Efficiency and Safety of the Selective Relaxant Binding Agent Adamgammadex Sodium for Reversing Rocuronium-Induced Deep Neuromuscular Block: A Single-Center, Open-Label, Dose-Finding, and Phase IIa Study

Abstract

Background: Rapid reversal of neuromuscular block after surgery and anesthesia is often necessary. Here, we reported the primary efficacy and safety data from a phase IIa study on adamgammadex sodium, a newly developed modified γ-cyclodextrin derivative.Methods: This was a phase IIa, single-center, randomized, open-label, and dose-finding study that enrolled 35 patients under general anesthesia who received the neuromuscular blocking agent rocuronium for induction and maintenance of neuromuscular blockade. The subjects were randomized to one of the five adamgammadex dose groups (2, 4, 6, 8, and 10 mg kg−1) and to the 4 mg kg−1 sugammadex group. Pharmacological efficacy was the recovery time from the start of adamgammadex or sugammadex administration to train-of-four (TOF) ratio ≥0.9, 0.8, and 0.7 among the different dose groups. Adverse events were recorded throughout the study.Results: The efficacy in reversing deep neuromuscular block was the same between 4 mg kg−1 sugammadex and adamgammadex. However, in the lowest dose groups of 2 and 4 mg kg−1 adamgammadex, adequate reversal could not be achieved in all subjects. The recovery time of TOF ratio to 0.9, 0.8, and 0.7 was shorter in the adamgammadex 10 mg kg−1 group than in the sugammadex 4 mg kg−1 group. The average values of the TOF ratio after 3 min of administration of adamgammadex 8 and 10 mg kg−1 and sugammadex 4 mg kg−1 were >90%. There were no serious adverse events after the use of adamgammadex, and no subjects had to be withdrawn from the trial.Conclusions: Adamgammadex enabled quick, predictable, and tolerable reversion of rocuronium-induced deep neuromuscular block in a dose-dependent manner. Adamgammadex doses of 6–10 mg kg−1 might be the recommended dose range for further exploration of efficacy. Clinical Trial Registration: This study was registered at chictr.org.cn, identifier: ChiCTR2000038391.

Adamgammadex in patients to reverse a moderate rocuronium‐induced neuromuscular block

“…In phase 1 study, the well‐tolerated dose of adamgammadex was 32 mg.kg −1 with linear pharmacokinetic properties 10 . In a phase II study, 11 adamgammadex at doses of 6 mg.kg −1 and 8 mg.kg −1 produced a similar effect on the reversion of rocuronium‐induced deep neuromuscular block compared to the 4 mg.kg −1 sugammadex dose.…”

“…In phase 1 study, the well-tolerated dose of adamgammadex was 32 mg.kg À1 with linear pharmacokinetic properties. 10 In a phase II study, 11 adamgammadex at doses of 6 mg. kg À1 and 8 mg.kg À1 produced a similar effect on the reversion of rocuronium-induced deep neuromuscular block compared to the 4 mg.kg À1 sugammadex dose. This clinical study investigated the effectiveness, safety and pharmacokinetics of the administration of adamgammadex to reverse the rocuronium-induced neuromuscular blockade at the reappearance of the second train-of-four (TOF) count (T 2 ) in patients.…”

Comparison of the Efficacy and Safety of Adamgammadex with Sugammadex for Reversal of Rocuronium-Induced Neuromuscular Block: Results of a Phase II Clinical Trial

“…This study compared the efficacy of adamgammadex and sugammadex for moderate neuromuscular block, and the dose choice was an important factor. The recovery time of the TOF ratio to 0.9 induced by adamgammadex at a dose of 4 mg kg −1 was significantly longer than that of sugammadex for rocuronium-induced deep neuromuscular block [ 10 ], and adamgammadex had a similar effect at a dose of 6 mg kg −1 . The reason may be related to the chemical structure [ 7 ].…”

“…In a dose-finding study [ 9 ], the time of it took for the train-of-four (TOF) ratio to return to 0.9 in the group that received saline decreased from 39.3 min to within 3 min in the adamgammadex group. In a phase IIa study [ 10 ], compared with sugammadex, a similar recovery time of rocuronium-induced deep neuromuscular block was observed in patients administered adamgammadex. Overall, adamgammadex was found to be effective for the reversal of a rocuronium-induced neuromuscular block.…”

“…Patients were randomised sequentially into different groups according to the random number ( n = 20 in each dose group). The doses of adamgammadex were 4 and 6 mg kg −1 according to previous studies [ 7 , 9 , 10 ]. The positive control, sugammadex, was dosed at 2 mg kg −1 , based on the dosing information published by the Merck & Co., Inc. (Rahway, NJ, USA).…”