Dose-Finding Pediatric and Adult Trial With Sugammadex (Org 25969, MK-8616, SCH 900616) (19.4.306) (MK-8616-034) (P05961)

Study Overview
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Brief Summary
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The purpose of this study is: to explore the dose-response relation of sugammadex (Org 25969, MK-8616, SCH 900616) given as a reversal agent at reappearance of T2 after 0.6 mg.kg-1 rocuronium in pediatric and adult participants to explore the pharmacokinetics (PK) of sugammadex in pediatric and adult participants, and to evaluate the safety of sugammadex in pediatric and adult participants.

Official Title
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A Multi-Center, Randomized, Parallel Dose-Finding, Safety Assessor-Blinded Trial to Explore the Efficacy, Safety and Pharmacokinetics of Four Doses of Org 25969 and Placebo in Pediatric and Adult Subjects.

Conditions
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Anesthesia

Intervention / Treatment
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* Drug: Sugammadex 0.5 mg/kg
* Drug: Sugammadex 1 mg/kg
* Drug: Sugammadex 2 mg/kg
* Drug: Sugammadex 4 mg/kg
* Drug: Placebo
* Drug: Rocuronium bromide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: American Society of Anesthesiologists (ASA) class 1 - 2, between the ages of 28 days and 65 years inclusive, and between the ages of 2 and 65 years inclusive for Germany and between the ages of 6 and 65 years inclusive for Finland Scheduled for general anesthesia with an anticipated duration of anesthesia of at least 60 minutes, without further need for muscle relaxation other than one single dose of 0.6 mg/kg rocuronium Scheduled for surgical procedures in the supine position Participants who, and/or whose parent(s) or legal guardian(s) have given written informed consent [or appropriate assent, if applicable] Exclusion Criteria: Known or suspected neuromuscular disorders impairing neuromuscular blockade (NMB) and/or significant renal dysfunction, in Germany creatinine and blood urea nitrogen outside local reference ranges Known or suspected to have a (family) history of malignant hyperthermia Known or suspected to have an allergy to narcotics, muscle relaxants or other medication used during general anesthesia Use of medication expected to interfere with the rocuronium given in this trial, based on the dose and the time of administration Pregnancy Childbearing potential not using any of the following methods of birth control: condom or diaphragm with spermicide, vasectomized partner (>6 months), intrauterine device (IUD), abstinence Breast-feeding Prior participation in any study with Org 25969 (sugammadex) Participation in another clinical trial, not pre-approved by NV Organon, within 30 days of entering into study 19.4.306 (MK-8616-034, P05961)

Ages Eligible for Study
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Minimum Age: 28 Days
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sugammadex 0.5 mg/kg<br>Participants are to receive an intravenous (IV) single bolus dose of 0.6 mg/kg rocuronium. At reappearance of T2, an IV single bolus dose of 0.5 mg/kg sugammadex is to be given. | Drug: Sugammadex 0.5 mg/kg<br>* IV infusion<br>* Other names: SCH 900616;Drug: Rocuronium bromide<br>* IV infusion<br>* Other names: ESMERON®;|
| Experimental: Sugammadex 1 mg/kg<br>Participants are to receive an IV single bolus dose of 0.6 mg/kg rocuronium. At reappearance of T2, an IV single bolus dose of 1 mg/kg sugammadex is to be given. | Drug: Sugammadex 1 mg/kg<br>* IV infusion<br>* Other names: SCH 900616;Drug: Rocuronium bromide<br>* IV infusion<br>* Other names: ESMERON®;|
| Experimental: Sugammadex 2 mg/kg<br>Participants are to receive an IV single bolus dose of 0.6 mg/kg rocuronium. At reappearance of T2, an IV single bolus dose of 2 mg/kg sugammadex is to be given. | Drug: Sugammadex 2 mg/kg<br>* IV infusion<br>* Other names: SCH 900616;Drug: Rocuronium bromide<br>* IV infusion<br>* Other names: ESMERON®;|
| Experimental: Sugammadex 4 mg/kg<br>Participants are to receive an IV single bolus dose of 0.6 mg/kg rocuronium. At reappearance of T2, an IV single bolus dose of 4 mg/kg sugammadex is to be given. | Drug: Sugammadex 4 mg/kg<br>* IV infusion<br>* Other names: SCH 900616;Drug: Rocuronium bromide<br>* IV infusion<br>* Other names: ESMERON®;|
| Placebo Comparator: Placebo<br>Participants are to receive an IV single bolus dose of 0.6 mg/kg rocuronium. At reappearance of T2, an IV single 3-mL bolus dose of placebo (sodium chloride 0.9% solution) is to be given. | Drug: Placebo<br>* IV infusion<br>* Other names: sodium chloride 0.9% solution;Drug: Rocuronium bromide<br>* IV infusion<br>* Other names: ESMERON®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time From Start of Administration of Study Treatment (Sugammadex or Placebo) to Recovery T4/T1 Ratio to 0.9 | Neuromuscular functioning was monitored by applying repetitive Train-Of-Four (TOF) electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 & T4 refer to the magnitudes (heights) of the first & fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0) indicates the extent of recovery from neuromuscular blockade (NMB). In this study, twitch responses were recorded until the T4/T1 Ratio reached ≥0.9, the minimum acceptable ratio that indicated recovery from NMB. A faster time to recovery of the T4/T1 Ratio to 0.9 indicates a faster recovery from NMB. | From start of sugammadex or palcebo administration to recovery of T4/T1 ratio to 0.9 (ranging from  0.5 minutes to  30 minutes from sugammadex or placebo administration) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time From Start of Administration of Study Treatment (Sugammadex or Placebo) to Recovery T4/T1 Ratio to 0.7 | Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 & T4 refer to the magnitudes (heights) of the first & fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0) indicates the extent of recovery from NMB. A faster time to recovery of the T4/T1 Ratio to 0.7 indicates a faster recovery from NMB. | From start of sugammadex or placebo administration to recovery of T4/T1 ratio to 0.7 (ranging from  0.4 minutes to  20 minutes from sugammadex or placebo administration) | 
| Time From Start of Administration of Study Treatment (Sugammadex or Placebo) to Recovery T4/T1 Ratio to 0.8 | Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 & T4 refer to the magnitudes (heights) of the first & fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0) indicates the extent of recovery from NMB. A faster time to recovery of the T4/T1 Ratio to 0.8 indicates a faster recovery from NMB. | From start of sugammadex or placebo administration to recovery of T4/T1 ratio to 0.8 (ranging from  0.5 minutes to  25 minutes from sugammadex or placebo administration) |