W. Joseph Herring, MD, PhD1, Tiffany Woo, MS1, Christopher Assaid, PhD1, Terri Monk, MD2, Scott Groudine, MD3. 1Merck & Co., Inc., 2University of Missouri, 3Albany Medical Center
Objective of the technology: Sugammadex, a modified gamma cyclodextrin, is a novel reversal agent with the unique ability to encapsulate the neuromuscular blocking agents (NMBAs) rocuronium and vecuronium, preventing their binding to nicotinic receptors at the neuromuscular junction, thereby reversing neuromuscular blockade (NMB). This innovative mechanism of action distinguishes sugammadex from other reversal agents based on the inhibition of acetylcholine esterase which has no effect on cholinergic neurotransmitters/ receptors which allows for reliable and rapid reversal of both NMB, providing flexibility for use in laparoscopic procedures. Analysis of pooled efficacy data from the global sugammadex clinical database (N=1187) was performed to evaluate potential effects of the subject characteristics of age, body mass index (BMI), sex, ASA class, race and ethnicity. Results of the pooled analyses showed similar geometric mean recovery times within each subpopulation category for both sugammadex 2 and 4 mg/kg. Adverse event incidence was also similar within the subpopulations. No dose adjustment is therefore necessary based on these subject characteristics.
Description of the Technology and Method of Use: Sugammadex represents a fundamentally different approach to the reversal of NMB, compared with currently available options. The selective relaxant-binding agent sugammadex provides rapid reversal of rocuronium- and vecuronium-induced NMB when administered at 2 mg/kg for reversal of moderate (reappearance of T2 of the train-of-four [TOF]) NMB, and 4 mg/kg for deep (1-2 post-tetanic counts [PTC]) NMB. Analyses of key subject characteristics were performed across pooled data from the global sugammadex clinical database to evaluate potential impact on sugammadex efficacy, safety, or dosing requirements.ata were pooled across Phase I-III placebo-controlled studies from the sugammadex clinical database for healthy adult subjects and surgical patients who received sugammadex 2 mg/kg (for reversal of moderate NMB [reappearance of T2]) or 4 mg/kg (deep NMB [1-2 PTC]) together with anesthesia for reversal of rocuronium- or vecuronium-induced NMB. Geometric mean (95% CI) time from study drug administration until recovery of the TOF ratio to 0.9 was evaluated by the subpopulations of age, sex, BMI, ASA class, race and ethnicity, for the pooled dataset by dose group. Evaluation of adverse event (AE) incidence was also conducted across these subpopulations.
Results: In total, 1187 patients were included who received sugammadex following rocuronium/vecuronium. Pooled data showed sugammadex-mediated overall recovery to be rapid: for reversal of moderate NMB (sugammadex 2 mg/kg), geometric mean (95% CI) recovery was 1.9 (1.8, 2.0) min and 2.9 (2.5, 3.4) min for rocuronium and vecuronium respectively; and for reversal of deep NMB (4 mg/kg) was 2.2 (2.1– 2.3) min and 3.8 (3.0– 5.0) min, respectively. Geometric mean (95% CI) times to recovery were similar within each subpopulation category (Table). AE incidence was similar within the subpopulations, with no clinically relevant differences between the treatment groups/doses.
Conclusions: Analysis of pooled data across the sugammadex database found no clinically relevant effect of age, sex, BMI, ASA class, race or ethnicity on efficacy of sugammadex 2 or 4 mg/kg. Sugammadex was generally well-tolerated in these demographic categories. Therefore, no dose adjustment is necessary based on these subject characteristics.