title: 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.
abstract: OBJECTIVE
  To investigate the potential effect of sugammadex on anti-Xa anticoagulantactivity of enoxaparin and the activated partial thromboplastin time (APTT) of unfractionated heparin (UFH).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Pieter-Jan
authors.initials: PJ
authors.lastname: De Kam
authors.forename: Annelieke C
authors.initials: AC
authors.lastname: Kruithof
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: van Lierop
authors.forename: Matthijs
authors.initials: M
authors.lastname: Moerland
authors.forename: Justin
authors.initials: J
authors.lastname: Dennie
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Troyer
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Langdon
authors.forename: David E
authors.initials: DE
authors.lastname: Gutstein
authors.forename: Jacobus
authors.initials: J
authors.lastname: Burggraaf
authors.forename: Rachid
authors.initials: R
authors.lastname: El Galta
mesh_terms: D000293:Adolescent; D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D017984:Enoxaparin / Q000494:pharmacology*; D065427:Factor Xa Inhibitors; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D000077122:Sugammadex; D055815:Young Adult; D047408:gamma-Cyclodextrins / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D047408:gamma-Cyclodextrins; D000077122:Sugammadex; D006493:Heparin