A Multi-Center, Randomized, Safety Assessor-Blinded, Placebo- Controlled, Phase II, Parallel Dose-Finding Trial in Subjects of ASA 1-3 to Assess the Efficacy and Safety of 5 Doses of Sugammadex Administered at 3 and 15 Minutes After Administration of 1.0 and 1.2 mg/kg Rocuronium Bromide
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 174
- 主要终点
- Mean Time From Start of Study Treatment Administration to Recovery of the T4/T1 Ratio to 0.9
研究概览
简要总结
The objective of this trial was to explore the dose-response relation of sugammadex (Org 25969; MK-8616) administered for the reversal of neuromuscular blockade (NMB) at 3 and 15 minutes following administration of 1.0 and 1.2 mg/kg of Esmeron® (rocuronium) in participants receiving surgery, classified as American Society of Anesthesiologists (ASA) class 1 (otherwise normal, healthy participant), class 2 (participant with mild systemic disease), or class 3 (participant with a severe systemic disease that limits activity, but is not incapacitating).
详细描述
In the United States, the highest dose recommended in the package insert of Zemuron® (i.e. the trade name for Esmeron® in the US) is 1.2 mg/kg whereas in Europe it is 1.0 mg/kg. For both doses, dose recommendations for reversal with sugammadex were to be found. Hence, the present trial was set up to explore the dose-response relation of sugammadex given as an NMB reversal agent at 3 and 15 minutes following administration of 1.0 and 1.2 mg/kg of Esmeron® in subjects of ASA 1 to 3. The sub-investigator who performed any subjective safety assessments after anesthesia was to be remained blinded.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants of ASA class 1 - 3, above or equal to the age of 18 years;
- •Participants scheduled for surgical procedures with an anticipated duration of anesthesia of at least 120 minutes, without further need for muscle relaxation other than for intubation;
- •Participants scheduled for surgical procedures in supine position;
- •Participants who had given written informed consent.
排除标准
- •Participants in whom a difficult intubation because of anatomical malformations was expected;
- •Participants known or suspected to have neuromuscular disorders impairing neuromuscular blocking and/or significant renal dysfunction;
- •Participants known or suspected to have a (family) history of malignant hyperthermia;
- •Participants known or suspected to have an allergy to narcotics, muscle relaxants or other medication used during general anesthesia;
- •Participants receiving medication known to interfere with neuromuscular blocking agents, such as anticonvulsants and Mg^2+;
- •Participants who had already participated in this trial;
- •Participants who had participated in another clinical trial, not pre-approved by the Sponsor, within 30 days of entering into this trial;
- •Female participants who were pregnant: in females, pregnancy was to be excluded both from medical history and by a human chorionic gonadotropin (hCG) test within 24 hours before surgery except in females who were not of childbearing potential, i.e. at least 2 years menopausal or who had undergone tubal ligation or an hysterectomy;
- •Female participants of childbearing potential not using any of the following methods of birth control (for one month): condom or diaphragm with spermicide, vasectomized partner (>6 months), intrauterine device (IUD), abstinence;
- •Female participants who were breast-feeding.
研究组 & 干预措施
Arm A. Placebo; 3 min after 1 mg/kg Esmeron®
Placebo (single intravenous (IV) bolus) administered 3 minutes (min) after the bolus intubation dose of 1 mg/kg Esmeron®.
干预措施: Placebo (Drug)
Arm A. Placebo; 3 min after 1 mg/kg Esmeron®
Placebo (single intravenous (IV) bolus) administered 3 minutes (min) after the bolus intubation dose of 1 mg/kg Esmeron®.
干预措施: Esmeron® (Drug)
Arm B. 2 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron®
Sugammadex (2 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1 mg/kg Esmeron®.
干预措施: Sugammadex (Drug)
Arm B. 2 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron®
Sugammadex (2 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1 mg/kg Esmeron®.
干预措施: Esmeron® (Drug)
Arm C. 4 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron®
Sugammadex (4 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1 mg/kg Esmeron®.
干预措施: Sugammadex (Drug)
Arm C. 4 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron®
Sugammadex (4 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1 mg/kg Esmeron®.
干预措施: Esmeron® (Drug)
Arm D. 8 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron®
Sugammadex (8 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1 mg/kg Esmeron®.
干预措施: Sugammadex (Drug)
Arm D. 8 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron®
Sugammadex (8 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1 mg/kg Esmeron®.
干预措施: Esmeron® (Drug)
Arm E. 12 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron®
Sugammadex (12 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1 mg/kg Esmeron®.
干预措施: Sugammadex (Drug)
Arm E. 12 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron®
Sugammadex (12 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1 mg/kg Esmeron®.
干预措施: Esmeron® (Drug)
Arm F. 16 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron®
Sugammadex (16 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1 mg/kg Esmeron®.
干预措施: Sugammadex (Drug)
Arm F. 16 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron®
Sugammadex (16 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1 mg/kg Esmeron®.
干预措施: Esmeron® (Drug)
Arm G. Placebo; 15 min after 1 mg/kg Esmeron®
Placebo (single intravenous (IV) bolus) administered 15 min after the bolus intubation dose of 1 mg/kg Esmeron®.
干预措施: Placebo (Drug)
Arm G. Placebo; 15 min after 1 mg/kg Esmeron®
Placebo (single intravenous (IV) bolus) administered 15 min after the bolus intubation dose of 1 mg/kg Esmeron®.
干预措施: Esmeron® (Drug)
Arm H. 2 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron®
Sugammadex (2 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1 mg/kg Esmeron®.
