A Multi-center, Randomized, Assessor-blinded, Phase II, Parallel Dose-finding Trial in Subjects of ASA Class 1 - 3 to Assess the Efficacy and Safety of 5 Doses of Org 25969 When Administered at 1-2 PTCs After Administration of Zemuron®
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 主要终点
- Time From Start of Administration of MK-8616 to Recovery T4/T1 Ratio to 0.9
研究概览
简要总结
The primary objective of this study is to explore the dose-response relation of MK-8616 (Org 25969) given as a reversal agent of Zemuron® at 1 to 2 post tetanic counts (PTCs); both Zemuron® and MK-8616 are administered by intravenous (iv) infusion. Another goal of the study is to evaluate the safety of single doses of MK-8616 administered to participants of American Society of Anesthesiologists (ASA) Physical Status Class 1 (otherwise normal, healthy participant); Class 2 (participant with a mild systemic disease); or Class 3 (participant with a severe systemic disease that limits activity, but is not incapacitating).
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
- Double (Participant, Outcomes Assessor)
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
- •Has an ASA Class of 1 to 3
- •Is scheduled for surgical procedures (excluding dental and neck surgeries) with an anticipated duration of anesthesia of ≥45 minutes with the use of Zemuron®
排除标准
- •Is undergoing dental or neck surgery
- •Has anatomical malformation that would impede intubation
- •Has or is suspected to have neuromuscular disorders impairing neuromuscular block and/or significant renal dysfunction
- •Is known or suspected to have a family history of malignant hyperthermia
- •Is known or suspected to have an allergy to narcotics, muscle relaxants, or other medications used during general anesthesia
- •Is pregnant
- •Is a female of childbearing potential not using 1 of the following methods of birth control: condom or diaphragm with spermicide, vasectomized partner (<6 months), intrauterine device (IUD), or abstinence
- •Is breast-feeding
- •Has already participated in the study
- •Has participated in another clinical trial, not pre-approved by Organon Pharmaceuticals USA within 30 days of entering this study
研究组 & 干预措施
1) Zemuron® 0.6 mg/kg + MK-8616 0.5 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 0.6 mg/kg followed by MK-8616 0.5 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced neuromuscular blockade (NMB) reaches 1 to 2 PTCs.
干预措施: MK-8616 (Drug)
1) Zemuron® 0.6 mg/kg + MK-8616 0.5 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 0.6 mg/kg followed by MK-8616 0.5 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced neuromuscular blockade (NMB) reaches 1 to 2 PTCs.
干预措施: Zemuron® (Drug)
2) Zemuron® 1.2 mg/kg + MK-8616 0.5 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 1.2 mg/kg followed by MK-8616 0.5 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
干预措施: MK-8616 (Drug)
2) Zemuron® 1.2 mg/kg + MK-8616 0.5 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 1.2 mg/kg followed by MK-8616 0.5 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
干预措施: Zemuron® (Drug)
3) Zemuron® 0.6 mg/kg + MK-8616 1.0 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 0.6 mg/kg followed by MK-8616 1.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
干预措施: MK-8616 (Drug)
3) Zemuron® 0.6 mg/kg + MK-8616 1.0 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 0.6 mg/kg followed by MK-8616 1.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
干预措施: Zemuron® (Drug)
4) Zemuron® 1.2 mg/kg + MK-8616 1.0 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 1.2 mg/kg followed by MK-8616 1.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
干预措施: MK-8616 (Drug)
4) Zemuron® 1.2 mg/kg + MK-8616 1.0 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 1.2 mg/kg followed by MK-8616 1.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
干预措施: Zemuron® (Drug)
5) Zemuron® 0.6 mg/kg + MK-8616 2.0 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 0.6 mg/kg followed by MK-8616 2.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
干预措施: MK-8616 (Drug)
5) Zemuron® 0.6 mg/kg + MK-8616 2.0 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 0.6 mg/kg followed by MK-8616 2.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
干预措施: Zemuron® (Drug)
6) Zemuron® 1.2 mg/kg + MK-8616 2.0 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 1.2 mg/kg followed by MK-8616 2.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
干预措施: MK-8616 (Drug)
6) Zemuron® 1.2 mg/kg + MK-8616 2.0 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 1.2 mg/kg followed by MK-8616 2.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
干预措施: Zemuron® (Drug)
7) Zemuron® 0.6 mg/kg + MK-8616 4.0 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 0.6 mg/kg followed by MK-8616 4.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
干预措施: MK-8616 (Drug)
7) Zemuron® 0.6 mg/kg + MK-8616 4.0 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 0.6 mg/kg followed by MK-8616 4.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
干预措施: Zemuron® (Drug)
8) Zemuron® 1.2 mg/kg + MK-8616 4.0 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 1.2 mg/kg followed by MK-8616 4.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
干预措施: MK-8616 (Drug)
8) Zemuron® 1.2 mg/kg + MK-8616 4.0 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 1.2 mg/kg followed by MK-8616 4.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
干预措施: Zemuron® (Drug)
9) Zemuron® 0.6 mg/kg + MK-8616 8.0 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 0.6 mg/kg followed by MK-8616 8.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
干预措施: MK-8616 (Drug)
9) Zemuron® 0.6 mg/kg + MK-8616 8.0 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 0.6 mg/kg followed by MK-8616 8.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
干预措施: Zemuron® (Drug)
10) Zemuron® 1.2 mg/kg + MK-8616 8.0 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 1.2 mg/kg followed by MK-8616 8.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
干预措施: MK-8616 (Drug)
10) Zemuron® 1.2 mg/kg + MK-8616 8.0 mg/kg
Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 1.2 mg/kg followed by MK-8616 8.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
干预措施: Zemuron® (Drug)
结局指标
主要结局
Time From Start of Administration of MK-8616 to Recovery T4/T1 Ratio to 0.9
时间窗: Up to 90 minutes
The mean time from the start of MK-8616 administration to recovery T4/T1 ratio of 0.9 was determined. Less time indicates faster recovery from NMB. The ratio of T4 (fourth twitch; amplitude of fourth response to train of four \[TOF\] stimulation is expressed as percent of control T4) over T1 (first twitch; amplitude of first response to TOF stimulation is expressed as percent of control T1) ranges from 0 (complete loss of T4 twitch response) to 1.0 (complete recovery of T4 twitch response). For TOF stimulation, 4 consecutive square wave supra-maximal stimuli of 0.2 msec duration were delivered at 2 Hz every 15 seconds. Neuromuscular monitoring was performed with the TOF-Watch® SX.
次要结局
- Percentage of Participants Experiencing ≥1 Adverse Events (AEs)(Up to 7 days following MK-8616 administration)