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

Phase 3

Completed

• Conditions: Anesthesia
• Interventions: Drug: Sugammadex 4 mg/kg; Drug: Sugammadex 0.5 mg/kg; Drug: Sugammadex 1 mg/kg; Drug: Sugammadex 2 mg/kg; Drug: Placebo; Drug: Rocuronium bromide

• Registration Number: NCT00421148
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2005-05-30
• Primary Completion: 2006-05-31
• Study Completion: 2006-06-02
• Study First Submitted: 2007-01-08
• Study First Submitted QC: 2007-01-08
• Study First Posted: 2007-01-11
• Status Verified: 2018-08
• Results First Submitted: 2018-08-08
• Results First Submitted QC: 2018-08-08
• Last Update Submitted: 2018-08-08
• Results First Posted: 2019-01-28
• Last Update Posted: 2019-01-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 94

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sugammadex 4 mg/kg	Sugammadex 4 mg/kg	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.
Sugammadex 0.5 mg/kg	Sugammadex 0.5 mg/kg	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.
Placebo	Rocuronium bromide	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.
Sugammadex 1 mg/kg	Sugammadex 1 mg/kg	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.
Sugammadex 2 mg/kg	Sugammadex 2 mg/kg	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.
Placebo	Placebo	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.
Sugammadex 0.5 mg/kg	Rocuronium bromide	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.
Sugammadex 2 mg/kg	Rocuronium bromide	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.
Sugammadex 1 mg/kg	Rocuronium bromide	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.
Sugammadex 4 mg/kg	Rocuronium bromide	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.

Primary Outcome Measures

Name	Time	Method
Time From Start of Administration of Study Treatment (Sugammadex or Placebo) to Recovery T4/T1 Ratio to 0.9	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)	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.

Secondary Outcome Measures

Name	Time	Method
Time From Start of Administration of Study Treatment (Sugammadex or Placebo) to Recovery T4/T1 Ratio to 0.7	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)	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.
Time From Start of Administration of Study Treatment (Sugammadex or Placebo) to Recovery T4/T1 Ratio to 0.8	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)	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.