干预措施: Sugammadex (Drug)
Arm H. 2 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron®
Sugammadex (2 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1 mg/kg Esmeron®.
干预措施: Esmeron® (Drug)
Arm I. 4 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron®
Sugammadex (4 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1 mg/kg Esmeron®.
干预措施: Sugammadex (Drug)
Arm I. 4 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron®
Sugammadex (4 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1 mg/kg Esmeron®.
干预措施: Esmeron® (Drug)
Arm J. 8 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron®
Sugammadex (8 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1 mg/kg Esmeron®.
干预措施: Sugammadex (Drug)
Arm J. 8 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron®
Sugammadex (8 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1 mg/kg Esmeron®.
干预措施: Esmeron® (Drug)
Arm K. 12 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron®
Sugammadex (12 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1 mg/kg Esmeron®.
干预措施: Sugammadex (Drug)
Arm K. 12 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron®
Sugammadex (12 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1 mg/kg Esmeron®.
干预措施: Esmeron® (Drug)
Arm L. 16 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron®
Sugammadex (16 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1 mg/kg Esmeron®.
干预措施: Sugammadex (Drug)
Arm L. 16 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron®
Sugammadex (16 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1 mg/kg Esmeron®.
干预措施: Esmeron® (Drug)
Arm M. Placebo; 3 min after 1.2 mg/kg Esmeron®
Placebo (single IV bolus) administered 3 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.
干预措施: Placebo (Drug)
Arm M. Placebo; 3 min after 1.2 mg/kg Esmeron®
Placebo (single IV bolus) administered 3 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.
干预措施: Esmeron® (Drug)
Arm N. 2 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron®
Sugammadex (2 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.
干预措施: Sugammadex (Drug)
Arm N. 2 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron®
Sugammadex (2 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.
干预措施: Esmeron® (Drug)
Arm O. 4 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron®
Sugammadex (4 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.
干预措施: Sugammadex (Drug)
Arm O. 4 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron®
Sugammadex (4 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.
干预措施: Esmeron® (Drug)
Arm P. 8 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron®
Sugammadex (8 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.
干预措施: Sugammadex (Drug)
Arm P. 8 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron®
Sugammadex (8 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.
干预措施: Esmeron® (Drug)
Arm Q. 12 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron®
Sugammadex (12 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.
干预措施: Sugammadex (Drug)
Arm Q. 12 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron®
Sugammadex (12 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.
干预措施: Esmeron® (Drug)
Arm R. 16 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron®
Sugammadex (16 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.
干预措施: Sugammadex (Drug)
Arm R. 16 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron®
Sugammadex (16 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.
干预措施: Esmeron® (Drug)
Arm S. Placebo; 15 min after 1.2 mg/kg Esmeron®
Placebo (single IV bolus) administered 15 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.
干预措施: Placebo (Drug)
Arm S. Placebo; 15 min after 1.2 mg/kg Esmeron®
Placebo (single IV bolus) administered 15 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.
干预措施: Esmeron® (Drug)
Arm T. 2 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron®
Sugammadex (2 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.
干预措施: Sugammadex (Drug)
Arm T. 2 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron®
Sugammadex (2 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.
干预措施: Esmeron® (Drug)
Arm U. 4 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron®
Sugammadex (4 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.
干预措施: Sugammadex (Drug)
Arm U. 4 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron®
Sugammadex (4 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.
干预措施: Esmeron® (Drug)
Arm V. 8 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron®
Sugammadex (8 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.
干预措施: Sugammadex (Drug)
Arm V. 8 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron®
Sugammadex (8 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.
干预措施: Esmeron® (Drug)
Arm W. 12 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron®
Sugammadex (12 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.
干预措施: Sugammadex (Drug)
Arm W. 12 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron®
Sugammadex (12 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.
干预措施: Esmeron® (Drug)
Arm X. 16 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron®
Sugammadex (16 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.
干预措施: Sugammadex (Drug)
Arm X. 16 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron®
Sugammadex (16 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1.2 mg/kg Esmeron®.
干预措施: Esmeron® (Drug)
结局指标
主要结局
Mean Time From Start of Study Treatment Administration to Recovery of the T4/T1 Ratio to 0.9
时间窗: Up to 240 minutes following administration of study treatment
Mean time from start of study treatment administration to recovery of participant T4/T1 ratio to 0.9 was assessed through the repeated application (every 15 seconds) of an electrical stimulation protocol. Specifically, 4 electrical stimulations were applied to the ulnar nerve and the magnitude of the twitch response of the adductor pollicis muscle (i.e. thumb twitch response) was assessed. With T4 and T1 referring to the respective magnitude of the fourth and first thumb twitch during nerve stimulation, the T4/T1 ratio indicates the current degree of neuromuscular blockade (NMB) present in the participant as a decimal from 0 (loss of T4 twitch) to 1 (no NMB). Further, reduced recovery time of the T4/T1 ratio to 0.9 indicates faster recovery from NMB. Summary data, originally presented in the format of units "minutes:seconds" (mm:ss), was reformatted to be presented in the single unit of "minutes" (min).
次要结局
- Mean Time From Start of Study Treatment Administration to Recovery of the T4/T1 Ratio to 0.7(Up to 180 minutes following administration of study treatment)
- Number of Participants Experiencing an Adverse Event(Up to 7 days following administration of study treatment)
- Mean Time From Start of Study Treatment Administration to Recovery of the T4/T1 Ratio to 0.8(Up to 200 minutes following administration of study treatment)