) vs. anticoagulant plus placebo. The pre-specified threshold for a potential effect of clinical relevance was a 90% upper confidence limit (UCL) > 1.50. In part 1 (n = 13), the 90% UCLs were 1.07 and 1.08 for GMRs of anti-Xa activity after dosing with 4 and 16 mg/kg sugammadex, respectively. In part 2 (n = 43), the 90% UCLs for GMRs of APTT were 1.06 and 1.15. Neither sugammadex dose produced a treatment effect that met the pre-specified criterion for potential clinical relevance. Treatments were generally well tolerated. In healthy subjects, treatment with 4 mg/kg and 16 mg/kg sugammadex did not change either anti-Xa activity or APTT to a clinically meaningful extent following pretreatments with enoxaparin or UFH.