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 Aged Birth to <2 Years
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 137
- 试验地点
- 39
- 主要终点
- Part A: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) for Sugammadex
研究概览
简要总结
This study will evaluate the efficacy, safety, and pharmacokinetics (PK) of sugammadex (MK-8616) for reversal of both moderate and deep neuromuscular blockade (NMB) in pediatric participants aged birth to <2 years. The primary hypothesis of this study is that sugammadex is superior to neostigmine in reversing moderate NMB as measured by time to neuromuscular recovery.
详细描述
This trial will be conducted in two parts: Part A and Part B. In Part A, PK sampling will be conducted to identify the pediatric dose providing sugammadex exposure comparable to the next oldest age cohort. For Part B participants, the efficacy of sugammadex (i.e. neuromuscular recovery / time to extubation) 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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Part A will be open-label, while Part B will be double-blinded.
入排标准
- 年龄范围
- 1 Day 至 2 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Categorized as American Society of Anesthesiologists (ASA) Physical Status Class 1, 2, or
- •Has a planned non-emergent surgical procedure or clinical situation (e.g., intubation) that requires moderate or deep NMB with either rocuronium or vecuronium.
- •Has a surgical procedure or clinical situation that would allow neuromuscular monitoring techniques to be applied for neuromuscular transmission monitoring.
- •Is male or female, between birth and <2 years of age.
排除标准
- •Is a preterm infant or neonate <36 weeks gestational age at birth.
- •Has any clinically significant condition or situation (e.g., anatomical malformation that complicates intubation) other than the condition requiring the use of NMBA 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.
- •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.
- •Is expected to require mechanical ventilation after the procedure.
- •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.
- •Use of medication expected to interfere with study treatments given in this trial.
- •Has been previously treated with sugammadex or has participated in a sugammadex clinical trial within 30 days of signing the informed consent form of this current 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
Part A. Sugammadex 2 mg/kg
Participants received a single intravenous (IV) bolus of sugammadex at 2 mg/kg for moderate NMB reversal.
干预措施: Sugammadex 2 mg/kg (Drug)
Part A. Sugammadex 4 mg/kg
Participants received a single IV bolus of sugammadex at 4 mg/kg for deep NMB reversal.
干预措施: Sugammadex 4 mg/kg (Drug)
Part B. Sugammadex 2 mg/kg
Participants received a single IV bolus of sugammadex at 2 mg/kg for moderate NMB reversal.
干预措施: Sugammadex 2 mg/kg (Drug)
Part B. Sugammadex 4 mg/kg
Participants received a single IV bolus of sugammadex at 4 mg/kg for deep NMB reversal.
干预措施: Sugammadex 4 mg/kg (Drug)
Part B. Neostigmine
Participants received a single IV 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) based on availability and/or contraindications, for moderate NMB reversal.
干预措施: Neostigmine + Glycopyrrolate (Drug)
Part B. Neostigmine
Participants received a single IV 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) based on availability and/or contraindications, for moderate NMB reversal.
干预措施: Neostigmine + Atropine (Drug)
结局指标
主要结局
Part A: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) for Sugammadex
时间窗: Day 1: 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose
Pharmacokinetic (PK) blood samples were collected in Part A from pediatric participants at multiple collection times post administration of sugammadex using a sparse sampling approach and used to determine AUC0-inf for sugammadex. As pre-specified by the Statistical Analysis Plan (SAP) for the PK analysis, all PK parameters were analyzed and reported by Part A age cohort (birth to \<27 days, 28 days to \<3 months, 3 to \<6 months, and 6 months to \< 2 years) for each dose (2 mg and 4 mg).
Part A: Area Under the Plasma Concentration Time Curve up to the Interpolated Concentration at 1 Hour Post Dose (AUC0-1hr) for Sugammadex
时间窗: Day 1: 2, 15, 30, and 60 minutes (1 hour) post-dose
PK blood samples were collected in Part A from pediatric participants at multiple collection times post administration of sugammadex using a sparse sampling approach and used to determine AUC0-1hr for sugammadex. As pre-specified by the SAP for the PK analysis, all PK parameters were analyzed and reported by Part A age cohort (birth to \<27 days, 28 days to \<3 months, 3 to \<6 months, and 6 months to \< 2 years) for each dose (2 mg and 4 mg).
