Comparison of 2.0 mg/kg Sugammadex and Neostigmine at Reappearance of T2 in Chinese and European Subjects (Study 19.4.324)(P05768AM1)(COMPLETED)

A Multi-center, Randomized, Parallel-group, Active-controlled, Safety-assessor Blinded Trial, Comparing the Efficacy and Safety of 2.0 mg.Kg-1 Sugammadex With 50 μg.Kg-1 Neostigmine Administered at Reappearance of T2 After Rocuronium in Chinese and European ASA I-III Subjects Undergoing Elective Surgery Under Propofol Anesthesia

The present trial was set up to evaluate the efficacy and safety of 2.0 mg.kg-1 sugammadex compared to neostigmine administered at reappearance of T2 in Chinese and Caucasian subjects for registration purposes in China.

Study Overview

• Status: Completed
• Conditions: Anesthesia, General; Neuromuscular Blockade
• Intervention / Treatment: Drug: Sugammadex; Drug: neostigmine

• Study Type: Interventional
• Enrollment (Actual): 308
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

-Subjects who are willing to provide informed consent; be between 18 and 64 years old; are American Society of Anaesthesiology (ASA) class 1-3 (extremes included); scheduled for elective surgery under general anesthesia, allowing stable neuromuscular monitoring, which requires neuromuscular blockade using rocuronium; be compliant with the dose/visit schedules, and use an accepted method of contraception (if applicable).

For China only: Subjects of Chinese descent born in China, never emigrated out of China and have a Chinese home address. For Europe only: Subjects of Caucasian descent born in Europe, never emigrated out of Europe and have a European home address.

Exclusion Criteria:

-Subjects with expected difficult intubation, neuromuscular disorders affecting neuromuscular blockade, significant renal/hepatic dysfunction, use of a tourniquet, (family) history of malignant hyperthermia, allergy to general anesthesia medications, contraindication to study drugs, breast feeding, pregnant, participation in previous or new trials, a clinically significant condition that may interfere with the trial, or membership in the (family of) study/sponsor staff.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sugammadex in Caucasian Subjects; At reappearance of T2 after the last dose of rocuronium, 2.0 mg.kg-1 sugammadex was administered.	Drug: Sugammadex; After induction of anesthesia an intubation dose of 0.6 mg/kg rocuronium was administered. Maintenance doses of 0.1-0.2 mg/kg rocuronium intravenous (IV) could be administered if necessary. At reappearance of T2 after the last administration of rocuronium, an IV single bolus dose of 2.0 mg/kg sugammadex was administered.; Other Names: Org 25969, Bridion®
Active Comparator: Neostigmine in Caucasian Subjects; At reappearance of T2 after the last dose of rocuronium, 50 μg.kg-1 neostigmine (combined with 10-20 μg.kg-1 atropine, in a ratio ranging from 2.5:1 to 5:1) was administered.	Drug: neostigmine; After induction of anesthesia an intubation dose of 0.6 mg/kg rocuronium was administered. Maintenance doses of 0.1-0.2 mg/kg rocuronium IV could be administered if necessary. At reappearance of T2 after the last administration of rocuronium, an IV single bolus dose of 50 µg/kg neostigmine (combined with 10-20 μg.kg-1 atropine, in a ratio ranging from 2.5:1 to 5:1) was administered.; Other Names: Neostigmine with atropine
Experimental: Sugammadex in Chinese Subjects; At reappearance of T2 after the last dose of rocuronium, 2.0 mg.kg-1 sugammadex was administered.	Drug: Sugammadex; After induction of anesthesia an intubation dose of 0.6 mg/kg rocuronium was administered. Maintenance doses of 0.1-0.2 mg/kg rocuronium intravenous (IV) could be administered if necessary. At reappearance of T2 after the last administration of rocuronium, an IV single bolus dose of 2.0 mg/kg sugammadex was administered.; Other Names: Org 25969, Bridion®
Active Comparator: Neostigmine in Chinese Subjects; At reappearance of T2 after the last dose of rocuronium, 50 μg.kg-1 neostigmine (combined with 10-20 μg.kg-1 atropine, in a ratio ranging from 2.5:1 to 5:1) was administered.	Drug: neostigmine; After induction of anesthesia an intubation dose of 0.6 mg/kg rocuronium was administered. Maintenance doses of 0.1-0.2 mg/kg rocuronium IV could be administered if necessary. At reappearance of T2 after the last administration of rocuronium, an IV single bolus dose of 50 µg/kg neostigmine (combined with 10-20 μg.kg-1 atropine, in a ratio ranging from 2.5:1 to 5:1) was administered.; Other Names: Neostigmine with atropine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time From Start of Administration of Investigational Medicinal Product (IMP) to Recovery of the 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 and assessing twitch response at the adductor pollicis muscle. Nerve stimulation was to continue until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached >= 0.9. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade, with a value of 1.0 representing full recovery. The primary analysis was the comparison between sugammadex & neostigmine among Chinese subjects; other comparisons were secondary.	start of administration of sugammadex/neostigmine to recovery from neuromuscular blockade

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.7 and 0.8.	Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade.	start of administration of sugammadex/neostigmine to recovery from neuromuscular blockade

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Wu X, Oerding H, Liu J, Vanacker B, Yao S, Dahl V, Xiong L, Claudius C, Yue Y, Huang Y, Abels E, Rietbergen H, Woo T. Rocuronium blockade reversal with sugammadex vs. neostigmine: randomized study in Chinese and Caucasian subjects. BMC Anesthesiol. 2014 Jul 12;14:53. doi: 10.1186/1471-2253-14-53. eCollection 2014.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: January 15, 2009
• First Submitted That Met QC Criteria: January 16, 2009
• First Posted (Estimate): January 21, 2009

Study Record Updates

• Last Update Posted (Estimate): November 1, 2015
• Last Update Submitted That Met QC Criteria: October 30, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Enzyme Inhibitors; Adjuvants, Anesthesia; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Cholinesterase Inhibitors; Mydriatics; Parasympathomimetics; Atropine; Neostigmine
• Other Study ID Numbers: P05768; 19.4.324