A Phase 4 Double-Blinded, Randomized, Active Comparator-Controlled Clinical Trial to Study the Efficacy, Safety, and Pharmacokinetics of Sugammadex (MK-8616) for Reversal of Neuromuscular Blockade in Pediatric Participants
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 288
- 试验地点
- 30
- 主要终点
- Area Under the Plasma Concentration-Time Curve (AUC) From Dosing to Infinity (AUC0-∞) of Sugammadex [Part A]
研究概览
简要总结
This trial will evaluate the efficacy, safety, and pharmacokinetics of sugammadex for the reversal of both moderate and deep neuromuscular blockade (NMB) induced by either rocuronium or vecuronium in pediatric participants. The primary efficacy hypothesis of this investigation is that sugammadex is superior to neostigmine in reversing moderate NMB in pediatric participants as measured by time to recovery to a train-of-four (TOF) ratio of ≥0.9.
详细描述
This trial will be conducted in two parts: Part A and Part B. In Part A, pharmacokinetic (PK) sampling will be conducted to identify the pediatric dose providing sugammadex exposure similar to adults. For Part B participants, the efficacy of sugammadex (i.e. time to recovery of the TOF ratio) will be assessed. Further, safety analyses will be conducted in both Parts A and B. Following completion of Part A, an interim analysis (IA) of the PK and safety data will be performed. Once the appropriate doses are confirmed and safety data is assessed for the 2 doses of sugammadex, then Part B will commence.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 2 Years 至 16 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be categorized as American Society of Anesthesiologists (ASA) Physical Status Class 1, 2, or
- •Have a planned non-emergent surgical procedure or clinical situation (e.g., intubation) that requires moderate or deep NMB with either rocuronium or vecuronium.
- •Have a planned surgical procedure or clinical situation that would allow objective neuromuscular monitoring techniques to be applied with access to the arm for neuromuscular transmission monitoring.
- •Age between 2 to <17 years at Visit
- •If female, may participate if she is not pregnant, not breastfeeding, and at least one of the following: 1) Not a woman of childbearing potential (WOCBP); or 2) A WOCBP who agrees to follow the study contraceptive guidance during the treatment period and for at least 7 days after the last dose of study treatment.
排除标准
- •Has any clinically significant condition or situation (eg, anatomical malformation that complicates intubation) other than the condition being studied that, in the opinion of the investigator, would interfere with the trial evaluations or optimal participation in the trial.
- •Has a neuromuscular disorder that may affect NMB and/or trial assessments.
- •Is dialysis-dependent or has (or is suspected of having) severe renal insufficiency (defined as estimated glomerular filtration rate (eGFR) <30 ml/min).
- •Has or is suspected of having a family or personal history of malignant hyperthermia.
- •Has or is suspected of having an allergy to study treatments or its/their excipients, to opioids/opiates, muscle relaxants or their excipients, or other medication(s) used during general anesthesia.
- •Has received or is planned to receive toremifene and/or fusidic acid via IV administration within 24 hours before or within 24 hours after administration of study treatment.
- •Has been previously treated with sugammadex or has participated in a sugammadex clinical trial.
- •Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 30 days of signing the informed consent/assent for this current trial.
研究组 & 干预措施
Sugammadex 2 mg/kg (Part B)
Single i.v. bolus of sugammadex at 2 mg/kg.
干预措施: Sugammadex 2 mg/kg (Drug)
Sugammadex 4 mg/kg (Part B)
Single i.v. bolus of sugammadex at 4 mg/kg.
干预措施: Sugammadex 4 mg/kg (Drug)
Sugammadex 2 mg/kg (Part A)
Single intravenous (i.v.) bolus of sugammadex at 2 mg/kg.
干预措施: Sugammadex 2 mg/kg (Drug)
Sugammadex 4 mg/kg (Part A)
Single i.v. bolus of sugammadex at 4 mg/kg.
干预措施: Sugammadex 4 mg/kg (Drug)
Neostigmine (Part B)
Single i.v. bolus containing neostigmine (50 μg/kg; up to 5 mg maximum dose) in combination with either glycopyrrolate (10 μg/kg) or atropine sulfate (20 μg/kg).
干预措施: Neostigmine + Glycopyrrolate (Drug)
Neostigmine (Part B)
Single i.v. bolus containing neostigmine (50 μg/kg; up to 5 mg maximum dose) in combination with either glycopyrrolate (10 μg/kg) or atropine sulfate (20 μg/kg).
干预措施: Neostigmine + Atropine (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-Time Curve (AUC) From Dosing to Infinity (AUC0-∞) of Sugammadex [Part A]
时间窗: 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose
The AUCo-∞ for sugammadex, defined as the area under the plasma concentration versus time plot, was determined in each Part A arm.
Plasma Clearance (CL) of Sugammadex [Part A]
时间窗: 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose
The CL of sugammadex, defined as the rate of elimination relative to plasma concentration, was determined in each Part A arm.
Apparent Volume of Distribution (Vz) of Sugammadex [Part A]
时间窗: 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose
The Vz of sugammadex, defined as the amount of drug administered relative to plasma concentrations, was determined in each Part A arm.
Maximum Plasma Concentration (Cmax) of Sugammadex [Part A]
时间窗: 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose
The Cmax of sugammadex, defined as the maximum plasma concentration, was determined in each Part A arm.
Plasma Half-Life (t½) of Sugammadex [Part A]
时间窗: 2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose
The t½ of sugammadex, defined as the time required for the plasma concentration to decrease to 50% of maximum, was determined in each Part A arm.
Percentage of Participants With ≥1 Adverse Event (AE) [Parts A and B]
时间窗: Up to 7 days
The percentage of participants with ≥1 AE(s) for up to 7 days after treatment was determined for each treatment group, pooled according to treatment received. An AE is defined as any unfavorable and unintended medical occurrence, symptom, or disease witnessed in a participant, regardless of whether or not a causal relationship with the study treatment can be demonstrated.
Time to Recovery of Participant Train-of-Four (TOF) Ratio to ≥0.9 [Part B]
时间窗: Up to 30 minutes post-dose
The time to recovery of TOF ratio to ≥0.9 after administration of study intervention was determined for each Part B arm. The TOF ratio is the ratio of the magnitude of the fourth (T4) and first (T1) thumb twitches elicited by 4 electrical stimulations of the ulnar nerve, indicating the current degree of NMB as a decimal from 0 (loss of T4 twitch) to 1 (no NMB). Values closer to 1 indicate less NMB. Per protocol, the efficacy analysis is based on comparison of the Part B: Sugammadex 2 mg arm versus the Part B: Neostigmine + (Glycopyrrolate or Atropine) arm.
次要结局
- Time to Recovery of Participant TOF Ratio to ≥0.7 [Part B](Up to 30 minutes post-dose)
- Time to Recovery of Participant TOF Ratio to ≥0.8 [Part B](Up to 30 minutes post-dose)