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

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.

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.

Study Overview

• Status: Completed
• Conditions: Anesthesia
• Intervention / Treatment: Drug: Placebo; Drug: Sugammadex 0.5 mg/kg; Drug: Rocuronium bromide; Drug: Sugammadex 1 mg/kg; Drug: Sugammadex 2 mg/kg; Drug: Sugammadex 4 mg/kg

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 weeks to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Sugammadex 0.5 mg/kg; IV infusion; Other Names: Org 25969; MK-8616; SCH 900616; Drug: Rocuronium bromide; IV infusion; Other Names: ESMERON®
Experimental: 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.	Drug: Rocuronium bromide; IV infusion; Other Names: ESMERON®; Drug: Sugammadex 1 mg/kg; IV infusion; Other Names: Org 25969; MK-8616; SCH 900616
Experimental: 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.	Drug: Rocuronium bromide; IV infusion; Other Names: ESMERON®; Drug: Sugammadex 2 mg/kg; IV infusion; Other Names: Org 25969; MK-8616; SCH 900616
Experimental: 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.	Drug: Rocuronium bromide; IV infusion; Other Names: ESMERON®; Drug: Sugammadex 4 mg/kg; IV infusion; Other Names: Org 25969; MK-8616; SCH 900616
Placebo Comparator: 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.	Drug: Placebo; IV infusion; Other Names: sodium chloride 0.9% solution; Drug: Rocuronium bromide; IV infusion; Other Names: ESMERON®

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Plaud B, Meretoja O, Hofmockel R, Raft J, Stoddart PA, van Kuijk JH, Hermens Y, Mirakhur RK. Reversal of rocuronium-induced neuromuscular blockade with sugammadex in pediatric and adult surgical patients. Anesthesiology. 2009 Feb;110(2):284-94. doi: 10.1097/ALN.0b013e318194caaa.

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2005
• Primary Completion (Actual): May 31, 2006
• Study Completion (Actual): June 2, 2006

Study Registration Dates

• First Submitted: January 8, 2007
• First Submitted That Met QC Criteria: January 8, 2007
• First Posted (Estimate): January 11, 2007

Study Record Updates

• Last Update Posted (Actual): January 28, 2019
• Last Update Submitted That Met QC Criteria: August 8, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Anticonvulsants; Neuromuscular Agents; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Bromides; Rocuronium
• Other Study ID Numbers: P05961 (Other Identifier: Schering-Plough Protocol Number); 2004-003819-23 (EudraCT Number); 19.4.306 (Other Identifier: Organon Protocol Number); MK-8616-034 (Other Identifier: Merck Protocol Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No