Part A: Area Under the Plasma Concentration Time Curve up to the Interpolated Concentration at 4 Hours Post Dose (AUC0-4hr) for Sugammadex
时间窗: Day 1: 2, 15, 30, 60, and 240 minutes (4 hours) post-dose
PK blood samples were collected in Part A from pediatric participants at multiple collection times post administration of sugammadex using a sparse sampling approach and used to determine AUC0-4hr for sugammadex. As pre-specified by the SAP for the PK analysis, all PK parameters were analyzed and reported by Part A age cohort (birth to \<27 days, 28 days to \<3 months, 3 to \<6 months, and 6 months to \< 2 years) for each dose (2 mg and 4 mg).
Part A: Maximum Plasma Concentration (Cmax) of Sugammadex
时间窗: Day 1: 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose
PK blood samples were collected in Part A from pediatric participants at multiple collection times post administration of sugammadex using a sparse sampling approach and used to determine Cmax for sugammadex. As pre-specified by the SAP for the PK analysis, all PK parameters were analyzed and reported by Part A age cohort (birth to \<27 days, 28 days to \<3 months, 3 to \<6 months, and 6 months to \< 2 years) for each dose (2 mg and 4 mg).
Part A: Plasma Clearance (CL) of Sugammadex
时间窗: Day 1: 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose
PK blood samples were collected in Part A from pediatric participants at multiple collection times post administration of sugammadex using a sparse sampling approach and used to determine CL for sugammadex. As pre-specified by the SAP for the PK analysis, all PK parameters were analyzed and reported by Part A age cohort (birth to \<27 days, 28 days to \<3 months, 3 to \<6 months, and 6 months to \< 2 years) for each dose (2 mg and 4 mg).
Part A: Apparent Volume of Distribution (Vd) for Sugammadex
时间窗: Day 1: 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose
PK blood samples were collected in Part A from pediatric participants at multiple collection times post administration of sugammadex using a sparse sampling approach and used to determine Vd for sugammadex. As pre-specified by the SAP for the PK analysis, all PK parameters were analyzed and reported by Part A age cohort (birth to \<27 days, 28 days to \<3 months, 3 to \<6 months, and 6 months to \< 2 years) for each dose (2 mg and 4 mg).
Apparent Volume of Distribution at Steady State (Vss) for Sugammadex
时间窗: Day 1: 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose
PK blood samples were collected in Part A from pediatric participants at multiple collection times post administration of sugammadex using a sparse sampling approach and used to determine Vss for sugammadex. As pre-specified by the SAP for the PK analysis, all PK parameters were analyzed and reported by Part A age cohort (birth to \<27 days, 28 days to \<3 months, 3 to \<6 months, and 6 months to \< 2 years) for each dose (2 mg and 4 mg).
Part A: Half-Life (t1/2) of Sugammadex in Plasma
时间窗: Day 1: 2, 15, 30, 60, 240 to 360, and 600 to 720 minutes post-dose
PK blood samples were collected in Part A from pediatric participants at multiple collection times post administration of sugammadex using a sparse sampling approach and used to determine t½ for sugammadex. As pre-specified by the SAP for the PK analysis, all PK parameters were analyzed and reported by Part A age cohort (birth to \<27 days, 28 days to \<3 months, 3 to \<6 months, and 6 months to \< 2 years) for each dose (2 mg and 4 mg).
Part B: Time to Neuromuscular Recovery (TTNMR) In Reversal of Moderate Block
时间窗: Within Day 1
Time to neuromuscular recovery was defined as the interval from administration of reversal agent to time to neuromuscular recovery. TTNMR could be assessed by 1 of 4 methods selected by the investigator, based on their judgment of what was technically feasible and clinically appropriate for the participant's procedure. These methods were inclusive of both clinical signs (head lift or hip flexion) and neuromuscular transmission monitoring using either a standard peripheral nerve stimulator or the technically challenging quantitative neuromuscular monitoring to train-of-four (TOF) ratio ≥0.9. As pre-specified by the protocol and SAP, TTNMR was analyzed only in Part B participants under the setting of moderate block for comparison of sugammadex 2 mg to neostigmine.
Parts A and B: Percentage of Participants With Adverse Events (AEs) Up To 7 Days Post Administration of Study Medication
时间窗: Up to Day 7
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. As pre-specified by the protocol and SAP, the primary analysis of safety combined data across Part A and Part B (and across age cohorts) and included all AEs that occurred up to 7 days post administration of study medication. The percentage of participants with an AE was reported by treatment and dose received.
次要结局
- Part B: Time to Extubation In Reversal of Moderate Block(Within Day 1)